Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease.

PubMed

Thomas, E; Wade, A; Crawford, G; Jenner, B; Levinson, N; Wilkinson, J

2014-03-01

The alginate-antacid, Gaviscon Double Action (Gaviscon DA; Reckitt Benckiser, Slough, UK) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction. The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design. A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease (GERD) patients. A randomised, double-blind, parallel group study was performed in 110 patients with symptoms of GERD. Patients received Gaviscon DA or placebo tablets for 7 consecutive days. The primary endpoint compared the change in overall Reflux Disease Questionnaire (RDQ) symptom score (combined heartburn/regurgitation/dyspepsia). Secondary endpoints assessed individual dimensions, GERD dimension (heartburn and regurgitation) and overall treatment evaluation (OTE). There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group (Least Squares Mean difference -0.55; P = 0.0033), and for each of the dimensions independently. Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [mean (standard deviation) OTE 4.1 (2.44) vs. 1.9 (3.34); P = 0.0005]. No differences in the incidence of adverse events were observed between treatment groups. Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance. Larger scale clinical investigations of medications targeting the acid pocket are warranted. (EudraCT, 2012-002188-84). © 2014 John Wiley & Sons Ltd.

Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

PubMed

Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

2016-11-29

Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial.

PubMed

Luedtke, Kerstin; Rushton, Alison; Wright, Christine; Jürgens, Tim; Polzer, Astrid; Mueller, Gerd; May, Arne

2015-04-16

To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain. Double blind parallel group randomised controlled trial with six months' follow-up conducted May 2011-March 2013. Participants, physiotherapists, assessors, and analyses were blinded to group allocation. Interdisciplinary chronic pain centre. 135 participants with non-specific chronic low back pain >12 weeks were recruited from 225 patients assessed for eligibility. Participants were randomised to receive anodal (20 minutes to motor cortex at 2 mA) or sham transcranial direct current stimulation (identical electrode position, stimulator switched off after 30 seconds) for five consecutive days immediately before cognitive behavioural management (four week multidisciplinary programme of 80 hours). Two primary outcome measures of pain intensity (0-100 visual analogue scale) and disability (Oswestry disability index) were evaluated at two primary endpoints after stimulation and after cognitive behavioural management. Analyses of covariance with baseline values (pain or disability) as covariates showed that transcranial direct current stimulation was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval -8.69 mm to 6.3 mm; P=0.68)) and disability (difference between groups 1 point (-1.73 to 1.98; P=0.86)) and did not influence the outcome of cognitive behavioural management (difference between group 3 mm (-10.32 mm to 6.73 mm); P=0.58; difference between groups on Oswestry disability index 0 point (-2.45 to 2.62); P=0.92). The stimulation was well tolerated with minimal transitory side effects. This results of this trial on the effectiveness of transcranial direct current stimulation for the reduction of pain and disability do not support its clinical use for managing non-specific chronic low back pain.Trial registration Current controlled trials ISRCTN89874874. © Luedtke et al 2015.

Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

PubMed Central

Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

2004-01-01

Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial.

PubMed

Devos, David; Moreau, Caroline; Maltête, David; Lefaucheur, Romain; Kreisler, Alexandre; Eusebio, Alexandre; Defer, Gilles; Ouk, Thavarak; Azulay, Jean-Philippe; Krystkowiak, Pierre; Witjas, Tatiana; Delliaux, Marie; Destée, Alain; Duhamel, Alain; Bordet, Régis; Defebvre, Luc; Dujardin, Kathy

2014-06-01

Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 (-25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. Clinicaltrials.gov reference: NCT00767091.

Effect of liraglutide on physical performance in type 2 diabetes (LIPER2): A randomised, double-blind, controlled trial.

PubMed

Wägner, Ana María; Miranda-Calderín, Guillermo; Ugarte-Lopetegui, Miren Arantza; Marrero-Santiago, Héctor; Suárez-Castellano, Laura; Alberiche-Ruano, María Del Pino; Castillo-García, Nuria; López-Madrazo, María José; Alemán, Carolina; Martínez-Mancebo, Carla; López-Ríos, Laura; Díez Del Pino, Alicia; Nóvoa-Mogollón, Francisco Javier

2016-12-15

Preclinical studies and small clinical trials suggest that glucagon-like peptide 1 (GLP1) may have a positive effect on ventricular function. Liraglutide is a GLP1-analogue used in the treatment of type 2 diabetes. LIPER2 is a phase IV, randomised, double-blind, placebo-controlled, parallel-design trial, assessing the effect of 6 months' liraglutide 1.8 mg/d on measures of cardiac function and physical performance in patients with type 2 diabetes. A total of 30 patients with type 2 diabetes will be included, if their HbA1c is between 7 and 10% while on oral agents (including metformin if tolerated and not contraindicated), a maximum of 2 intermediate or long-acting insulin injections per day or a combination of both. After their baseline examinations, patients are randomised to receive a daily subcutaneous liraglutide or placebo injection (titrated to 1.8 mg/d if tolerated) for 6 months. The primary end-point is the maximal oxygen consumption during cycle ergometry at the end of the study period. Other end-points include distance covered during a 6-min walk test, left ventricular ejection fraction and other measures of ventricular systolic and diastolic functions assessed by echocardiography, heart rate, blood pressure, pro-brain natriuretic peptide, C-reactive protein, HbA1c, lipids, apolipoprotein B, body weight and waist girth. Safety end-points include adverse event reporting, blood count, kidney and liver function, amylase, lipase, electrolytes, calcitonin, CA19.9 and pregnancy test for fertile women. At the time of this report, recruitment is still ongoing. Results are expected to be reported in December 2016.

A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy

PubMed Central

Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee; Smolen, Josef S

2017-01-01

Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181. PMID:26318384

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

PubMed Central

Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

2013-01-01

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

PubMed Central

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-01-01

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study.

PubMed

Taylor, Peter C; Schiff, Michael H; Wang, Qingmin; Jiang, Yusang; Zhuang, Yanli; Kurrasch, Regina; Daga, Shruti; Rao, Ravi; Tak, Paul P; Hsu, Benjamin

2018-05-01

This randomised, double-blind, parallel-group, phase 3 study compared monotherapy with sirukumab, an anti-interleukin-6 cytokine monoclonal antibody, with adalimumab monotherapy in patients with rheumatoid arthritis (RA). Biologic-naïve patients with active RA who were inadequate responders or were intolerant to, or inappropriate for, methotrexate were randomised to subcutaneous sirukumab 100 mg every 2 weeks (n=187), sirukumab 50 mg every 4 weeks (n=186) or adalimumab 40 mg every 2 weeks (n=186). Primary endpoints at week 24 were change from baseline in Disease Activity Score in 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) and proportion of patients achieving an American College of Rheumatology (ACR) 50 response; these endpoints were tested in sequential order. This study is registered at EudraCT (number: 2013-001417-32) and ClinicalTrials.gov (number: NCT02019472). Significantly greater improvements from baseline in mean (SD) DAS28 (ESR) were observed at week 24 with sirukumab 100 mg every 2 weeks (-2.96 (1.580)) versus adalimumab 40 mg every 2 weeks (-2.19 (1.437); P<0.001). Sirukumab 50 mg every 4 weeks also showed significantly greater improvement from baseline at week 24 in DAS28 (ESR) (-2.58 (1.524)) compared with adalimumab (P=0.013). The ACR50 response rates with the 100 mg (35.3%) and 50 mg (26.9%) doses of sirukumab were comparable to that with adalimumab (31.7%) at week 24. The safety profile of sirukumab was consistent with that observed with anti-interleukin-6 receptor antibodies. A dose-related effect on the incidence of injection-site reactions was observed with sirukumab. Sirukumab monotherapy showed greater improvements in DAS28 (ESR), but similar ACR50 response rates, versus adalimumab monotherapy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

PubMed Central

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-01-01

Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

PubMed

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-08-07

Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥ 140 mm Hg and home BP ≥ 130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K(+), clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study.

PubMed

Matsuoka, Hiromichi; Ishiki, Hiroto; Iwase, Satoru; Koyama, Atsuko; Kawaguchi, Takashi; Kizawa, Yoshiyuki; Morita, Tatsuya; Matsuda, Yoshinobu; Miyaji, Tempei; Ariyoshi, Keisuke; Yamaguchi, Takuhiro

2017-08-28

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics approval was obtained at all participating sites.The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. UMIN000017647; Pre-results. 2.2, 26 April 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effect of Beta Adrenergic Blockade on Ratings of Perceived Exertion.

DTIC Science & Technology

1984-01-01

exrcis is uvo Hughson, et al. (47) investigated the effect of beta blockade using a single, 100-mg oral dose of metoprolol or matched placebo on 12...administered either placebo, propranolol (80 mug) or metoprolol (100 mug) in a double- blind, randomised manner. Before the muscle-strength tests were...The non-selective BABA propranolol and the selective agent metoprolol were compared with a placebo in a double blind cross-over design. Measurements

Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

PubMed Central

Evans, E Glyn V; Sigurgeirsson, Bárdur

1999-01-01

Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatmentContinuous terbinafine should be the current treatment of choice for onychomycosis PMID:10205099

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

PubMed Central

2012-01-01

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au) ACTRN12611000092998 PMID:23241329

Effects of a probiotic intervention in acute canine gastroenteritis--a controlled clinical trial.

PubMed

Herstad, H K; Nesheim, B B; L'Abée-Lund, T; Larsen, S; Skancke, E

2010-01-01

To evaluate the effect of a probiotic product in acute self-limiting gastroenteritis in dogs. Thirty-six dogs suffering from acute diarrhoea or acute diarrhoea and vomiting were included in the study. The trial was performed as a randomised, double blind and single centre study with stratified parallel group design. The animals were allocated to equal looking probiotic or placebo treatment by block randomisation with a fixed block size of six. The probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus licheniformis and Lactobacillus farciminis. The time from initiation of treatment to the last abnormal stools was found to be significantly shorter (P = 0.04) in the probiotic group compared to placebo group, the mean time was 1.3 days and 2.2 days, respectively. The two groups were found nearly equal with regard to time from start of treatment to the last vomiting episode. The probiotic tested may reduce the convalescence time in acute self-limiting diarrhoea in dogs.

Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus.

PubMed

Derumeaux, Geneviève; Ernande, Laura; Serusclat, André; Servan, Evelyne; Bruckert, Eric; Rousset, Hugues; Senn, Stephen; Van Gaal, Luc; Picandet, Brigitte; Gavini, François; Moulin, Philippe

2012-01-01

REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30 ± 0.80 to 7.77 ± 1.31 versus pioglitazone: from 8.30 ± 0.80 to 7.45 ± 1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug.

Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial

PubMed Central

Tarnow, Lise; Frandsen, Merete; Nielsen, Bente B; Hansen, Birgitte V; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

2009-01-01

Objectives To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes. Design Randomised, double blind, double dummy, parallel trial. Setting Secondary care in Denmark between 2003 and 2006. Participants Non-obese patients (BMI ≤27) with preserved beta cell function. Interventions After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA1c) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA1c concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached. Main outcome measure HbA1c concentration. Results Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments −2.51 kg, 95% confidence interval −4.07 to −0.95). Conclusions In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide. Trial registration NCT00118963 PMID:19900993

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

PubMed

Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients - protocol for a double-blind, placebo-controlled randomised trial.

PubMed

Dogar, Omara; Barua, Deepa; Boeckmann, Melanie; Elsey, Helen; Fatima, Razia; Gabe, Rhian; Huque, Rumana; Keding, Ada; Khan, Amina; Kotz, Daniel; Kralikova, Eva; Newell, James N; Nohavova, Iveta; Parrott, Steve; Readshaw, Anne; Renwick, Lottie; Sheikh, Aziz; Siddiqi, Kamran

2018-04-20

Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine - a low-cost plant-derived nicotine substitute - for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomised trial. TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. Newly diagnosed (in the last four weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n= 2,388). The primary outcome measure is biochemically verified continuous abstinence from smoking at six months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and tuberculosis (TB) outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke. This article is protected by copyright. All rights reserved.

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

PubMed

Hollis, Chris; Hall, Charlotte L; Guo, Boliang; James, Marilyn; Boadu, Janet; Groom, Madeleine J; Brown, Nikki; Kaylor-Hughes, Catherine; Moldavsky, Maria; Valentine, Althea Z; Walker, Gemma M; Daley, David; Sayal, Kapil; Morriss, Richard

2018-04-26

Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

[Problems of study designs with randomization, blinding and placebos].

PubMed

Heusser, P

1999-04-01

As randomised double-blind trials are not rarely demanded as a prerequisite for the scientific acceptance of complementary medicine, the author has analysed the soundness of this demand on the basis of the international literature. As a result there appeared a number of methodological, practical and ethical problems which question the theoretically deduced primal value of this study design relative to the needs of medical practice and of health insurance issues. The experimental instruments of randomisation, blinding and placebo deliberately exclude essential therapeutic factors which are integral elements of complementary medical concepts; therefore, it is suggested to supplement quantitatively and collectively oriented experimental research by non-experimental procedures, which adequately reflect the context- and practice-related individual reality.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

PubMed

Holtzheimer, Paul E; Husain, Mustafa M; Lisanby, Sarah H; Taylor, Stephan F; Whitworth, Louis A; McClintock, Shawn; Slavin, Konstantin V; Berman, Joshua; McKhann, Guy M; Patil, Parag G; Rittberg, Barry R; Abosch, Aviva; Pandurangi, Ananda K; Holloway, Kathryn L; Lam, Raymond W; Honey, Christopher R; Neimat, Joseph S; Henderson, Jaimie M; DeBattista, Charles; Rothschild, Anthony J; Pilitsis, Julie G; Espinoza, Randall T; Petrides, Georgios; Mogilner, Alon Y; Matthews, Keith; Peichel, DeLea; Gross, Robert E; Hamani, Clement; Lozano, Andres M; Mayberg, Helen S

2017-11-01

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical). Copyright © 2017 Elsevier Ltd. All rights reserved.

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

PubMed

O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

2013-03-01

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial.

PubMed

Kragsnaes, Maja Skov; Kjeldsen, Jens; Horn, Hans Christian; Munk, Heidi Lausten; Pedersen, Finn Moeller; Holt, Hanne Marie; Pedersen, Jens Kristian; Holm, Dorte Kinggaard; Glerup, Henning; Andersen, Vibeke; Fredberg, Ulrich; Kristiansen, Karsten; Christensen, Robin; Ellingsen, Torkell

2018-04-27

An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA. This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study. This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s). NCT03058900; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy.

PubMed

Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee; Smolen, Josef S

2017-01-01

To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. NCT01936181. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

PubMed

Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

2011-09-21

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Current controlled trials ISRCTN83178718.

Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period

PubMed Central

Mofid, Layla S; Casapía, Martín; Montresor, Antonio; Rahme, Elham; Fraser, William D; Marquis, Grace S; Vercruysse, Jozef; Allen, Lindsay H; Gyorkos, Theresa W

2015-01-01

Introduction Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes. Methods and analysis A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis. Ethics and dissemination Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences. Trial registration number Clinicaltrials.gov: NCT01748929. PMID:26084556

Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period.

PubMed

Mofid, Layla S; Casapía, Martín; Montresor, Antonio; Rahme, Elham; Fraser, William D; Marquis, Grace S; Vercruysse, Jozef; Allen, Lindsay H; Gyorkos, Theresa W

2015-06-17

Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes. A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis. Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences. Clinicaltrials.gov: NCT01748929. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial.

PubMed

Petersen, Eiko E; Genet, Margherita; Caserini, Maurizio; Palmieri, Renata

2011-01-01

A randomised, double blind, parallel groups, placebo controlled clinical trial was conducted to assess the efficacy and safety profile of 250 mg ascorbic acid (Vit. C, Vagi C) in women with bacterial vaginosis (BV). Overall, 277 out-patients with at least three of the following signs (white discharge that smoothly coats the vaginal walls, pH of vaginal fluid > 4.5, a fishy odour of vaginal discharge before or after addition of 10% KOH and presence of clue cells on microscopic examination) were randomised to apply a tablet deeply into the vagina once daily for 6 days. The primary efficacy endpoint was the cure rate, defined as the recovery of all inclusion criteria. In the intent-to-treat (ITT) population, cure was achieved by 55.3% of patients with Vit. C (n=141) and by 25.7% of patients with placebo (n=136). The between-group difference was 29.6% (p < 0.001). In the per-protocol (PP) population, cure rate was 66.4% with Vit. C (n=116) and 27.1% with placebo (n = 118), respectively. Between-group difference was 39.3% (p < 0.001). In a subset of patients with centralised evaluation of the vaginal swab, cure in ITT was achieved by 86.3% of patients with Vit. C (n=51) and by 7.6% of patients with placebo (n=53), the between-group difference was 78.7% (p < 0.0001). Cure rate in PP was 86.0% with Vit. C (n=50) and 6.1% with placebo (n=49), between-group difference was 79.9% (p < 0.0001). Both Vit. C and placebo were well tolerated and no differences in safety profile were evident between groups. The results support an effective and safe use of silicon-coated Vit. C vaginal tablets in the management of BV.

Reflexology has no immediate haemodynamic effect in patients with chronic heart failure: a double blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2013-08-01

This study measured the effects of reflexology in 12 reflexology-naive patients with chronic heart failure in a placebo-controlled, double blind randomised controlled study design. Outcomes included 'beat-to-beat' non-invasive continuous measurement of cardiovascular parameters and measurement of state of anxiety and pain/discomfort. There were no changes in any of the haemodynamic parameters measured (all p > 0.05). Perceived state of anxiety was significantly reduced post treatment in the control group only (p = 0.03). Reflexology applied to the feet of patients with chronic heart failure appears to have no immediate haemodynamic effects. While any long term treatment effect is uncertain, it would appear that reflexology is safe for use in this patient group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

PubMed

Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial.

PubMed

ten Hoedt, Amber E; de Sonneville, Leo M J; Francois, Baudouin; ter Horst, Nienke M; Janssen, Mirian C H; Rubio-Gozalbo, M Estela; Wijburg, Frits A; Hollak, Carla E M; Bosch, Annet M

2011-02-01

The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients' mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted "diet for life" might be an advisable option for many.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Comparison of Fucithalmic viscous eye drops and Chloramphenicol eye ointment as a single treatment in corneal abrasion.

PubMed

Boberg-Ans, G; Nissen, K R

1998-02-01

To compare the healing of the cornea and the incidence of infection after traumatic corneal epithelial defect after single treatment with double bandage combined with either Fucithalmic single unit dose eye drops or chloramphenicol eye ointment. This is a single-centre, randomised, single-blind, parallel-group study of 144 patients with accidental corneal abrasion or corpus alieni cornea who were referred to the Eye Department at Gentofte Hospital. The injured eye was examined with a photo slit-lamp before and 24 hours after treatment. The size of the abrasion was recorded and calculated on a PCX computerized video system and by slit-lamp photography. The Fucithalmic and chloramphenicol ointment treated groups showed no significant difference in corneal healing, local side effects, or signs of local infection.

Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial.

PubMed

Goebel, Andreas; Shenker, Nicholas; Padfield, Nick; Shoukrey, Karim; McCabe, Candida; Serpell, Mick; Sanders, Mark; Murphy, Caroline; Ejibe, Amaka; Milligan, Holly; Kelly, Joanna; Ambler, Gareth

2014-10-24

Longstanding complex regional pain syndrome (CRPS) is refractory to treatment with established analgesic drugs in most cases, and for many patients, alternative pain treatment approaches, such as with neuromodulation devices or rehabilitation methods, also do not work. The development of novel, effective treatment technologies is, therefore, important. There are preliminary data suggesting that low-dose immunoglobulin treatment may significantly reduce pain from longstanding CRPS. LIPS is a multicentre (United Kingdom), double-blind, randomised parallel group, placebo-controlled trial, designed to evaluate the efficacy, safety, and tolerability of intravenous immunoglobulin (IVIg) 0.5 g/kg plus standard treatment, versus matched placebo plus standard treatment in 108 patients with longstanding complex regional pain syndrome. Participants with moderate or severe CRPS of between 1 and 5 years duration will be randomly allocated to receive IVIg 0.5 g/kg (IntratectTM 50 g/l solution for infusion) or matching placebo administered day 1 and day 22 after randomisation, followed by two optional doses of open-label medication on day 43 after randomisation and on day 64 after randomisation. The primary outcome is the patients' pain intensity in the IVIG group compared with the placebo group, between 6 and 42 days after randomisation. The primary trial objective is to confirm the efficacy and confidently determine the effect size of the IVIG treatment technology in this group of patients. ISRCTN42179756 (Registered 28 June 13).

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study.

PubMed

Müllner, E; Plasser, E; Brath, H; Waldschütz, W; Forster, E; Kundi, M; Wagner, K-H

2014-10-01

Low adiponectin levels are discussed as risk factor for cardiovascular events. This is of special importance in individuals with type 2 diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The present study aimed to investigate the effect of two plant oils rich in polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics (OAD). Ninety-two subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid profile, tocopherol, adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline, during and after the intervention. Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks compared to baseline) was observed, albeit not significantly different from T2DM-OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by the intervention. The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects, independently of the administered plant oil. © 2013 The British Dietetic Association Ltd.

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department.

PubMed

Ong, Marcus Eng Hock; Tiah, Ling; Leong, Benjamin Sieu-Hon; Tan, Elaine Ching Ching; Ong, Victor Yeok Kein; Tan, Elizabeth Ai Theng; Poh, Bee Yen; Pek, Pin Pin; Chen, Yuming

2012-08-01

To compare vasopressin and adrenaline in the treatment of patients with cardiac arrest presenting to or in the Emergency Department (ED). A randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals. Eligible cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged >16 (aged>21 for one hospital) were randomly assigned to intravenous adrenaline (1mg) or vasopressin (40 IU) at ED. Patients with traumatic cardiac arrest or contraindication for cardiopulmonary resuscitation (CPR) were excluded. Patients received additional open label doses of adrenaline as per current guidelines. Primary outcome was survival to hospital discharge (defined as participant discharged alive or survival to 30 days post-arrest). The study recruited 727 participants (adrenaline = 353; vasopressin = 374). Baseline characteristics of the two groups were comparable. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p = 0.27, RR = 1.72, 95% CI = 0.65-4.51). After adjustment for race, medical history, bystander CPR and prior adrenaline given, more participants survived to hospital admission with vasopressin (22.2%) than with adrenaline (16.7%) (p = 0.05, RR = 1.43, 95% CI = 1.02-2.04). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times. Combination of vasopressin and adrenaline did not improve long term survival but seemed to improve survival to admission in patients with prolonged cardiac arrest. Further studies on the effect of vasopressin combined with therapeutic hypothermia on patients with prolonged cardiac arrest are needed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

PubMed

Blichfeldt-Eckhardt, M R; Laursen, C B; Berg, H; Holm, J H; Hansen, L N; Ørding, H; Andersen, C; Licht, P B; Toft, P

2016-12-01

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Comparative investigations on the efficacy of articaine 4% (epinephrine 1:200,000) and articaine 2% (epinephrine 1:200,000) in local infiltration anaesthesia in dentistry--a randomised double-blind study.

PubMed

Hintze, A; Paessler, L

2006-06-01

A randomised double-blind study investigated 155 patients with tooth extractions in the mandibular and maxillary jaws for a loss of anaesthetic potency when reducing the concentration of the active in articaine solutions. Tests were performed on the preparations of articaine 4% with a 1:200,000 addition of epinephrine (Ultracain D-S) and articaine 2% with a 1:200,000 addition of epinephrine (Ultracain 2%-Suprarenin). Local infiltration anaesthesia was the chosen method of anaesthesia. The most noticeable difference observed between the two injection solutions concerned the duration of anaesthesia, which was significantly shortened under the low-dose solution. The 4% articaine solution did not prove superior in local anaesthetic effect. Articaine 2% with epinephrine 1:200,000, therefore, can be considered a suitable local anaesthetic for tooth extractions.

Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial.

PubMed

White, David J; Cox, Katherine H M; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B

2015-10-30

This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18-40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the "depression-dejection" subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults.

[Double-blind randomized comparative study of nicergoline naftidrofuryl on the quality of life in chronic obliterative arteriopathy of lower limbs with intermittent claudication].

PubMed

Meilhac, B; Montestruc, F; Aubin, F; Djian, F; Rouffy, J

1997-01-01

The functional limitation of patients with obliterative arterial disease, and with intermittent claudication, damages their quality of life. The purpose of this trial was to compare the effects of nicergoline and naftidrofuryl on the quality of life and the functional discomfort of the 131 patients with claudication. It was a multicentre, randomised, double-blind trial with parallel groups. The patients were asked to complete a quality of life questionnaire and a Visual Analogue Scale, and to evaluate the number of steps on flat ground before the pain began. After 6 months of treatment, we observed, for all treatments combined, a significant improvement (p = 0.0001) in the quality of life and in the functional discomfort. Three variables favoured nicergoline: the estimated time before the onset of the pain (p = 0.003), the functional discomfort quantified by the Visual Analogue Scale (p < 0.05), the distance covered on flat ground (p = 0.013). The other variables, and especially the total score on the self-questionnaire, confirmed this impression, without reaching significance (p = 0.136). The data suggest that in terms of quality of life nicergoline is superior. The clinical tolerance is good and comparable between the two treatments.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial

PubMed Central

Fernie, Gordon; Currie, James; Perrin, Jennifer S.; Stewart, Caroline A.; Anderson, Virginica; Bennett, Daniel M.; Hay, Steven; Reid, Ian C.

2017-01-01

Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT. PMID:28254962

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

PubMed Central

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320. PMID:27412105

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting.

PubMed

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-07-13

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). ISRCTN84528320. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus

PubMed Central

Derumeaux, Geneviève; Ernande, Laura; Serusclat, André; Servan, Evelyne; Bruckert, Eric; Rousset, Hugues; Senn, Stephen; Van Gaal, Luc; Picandet, Brigitte; Gavini, François; Moulin, Philippe

2012-01-01

Objectives REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. Methods Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA1c. Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. Results At baseline, patients were 59.1±10.5 years old with HbA1c 8.3±0.8%, and DM duration 7.1±6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30±0.80 to 7.77±1.31 versus pioglitazone: from 8.30±0.80 to 7.45±1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. Conclusion After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug. Trial registration www.controlled-trials.com ISRCTN 27354239. isrctn27354239 PMID:22723853

Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis

PubMed Central

Schapowal, Andreas

2002-01-01

Objectives To compare the efficacy and tolerability of butterbur (Petasites hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay fever). Design Randomised, double blind, parallel group comparison. Setting Four outpatient general medicine and allergy clinics in Switzerland and Germany. Participants 131 patients were screened for seasonal allergic rhinitis and 125 patients were randomised (butterbur 61; cetirizine 64). Interventions Butterbur (carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or cetirizine, one tablet in the evening, both given for two consecutive weeks. Main outcome measures Scores on SF-36 questionnaire and clinical global impression scale. Results Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups). Both treatments were well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse events were associated with sedative effects (drowsiness and fatigue) despite the drug being considered a non-sedating antihistamine. Conclusions The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors. Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided. What is already known on this topicSeasonal allergic rhinitis (hay fever) is common in countries with temperate climates.Most patients have their symptoms treated for short periods, particularly during peaks in atmospheric pollen countWhat this study addsAfter two weeks, the effects of butterbur and cetirizine were comparable in patients with hay feverButterbur produced fewer sedating effects than cetirizineButterbur should be considered when the sedating effects of antihistamines must be avoided PMID:11799030

Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with uterine fibroids: a protocol for a randomised controlled trial.

PubMed

Jung, Jeeyoun; Lee, Ju Ah; Ko, Mi Mi; You, Sooseong; Lee, Eunhee; Choi, Jiae; Kang, Byoung-Kab; Lee, Myeong Soo

2016-11-24

Gyejibongneyong-hwan (GBH), or the Guizhi Fuling Formula in Chinese, is widely used to treat uterine fibroids in East Asian countries including Korea, China and Japan. This study will assess the efficacy and safety of the GBH formula for the treatment of dysmenorrhoea. This study will be a randomised double-blind controlled trial with two parallel arms: the GBH group and the placebo group. This trial will recruit 38 women between 18 and 45 years of age with secondary dysmenorrhoea with uterine fibroids. The investigational drugs, either GBH or placebo, will be administered to the participants three times per day for two menstrual periods (8 weeks). The participants will be followed up for three menstrual cycles after administration of the drugs. The primary outcome will be the Numeric Rating Scale score of average menstrual pain. All analyses will be performed with SAS (V.9.1.3; SAS Institute, Cary, North Carolina, USA) by a statistician blinded to the allocation of the groups. Statistical analysis will be undertaken on the intent-to-treat (ITT) basis with a 95% CI using the last observation carried forward for missing values. The ITT analysis will include all randomised patients. This research protocol has been reviewed and approved by the institutional review boards of the trial centre (number WSOH IRB 1606-03). Written informed consent will be obtained from all study participants prior to enrolment in the study. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print. KCT0001967. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Consumption of a calcium and vitamin D-fortified food product does not affect iron status during initial military training: a randomised, double-blind, placebo-controlled trial.

PubMed

Hennigar, Stephen R; Gaffney-Stomberg, Erin; Lutz, Laura J; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

2016-02-28

Ca/vitamin D supplementation maintains bone health and decreases stress fracture risk during initial military training (IMT); however, there is evidence that Ca may negatively affect the absorption of other critical micronutrients, particularly Fe. The objective of this randomised, double-blind, placebo-controlled trial was to determine whether providing 2000 mg/d Ca and 25 µg/d vitamin D in a fortified food product during 9 weeks of military training affects Fe status in young adults. Male (n 98) and female (n 54) volunteers enrolled in US Army basic combat training (BCT) were randomised to receive a snack bar with Ca/vitamin D (n 75) or placebo (snack bar without Ca/vitamin D; n 77) and were instructed to consume 2 snack bars/d between meals throughout the training course. Circulating ionised Ca was higher (P0·05) in markers of Fe status between placebo and Ca/vitamin D groups. Collectively, these data indicate that Ca/vitamin D supplementation through the use of a fortified food product consumed between meals does not affect Fe status during IMT.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

PubMed Central

2011-01-01

Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Discussion Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Trial registration Current controlled trials ISRCTN83178718 PMID:21936930

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

PubMed Central

Marchand, R.

1993-01-01

Three recent articles are examined in which research using the double-blind randomised clinical trial, the case control study, and the quasi-cohort study is described. Understanding the advantages and disadvantages of these methods makes it easier to grasp the pneumococcal vaccine controversy and make an informed choice. PMID:8499794

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

PubMed

Jakubowski, Joseph A; Hoppe, Carolyn C; Zhou, Chunmei; Smith, Brendan E; Brown, Patricia B; Heath, Lori E; Inusa, Baba; Rees, David C; Small, David S; Gupta, Neehar; Yao, Suqin; Heeney, Matthew; Kanter, Julie

2017-02-28

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12 ® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8  ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

PubMed

Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

2016-01-01

The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian). Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 10(10) pu, 35 [38%] to 2·5 × 10(10) pu, 35 [38%] to 5 × 10(10) pu, and 11 [12%] to 1 × 10(11) pu) and 20 in the USA (ten [50%] to 1 × 10(10) pu and ten [50%] to 1 × 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 10(10) and two [2%] received 1 × 10(11) pu) and four (20%) of 20 in the USA (all received 1 × 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. 1 × 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. Copyright © 2016 Tapia et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study

PubMed Central

Grins, Edgars; Dardashti, Alain; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

2016-01-01

Introduction Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia–reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia–reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. Methods and analysis Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15–90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. Ethics and dissemination The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study. Trial registration number NCT02397213; Pre-results. PMID:27979834

Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

PubMed Central

Savitz, Jonathan; Preskorn, Sheldon; Teague, T Kent; Drevets, Douglas; Yates, William

2012-01-01

Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1). Methods and analysis 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery–Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines. Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every 6 months. Results of the study will be published in peer-reviewed publications. Trial registration number Clinical Trials.gov: NCT01429272. PMID:22357572

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

PubMed

Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

2017-11-24

Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial.

PubMed

Cawello, Willi; Mueller-Voessing, Christa; Andreas, Jens-Otto

2014-05-01

Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide. To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of digoxin administered in combination with lacosamide or placebo. Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs. Interaction was excluded if the 90 % confidence interval (CI) for the geometric mean ratio of AUC24,ss and C max,ss fell within the acceptance range for bioequivalence (0.8-1.25). The point estimates (90 % CI) of the geometric mean ratios for co-administration of digoxin with lacosamide versus digoxin alone for AUC(24,ss) [1.024 (0.979-1.071)] and C(max,ss) [1.049 (0.959-1.147)] were within the acceptance range for bioequivalence. Digoxin and lacosamide co-administration was generally well-tolerated. A small numerical increase in the mean PR interval following co-administered digoxin + lacosamide was observed versus digoxin alone and versus pre-treatment baseline values (178.5 vs. 170.4 or 166.8 ms, respectively). The RR interval increased in parallel. The change was not considered clinically relevant. Co-administration of steady-state digoxin (0.25 mg/day) with multiple-dose lacosamide (400 mg/day) versus digoxin alone revealed no differences in digoxin disposition.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

A randomised, double-blinded clinical study on the efficacy of multimedia presentation using an iPad for patient education of postoperative hip surgery patients in a public hospital in Singapore.

PubMed

Dallimore, Rachel-Kim; Asinas-Tan, Marxengel Leonin; Chan, Daryl; Hussain, Suharti; Willett, Catherine; Zainuldin, Rahizan

2017-09-01

This study compared patient satisfaction and recall of physiotherapy patient education among patients who had undergone hip surgery, with information presented via an iPad versus a standard paper booklet. Patients who had undergone hip surgery joined and completed this single-centre study, which utilised a randomised parallel group design. They were randomly allocated to either Group A (received information on hip surgery physiotherapy via an iPad) or Group B (received the same information via a paper booklet). The participants were blinded to the intervention received by the other group and the testers were blinded to the intervention received by the participants. The interventions were carried out during the patients' first four postoperative physiotherapy sessions. The outcome measures were recorded using pre-validated questionnaires. A total of 42 participants (mean age 70 ± 12 years) were recruited. After the intervention, patients in both groups had improved recall of the information presented during patient education. However, the patients in Group A had a significantly better recall score than those in Group B (4.0 points higher, p < 0.001). The level of patient satisfaction was also significantly higher in Group A than in Group B (8.5 points higher, p < 0.001). While the use of an iPad and a paper booklet both had positive outcomes for patient recall and satisfaction, the use of an iPad was found to be more effective at improving patient satisfaction and recall of physiotherapy patient education in the present study. Copyright: © Singapore Medical Association

Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I.

PubMed

Grunze, Heinz; Kotlik, Eduardo; Costa, Raquel; Nunes, Teresa; Falcão, Amílcar; Almeida, Luis; Soares-da-Silva, Patrício

2015-03-15

Eslicarbazepine acetate (ESL) is an anticonvulsant approved as an adjunctive therapy in adults with partial-onset seizures. To evaluate the efficacy, safety and tolerability of ESL in the treatment of acute mania and prevention of recurrence in bipolar disorder I. Two 3-week multicentre, double-blind, randomised, placebo-controlled studies in acute mania (study BIA-2093-203: dose titrated by response, ESL 600-1800mg or 800-2400mg, once-daily; study BIA-2093-204: fixed doses of 600, 1200 and 1800mg, once-daily) were followed by a recurrence prevention study consisting of a 2-week open-label period (900mg, once-daily) continued by a double-blind, parallel-group, fixed dose (300, 900 and 1800mg, once-daily) period for a minimum of 6 months. The primary endpoint was changed from baseline until the end of the 3-week treatment period in Young Mania Rating Scale (YMRS) in studies BIA-2093-203 and BIA-2093-204, and the proportion of patients showing no worsening according to the Clinical Global Impressions - Bipolar Version (CGI-BP) over Part II in study BIA-2093-205. In study BIA-2093-203 (n=160, ITT), neither dose group was statistically different from placebo in the primary endpoint, though the ESL 800-2400mg showed a greater reduction in YMRS score (p=0.0523). CGI-BP score changes for mania and overall bipolar illness indicate a significant improvement in patient symptomatology for the ESL 800-2400mg group (from preceding and worst phase) and for ESL 600-1800mg group (from worst phase only) when compared to placebo. Study BIA-2093-204 (n=38) results were inconclusive due to premature termination caused by recruitment difficulties. In study BIA-2093-205 (n=85, ITT), at least 50% of patients showed no worsening in all treatment groups (p=0.250). ESL adverse events were mostly of mild and moderate intensities and consistent with previously reported observations for ESL. ESL treatment was not significantly different from placebo in manic patients in the primary outcome, but secondary outcomes may be suggestive of efficacy. The recurrence prevention study provides preliminary support for efficacy of ESL in patients recovered from an acute manic episode. Copyright © 2014 Elsevier B.V. All rights reserved.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

PubMed

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

PubMed Central

Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-01-01

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0–10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results. PMID:28716797

Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study.

PubMed

Widrig, Reto; Suter, Andy; Saller, Reinhard; Melzer, Jörg

2007-04-01

The use of topical preparations for symptom relief is common in osteoarthritis. The effects of ibuprofen (5%) and arnica (50 g tincture/100 g, DER 1:20), as gel preparations in patients with radiologically confirmed and symptomatically active osteoarthritis of interphalangeal joints of hands, were evaluated in a randomised, double-blind study in 204 patients, to ascertain differences in pain relief and hand function after 21 days' treatment. Diagnosis was according to established criteria; primary endpoints were pain intensity and hand function; statistical design was as per current regulatory guidelines for testing topical preparations. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1%) on ibuprofen and by five patients (4.8%) on arnica. Our results confirm that this preparation of arnica is not inferior to ibuprofen when treating osteoarthritis of hands.

Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial

PubMed Central

White, David J.; Cox, Katherine H. M.; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B.

2015-01-01

This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults. PMID:26529011

Randomised clinical trial: the clinical efficacy and safety of an alginate-antacid (Gaviscon Double Action) versus placebo, for decreasing upper gastrointestinal symptoms in symptomatic gastroesophageal reflux disease (GERD) in China.

PubMed

Sun, J; Yang, C; Zhao, H; Zheng, P; Wilkinson, J; Ng, B; Yuan, Y

2015-10-01

There is a paucity of large-scale studies evaluating the clinical benefit of the Gaviscon Double Action (DA) alginate-antacid formulation for treating gastroesophageal reflux disease (GERD) symptoms. Randomised double-blind placebo-controlled parallel-group study to evaluate efficacy and safety of Gaviscon DA in reducing heartburn, regurgitation and dyspepsia symptoms in individuals with mild-to-moderate GERD in China. Participants with symptomatic GERD (n = 1107) were randomised to receive Gaviscon DA or placebo (two tablets four times daily) for seven consecutive days. The primary endpoint compared the change in Reflux Disease Questionnaire (RDQ) score for the GERD (heartburn + regurgitation) dimension between Gaviscon DA and placebo. Secondary endpoints compared the change in RDQ scores for individual heartburn, regurgitation and dyspepsia dimensions, overall treatment evaluation (OTE) scores and incidence of adverse events (AEs). Mean RDQ GERD scores: 2.51 for Gaviscon DA and 2.50 for placebo at baseline; 1.25 for Gaviscon DA and 1.46 for placebo post treatment. Gaviscon DA was statistically superior to placebo in reducing GERD and dyspepsia RDQ scores [least-squares mean (LSM) difference: GERD -0.21, P < 0.0001; dyspepsia -0.18, P = 0.0004], despite a substantial placebo response. The Gaviscon DA group reported more favourable overall treatment responses than the placebo group across all OTE categories (P < 0.0001). Superior relief of GERD symptoms was observed both in those with non-erosive and those with erosive reflux disease (LSM difference -0.14 [P = 0.038] and -0.29 [P < 0.0001] respectively). Incidence of AEs was similar in both groups. Gaviscon DA tablets provide effective and safe reduction in acid reflux and dyspepsia symptoms in Chinese individuals with mild-to-moderate GERD. ClinicalTrials.gov: NCT01869491. © 2015 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. European Commission 7th Framework Programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.

PubMed

Wieshammer, S; Hetzel, M; Hetzel, J; Kochs, M; Hombach, V

1993-07-01

To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics. Randomised, double blind, placebo controlled, 16 week treatment periods. Outpatient clinic at a university hospital. 54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study. After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics. Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure. The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment. The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.

Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC-2): Trial protocol.

PubMed

Perkins, Gavin D; Quinn, Tom; Deakin, Charles D; Nolan, Jerry P; Lall, Ranjit; Slowther, Anne-Marie; Cooke, Matthew; Lamb, Sarah E; Petrou, Stavros; Achana, Felix; Finn, Judith; Jacobs, Ian G; Carson, Andrew; Smyth, Mike; Han, Kyee; Byers, Sonia; Rees, Nigel; Whitfield, Richard; Moore, Fionna; Fothergill, Rachael; Stallard, Nigel; Long, John; Hennings, Susie; Horton, Jessica; Kaye, Charlotte; Gates, Simon

2016-11-01

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024). Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention

PubMed Central

Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John

2016-01-01

Introduction Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. Methods and analysis 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethics and dissemination Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. Trial registration number ChiCTR-IOR-15006971. PMID:27334883

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

PubMed Central

Bennell, Kim; Bowles, Kelly-Ann; Payne, Craig; Cicuttini, Flavia; Osborne, Richard; Harris, Anthony; Hinman, Rana

2007-01-01

Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259. PMID:17892539

Efficacy test of a toothpaste in reducing extrinsic dental stain

NASA Astrophysics Data System (ADS)

Agustanti, A.; Ramadhani, S. A.; Adiatman, M.; Rahardjo, A.; Callea, M.; Yavuz, I.; Maharani, D. A.

2017-08-01

This clinical trial compared the external dental stain reduction achieved by tested toothpaste versus placebo in adult patients. In this double-blind, parallel, randomised clinical trial, 45 female volunteers with a mean age of 20 years old were included. All study subjects front teeth were topically applicated with Silver Diamine Fluoride (SDF) to create external dental stains. Subjects were randomized into test (n=22) and control (n=23) groups. Toothpastes were used for two days to analyse the effects of removing external stains on the labial surfaces of all anterior teeth. VITA Easyshade Advance 4.0 was used to measure dental extrinsic stains changes. The analysis showed statistically significant efficacy of the tested toothpaste in reducing external dental stain caused by SDF, comparing to the placebo toothpaste, after one and two days of usage. The tested toothpaste was effective in reducing dental stain.

Better early functional outcome after short stem total hip arthroplasty? A prospective blinded randomised controlled multicentre trial comparing the Collum Femoris Preserving stem with a Zweymuller straight cementless stem total hip replacement for the treatment of primary osteoarthritis of the hip

PubMed Central

van Oldenrijk, Jakob; Scholtes, Vanessa A B; van Beers, Loes W A H; Geerdink, Carel H; Niers, Bob B A M; Runne, Wouter; Bhandari, Mohit; Poolman, Rudolf W

2017-01-01

Objectives Primary aim was to compare the functional results at 3 months and 2 years between short and conventional cementless stem total hip arthroplasty (THA). Secondary aim was to determine the feasibility of a double-blind implant-related trial. Design A prospective blinded randomised controlled multicentre trial in patients with osteoarthritis of the hip. All patients, research assistants, clinical assessors, investigators and data analysts were blinded to the type of prosthesis. Population: 150 patients between 18 and 70 years with osteoarthritis of the hip, 75 in the short stem and 75 in the conventional stem group. Mean age: 60 years (SD 7). Interventions: the Collum Femoris Preserving short stem versus the Zweymuller Alloclassic conventional stem. Main outcome measures The Dutch version of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Secondary outcomes measures: Harris Hip Score, the Physical Component Scale of the SF12, the Timed Up and Go test, Pain and the EQ-5D. Feasibility outcomes: continued blinding, protocol adherence and follow-up success rate. Results No significant difference between the two groups. Mean HOOS total score in the short stem group increased 32.7 points from 36.6 (95% CI 32.9 to 40.2) preoperatively to 69.3 (95% CI 66.4 to 72.1) at 3 months follow-up. Mean HOOS total score in the conventional straight stem group increased 36.3 points from 37.1 (95% CI 33.9 to 40.3) preoperatively to 73.4 (95% CI 70.3 to 76.4) at 3 months follow-up. 91.2% of patients remained blinded at 2 years follow-up. Both protocol adherence and follow-up success rate were 98%. Conclusions Functional result at 3 months and 2 years after short stem THA is not superior to conventional cementless THA. There were more perioperative and postoperative complications in the short stem group. Direct comparison of two hip implants in a double-blinded randomised controlled trial is feasible. Trial registration number NTR1560. PMID:29042371

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH-1)

PubMed Central

Alam, Asim; Bopardikar, Ameya; Au, Shelly; Barrett, Jon; Callum, Jeannie; Kiss, Alex; Choi, Stephen

2017-01-01

Introduction Postpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Despite the availability of multiple uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA) has been shown to be a safe, effective and inexpensive therapeutic option for the treatment of PPH, however, its use prophylactically in mitigating the risk of PPH is unknown. This pragmatic randomised prospective trial assesses the feasibility and safety of administering TXA at the time of delivery for the prevention of PPH. Methods and analysis A pilot pragmatic randomised double-blinded placebo-controlled trial will be performed. 58 singleton parturients at term >32 weeks, undergoing either spontaneous vaginal delivery, or caesarean section will be randomised to receive 1 g of TXA or placebo (0.9% saline) intravenously. The primary outcome assessed will be the feasibility of administrating TXA, along with collecting data regarding safety of drug administration. The groups will also be analysed on efficacy of mitigating the onset of PPH and clinically relevant variables. Demographic, feasibility, safety and clinical endpoints will be summarised and the appropriate measures of central tendency and dispersion will be presented. Ethics and dissemination This protocol was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (number: 418-2016). The results will be disseminated in a peer-reviewed journal and at scientific meetings. Trial registration number NCT03069859; Pre-results. PMID:29025850

Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy.

PubMed

Moore, R A; McQuay, H J; Tomaszewski, J; Raba, G; Tutunaru, D; Lietuviete, N; Galad, J; Hagymasy, L; Melka, D; Kotarski, J; Rechberger, T; Fülesdi, B; Nizzardo, A; Guerrero-Bayón, C; Cuadripani, S; Pizà-Vallespir, B; Bertolotti, M

2016-01-22

Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain. Randomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8). The efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients. The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed. EU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013).

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

PubMed

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

2017-06-01

Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebo-controlled trial.

PubMed

Shinkai, Shoji; Toba, Masamichi; Saito, Takao; Sato, Ikutaro; Tsubouchi, Mina; Taira, Kiyoto; Kakumoto, Keiji; Inamatsu, Takashi; Yoshida, Hiroto; Fujiwara, Yoshinori; Fukaya, Taro; Matsumoto, Tetsuya; Tateda, Kazuhiro; Yamaguchi, Keizo; Kohda, Noriyuki; Kohno, Shigeru

2013-05-28

Oral intake of Lactobacillus pentosus strain b240 (b240) has been shown to enhance the secretion of salivary secretory IgA in elderly adults. However, its clinical benefits remain to be determined. We tested the hypothesis that b240 exerts a protective effect against the common cold in elderly adults. The design of the present study was a randomised, double-blind, placebo-controlled trial (RCT) with parallel three-group comparison. For this purpose, 300 eligible elderly adults were randomly allocated to one of three groups, namely a placebo, low-dose or high-dose b240 group. Participants in the low-dose and high-dose b240 groups were given tablets containing 2 × 10(9) or 2 × 10(10) cells, respectively, of heat-killed b240, while those in the placebo group were given tablets without b240. Each group consumed their respective tablets once daily for 20 weeks. The common cold was assessed on the basis of a diary. Change in quality of life was evaluated using the SF-36. Of the total participants, 280 completed the 20-week RCT. The accumulated incidence rate of the common cold was 47·3, 34·8 and 29·0 % for the placebo, low-dose b240 and high-dose b240 groups, respectively (P for trend = 0·012). Lower incidence rates were consistently observed throughout the experimental period in the b240 groups (log-rank test, P= 0·034). General health perception, as determined by the SF-36®, dose-dependently increased in the b240 groups ( P <0·025). In conclusion, oral intake of b240 significantly reduced the incidence rate of the common cold in elderly adults, indicating that b240 might be useful in improving resistance against infection through mucosal immunity.

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial

PubMed Central

Ross, J D C; Cronjé, H S; Paszkowski, T; Rakoczi, I; Vildaite, D; Kureishi, A; Alefelder, M; Arvis, P; Reimnitz, P

2006-01-01

Objective This multinational, multicentre, prospective, randomised, double blind, parallel group, non‐inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. Methods Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). Results Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5–24 days post‐therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: −5.7% to 4.0%). At follow up (28–42 days post‐therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: −8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: −8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). Conclusion In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events. PMID:16723364

A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis

PubMed Central

Berenbaum, Francis; Grifka, Joachim; Cazzaniga, Sara; D'Amato, Massimo; Giacovelli, Giampaolo; Chevalier, Xavier; Rannou, Francois; Rovati, Lucio C; Maheu, Emmanuel

2012-01-01

Objectives To compare the effects of an intermediate molecular weight (MW) intra-articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms. Methods Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800–1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500–730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0–100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates Results The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>−9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated. Conclusions Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety. PMID:22294639

Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial.

PubMed

Bousser, Marie-Germaine; Amarenco, Pierre; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; de Cordoüe, Agnès; Fratacci, Marie-Dominique

2011-06-11

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints. The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost. Servier, France. Copyright © 2011 Elsevier Ltd. All rights reserved.

PRECISE - pregabalin in addition to usual care for sciatica: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Sciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica. Methods/Design PRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant’s optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives. Discussion This study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica. Trial registration ClinicalTrial.gov, ACTRN 12613000530729 PMID:23845078

PRECISE - pregabalin in addition to usual care for sciatica: study protocol for a randomised controlled trial.

PubMed

Mathieson, Stephanie; Maher, Christopher G; McLachlan, Andrew J; Latimer, Jane; Koes, Bart W; Hancock, Mark J; Harris, Ian; Day, Richard O; Pik, Justin; Jan, Stephen; Billot, Laurent; Lin, Chung-Wei Christine

2013-07-11

Sciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica. PRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant's optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives. This study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica. ClinicalTrial.gov, ACTRN 12613000530729.

Effects of kinesiotaping on foot posture in participants with pronated foot: a quasi-randomised, double-blind study.

PubMed

Luque-Suarez, Alejandro; Gijon-Nogueron, Gabriel; Baron-Lopez, Francisco Javier; Labajos-Manzanares, Maria Teresa; Hush, Julia; Hancock, Mark Jonathan

2014-03-01

To investigate whether kinesiotaping improves excessive foot pronation compared with sham kinesiotaping. Quasi-randomised, double-blind study. One primary care centre. One hundred and thirty participants were screened for inclusion. Sixty-eight participants with pronated feet [Foot Posture Index (FPI)≥ 6] were enrolled, and the follow-up rate was 100%. Participants were allocated into one of two groups: an experimental kinesiotaping group (KT1) and a sham taping group (KT2). Measures were collected by a blinded assessor at baseline, and 1 minute, 10 minutes, 60 minutes and 24 hours after taping. The primary outcome was total FPI score, and the secondary outcome was rear-foot FPI score. There were no significant differences in total FPI score between kinesiotaping and sham taping at any time point. Similarly, there were no significant differences in rear-foot FPI score, apart from at 60-minute follow-up when the difference between groups was significant (P=0.04) but the effect size was very small (0.85 points on the rear-foot FPI score between -6 and +6). Kinesiotaping does not correct foot pronation compared with sham kinesiotaping in people with pronated feet. Copyright © 2013 Chartered Society of Physiotherapy. All rights reserved.

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

PubMed Central

2013-01-01

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed

Barker, D P; Simpson, J; Pawula, M; Barrett, D A; Shaw, P N; Rutter, N

1995-07-01

To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed Central

Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.

1995-01-01

AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

PubMed

Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Nobuko; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kanouchi, Tadashi; Kohara, Nobuo; Kawamoto, Michi; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Hirata, Koichi; Kokubun, Norito; Masuda, Ray; Kaneko, Juntaro; Yabe, Ichiro; Sasaki, Hidenao; Kaida, Ken-Ichi; Takazaki, Hiroshi; Suzuki, Norihiro; Suzuki, Shigeaki; Nodera, Hiroyuki; Matsui, Naoko; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu

2018-06-01

Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exploratory double-blind, parallel-group, placebo-controlled extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

PubMed

2017-10-01

Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer-term efficacy and safety. Patients given edaravone in the first 24-week phase III study (Cycles 1-6) were randomised to edaravone (E-E) or placebo (E-P) in the subsequent 24-week double-blind period (Cycles 7-12). Patients given placebo in phase III were switched to edaravone (P-E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13-15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy-expected subpopulation (EESP) defined by post-hoc analysis of the first phase III study. The least-squares mean and standard error of the intergroup difference (E-E vs. E-P) of change in the ALSFRS-R score from Cycles 7-12 was 1.16 ± 0.93 (p = 0.2176) in the FAS, and 1.85 ± 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E-E group throughout Cycles 1-15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E-E than in E-P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.

A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life.

PubMed

Cappello, Carmelina; Tremolaterra, Fabrizio; Pascariello, Annalisa; Ciacci, Carolina; Iovino, Paola

2013-03-01

The aim of this study is to test in a double-blinded, randomised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms, colonic transit and quality of life in irritable bowel syndrome (IBS) patients who meet Rome III criteria. There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS. This is a double-blinded, randomised placebo-controlled study of a symbiotic mixture (Probinul, 5 g bid) over 4 weeks after 2 weeks of run-in. The primary endpoints were global satisfactory relief of abdominal flatulence and bloating. Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief. The secondary endpoints were change in abdominal bloating, flatulence, pain and urgency by a 100-mm visual analog scale, stool frequency and bowel functions on validated adjectival scales (Bristol Scale and sense of incomplete evacuation). Pre- and post-treatment colonic transit time (Metcalf) and quality of life (SF-36) were assessed. Sixty-four IBS patients (symbiotic n = 32, 64 % females, mean age 38.7 ± 12.6 years) were studied. This symbiotic mixture reduced flatulence over a 4-week period of treatment (repeated-measures analysis of covariance, p < 0.05). Proportions of responders were not significantly different between groups. At the end of the treatment, a longer rectosigmoid transit time and a significant improvement in most SF-36 scores were observed in the symbiotic group. This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients, a lack of adverse events and a good side-effect profile; however, it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating. Further studies are warranted.

Impact on caesarean section rates following injections of sterile water (ICARIS): a multicentre randomised controlled trial.

PubMed

Lee, Nigel; Mårtensson, Lena B; Homer, Caroline; Webster, Joan; Gibbons, Kristen; Stapleton, Helen; Dos Santos, Natalie; Beckmann, Michael; Gao, Yu; Kildea, Sue

2013-05-03

Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate. A double blind randomised placebo controlled trialSetting: Maternity hospitals in AustraliaParticipants: 1866 women in labour, ≥18 years of age who have a singleton pregnancy with a fetus in a cephalic presentation at term (between 37 + 0 and 41 + 6 weeks gestation), who assess their back pain as equal to or greater than seven on a visual analogue scale when requesting analgesia and able to provide informed consent. Participants will be randomised to receive either 0.1 to 0.3 millilitres of sterile water or a normal saline placebo via four intradermal injections into four anatomical points surrounding the Michaelis' rhomboid over the sacral area. Two injections will be administered over the posterior superior iliac spine (PSIS) and the remaining two at two centimetres posterior, and one centimetre medial to the PSIS respectively. Proportion of women who have a caesarean section in labour.Randomisation: Permuted blocks stratified by research site.Blinding (masking):Double-blind trial in which participants, clinicians and research staff blinded to group assignment. Funded by the National Health and Medical Research CouncilTrial registration:Australian New Zealand Clinical Trials Registry (No ACTRN12611000221954). Sterile water injections, which may have a positive effect on reducing the CS rate, have been shown to be a safe and simple analgesic suitable for most maternity settings. A procedure that could reduce intervention rates without adversely affecting safety for mother and baby would benefit Australian families and taxpayers and would reduce requirements for maternal operating theatre time. Results will have external validity, as the technique may be easily applied to maternity populations outside Australia. In summary, the results of this trial will contribute High level evidence on the impact of SWI on intrapartum CS rates and provide evidence of the analgesic effect of SWI on back pain.

Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

PubMed

Kothny, Wolfgang; Lukashevich, Valentina; Foley, James E; Rendell, Marc S; Schweizer, Anja

2015-09-01

There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR <30 ml min(-1) [1.73 m](-2) were randomised (via interactive voice response technology) to vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events. In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles. At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI. ClinicalTrials.gov NCT00616811 (completed) This study was planned and conducted by Novartis.

Immunoglobulin for necrotising soft tissue infections (INSTINCT): protocol for a randomised trial.

PubMed

Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl; Perner, Anders

2016-07-01

Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may have beneficial effects. However, IVIG may also have adverse effects. With this trial we will estimate the effects of IVIG on a patient-reported outcome and other patient-centred outcomes in patients with NSTI. INSTINCT is a randomised, double-blinded, parallel-group, placebo-controlled trial with concealed allocation of patients with NSTI 1:1 to IVIG or an equal volume of 0.9% saline. Patients are recruited at Rigshospitalet, Denmark. The primary outcome is the physical component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey as assessed six months after randomisation. Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. This study will be the only completed trial testing IVIG for NSTI, thereby providing important data on a severely sick patient group. The trial is supported by CSL Behring in the form of trial medication and a € 92,182 grant for trial conduct, research, nurse salary and statistical analyses. The trial is registered with clinicaltrials.gov (NCT02111161). .

The efficacy and safety of extended-release methylphenidate following traumatic brain injury: a randomised controlled pilot study.

PubMed

Dymowski, Alicia R; Ponsford, Jennie L; Owens, Jacqueline A; Olver, John H; Ponsford, Michael; Willmott, Catherine

2017-06-01

To investigate the feasibility, safety and efficacy of extended-release methylphenidate in enhancing processing speed, complex attentional functioning and everyday attentional behaviour after traumatic brain injury. Seven week randomised, placebo-controlled, double-blind, parallel pilot study. Inpatient and outpatient Acquired Brain Injury Rehabilitation Program. Eleven individuals with reduced processing speed and/or attention deficits following complicated mild to severe traumatic brain injury. Participants were allocated using a blocked randomisation schedule to receive daily extended-release methylphenidate (Ritalin ® LA at a dose of 0.6 mg/kg) or placebo (lactose) in identical capsules. Tests of processing speed and complex attention, and ratings of everyday attentional behaviour were completed at baseline, week 7 (on-drug), week 8 (off-drug) and 9 months follow-up. Vital signs and side effects were monitored from baseline to week 8. Three percent ( n = 11) of individuals screened participated (mean post-traumatic amnesia duration = 63.80 days, SD = 45.15). Results were analysed for six and four individuals on methylphenidate and placebo, respectively. Groups did not differ on attentional test performance or relative/therapist ratings of everyday attentional behaviour. One methylphenidate participant withdrew due to difficulty sleeping. Methylphenidate was associated with trends towards increased blood pressure and reported anxiety. Methylphenidate was not associated with enhanced processing speed, attentional functioning or everyday attentional behaviour after traumatic brain injury. Alternative treatments for attention deficits after traumatic brain injury should be explored given the limited feasibility of methylphenidate in this population.

The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial.

PubMed

Sumukadas, Deepa; Price, Rosemary; McMurdo, Marion E T; Rauchhaus, Petra; Struthers, Allan; McSwiggan, Stephen; Arnold, Graham; Abboud, Rami; Witham, Miles

2018-01-01

double-blind, parallel group, placebo-controlled randomised trial. we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). perindopril did not improve postural sway in older people at risk of falls. ISRCTN58995463. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

PubMed Central

Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

2011-01-01

Objective To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). Design An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline ‘trigger meals’ and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. Setting Outpatient internal medicine practice clinic. Patients 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised ‘food triggers’, no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11–30 years and 16% for more than 40 years. Interventions After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. Main outcome measures The primary analysis was number of patients who chose PEZ over placebo for the extended use. Results Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. Conclusions PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID:22095308

Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients.

PubMed

W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

2012-01-01

Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds.

Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients

PubMed Central

W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

2012-01-01

Background: Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. Objectives: The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. Methods: The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. Results: There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). Conclusions: The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds. PMID:23071904

The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: A randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults

PubMed Central

2011-01-01

Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein. Methods The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437 PMID:22011460

A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome.

PubMed

Klupp, Nerida L; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z; Chang, Dennis H

2016-08-11

This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [-0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [-0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705.

A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome

PubMed Central

Klupp, Nerida L.; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z.; Chang, Dennis H.

2016-01-01

This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [−0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [−0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742

The Explicit Learning of New Names for Known Objects Is Improved by Dexamphetamine

ERIC Educational Resources Information Center

Whiting, Emma; Chenery, Helen J.; Chalk, Jonathan; Darnell, Ross; Copland, David A.

2008-01-01

A randomised, double-blind, placebo-controlled, between subjects study design (N=37) was used to investigate the effects of dexamphetamine on explicit new name learning. Participants ingested 10 mg of dexamphetamine or placebo daily over 5 consecutive mornings before learning new names for 50 familiar objects plus fillers. The dexamphetamine group…

A randomised trial of the effect of the glycine reuptake inhibitor Org 25935 on cognitive performance in healthy male volunteers.

PubMed

Christmas, David; Diaper, Alison; Wilson, Sue; Rich, Ann; Phillips, Suzanne; Udo de Haes, Joanna; Sjogren, Magnus; Nutt, David

2014-03-01

Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers. A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken. There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild. A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.

Does transcutaneous electrical nerve stimulation (TENS) alleviate the pain experienced during bone marrow sampling in addition to standard techniques? A randomised, double-blinded, controlled trial.

PubMed

Tucker, David L; Rockett, Mark; Hasan, Mehedi; Poplar, Sarah; Rule, Simon A

2015-06-01

Bone marrow aspiration and trephine (BMAT) biopsies remain important tests in haematology. However, the procedures can be moderately to severely painful despite standard methods of pain relief. To test the efficacy of transcutaneous electrical nerve stimulation (TENS) in alleviating the pain from BMAT in addition to standard analgesia using a numerical pain rating scale (NRS). 70 patients requiring BMAT were randomised (1:1) in a double-blind, placebo-controlled trial. -35 patients received TENS impulses at a strong but comfortable amplitude (intervention group) and 35 patients received TENS impulses just above the sensory threshold (control group) (median pulse amplitude 20 and 7 mA, respectively). Patients and operators were blinded to group allocation. Pain assessments were made using a numerical pain scale completed after the procedure. No significant difference in NRS pain recalled after the procedure was detected (median pain score 5.7 (95% CI 4.8 to 6.6) in control vs 5.6 (95% CI 4.8 to 6.4) in the intervention group). However, 100% of patients who had previous experience of BMAT and >94% of participants overall felt they benefited from using TENS and would recommend it to others for this procedure. There were no side effects from the TENS device, and it was well tolerated. TENS is a safe, non-invasive adjunct to analgesia for reducing pain during bone marrow biopsy and provides a subjective benefit to most users; however, no objective difference in pain scores was detected when using TENS in this randomised controlled study. NCT02005354. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

PubMed

Lam, Ching; Tan, Wei; Leighton, Matthew; Hastings, Margaret; Lingaya, Melanie; Falcone, Yirga; Zhou, Xiaoying; Xu, Luting; Whorwell, Peter; Walls, Andrew F; Zaitoun, Abed; Montgomery, Alan; Spiller, Robin

2016-01-01

Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. NCT01316718. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial.

PubMed

Sjølie, Anne Katrin; Klein, Ronald; Porta, Massimo; Orchard, Trevor; Fuller, John; Parving, Hans Henrik; Bilous, Rudy; Chaturvedi, Nish

2008-10-18

Diabetic retinopathy remains a leading cause of visual loss in people of working age. We examined whether candesartan treatment could slow the progression and, secondly, induce regression of retinopathy in people with type 2 diabetes. We did a randomised, double-blind, parallel-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. 1905 participants (aged 37-75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio [HR] 0.87, 95% CI 0.70-1.08, p=0.20). Regression on active treatment was increased by 34% (1.34, 1.08-1.68, p=0.009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy.

Probiotic-enriched foods and dietary supplement containing SYNBIO positively affects bowel habits in healthy adults: an assessment using standard statistical analysis and Support Vector Machines.

PubMed

Silvi, Stefania; Verdenelli, M Cristina; Cecchini, Cinzia; Coman, M Magdalena; Bernabei, M Simonetta; Rosati, Jessica; De Leone, Renato; Orpianesi, Carla; Cresci, Alberto

2014-12-01

A randomised, double-blind, placebo-controlled, parallel group study assessed in healthy adults how daily consumption of the probiotic combination SYNBIO®, administered in probiotic-enriched foods or in a dietary supplement, affected bowel habits. Primary and secondary outcomes gave the overall assessment of bowel well-being, while a Psychological General Well-Being Index compiled by participants estimated the health-related quality of life as well as the gastrointestinal tolerance determined with the Gastrointestinal Symptom Rating Scale. Support Vector Machine models for classification problems were used to validate the total outcomes on bowel well-being. SYNBIO® consumption improved bowel habits of volunteers consuming the probiotic foods or capsules, while the same effects were not registered in the control groups. The recovery of probiotic bacteria from the faeces of a cohort of 100 subjects for each supplemented group showed the persistence of strains in the gastrointestinal tract.

'Complementary ENT': a systematic review of commonly used supplements.

PubMed

Karkos, P D; Leong, S C; Arya, A K; Papouliakos, S M; Apostolidou, M T; Issing, W J

2007-08-01

To assess the evidence surrounding the use of certain complementary supplements in otolaryngology. We specifically focussed on four commonly used supplements: spirulina, Ginkgo biloba, Vertigoheel and nutritional supplements (cod liver oil, multivitamins and pineapple enzyme). A systematic review of the English and foreign language literature. in vivo human studies. animal trials, in vitro studies and case reports. We also excluded other forms of 'alternative medicine' such as reflexology, acupuncture and other homeopathic remedies. Lack of common outcome measures prevented a formal meta-analysis. Three studies on the effects of spirulina in allergy, rhinitis and immunomodulation were found. One was a double-blind, placebo, randomised, controlled trial (RCT) of patients with allergic rhinitis, demonstrating positive effects in patients fed spirulina for 12 weeks. The other two studies, although non-randomised, also reported a positive role for spirulina in mucosal immunity. Regarding the use of Ginkgo biloba in tinnitus, a Cochrane review published in 2004 showed no evidence for this. The one double-blind, placebo-controlled trial that followed confirmed this finding. Regarding the use of Vertigoheel in vertigo, two double-blind RCTs and a meta-analysis were identified. The first RCT suggested that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine. The second RCT suggested that Vertigoheel was a suitable alternative to G. biloba in the treatment of atherosclerosis-related vertigo. A meta-analysis of only four clinical trials confirms that Vertigoheel was equally effective compared with betahistine, G. biloba and dimenhydrinate. Regarding multivitamins and sinusitis, two small paediatric pilot studies reported a positive response for chronic sinusitis and otitis media following a course of multivitamins and cod liver oil. Regarding bromelain (pineapple enzyme) and sinusitis, one randomised, multicentre trial including 116 children compared bromelain monotherapy to bromelain with standard therapy and standard therapy alone, for the treatment of acute sinusitis. The bromelain monotherapy group showed a faster recovery compared with the other groups. The positive effects of spirulina in allergic rhinitis and of Vertigoheel in vertigo are based on good levels of evidence, but larger trials are required. There is overwhelming evidence that G. biloba may play no role in tinnitus. There is limited evidence for the use of multivitamins in sinus symptoms, and larger randomised trials are required.

Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial.

PubMed

Neri, Elena; Maestro, Alessandra; Minen, Federico; Montico, Marcella; Ronfani, Luca; Zanon, Davide; Favret, Anna; Messi, Gianni; Barbi, Egidio

2013-09-01

To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children. A double-blind, randomised, controlled, non-inferiority trial was conducted in the paediatric emergency department of a research institute. One hundred and thirty-one children aged 4-17 years with suspected bone fracture or dislocation were enrolled. Eligible children were randomised to ketorolac (0.5 mg/kg) and placebo, or to tramadol (2 mg/kg) and placebo by sublingual administration, using a double-dummy technique. Pain was assessed by the patients every 20 min, for a maximum period of 2 h, using the McGrath scale for patients up to 6 years of age, and the Visual Analogue Scale for those older than 6 years of age. The mean pain scores fell significantly from eight to four and five in the ketorolac and tramadol groups, respectively, by 100 min (Wilcoxon sign rank test, p<0.001). The mean pain scores for ketorolac were lower than those for tramadol, but these differences were not significant at any time point (Mann-Whitney U Test, p values: 0-20 min: 0.167; 20-40 min: 0.314; 40-60 min: 0.223; 60-80 min: 0.348; 80-100 min: 0.166; 100-120 min: 0.08). The rescue dose of paracetamol-codeine was administered in 2/60 children in the ketorolac group versus 8/65 in the tramadol group (Fisher exact test, p=0.098). There were no statistically significant differences between the two groups in the frequency of adverse effects. Both sublingual ketorolac and tramadol were equally effective for pain management in children with suspected fractures or dislocations.

Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period

USDA-ARS?s Scientific Manuscript database

Introduction Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this popul...

Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period

USDA-ARS?s Scientific Manuscript database

Introduction: Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this popula...

A prospective randomised double-blind placebo-controlled trial to assess the effect of diuretics on shockwave lithotripsy of calculi.

PubMed

Sabharwal, Sagar; Jeyaseelan, L; Panda, Arabind; Gnanaraj, Lionel; Kekre, Nitin S; Devasia, Antony

2017-12-01

To assess the effect of diuretics with shockwave lithotripsy (SWL) on the treatment of renal and upper ureteric calculi. Adult patients with a solitary non-obstructive radio-opaque renal or upper ureteric calculus with normal renal function were included. They were prospectively randomised to receive either SWL with placebo or SWL with diuretics (40 mg parenteral furosemide) in a double-blind manner with a sample size of 48 patients in each arm. The primary outcomes were the SWL success and failure rates. The secondary outcomes were the number of shocks and sessions. Complete fragmentation was achieved in 89.6% of the patients in the furosemide arm as compared to 81.3% in the placebo arm. Clearance was achieved in 77.1% of the patients in the furosemide arm as compared to 70.8% in the placebo arm. The number of shocks and the number of sessions were higher in the placebo arm. These differences were not statistically significant. The use of diuretics along with SWL treatment of renal and upper ureteric calculi does not show a statistically significant improvement in fragmentation or clearance.

The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial.

PubMed

Thompson, Kiara; Hosking, Holly; Pederick, Wayne; Singh, Indu; Santhakumar, Abishek B

2017-09-01

The anti-thrombotic properties of anthocyanin (ACN) supplementation was evaluated in this randomised, double-blind, placebo (PBO) controlled, cross-over design, dietary intervention trial in sedentary population. In all, sixteen participants (three males and thirteen females) consumed ACN (320 mg/d) or PBO capsules for 28 d followed by a 2-week wash-out period. Biomarkers of thrombogenesis and platelet activation induced by ADP; platelet aggregation induced by ADP, collagen and arachidonic acid; biochemical, lipid, inflammatory and coagulation profile were evaluated before and after supplementation. ACN supplementation reduced monocyte-platelet aggregate formation by 39 %; inhibited platelet endothelial cell adhesion molecule-1 expression by 14 %; reduced platelet activation-dependant conformational change and degranulation by reducing procaspase activating compound-1 (PAC-1) (↓10 %) and P-selectin expression (↓14 %), respectively; and reduced ADP-induced whole blood platelet aggregation by 29 %. Arachidonic acid and collagen-induced platelet aggregation; biochemical, lipid, inflammatory and coagulation parameters did not change post-ACN supplementation. PBO treatment did not have an effect on the parameters tested. The findings suggest that dietary ACN supplementation has the potential to alleviate biomarkers of thrombogenesis, platelet hyperactivation and hyper-aggregation in sedentary population.

Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial.

PubMed

Mofidi, Fatemeh; Poustchi, Hossein; Yari, Zahra; Nourinayyer, Babak; Merat, Shahin; Sharafkhah, Maryam; Malekzadeh, Reza; Hekmatdoost, Azita

2017-03-01

Although non-alcoholic fatty liver disease (NAFLD) is the leading aetiology of liver disorders in the world, there is no proven treatment for NAFLD patients with normal or low BMI. The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI. In this randomised, double-blind, placebo-controlled, clinical trial, fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks. Both groups were advised to follow a healthy lifestyle. At the end of the study, hepatic steatosis and fibrosis reduced in both groups; however, the mean reduction was significantly greater in the synbiotic group rather than in the placebo group (P<0·001). Furthermore, serum levels of fasting blood sugar, TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group (P<0·05). Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI, at least partially through reduction in inflammatory indices. Further studies are needed to address the exact mechanism of action of these effects.

Dexmedetomidine oromucosal gel for noise-associated acute anxiety and fear in dogs-a randomised, double-blind, placebo-controlled clinical study.

PubMed

Korpivaara, M; Laapas, K; Huhtinen, M; Schöning, B; Overall, K

2017-04-08

The aim of this randomised, double-blind, placebo-controlled, clinical-field study was to evaluate the effect of dexmedetomidine oromucosal gel at subsedative doses in alleviation of noise-associated acute anxiety and fear in dogs. On New Year's Eve, 182 dogs with a history of acute anxiety and fear associated with fireworks received treatment as needed up to five times: 89 dogs received dexmedetomidine and 93 dogs received placebo. For the primary efficacy variables, dog owners assessed the overall treatment effect as well as signs and extent of anxiety and fear. The overall treatment effect was statistically significant (P<0.0001). An excellent or good treatment effect was reported for a higher proportion of dogs treated with dexmedetomidine (64/89, 72 per cent) than those receiving placebo (34/93, 37 per cent). Additionally, dexmedetomidine-treated dogs expressed significantly (P<0.0314) fewer signs of fear and anxiety despite the noise of fireworks. No local tolerance or clinical safety concerns occurred during the study. This study demonstrated that oromucosal dexmedetomidine at subsedative doses alleviates noise-associated acute anxiety and fear in dogs. British Veterinary Association.

Comparison of lidocaine spray and paracervical block application for pain relief during first-trimester surgical abortion: A randomised, double-blind, placebo-controlled trial.

PubMed

Aksoy, Huseyin; Aksoy, Ulku; Ozyurt, Sezin; Ozoglu, Nil; Acmaz, Gokhan; Aydın, Turgut; İdem Karadağ, Özge; Tayyar, Ahter Tanay

2016-07-01

Surgical abortion is one of the most frequently performed gynaecological procedures and its associated pain has always been a problem in gynaecology. Here we studied the analgesic efficacy of lidocaine spray and paracervical block (PCB) in patients undergoing first-trimester surgical abortion. A randomised double-blind placebo-controlled study was conducted on 108 women requesting pregnancy termination. The subjects were randomly assigned into four groups: Group 1 (PCB plus lidocaine spray) (n=27), Group 2 (PCB) (n=27), Group 3 (lidocaine spray) (n=27) and Group 4 (placebo) (n=27). Intra-procedural and post-procedural pain scores were measured with a standard visual analogue scale (VAS). The median VAS scores during procedure in placebo, lidocaine spray, PCB plus lidocaine spray and PCB groups were 8 (7-9), 5 (4-8), 4 (3-4) and 5 (3-5), respectively. The most effective method of pain relief during first-trimester abortion can be achieved through a combined use of PCB plus lidocaine spray. Therefore, lidocaine spray is a non-invasive complementary anaesthetic method versus traditional PCB for first-trimester surgical abortion.

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

PubMed

Rao, Amanda; Steels, Elizabeth; Inder, Warrick J; Abraham, Suzanne; Vitetta, Luis

2016-06-01

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

Local anaesthetic on Filshie clips for pain relief after tubal sterilisation: a randomised double-blind controlled trial.

PubMed

Ezeh, U O; Shoulder, V S; Martin, J L; Breeson, A J; Lamb, M D; Vellacott, I D

1995-07-08

Pain during tubal sterilisation is thought to be due to either ischaemia or pressure at the site of impact of sterilising devices on the fallopian tubes. We have evaluated the effectiveness of an application of 2% lignocaine gel to Filshie clips to relieve postoperative pain. In a randomised double-blind placebo-controlled study, 80 healthy women undergoing tubal sterilisation under general anaesthesia at the County Hospital, Lincoln, UK, were allocated to be sterilised by Flishie clips covered with 2% lignocaine gel or K-Y gel as placebo. Pelvic pain was assessed, with a 100 mm visual analogue scale, at 1 hour, at hospital discharge, and time of first analgesia or any other time analgesia was demanded. The lignocaine-treated group had significantly longer time to first analgesia, less pain at 1 hour, less nausea and vomiting, and shorter recovery time. Fewer lignocaine-treated patients needed additional analgesia and they required fewer opioids. There was no case of failed sterilisation or adverse reaction to lignocaine. The application of local anaesthetic gel to Filshie clips is a safe, non-invasive, and effective method of relieving postoperative pain during laparoscopic tubal sterilisation.

An open-label six-month extension study to investigate the safety and efficacy of an extract of Artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee.

PubMed

Hunt, Sheena; Stebbings, Simon; McNamara, Debra

2016-10-28

This six-month single-centre open-label extension study, conducted at the University of Otago, Dunedin, follows from a previously published 12-week pilot double-blind randomised placebo-controlled study of dietary supplement, Arthrem® (ART) in patients with osteoarthritis (OA) of the hip or knee. The pilot double-blind study showed that treatment with ART 150 mg twice-daily was associated with clinically relevant pain reduction. The extension study aims were to assess longer-term safety and efficacy during six months' treatment following the pilot trial. Patients who completed the pilot double-blind study had the option to continue on open-label treatment with ART for a further six months. Safety was assessed by adverse event monitoring and laboratory tests at three and six months. Efficacy was assessed at three and six months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®). Thirty-four patients entered the optional extension and 28 completed six months' treatment. ART was well tolerated when taken for up to nine months. Improvements in WOMAC® efficacy parameters reported in the double-blind phase of the study were maintained over six months. ART appears to be a safe and effective alternative for managing the symptoms of OA over an extended period.

3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

PubMed

Gross, Volker; Bunganic, Ivan; Belousova, Elena A; Mikhailova, Tatyana L; Kupcinskas, Limas; Kiudelis, Gediminas; Tulassay, Zsolt; Gabalec, Libor; Dorofeyev, Andrey E; Derova, Jelena; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2011-04-01

Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution. Copyright © 2010. Published by Elsevier B.V.

Towards evidence-based vitamin D supplementation in infants: vitamin D intervention in infants (VIDI) - study design and methods of a randomised controlled double-blinded intervention study.

PubMed

Helve, Otto; Viljakainen, Heli; Holmlund-Suila, Elisa; Rosendahl, Jenni; Hauta-Alus, Helena; Enlund-Cerullo, Maria; Valkama, Saara; Heinonen, Kati; Räikkönen, Katri; Hytinantti, Timo; Mäkitie, Outi; Andersson, Sture

2017-03-29

Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: 1. bone strength 2. infections and immunity 3. allergy, atopy and asthma 4. cognitive development 5. genetic regulation of mineral homeostasis METHODS/DESIGN: VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.

The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma.

PubMed

Buhl, R; Hanf, G; Solèr, M; Bensch, G; Wolfe, J; Everhard, F; Champain, K; Fox, H; Thirlwell, J

2002-11-01

The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as "excellent/good", compared with approximately 40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old.

PubMed

2015-09-01

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were titered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

PubMed Central

2015-01-01

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose. PMID:26517656

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention.

PubMed

Lai, Veronica Ka Wai; Lee, Anna; Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John; Joynt, Gavin Matthew

2016-06-22

Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethical approval has been obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. ChiCTR-IOR-15006971. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

PubMed

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study.

PubMed

Rizzardini, Giuliano; Eskesen, Dorte; Calder, Philip C; Capetti, Amedeo; Jespersen, Lillian; Clerici, Mario

2012-03-01

The present study investigated the ability of Bifidobacterium animalis ssp. lactis (BB-12®) and Lactobacillus paracasei ssp. paracasei (L. casei 431®) to modulate the immune system using a vaccination model in healthy subjects. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 211 subjects (56 % females, mean age 33·2 (sd 13·1) years). Subjects consumed a minimum of 10⁹ colony-forming units of BB-12® (capsule) or L. casei 431® (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a seasonal influenza vaccination was given. Plasma and saliva samples were collected at baseline and after 6 weeks for the analysis of antibodies, cytokines and innate immune parameters. Changes from baseline in vaccine-specific plasma IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the corresponding placebo group (L. casei 431®, P = 0·01 for IgG; P < 0·001 for remaining comparisons). The number of subjects obtaining a substantial increase in specific IgG (defined as ≥ 2-fold above baseline) was significantly greater in both probiotic groups v. placebo (BB-12®, P < 0·001 for IgG, IgG1 and IgG3; L. casei 431®, P < 0·001 for IgG1 and IgG3). Significantly greater mean fold increases for vaccine-specific secretory IgA in saliva were observed in both probiotic groups v. placebo (BB-12®, P = 0·017; L. casei 431®, P = 0·035). Similar results were observed for total antibody concentrations. No differences were found for plasma cytokines or innate immune parameters. Data herein show that supplementation with BB-12® or L. casei 431® may be an effective means to improve immune function by augmenting systemic and mucosal immune responses to challenge.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

PubMed

Villar-García, Judit; Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P; Artacho, Alejandro; D Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

PubMed Central

Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D´Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target. PMID:28388647

Antifatigue Effects of Panax ginseng C.A. Meyer: A Randomised, Double-Blind, Placebo-Controlled Trial

PubMed Central

Yoo, Sa-Ra; Lee, Jin-Seok; Han, Jong-Min; Lee, Nam-Hun; Ahn, Yo-Chan; Son, Chang-Gue

2013-01-01

The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day–1) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4±5.0 to 15.1±6.5 [95% CI 2.3∼8.2] for 1 g and 20.7±6.3 to 13.8±6.2 [95% CI −0.1∼4.2] for 2 g compared with placebo 20.9±4.5 to 18.8±2.9 [95% CI 4.1∼9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3±1.3 to 4.4±1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1±1.0 to 5.8±1.3 [95% CI 2.2 ∼3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. Trial Registration Clinical Research Information Service (CRIS) KCT0000048 PMID:23613825

TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.

PubMed

Olanow, C Warren; Schapira, Anthony H V; LeWitt, Peter A; Kieburtz, Karl; Sauer, Dirk; Olivieri, Gianfranco; Pohlmann, Harald; Hubble, Jean

2006-12-01

There is an important unmet medical need in Parkinson's disease for a neuroprotective treatment that slows or stops disease progression. TCH346 is a potent anti-apoptotic drug that protects against loss of dopaminergic neurons in laboratory models. Our aim was to assess TCH346 as a neuroprotective drug in patients with Parkinson's disease. Patients presenting at 45 international movement disorder clinics with early untreated Parkinson's disease were assessed as part of this parallel-group, double-blind, randomised controlled trial. 301 eligible patients were randomly assigned 12-18 months' treatment with TCH346 at a daily dose of 0.5 mg (n=78), 2.5 mg (n=79), or 10 mg (n=73), or placebo (n=71), followed by a 4 week washout period. The primary outcome measure was time to development of a disability requiring dopaminergic treatment. Secondary outcome measures were the annual rate of change in the unified Parkinson's disease rating scale (UPDRS) and the PDQ-39, a measure of quality of life. Analyses were by intention-to-treat. This study is pending registration with . 255 patients completed the study. TCH346 did not differ from placebo for any of the study outcomes. Treatment was needed in 26 (34%) patients in the TCH346 0.5 mg group, 30 (38%) in the TCH346 2.5 mg group, 24 (33%) in the TCH346 10 mg group, and 23 (32%) in the placebo group. There were no significant differences between groups. There were no differences between groups in the annual change in the UPDRS or PDQ-39 either. Few patients withdrew because of adverse events and none was judged to be related to the study intervention. TCH346 did not show evidence of a neuroprotective effect. The discrepancy between the preclinical promise of TCH346 and the clinical outcome could have arisen because of the use of laboratory models that do not accurately reflect the pathogenesis of Parkinson's disease, the doses of study drug used, insensitive clinical endpoints, and the patient population selected for study.

The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial--study protocol.

PubMed

Lee, Dong-Hyo; Seo, Eun-Sung; Hong, Jin-Tae; Lee, Gang-Tai; You, Young-Kyoung; Lee, Kun-Kook; Jo, Ga-Won; Kim, Nam-Kwen

2013-11-25

Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition.This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ health-related quality of life questionnaires to assess changes in the quality of life. The results of this study will be used to present the evidence needed to request advertising/display allowances, in compliance with the recently amended Cosmetics Act for advertisement in Korea. Current Controlled Trials ISRCTN46216631.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

PubMed Central

Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

2016-01-01

Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31). PMID:25425655

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

PubMed

Sng, Ban Leong; Du, Wei; Lee, Man Xin; Ithnin, Farida; Mathur, Deepak; Leong, Wan Ling; Sultana, Rehena; Han, Nian-Lin R; Sia, Alex Tiong Heng

2018-05-01

Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. A randomised, double-blind controlled trial. Single-centre, KK Women's and Children's Hospital, Singapore. Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. Clinicaltrials.gov identifier: NCT02277730.

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

PubMed

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel; Pedersen, Niels Anker; Dahl, Jørgen Berg; Schrøder, Henrik Morville; Bülow, Hans Henrik; Bjørck, Jan Gottfrid; Overgaard, Søren; Mathiesen, Ole; Wetterslev, Jørn

2017-10-10

Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results. The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting. ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

PubMed Central

2014-01-01

Background The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. Discussion Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. Trial registration ClinicalTrials.gov: NCT01119014 PMID:25015535

Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration.

PubMed

Collum, L M; Logan, P; McAuliffe-Curtin, D; Hung, S O; Patterson, A; Rees, P J

1985-11-01

Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.

Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

PubMed

Schilling, J; Mueller, R S

2012-07-28

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial.

PubMed

Mogollon, Jaime Andres; Boivin, Catherine; Lemieux, Simone; Blanchet, Claudine; Claveau, Joël; Dodin, Sylvie

2014-06-27

Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20-65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Our study failed to demonstrate a statistically-significant protective effect of HFC vs. LFC consumption on skin sensitivity to UV radiation as measured by MED. ClinicalTrials.gov identifier: NCT01444625.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

PubMed

Pandey, Sanjay; Srivanitchapoom, Prachaya; Kirubakaran, Richard; Berman, Brian D

2018-01-05

Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial.

PubMed

Nieminen, Heta; Syrjänen, Ritva K; Puumalainen, Taneli; Sirén, Päivi; Palmu, Arto A

2015-07-17

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents' decision on their child's study participation. A questionnaire designed to evaluate parents' attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1484 who participated in the trial and 1485 who did not participate. Altogether 1438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1484) than among FinIP non-participants (32%, 473/1485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase.

PubMed

Gupta, Ajay; Thompson, David; Whitehouse, Andrew; Collier, Tim; Dahlof, Bjorn; Poulter, Neil; Collins, Rory; Sever, Peter

2017-06-24

In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40-79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest-muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment-and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7-3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2-2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88-1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75-1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56-0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57-1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08-1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10-1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06-1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04-1·88]; p=0·03), which were reported more commonly by statin users than by non-users. These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Pfizer, Servier Research Group, and Leo Laboratories. Copyright © 2017 Elsevier Ltd. All rights reserved.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

Dietary grape powder increases IL-1ß and IL-6 production by lipopolysaccharide-activated monocytes and reduces plasma concentrations of large LDL-cholesterol particles in obese humans

USDA-ARS?s Scientific Manuscript database

Obesity increases the risk of developing cardiovascular disease, hypertension, type 2 diabetes, and bacterial and viral infections when compared to the normal weight population. In a 9 wk randomised, double-blind crossover study, 24 obese subjects between 20-60 y old and with a BMI between 30-45 k...

Randomised, placebo-controlled, double-blind, split-face study on the clinical efficacy of Tricutan on skin firmness.

PubMed

Sommerfeld, B

2007-11-01

Tricutan is a combination product of herbal extracts traditionally used for treatment of skin conditions, together with dimethylaminoethanol. The effectiveness of Tricutan in improving skin firmness and elasticity in photoaged facial skin was examined in a randomised, placebo-controlled, double-blind, split-face study in 28 women, 34-67 years old. Treatment with Tricutan and placebo was given for 4 weeks. Skin firmness and elasticity was evaluated using the speed of propagation of ultrasound shear waves in the skin as end point (Reviscometer RVM 600). The study was completed by 25 women. The Tricutan treatment resulted in a significantly reduced propagation speed indicating increased firmness. There was no immediate effect by Tricutan application on propagation speed. At self evaluation the women evaluated the treatment effect of Tricutan to be significantly better than the treatment effect of placebo. The clinical evaluation also showed Tricutan to give a significantly better treatment result than placebo. Tolerance to Tricutan was generally good. However, three women did not complete the study because of mild irritative contact dermatitis. The results show that Tricutan can increase skin firmness both objectively and subjectively. Further studies are warranted, especially to investigate if Tricutan can delay the need for surgical face-lift procedures.

A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

PubMed

Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

2013-07-01

Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease.

PubMed

Martin-Bastida, Antonio; Ward, Roberta J; Newbould, Rexford; Piccini, Paola; Sharp, David; Kabba, Christina; Patel, Maneesh C; Spino, Michael; Connelly, John; Tricta, Fernando; Crichton, Robert R; Dexter, David T

2017-05-03

Parkinson's disease (PD) is associated with increased iron levels in the substantia nigra (SNc). This study evaluated whether the iron chelator, deferiprone, is well tolerated, able to chelate iron from various brain regions and improve PD symptomology. In a randomised double-blind, placebo controlled trial, 22 early onset PD patients, were administered deferiprone, 10 or 15 mg/kg BID or placebo, for 6 months. Patients were evaluated for PD severity, cognitive function, depression rating and quality of life. Iron concentrations were assessed in the substantia nigra (SNc), dentate and caudate nucleus, red nucleus, putamen and globus pallidus by T2* MRI at baseline and after 3 and 6 months of treatment. Deferiprone therapy was well tolerated and was associated with a reduced dentate and caudate nucleus iron content compared to placebo. Reductions in iron content of the SNc occurred in only 3 patients, with no changes being detected in the putamen or globus pallidus. Although 30 mg/kg deferiprone treated patients showed a trend for improvement in motor-UPDRS scores and quality of life, this did not reach significance. Cognitive function and mood were not adversely affected by deferiprone therapy. Such data supports more extensive clinical trials into the potential benefits of iron chelation in PD.

Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults.

PubMed

Wiffen, Philip J; Knaggs, Roger; Derry, Sheena; Cole, Peter; Phillips, Tudor; Moore, R Andrew

2016-12-27

Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.

PubMed

Al-Lamee, Rasha; Thompson, David; Dehbi, Hakim-Moulay; Sen, Sayan; Tang, Kare; Davies, John; Keeble, Thomas; Mielewczik, Michael; Kaprielian, Raffi; Malik, Iqbal S; Nijjer, Sukhjinder S; Petraco, Ricardo; Cook, Christopher; Ahmad, Yousif; Howard, James; Baker, Christopher; Sharp, Andrew; Gerber, Robert; Talwar, Suneel; Assomull, Ravi; Mayet, Jamil; Wensel, Roland; Collier, David; Shun-Shin, Matthew; Thom, Simon A; Davies, Justin E; Francis, Darrel P

2018-01-06

Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is low-dose amitriptyline effective in the management of chronic low back pain? Study protocol for a randomised controlled trial.

PubMed

Urquhart, Donna M; Wluka, Anita E; Sim, Malcolm R; van Tulder, Maurits; Forbes, Andrew; Gibson, Stephen J; Arnold, Carolyn; Fong, Chris; Anthony, Shane N; Cicuttini, Flavia M

2016-10-22

Low back pain is a major clinical and public health problem, with limited evidence-based treatments. Low-dose antidepressants are commonly used to treat pain in chronic low back pain. However, their efficacy is unproven. The aim of this pragmatic, double-blind, randomised, placebo-controlled trial is to determine whether low-dose amitriptyline (an antidepressant) is more effective than placebo in reducing pain in individuals with chronic low back pain. One hundred and fifty individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics, advertising in local media and posting of flyers in community locations. They will be randomly allocated to receive either low-dose amitriptyline (25 mg) or an active placebo (benztropine mesylate, 1 mg) for 6 months. The primary outcome measure of pain intensity will be assessed at baseline, 3 and 6 months using validated questionnaires. Secondary measures of self-reported low back disability, work absence and hindrance in the performance of paid/unpaid work will also be examined. Intention-to-treat analyses will be performed. This pragmatic, double-blind, randomised, placebo-controlled trial will provide evidence regarding the effectiveness of low-dose antidepressants compared with placebo in reducing pain, disability, work absenteeism and hindrance in work performance in individuals with chronic low back pain. This trial has major public health and clinical importance as it has the potential to provide an effective approach to the management of chronic low back pain. Australian New Zealand Clinical Trials Registry: ACTRN12612000131853 ; registered on 30 January 2012.

Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate

PubMed Central

2013-01-01

Background Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania. Methods/design A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression–Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-‘Vigilance Algorithm Leipzig’ (VIGALL). Discussion A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives. Trial registration ClinicalTrials.gov: NCT 01541605 PMID:23446109

Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial.

PubMed

Medina-Vera, A J; Novoa, L M

2017-02-01

To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739±0.016μg/kg/min, Group 2: 0.0741±0.018μg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Combining rigour with relevance: a novel methodology for testing Chinese herbal medicine.

PubMed

Flower, Andrew; Lewith, George; Little, Paul

2011-03-24

There is a need to develop an evidence base for Chinese herbal medicine (CHM) that is both rigorous and reflective of good practice. This paper proposes a novel methodology to test individualised herbal decoctions using a randomised, double blinded, placebo controlled clinical trial. A feasibility study was conducted to explore the role of CHM in the treatment of endometriosis. Herbal formulae were pre-cooked and dispensed as individual doses in sealed plastic sachets. This permitted the development and testing of a plausible placebo decoction. Participants were randomised at a distant pharmacy to receive either an individualised herbal prescription or a placebo. The trial met the predetermined criteria for good practice. Neither the participants nor the practitioner-researcher could reliably identify group allocation. Of the 28 women who completed the trial, in the placebo group (n=15) 3 women (20%) correctly guessed they were on placebo, 8 (53%) thought they were on herbs and 4 (27%) did not know which group they had been allocated to. In the active group (n=13) 2 (15%) though they were on placebo, 8 (62%) thought they were on herbs and 3 (23%) did not know. Randomisation, double blinding and allocation concealment were successful and the study model appeared to be feasible and effective. It is now possible to subject CHM to rigorous scientific scrutiny without compromising model validity. Improvement in the design of the placebo using food colourings and flavourings instead of dried food will help guarantee the therapeutic inertia of the placebo decoction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP).

PubMed

Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas

2016-07-07

In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. NCT02254980. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP)

PubMed Central

Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas

2016-01-01

Introduction In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. Methods and analysis In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. Results Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. Ethics and dissemination The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. Trial registration number NCT02254980. PMID:27388352

Low-level laser therapy for pain relief after episiotomy: a double-blind randomised clinical trial.

PubMed

Santos, Jaqueline de O; de Oliveira, Sonia M J V; da Silva, Flora M B; Nobre, Moacyr R C; Osava, Ruth H; Riesco, Maria L G

2012-12-01

To evaluate the effectiveness of a low-level laser therapy for pain relief in the perineum following episiotomy during childbirth. Laser irradiation is a painless and non-invasive therapy for perineal pain treatment and its effects have been investigated in several studies, with no clear conclusion on its effectiveness. A double-blind randomised controlled clinical trial. One hundred and fourteen women who underwent right mediolateral episiotomies during vaginal birth in an in-hospital birthing centre in São Paulo, Brazil and reported pain ≥ 3 on a numeric scale (0-10) were randomised into three groups of 38 women each: two experimental groups (treated with red and infrared laser) and a control group. The experimental groups were treated with laser applied at three points directly on the episiotomy after suturing in a single session between 6-56 hours postpartum. We used a diode laser with wavelengths of 660 nm (red laser) and 780 nm (infrared laser). The control group participants underwent all laser procedures, excluding the emission of irradiation. The participants and the pain scores evaluator were blinded to the type of intervention. The perineal pain scores were assessed at three time points: before, immediately after and 30 minutes after low-level laser therapy. The comparison of perineal pain between the three groups showed no significant differences in the three evaluations (p = 0.445), indicating that the results obtained in the groups treated with low-level laser therapy were equivalent to the control group. Low-level laser therapy did not decrease the intensity of perineal pain reported by women who underwent right mediolateral episiotomy. The effect of laser in perineal pain relief was not demonstrated in this study. The dosage may not have been sufficient to provide relief from perineal pain after episiotomy during a vaginal birth. © 2012 Blackwell Publishing Ltd.

A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

PubMed

Micallef, J; Soubrouillard, C; Guet, F; Le Guern, M E; Alquier, C; Bruguerolle, B; Blin, O

2001-06-01

This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

Multicenter, double-blind, parallel group study investigating the non-inferiority of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2% ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.

PubMed

Buechner, Stanislaw A

2014-06-01

This study investigated the non-inferiority of efficacy and tolerance of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in the treatment of scalp seborrheic dermatitis. A randomized, double-blind, comparative, parallel group, multicenter study was done. A total of 274 patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice-weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global change [Clinical Global Impressions (CGIs) and Patient Global Impressions (PGIs)]. Miconazole shampoo is at least as effective and safe as ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

2015-01-01

The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were detected for chair-time (P = 0.3524), for VAS pain immediately after surgery (P = 0.5644), VAS pain after 1 week (P = 0.5074) and VAS pain after 2 weeks (P = 0.6950). A slight difference (0.24 mm, 95%CI from 0.0004 to 0.47, P = 0.0464) was detected in radiographic peri-implant bone loss favouring the CJ group. No significant differences, except for radiographic bone loss, were observed in this randomised controlled trial comparing anorganic bovine bone with collagen porcine membranes versus synthetic resorbable bone made of pure β-tricalcium phosphate with pericardium collagen membranes for horizontal augmentation.

Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial.

PubMed

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-02-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep variables at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings. The side effect profile was low and not significantly different between the two arms.

Double-blind multicentre UK hospital studies of isoxicam vs naproxen

PubMed Central

Cardoe, N.; Hart, F. Dudley

1986-01-01

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks. 10 Patients thought that isoxicam was more effective than naproxen, to a significant difference. 11 In both trials, the two drugs were well tolerated and had similar side effects profiles, with the majority of adverse experiences being associated with the digestive system; no side effect was severe. PMID:3620277

A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery

PubMed Central

Bagger-Sjöbäck, Dan; Strömbäck, Karin; Hakizimana, Pierre; Plue, Jan; Larsson, Christina; Hultcrantz, Malou; Papatziamos, Georgios; Smeds, Henrik; Danckwardt-Lillieström, Niklas; Hellström, Sten; Johansson, Ann; Tideholm, Bo; Fridberger, Anders

2015-01-01

Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed) and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy. Trial Registration ClinicalTrials.gov NCT00525551 PMID:25763866

Prenatal omega-3 fatty acid supplementation does not affect offspring telomere length and F2-isoprostanes at 12 years: A double blind, randomized controlled trial.

PubMed

See, V H L; Mas, E; Burrows, S; O'Callaghan, N J; Fenech, M; Prescott, S L; Beilin, L J; Huang, R C; Mori, T A

2016-09-01

Oxidative stress and nutritional deficiency may influence the excessive shortening of the telomeric ends of chromosomes. It is known that stress exposure in intrauterine life can produce variations in telomere length (TL), thereby potentially setting up a long-term trajectory for disease susceptibility. To assess the effect of omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy on telomere length and oxidative stress in offspring at birth and 12 years of age (12y). In a double-blind, placebo-controlled, parallel-group study, 98 pregnant atopic women were randomised to 4g/day of n-3 LCPUFA or control (olive oil [OO]), from 20 weeks gestation until delivery. Telomere length as a marker of cell senescence and plasma and urinary F2-isoprostanes as a marker of oxidative stress were measured in the offspring at birth and 12y. Maternal n-3 LCPUFA supplementation did not influence offspring telomere length at birth or at 12y with no changes over time. Telomere length was not associated with F2-isoprostanes or erythrocyte total n-3 fatty acids. Supplementation significantly reduced cord plasma F2-isoprostanes (P<0.001), with a difference in the change over time between groups (P=0.05). However, the differences were no longer apparent at 12y. Between-group differences for urinary F2-isoprostanes at birth and at 12y were non-significant with no changes over time. This study does not support the hypothesis that n-3 LCPUFA during pregnancy provides sustained effects on postnatal oxidative stress and telomere length as observed in the offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

PubMed

Langhorst, J; Varnhagen, I; Schneider, S B; Albrecht, U; Rueffer, A; Stange, R; Michalsen, A; Dobos, G J

2013-09-01

The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18. © 2013 John Wiley & Sons Ltd.

Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies.

PubMed

Dréno, Brigitte; Bettoli, Vincenzo; Ochsendorf, Falk; Layton, Alison M; Perez, Montserrat; Dakovic, Rada; Gollnick, Harald

2014-01-01

The efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% (Clin-RA) were evaluated in three 12-week randomised studies. To perform a pooled analysis of data from these studies to evaluate Clin-RA's efficacy and safety in a larger overall population, in subgroups of adolescents and according to acne severity. 4550 patients were randomised to Clin-RA, clindamycin, tretinoin and vehicle. Evaluations included percentage change in lesions, treatment success rate, proportions of patients with ≥50% or ≥80% continuous reduction in lesions, adverse events and cutaneous tolerability. In the overall population, the percentage reduction in inflammatory, non-inflammatory and total lesions and the treatment success rate were significantly greater with Clin-RA compared with clindamycin, tretinoin and vehicle alone (all p<0.01). The percentage reduction in all types of lesions was also significantly greater with Clin-RA in the adolescent subgroup (2915 patients, p<0.002) and in patients with mild/moderate acne (3662 patients, p<0.02) versus comparators. In patients with severe acne (n = 880), the percentage reduction in all lesion types was significantly greater with Clin-RA versus vehicle (p<0.0001). A greater proportion of Clin-RA treated patients had a ≥50% or ≥80% continuous reduction in all types of lesions at week 12 compared with clindamycin, tretinoin and vehicle. Adverse event frequencies in the active and vehicle groups were similar. Baseline-adjusted mean tolerability scores over time were <1 (mild) and similar in all groups. Clin-RA is safe, has superior efficacy to its component monotherapies and should be considered as one of the first-line therapies for mild-to-moderate facial acne.

A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.

PubMed

McAndrew, Amy; Lawn, Will; Stevens, Tobias; Porffy, Lilla; Brandner, Brigitta; Morgan, Celia J A

2017-04-04

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series

PubMed Central

Taylor, Morag A; Reilly, David; Llewellyn-Jones, Robert H; McSharry, Charles; Aitchison, Tom C

2000-01-01

Objective To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Design Randomised, double blind, placebo controlled, parallel group, multicentre study. Setting Four general practices and a hospital ear, nose, and throat outpatient department. Participants 51 patients with perennial allergic rhinitis. Intervention Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Main outcome measures Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Results Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). Conclusion The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo. PMID:10948025

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

PubMed

Brown, Sarah; Smith, Isabelle L; Brown, Julia M; Hulme, Claire; McGinnis, Elizabeth; Stubbs, Nikki; Nelson, E Andrea; Muir, Delia; Rutherford, Claudia; Walker, Kay; Henderson, Valerie; Wilson, Lyn; Gilberts, Rachael; Collier, Howard; Fernandez, Catherine; Hartley, Suzanne; Bhogal, Moninder; Coleman, Susanne; Nixon, Jane E

2016-12-20

Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

Comparison of two shampoos for treatment of Malassezia pachydermatis-associated seborrhoeic dermatitis in basset hounds.

PubMed

Bond, R; Rose, J F; Ellis, J W; Lloyd, D H

1995-03-01

A randomised-double-blind parallel study compared the clinical and antimicrobial efficacies of a miconazole-chlorhexidine shampoo with a selenium sulphide shampoo for the treatment of seborrhoeic dermatitis associated with Malassezia pachydermatis in 33 basset hounds. All 16 miconazole-chlorhexidine treated hounds and 11 of 17 selenium sulphide treated hounds improved when shampooed at three-day intervals for three weeks. The miconazole-chlorhexidine treated hounds showed significantly greater reductions in pruritus (P < 0.01), erythema (P < 0.001), exudation (P < 0.01) and overall severity (P < 0.001), and in counts of M pachydermatis (P < 0.001), total bacteria (P < 0.001) and coagulase-positive staphylococci (P < 0.001), when compared to the selenium sulphide treated group. Improvements in scaling and coat condition did not vary significantly between the two groups. These results indicate that seborrhoeic dermatitis in basset hounds is often associated with elevated cutaneous populations of M pachydermatis and bacteria, and that the miconazole-chlorhexidine shampoo is more effective than the selenium sulphide product for the treatment for this disease.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

PubMed Central

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-01-01

Objective To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Methods Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity. Results AUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Conclusions Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. Trial registration number EudraCT number 2012-000785-37; Results. PMID:27466231

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

PubMed Central

Naumann, M; Lowe, N J

2001-01-01

Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks PMID:11557704

Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial.

PubMed

Schrijver, Edmée J M; de Vries, Oscar J; van de Ven, Peter M; Bet, Pierre M; Kamper, Ad M; Diepeveen, Sabine H A; van Marum, Rob J; van Strien, Astrid M; Anten, Sander; Lagaay, Anne M; Boelaarts, Leo; Bloemers, Frank W; Kramer, Mark H H; Nanayakkara, Prabath W B

2018-01-01

because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients. this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age ≥70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes. intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted. prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

Efficacy and safety of the Shexiang Baoxin Pill for the treatment of coronary artery disease not amenable to revascularisation: study protocol for a randomised, placebo-controlled, double-blinded trial

PubMed Central

Tian, Pan-pan; Li, Jun; Gao, Jian; Li, Ying

2018-01-01

Introduction Coronary artery disease (CAD) not amenable to revascularisation indicates that the coronary arteries have severe diffuse lesions or calcifications, or that CAD is complicated with severe multiple-organ disease. Currently, Western medicines available for the treatment of CAD not amenable to revascularisation are limited. Shexiang Baoxin Pill (SBP), a type of Chinese patent medicine, has been widely used to treat CAD in China for many years. Previous studies have shown that long-term administration of SBP (1–2 pills three times daily, for at least 6 months) for treatment of CAD is effective and safe, with a significant, long-term effect. This study aims to evaluate the efficacy and safety of SBP in patients with CAD not amenable to revascularisation. Methods and analysis This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 440 participants will be randomly allocated to two groups: the intervention group and the placebo group. Based on conventional treatment with Western medicine, the intervention group will be treated with SBP and the placebo group will be treated with SBP placebo. The primary outcomes include major adverse cardiovascular events (including angina, acute myocardial infarction, pulmonary embolism and aortic dissection). The secondary outcomes include C reactive protein, B-type natriuretic peptide, ECG, echocardiographic parameters (ejection fraction percentage and the E/A ratio) and hospital readmission rates due to CAD. Assessments will be performed at baseline (before randomisation) and at 24 weeks after randomisation. Ethics and dissemination The protocol has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (reference: 2016-129-KY-01). The results of this study will be published in a peer-reviewed journal and will be used as a basis for a multisite trial. Trial registration number NCT03072121; Pre-results. PMID:29444778

EFFECT of daily antiseptic body wash with octenidine on nosocomial primary bacteraemia and nosocomial multidrug-resistant organisms in intensive care units: design of a multicentre, cluster-randomised, double-blind, cross-over study

PubMed Central

Meißner, Anne; Hasenclever, Dirk; Brosteanu, Oana; Chaberny, Iris Freya

2017-01-01

Introduction Nosocomial infections are serious complications that increase morbidity, mortality and costs and could potentially be avoidable. Antiseptic body wash is an approach to reduce dermal micro-organisms as potential pathogens on the skin. Large-scale trials with chlorhexidine as the antiseptic agent suggest a reduction of nosocomial infection rates. Octenidine is a promising alternative agent which could be more effective against Gram-negative organisms. We hypothesise that daily antiseptic body wash with octenidine reduces the risk of intensive care unit (ICU)-acquired primary bacteraemia and ICU-acquired multidrug-resistant organisms (MDRO) in a standard care setting. Methods and analysis EFFECT is a controlled, cluster-randomised, double-blind study. The experimental intervention consists in using octenidine-impregnated wash mitts for the daily routine washing procedure of the patients. This will be compared with using placebo wash mitts. Replacing existing washing methods is the only interference into clinical routine. Participating ICUs are randomised in an AB/BA cross-over design. There are two 15-month periods, each consisting of a 3-month wash-out period followed by a 12-month intervention and observation period. Randomisation determines only the sequence in which octenidine-impregnated or placebo wash mitts are used. ICUs are left unaware of what mitts packages they are using. The two coprimary endpoints are ICU-acquired primary bacteraemia and ICU-acquired MDRO. Endpoints are defined based on individual ward-movement history and microbiological test results taken from the hospital information systems without need for extra documentation. Data on clinical symptoms of infection are not collected. EFFECT aims at recruiting about 45 ICUs with about 225 000 patient-days per year. Ethics and dissemination The study was approved by the ethics committee of the University of Leipzig (number 340/16-ek) in November 2016. Findings will be published in peer-reviewed journals. Trial registration number DRKS-ID: DRKS00011282. PMID:29122787

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Palacio, M; Cobo, T; Antolín, E; Ramirez, M; Cabrera, F; Mozo de Rosales, F; Bartha, J L; Juan, M; Martí, A; Oros, D; Rodríguez, À; Scazzocchio, E; Olivares, J M; Varea, S; Ríos, J; Gratacós, E

2016-11-01

To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. Multicentre, randomised, double-blind, placebo-controlled trial. Twelve tertiary care centres in Spain. A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. Maintenance progesterone in 258 women after arrested PTL showed no benefit. © 2016 Royal College of Obstetricians and Gynaecologists.

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study

PubMed Central

Cohen, Stanley; Genovese, Mark C; Choy, Ernest; Perez-Ruiz, Fernando; Matsumoto, Alan; Pavelka, Karel; Pablos, Jose L; Rizzo, Warren; Hrycaj, Pawel; Zhang, Nan; Shergy, William; Kaur, Primal

2017-01-01

Objectives ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. Methods In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. Results A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Conclusions Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. Trial registration number NCT01970475; Results. PMID:28584187

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Sztajnbok, Flavio; Goldenstein-Schainberg, Claudia; Scheinberg, Morton; Penades, Immaculada Calvo; Fischbach, Michael; Orozco, Javier; Hashkes, Philip J; Hom, Christine; Jung, Lawrence; Lepore, Loredana; Oliveira, Sheila; Wallace, Carol A; Sigal, Leonard H; Block, Alan J; Covucci, Allison; Martini, Alberto; Giannini, Edward H

2008-08-02

Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Bristol-Myers Squibb.

Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial.

PubMed

Knowles, Charles H; Horrocks, Emma J; Bremner, Stephen A; Stevens, Natasha; Norton, Christine; O'Connell, P Ronan; Eldridge, Sandra

2015-10-24

Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory therapy for faecal incontinence. Data from case series suggest it has beneficial outcomes in 50-80% patients; however its effectiveness against sham electrical stimulation has not been investigated. We therefore aimed to assess the short-term efficacy of PTNS against sham electrical stimulation in adults with faecal incontinence. We did a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal NeuromodulaTion [CONFIDeNT]) in 17 specialist hospital units in the UK that had the skills to manage patients with faecal incontinence. Eligible participants aged 18 years or older with substantial faecal incontinence for whom conservative treatments (such as dietary changes and pelvic floor exercises) had not worked, were randomly assigned (1:1) to receive either PTNS (via the Urgent PC neuromodulation system) or sham stimulation (via a transcutaneous electrical nerve stimulation machine to the lateral forefoot) once per week for 12 weeks. Randomisation was done with permuted block sizes of two, four, and six, and was stratified by sex and then by centre for women. Patients and outcome assessors were both masked to treatment allocation for the 14-week duration of the trial (but investigators giving the treatment were not masked). The primary outcome was a clinical response to treatment, which we defined as a 50% or greater reduction in episodes of faecal incontinence per week. We assessed this outcome after 12 treatment sessions, using data from patients' bowel diaries. Analysis was by intention to treat, and missing data were multiply imputed. This trial is registered with the ISRCTN registry, number 88559475, and is closed to new participants. Between Jan 23, 2012, and Oct 31, 2013, we randomly assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the PTNS group and five from the sham group (mainly because they could not commit to receiving treatment every week). Two patients (one in each group) withdrew because of an adverse event that was unrelated to treatment (exacerbation of fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from bowel diaries in the PTNS group had a 50% or greater reduction in the number of episodes of faecal incontinence per week compared with 32 (31%) of 102 patients in the sham group (adjusted odds ratio 1·28, 95% CI 0·72-2·28; p=0·396). No serious adverse events related to treatment were reported in the trial. Seven mild, related adverse events were reported in each treatment group, mainly pain at the needle site (four in PTNS, three in sham). PTNS given for 12 weeks did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Further studies are warranted to determine its efficacy in the long term, and in patient subgroups (ie, those with urgency). National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial.

PubMed

Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

2016-01-01

This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life.

PubMed

Voss, Simon; Quail, Deborah; Dawson, Alison; Bäckström, Tjorbörn; Aguas, Fernanda; Erenus, Mithat; The, Hok Sien; Bonnar, John; De Geyter, Christian; Hunter, Myra; Nickelsen, Thomas

2002-08-01

To compare continuous combined hormone replacement therapy (ccHRT) and raloxifene with respect to compliance and quality of life, which were predefined secondary endpoints of a large, prospective study designed to investigate the uterine effects of both treatments. Double-blind, randomised controlled trial of six-month duration. One hundred and twenty-nine gynaecology hospital departments, clinics or practices specialised in women's healthcare, located in Europe, South Africa and Israel. Healthy postmenopausal women (n = 1008). Changes in quality of life using the Women's Health Questionnaire (WHQ) and compliance using a compliance questionnaire and pill count. Adverse event and early discontinuation rates and satisfaction with treatment using a visual analogue scale (VAS). Women taking raloxifene reported greater satisfaction with their treatment as assessed on the VAS (P = 0.004), and a lower proportion, as compared with ccHRT, reported being worried by the treatment (9.6% vs 20.2%, P < 0.01). Women taking ccHRT reported greater deterioration in scores from the WHQ for depressed mood and menstrual symptoms than those taking raloxifene (P < 0.01). For memory, vasomotor symptoms and sexual behaviour, the ccHRT group reported significantly greater mean improvements (P < 0.05). Over half (58.8%) of those taking raloxifene noticed no effect, 37.7% felt better and 3.4% felt worse as measured using the compliance questionnaire. Fifty percent of the women taking ccHRT felt better, 37.8% noticed no effect but over 10% felt worse. More women on raloxifene (94.6%) than on ccHRT (85.9%) reported that they were taking their double-blinded medication regularly (P < 0.01). A lower rate of adverse event-related discontinuations, the lack of negative effects on quality of life and a smaller proportion of women being worried by the drug treatment were associated with higher treatment satisfaction and better compliance in postmenopausal women taking ccHRT or raloxifene.

Hypocholesterolaemic effects of lupin protein and pea protein/fibre combinations in moderately hypercholesterolaemic individuals.

PubMed

Sirtori, Cesare R; Triolo, Michela; Bosisio, Raffaella; Bondioli, Alighiero; Calabresi, Laura; De Vergori, Viviana; Gomaraschi, Monica; Mombelli, Giuliana; Pazzucconi, Franco; Zacherl, Christian; Arnoldi, Anna

2012-04-01

The present study was aimed to evaluate the effect of plant proteins (lupin protein or pea protein) and their combinations with soluble fibres (oat fibre or apple pectin) on plasma total and LDL-cholesterol levels. A randomised, double-blind, parallel group design was followed: after a 4-week run-in period, participants were randomised into seven treatment groups, each consisting of twenty-five participants. Each group consumed two bars containing specific protein/fibre combinations: the reference group consumed casein+cellulose; the second and third groups consumed bars containing lupin or pea proteins+cellulose; the fourth and fifth groups consumed bars containing casein and oat fibre or apple pectin; the sixth group and seventh group received bars containing combinations of pea protein and oat fibre or apple pectin, respectively. Bars containing lupin protein+cellulose ( - 116 mg/l, - 4·2%), casein+apple pectin ( - 152 mg/l, - 5·3%), pea protein+oat fibre ( - 135 mg/l, - 4·7%) or pea protein+apple pectin ( - 168 mg/l, - 6·4%) resulted in significant reductions of total cholesterol levels (P<0·05), whereas no cholesterol changes were observed in the subjects consuming the bars containing casein+cellulose, casein+oat fibre or pea protein+cellulose. The present study shows the hypocholesterolaemic activity and potential clinical benefits of consuming lupin protein or combinations of pea protein and a soluble fibre, such as oat fibre or apple pectin.

Vitamins and psychological functioning: a mobile phone assessment of the effects of a B vitamin complex, vitamin C and minerals on cognitive performance and subjective mood and energy.

PubMed

Kennedy, David O; Veasey, Rachel C; Watson, Anthony W; Dodd, Fiona L; Jones, Emma K; Tiplady, Brian; Haskell, Crystal F

2011-01-01

Despite being widely consumed, the effects of multi-vitamin supplements on psychological functioning have received little research attention. Using a mobile phone testing paradigm, 198 males (30-55 years) in full-time employment took part in this randomised, placebo-controlled, double-blind, parallel-groups trial assessing the effects of a multi-vitamin/mineral on cognitive performance and psychological state/mood. Participants completed two cognitive tasks and a number of visual analogue scales (VAS) before and after a full day's work, on the day before, and 7, 14, 21 and 28 days after, commencing their treatment. Participants in the vitamin/mineral group rated themselves as having greater 'physical stamina' across assessments and weeks. They also rated themselves as having had greater 'concentration' and 'mental stamina' during the working day at the assessment carried out after a day's work, but not at the time of the assessment completed prior to work. Participants in this group also reported greater subjective 'alertness' on Bond-Lader mood scales during the post-work assessment on day 14 and both the pre and post-work assessments on day 28. These findings complement the results from the laboratory-based, randomised-controlled trial in the same cohort and suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation. Copyright © 2011 John Wiley & Sons, Ltd.

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study

PubMed Central

Schellenberg, R

2001-01-01

Objectives To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Design Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. Setting General medicine community clinics. Participants 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Interventions Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main outcome measures Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Results Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Conclusions Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome. PMID:11159568

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

PubMed

Schellenberg, R

2001-01-20

To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

Euiiyin-tang in the treatment of obesity: study protocol for a randomised controlled trial.

PubMed

Cheon, Chunhoo; Jang, Soobin; Park, Jeong-Su; Ko, Youme; Kim, Doh Sun; Lee, Byung Hoon; Song, Hyun Jong; Song, Yun-Kyung; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

2017-06-21

Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity. This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory. The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine. ClinicalTrials.gov, NCT01724099 . Registered on 2 November 2012.

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study.

PubMed

Khamashta, Munther; Merrill, Joan T; Werth, Victoria P; Furie, Richard; Kalunian, Kenneth; Illei, Gabor G; Drappa, Jorn; Wang, Liangwei; Greth, Warren

2016-11-01

The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE). 431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52. Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index-2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment. Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity. NCT01283139; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study.

PubMed

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W; Christensen, Karl; Olesen, Jes

2009-08-01

Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. In this randomised, double-blind, placebo-controlled crossover trial, 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months. Randomisation was by computer-generated list. Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura, migraine without aura, or other type of headache. Primary endpoints were a reduction in aura attacks with or without headache and a reduction in migraine headache days with or without an aura. Analysis was per protocol. This trial is registered, number NCT00332007. 39 patients were included in the study, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly different between placebo and tonabersat groups (3.0 days in each group; p=0.09). Tonabersat was well tolerated but overall had more side-effects than placebo. Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its known inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. Minster Pharmaceuticals; Lundbeck Foundation.

Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial.

PubMed

Willmott, C; Ponsford, J

2009-05-01

Most previous studies evaluating the use of methylphenidate following traumatic brain injury (TBI) have been conducted many years post-injury. This study evaluated the efficacy of methylphenidate in facilitating cognitive function in the inpatient rehabilitation phase. 40 participants with moderate-severe TBI (mean 68 days post-injury) were recruited into a randomised, crossover, double blind, placebo controlled trial. Methylphenidate was administered at a dose of 0.3 mg/kg twice daily and lactose in identical capsules served as placebo. Methylphenidate and placebo administration was randomised in a crossover design across six sessions over a 2 week period. Primary efficacy outcomes were neuropsychological tests of attention. No participants were withdrawn because of side effects or adverse events. Methylphenidate significantly increased speed of information processing on the Symbol Digit Modalities Test (95% CI 0.30 to 2.95, Cohen's d = 0.39, p = 0.02), Ruff 2 and 7 Test-Automatic Condition (95% CI 1.38 to 6.12, Cohen's d = 0.51, p = 0.003), Simple Selective Attention Task (95% CI -58.35 to -17.43, Cohen's d = 0.59, p = 0.001) and Dissimilar Compatible (95% CI -70.13 to -15.38, Cohen's d = 0.51, p = 0.003) and Similar Compatible (95% CI -74.82 to -19.06, Cohen's d = 0.55, p = 0.002) conditions of the Four Choice Reaction Time Task. Those with more severe injuries and slower baseline information processing speed demonstrated a greater drug response. Methylphenidate enhances information processing speed in the inpatient rehabilitation phase following TBI. This trial is registered with the Australian New Zealand Clinical Trials Registry (12607000503426).

Role of oral tramadol 50 mg in reducing pain associated with outpatient hysteroscopy: A randomised double-blind placebo-controlled trial.

PubMed

Hassan, AbdelGany; Haggag, Hisham

2016-02-01

Several drugs have been used to reduce hysteroscopy-associated pain. Although the Royal College of Obstetricians and Gynaecologists has recommended against the use of opiates in outpatient hysteroscopy, we wished to investigate if opioids can be used if the appropriate opioid was given in the appropriate dose. To study the effectiveness of tramadol 50 mg in reducing pain associated with outpatient hysteroscopy. A prospective randomised double-blind placebo-controlled trial conducted in the outpatient hysteroscopy clinic at Cairo University Hospital. Main outcome measures were the severity of pain during the procedure, immediately after the procedure and 30 minutes later assessed by a visual analogue scale (VAS). VAS of 0 indicates no pain and VAS of 10 indicates the worst possible pain. A total of 140 women who had diagnostic outpatient hysteroscopy were randomised to receive oral tramadol 50 mg or placebo one h before performing outpatient hysteroscopy. There was no difference between the groups in the age, parity, duration of the procedures or indications of hysteroscopy. The median pain score was significantly lower in the tramadol group during the procedure (5 vs 6; P = 0.013), immediately after the procedure (3 vs 4; P < 0.036), and 30 minute later (1 vs 2; P = 0.034). Two women in the tramadol group reported nausea, but this was mild and did not warrant cancelling the procedure. Oral administration of tramadol 50 mg before hysteroscopy reduces the pain evoked by the procedure and the drug was well tolerated by women. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

PubMed Central

Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

2004-01-01

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

Exploring the effect of space and place on response to exercise therapy for knee and hip pain—a protocol for a double-blind randomised controlled clinical trial: the CONEX trial

PubMed Central

Thorlund, Jonas Bloch; Ulrich, Roger S; Dieppe, Paul A; Roos, Ewa M

2015-01-01

Introduction Context effects are described as effects of a given treatment, not directly caused by the treatment itself, but rather caused by the context in which treatment is delivered. Exercise is a recommended core treatment in clinical guidelines for musculoskeletal disorders. Although moderately effective overall, variation is seen in size of response to exercise across randomised controlled trial (RCT) studies. Part of this variation may be related to the fact that exercise interventions are performed in different physical environments, which may affect participants differently. The study aims to investigate the effect of exercising in a contextually enhanced physical environment for 8 weeks in people with knee or hip pain. Methods and analysis The study is a double-blind RCT. Eligible participants are 35 years or older with persisting knee and/or hip pain for 3 months. Participants are randomised to one of three groups: (1) exercise in a contextually enhanced environment, (2) exercise in a standard environment and (3) waiting list. The contextually enhanced environment is located in a newly built facility, has large windows providing abundant daylight and overlooks a recreational park. The standard environment is in a basement, has artificial lighting and is marked by years of use; that is, resembling many clinical environments. The primary outcome is the participant's global perceived effect rated on a seven-point Likert scale after 8 weeks exercise. Patient-reported and objective secondary outcomes are included. Ethics and dissemination The Regional Scientific Ethical Committee for Southern Denmark has approved the study. Study findings will be disseminated in peer-reviewed publications and presented at national and international conferences. Trial registration number NCT02043613. PMID:25818278

Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

PubMed

Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

2011-09-01

There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of a double-blind, randomised controlled n--3 LCPUFA intervention trial in term infants.

PubMed

Meldrum, S J; D'Vaz, N; Dunstan, J; Mori, T A; Prescott, S L

2011-09-01

The Infant Fish Oil Supplementation Study is a double-blind randomised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids. Infants at high risk of developing allergic disease will be randomised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment. Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily (250-280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group (olive oil) from birth to 6 months of age. Allergy outcomes will be assessed by clinical history, clinical assessments and allergen skin prick tests at the 12, 30 and 60 month visits. Neurodevelopmental assessments to be conducted at 18 months, and language questionnaires at 12, 18 and 30 months. Samples will be collected from mothers antenatally, from infants at birth, and at clinic visits from 6 months onwards for immunological assessments. Fatty acid composition to be measured in erythrocytes and plasma (at birth and after the supplementation period) to assess the effect of the intervention on fatty acid status. Information on medical history, diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected. This study is designed to examine clinically relevant effects of a novel, non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood. Copyright © 2011 Elsevier Inc. All rights reserved.

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study

PubMed Central

Khamashta, Munther; Merrill, Joan T; Werth, Victoria P; Furie, Richard; Kalunian, Kenneth; Illei, Gabor G; Drappa, Jorn; Wang, Liangwei; Greth, Warren

2016-01-01

Objectives The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE). Methods 431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52. Results Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index−2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment. Conclusions Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity. Trial registration number NCT01283139; Results. PMID:27009916

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain.

PubMed

Coffey, Frank; Wright, John; Hartshorn, Stuart; Hunt, Paul; Locker, Thomas; Mirza, Kazim; Dissmann, Patrick

2014-08-01

To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. NCT01420159. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

PubMed Central

Coffey, Frank; Wright, John; Hartshorn, Stuart; Hunt, Paul; Locker, Thomas; Mirza, Kazim; Dissmann, Patrick

2014-01-01

Objective To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. Methods STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12–17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. Results A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of −18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. Conclusion The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. Trial registration number: NCT01420159. PMID:24743584

Comparison of gastroduodenal ulcer incidence in healthy Japanese subjects taking celecoxib or loxoprofen evaluated by endoscopy: a placebo-controlled, double-blind 2-week study.

PubMed

Sakamoto, C; Kawai, T; Nakamura, S; Sugioka, T; Tabira, J

2013-02-01

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2-selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis. To confirm the superiority of celecoxib, a cyclooxygenase-2-selective NSAID, to loxoprofen in the incidence of gastroduodenal (GD) endoscopic ulcers. A randomised, multicentre, placebo-controlled, double-blind, phase IV clinical trial in healthy Japanese volunteers [mean age 57.5 (range: 40-74) years; >70% female], stratified by Helicobacter pylori status at screening (~40% positive) and randomised 2:2:1 to receive celecoxib 100 mg b.d., loxoprofen 60 mg t.d.s. or placebo. Primary end point was incidence of any GD endoscopic ulcers after 2 weeks of treatment. Of 190 randomised subjects, 189 received at least one dose of celecoxib (n = 76), loxoprofen (n = 76), or placebo (n = 37). Incidence of GD ulcers was 1.4%, 27.6% and 2.7% in the celecoxib, loxoprofen and placebo groups respectively (P < 0.0001 in favour of the celecoxib group); incidence of adverse events (AEs) was 34.2%, 51.3% and 21.6% in the celecoxib, loxoprofen and placebo groups respectively. No serious or severe AEs were reported. Celecoxib 100 mg b.d. was superior to loxoprofen 60 mg t.d.s. regarding the incidence of gastro-duodenal endoscopic ulcers over 2 weeks. Celecoxib was well tolerated and no major safety concerns were observed. © 2012 Blackwell Publishing Ltd.

Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949

PubMed Central

Besselink, Marc GH; Timmerman, Harro M; Buskens, Erik; Nieuwenhuijs, Vincent B; Akkermans, Louis MA; Gooszen, Hein G

2004-01-01

Background Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. Methods/design PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. Conclusion The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis. PMID:15456517

Effect of a new treatment protocol called Functional Chewing Training on chewing function in children with cerebral palsy: a double-blind randomised controlled trial.

PubMed

Serel Arslan, S; Demir, N; Karaduman, A A

2017-01-01

Cerebral palsy (CP) is a group of permanent sensorimotor impairments. Children with CP have various feeding difficulties including chewing disorder, which may affect their nutritional status. Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. This study aimed to investigate the effect of FuCT on chewing function in children with CP. This study was designed as a double-blind, randomised controlled trial. Eighty CP children with chewing disorder were randomised and split between the FuCT group (31 males, 19 females; mean age 3·5 ± 1·9 years) and the control group (16 males, 14 females; 3·4 ± 2·3 years) receiving traditional oral motor exercises. Each group received the training programme for 12 weeks with weekly follow-up and with two evaluations at baseline and end of 12 weeks. Chewing function was evaluated by analysing video recordings and scored with the Karaduman Chewing Performance Scale (KCPS). The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to evaluate feeding behaviours of children. A significant improvement was observed in KCPS scores at 12 weeks after training in the FuCT group (P < 0·001), but no change was found in the control group (P = 0·07). A significant improvement was detected in all parameters of BPFAS at 12 weeks after training in the FuCT group (P < 0·001) and in four parameters of BPFAS in the control group (P = 0·02, P = 0·02). FuCT is an effective method to improve chewing function compared with traditional oral motor exercises. © 2016 John Wiley & Sons Ltd.

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

PubMed

Dahl, W J; Ford, A L; Coppola, J A; Lopez, D; Combs, W; Rohani, A; Ukhanova, M; Culpepper, T; Tompkins, T A; Christman, M; Mai, V

2016-02-01

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.

Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: a randomised, double blind, placebo controlled trial

PubMed Central

Stolz, D; Chhajed, P; Leuppi, J; Brutsche, M; Pflimlin, E; Tamm, M

2004-01-01

Background: Current British Thoracic Society guidelines do not recommend routinely the combined use of a benzodiazepine and opiate during flexible bronchoscopy (FB). A randomised, placebo controlled, double blind study was undertaken to determine whether hydrocodone in combination with midazolan improves cough suppression during FB without increasing the risk of desaturation. Methods: 120 patients were randomised to receive midazolam and 5 mg IV hydrocodone or midazolam and placebo with topical anaesthesia. Pulse oximetry was recorded continuously during FB. Bronchoscopists and nurses charted their perception of cough and the patients rated their discomfort during the procedure on a 10 cm visual analogue scale (VAS). Results: There was no significant difference between the two groups with regard to the indication for FB, duration of procedure (21 (11) min v 22 (10) min, p = 0.570), doses of supplemental lignocaine (171 (60) mg v 173 (66) mg, p = 0.766) and midazolam (4.5 (2.3) mg v 4.9 (2.7) mg, p = 0.309), lowest oxygen saturation (94.8 (2.7) v 94.9 (2.7), p = 0.433), and desaturations ⩽90%. Perception of cough by both the bronchoscopist and the nurse was significantly lower in the hydrocodone group (3 (0–10) and 3 (0–10)) than in the placebo group (6 (0–10) and 6 (0–10)), respectively (p = 0.001). According to the VAS scale, patients' tolerance was also significantly better with hydrocodone than with placebo (2 (0–8) v 3 (0–9), p = 0.043). Conclusion: The combination of midazolam and hydrocodone markedly reduces cough during FB without causing significant desaturation, especially when invasive diagnostic procedures are performed. PMID:15333854

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

PubMed

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-11-01

Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Is topical haloperidol a useful glaucoma treatment?

PubMed Central

Lavin, M. J.; Andrews, V.

1986-01-01

A randomised, double blind, single dose study of topical haloperidol, a dopamine receptor blocking drug, was performed on 20 healthy volunteers. After its administration a modest reduction in intraocular pressure was recorded over the six-hour study period, but the difference was not significant at the p less than 0.05 level. Although dopamine blocking agents are effective in reducing intraocular pressure in experimental animals, topical haloperidol appears unlikely to be clinically useful in the treatment of glaucoma. PMID:3718908

Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial.

PubMed

Carraro, G E; Russi, E W; Buechi, S; Bloch, Konrad E

2009-05-01

The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO(2) and pulse oximetry 60-160 min after drug intake. Subjects were encouraged to keep their eyes open. Mean +/- SD minute ventilation 120 min after alprazolam and placebo was similar (6.21 +/- 0.71 vs 6.41 +/- 1.12 L/min, P = NS). End-tidal PCO(2) and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 +/- 23% vs 31 +/- 13%, P < 0.05). More encouragements to keep the eyes open were required after alprazolam than after placebo (5.2 +/- 5.7 vs 1.3 +/- 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation.

The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study.

PubMed

Leung, K C M; McMillan, A S; Wong, M C M; Leung, W K; Mok, M Y; Lau, C S

2008-04-01

Cevimeline hydrochloride, a specific agonist of the M3 muscarinic receptor, is beneficial in the treatment of symptoms of xerostomia and xerophthalmia associated with Sjögren's syndrome (SS). Cevimeline has not been evaluated in southern Chinese patients. Furthermore, the effects of cevimeline on health-related quality of life and oral health status are not known. In this randomised, double-blind, placebo-controlled crossover study, patients received cevimeline 30 mg or matched placebo three times per day over 10 weeks followed by a 4-week washout period before treatment crossover. Participants self-completed the following questionnaires: Xerostomia Inventory (XI), the General Oral Health Assessment Index (GOHAI), the Ocular Surface Disease Index (OSDI) and the Medical Outcomes Short Form (SF-36). Clinical assessments included sialometry, examination of the oral cavity for the degree of xerostomia and dental complications of xerostomia. Fifty patients (22 primary SS and 28 secondary SS) were enrolled in the trial. Forty-four patients completed the study. There was a significant improvement in the XI and GOHAI scores as well as the objective rating of xerostomic signs of the oral cavity after treatment with cevimeline. However, there was no improvement in salivary flow rates and dry eye symptoms. SS patients had lower SF-36 scores, but these did not improve after treatment with cevimeline.

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

A double blind randomised controlled clinical trial on the effect of transcutaneous spinal electroanalgesia (TSE) on low back pain.

PubMed

Thompson, John W; Bower, Susanne; Tyrer, Stephen P

2008-04-01

A double blind randomised controlled clinical trial on the effect of transcutaneous spinal electroanalgesia (TSE) on low back pain was carried out in 58 patients attending a Pain Management Unit. Four TSE instruments, two active and two sham, were used and each patient was assigned randomly to one of these. Low back pain was rated by each patient using a visual analogue scale (VAS) immediately before and immediately after a single 20 min treatment of TSE and also daily for the week prior to, and the week following, the treatment. No significant difference in mean pain score was detected between the active and sham treated groups immediately after treatment or during the subsequent week. The Hospital, Anxiety and Depression scale (HAD) and the General Health Questionnaire (GHQ) were completed by each patient and there was a positive correlation between the scores achieved on these scales and the mean pain scores in both the active and sham treated groups. A post-trial problem was the discovery that the specification of the two active TSE machines differed from the manufacturer's specification. Thus, the output frequencies were either more (+10%) or less (-17%) while the maximum output voltages were both less (-40% and -20%), respectively. However, additional statistical analysis revealed no significant differences between the results obtained with the two active machines.

Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.

PubMed

Lin, Chun-Yuan; Liang, Sun-Yuan; Chang, Yue-Cune; Ting, Shuo-Yen; Kao, Ching-Ling; Wu, Yu-Hsin; Tsai, Guochuan E; Lane, Hsien-Yuan

2017-08-01

Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.

Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial

PubMed Central

Ciliberto, Heather; Ciliberto, Michael; Briend, Andreé; Ashorn, Per; Bier, Dennis; Manary, Mark

2005-01-01

Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor. PMID:15851401

Effect of a polysaccharide-rich hydrolysate from Saccharomyces cerevisiae (LipiGo®) in body weight loss: randomised, double-blind, placebo-controlled clinical trial in overweight and obese adults.

PubMed

Santas, Jonathan; Lázaro, Elisabet; Cuñé, Jordi

2017-09-01

In the present study we evaluated the weight loss effect of a polysaccharide-rich food supplement, LipiGo®, comprising a specific β-glucan-chitin-chitosan fraction (BGCC) obtained from the chemical hydrolysis of Saccharomyces cerevisiae, resulting as a by-product of the brewing process. A randomised, double-blind, placebo-controlled clinical trial was performed enrolling 56 overweight and obese subjects (body mass index, BMI, 25-35 kg m -2 ) who were not following any specific diet, and were given placebo or BGCC (3 g d -1 ) for 12 weeks. Results were analysed by intention-to-treat (ITT) and per-protocol (PP) methods. Body weight increased in the placebo group compared to baseline (ITT: 1.0 kg, P < 0.001; PP: 1.5 kg, P = 0.003), while it was slightly lowered in the BGCC group (ITT: -0.8 kg, P = 0.210; PP: -1.1 kg, P = 0.182). BGCC, but not the consumption of placebo, also resulted in a reduction of waist circumference and body fat compared to baseline. Results suggest that daily supplementation of BGCC may be useful for improving body weight and waist circumference in overweight and obese subjects, without relevant adverse effects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Rasagiline.

PubMed

Siddiqui, M Asif A; Plosker, Greg L

2005-01-01

Rasagiline is a second-generation potent, irreversible and selective inhibitor of monoamine-oxidase type B (MAO-B), which has been evaluated for the treatment of Parkinson's disease. Rasagiline also possesses neuroprotective properties that are independent of its MAO inhibitory activity. Unlike selegiline, rasagiline has no amphetamine-like metabolites and its major metabolite, 1-(R)-aminoindan, has demonstrated favourable pharmacological activity in experimental studies. Rasagiline has shown significant beneficial effects as monotherapy in the treatment of early Parkinson's disease. Monotherapy with rasagiline 1 or 2 mg once daily significantly attenuated the worsening of symptoms, compared with placebo, in patients with early Parkinson's disease in a randomised, double-blind trial (n = 404). Furthermore, patients treated with rasagiline for 12 months had less functional decline than patients whose treatment was delayed for 6 months (n = 371). In patients with moderate-to-advanced disease receiving background therapy with levodopa and additional anti-parkinsonian medications (n = 1159), rasagiline 0.5 or 1 mg once daily reduced the daily 'off' time by 0.49-0.94 hours relative to that in placebo recipients in two randomised, double-blind trials. The efficacy of rasagiline 1 mg once daily was similar to entacapone 200 mg administered with each levodopa dose. Rasagiline was generally well tolerated in clinical trials as both monotherapy and when administered with other antiparkinsonian drugs. Adverse events with rasagiline were generally similar in frequency to those seen in placebo or entacapone recipients.

Flutrimazole shampoo 1% versus ketoconazole shampoo 2% in the treatment of pityriasis versicolor. A randomised double-blind comparative trial.

PubMed

Rigopoulos, D; Gregoriou, S; Kontochristopoulos, G; Ifantides, A; Katsambas, A

2007-05-01

Flutrimazole is an imidazole derivative that has been proven to be efficient in superficial skin fungal infections. The aim of this randomised double-blind study was to compare for the first time, the efficiency and safety of flutrimazole 1% shampoo versus ketoconazole 2% shampoo in the treatment of tinea versicolor. Study population consisted of 60 patients with pityriasis versicolor diagnosed clinically and through direct microscopy and culture. Patients were randomly assigned to two groups: one instructed to apply flutrimazole shampoo 1% and one instructed to apply ketoconazole shampoo 2% both on head and body for 14 days. Patients were re-evaluated 14 days after the end of treatment clinically and through direct microscopy and culture. Twenty-one of 26 patients (80.8%) in the ketoconazole and 22 of 29 patients (75.9%) in the flutrimazole group had both visual healing and negative mycological evaluation. Comparison of the response between the two groups with the Yates' corrected chi-square was found statistically not significant (chi(2) = 0.19, d.f. = 1, P = 0.91). None of the patients in the two groups reported any adverse effects. Fourteen (53%) patients in the ketoconazole group and 23 (79%) in the flutrimazole group assessed the shampoos as cosmetically acceptable regarding texture, smell and foam properties. Flutrimazole shampoo 1% appears to present efficacy comparable with ketoconazole 2% in the treatment of tinea versicolor.

The efficacy of cyclosporine A in cats with presumed atopic dermatitis: a double blind, randomised prednisolone-controlled study.

PubMed

Wisselink, Marinus A; Willemse, Ton

2009-04-01

The objective of this study was to compare the efficacy of cyclosporine A (CsA) and prednisolone in feline atopic dermatitis (AD) in a randomised, controlled double blind study. Twenty-nine cats with feline AD were randomly allocated to two groups. Eleven cats were treated orally with prednisolone (1mg/kg SID) and 18 were treated with CsA (5mg/kg/day) for 4 weeks. At day 0 (D0) and D28, skin lesions were graded by means of the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies and intradermal allergy tests were performed at D0 and blood samples for haematology and serum biochemistry were collected at D0 and D28. During the trial the cat owners were asked to evaluate the intensity of the pruritus once weekly on a linear analog scale and to record side effects. Based on the CADESI there was no significant difference between the two groups in the amount of remission (P=0.0562) or in the number of cats that improved by >25% (P=0.0571). The effect of CsA and prednisolone on pruritus as evaluated by the owners was not significantly different (P=0.41) between the two groups. No serious side effects were observed. The conclusion was that CsA is an effective alternative to prednisolone therapy in cats with presumed atopic dermatitis.

Effects of infant cereals with different carbohydrate profiles on colonic function--randomised and double-blind clinical trial in infants aged between 6 and 12 months--pilot study.

PubMed

Bernal, María José; Periago, María Jesús; Martínez, Rosario; Ortuño, Inmaculada; Sánchez-Solís, Manuel; Ros, Gaspar; Romero, Fernando; Abellán, Pedro

2013-11-01

Infant cereals are often the elected foodstuff for beginning complementary feeding and provide carbohydrates which are different to those found in maternal milk. The objective of this preliminary study was to ascertain the colonic effects of two infant cereals, with different carbohydrate profiles, in a randomised and double-blind trial in healthy infants. Nineteen term infants between 6.3 and 9.8 months of age were enrolled, after written informed consent was obtained from parents. Ten subjects were allocated to take infant cereal A and nine, infant cereal B. An intervention period was 2 months, with five visits every 15 days, to take anthropometric measurements and faeces samples for the analysis of microbiota, short-chain fatty acids concentration (SCFA), pH value and secretory immunoglobulin A (sIgA). An adequate growth and stool frequency was registered in both intervention groups. Faecal counts of Bifidobacterium, Lactobacillus, Enterobacteriaceae, Enterococcus, Clostridium and Bacteroides did not show any statistical differences. However, a significantly (P < 0.05) higher butyric acid and sIgA, and lower faecal pH were observed in infants who had ingested infant cereal A, with a higher ratio complex/simple carbohydrates. In conclusion, small changes in the carbohydrate profile of infant cereals could lead to significant differences in parameters related to fermentative activity of intestinal microbiota.

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.

PubMed

Rambaldi, A; Jacobs, B P; Iaquinto, G; Gluud, C

2005-04-18

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (December 2003). Manufacturers and researchers in the field were contacted. Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. Thirteen randomised clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered adequately double-blinded. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.

Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well-Being in Postmenopausal Women-Rationale and Study Design.

PubMed

Evans, Hamish Michael; Howe, Peter Ranald Charles; Wong, Rachel Heloise Xiwen

2016-03-09

This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Effects of the carrier frequency of interferential current on pain modulation in patients with chronic nonspecific low back pain: a protocol of a randomised controlled trial.

PubMed

Corrêa, Juliana Barbosa; Costa, Leonardo Oliveira Pena; de Oliveira, Naiane Teixeira Bastos; Sluka, Kathleen A; Liebano, Richard Eloin

2013-06-27

Low back pain is an important public health problem that is associated with poor quality of life and disability. Among the electrophysical treatments, interferential current (IFC) has not been studied in patients with low back pain in a high-quality randomised controlled trial examining not only pain, but pain mechanisms and function. A three-arm randomised controlled trial with patient and assessor blinded to the group allocation. One hundred fifty patients with chronic, nonspecific low back pain from outpatient physical therapy clinics in Brazil. The patients will be randomly allocated into 3 groups (IFC 1 kHz, IFC 4 kHz or Placebo IFC). The interferential current will be applied three days per week (30 minutes per session) over four weeks. Pain intensity. The pressure pain threshold, global impression of recovery, disability, function, conditioned pain modulation and temporal summation of pain, discomfort caused by the current. All outcomes will be measured at 4 weeks and 4 months after randomisation. The between-group differences will be calculated by using linear mixed models and Tukey's post-hoc tests. The use of a placebo group and double-blinding assessor and patients strengthen this study. The present study is the first to compare different IFC carrier frequencies in patients with chronic low back pain. Brazilian Registry of Clinical Trials: http://RBR-8n4hg2.

The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial- study protocol

PubMed Central

2013-01-01

Background Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition. This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. Methods/Designs This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. Discussion This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ health-related quality of life questionnaires to assess changes in the quality of life. The results of this study will be used to present the evidence needed to request advertising/display allowances, in compliance with the recently amended Cosmetics Act for advertisement in Korea. Trial registration Current Controlled Trials ISRCTN46216631 PMID:24274317

A randomized controlled trial of intranasal ketamine in migraine with prolonged aura.

PubMed

Afridi, Shazia K; Giffin, Nicola J; Kaube, Holger; Goadsby, Peter J

2013-02-12

The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Eighteen subjects completed the study. Ketamine reduced the severity (p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. This study provides class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.

PubMed

Silberstein, S; Saper, J; Berenson, F; Somogyi, M; McCague, K; D'Souza, J

2008-02-12

To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.

Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.

PubMed

Merrill, Joan T; Wallace, Daniel J; Petri, Michelle; Kirou, Kyriakos A; Yao, Yihong; White, Wendy I; Robbie, Gabriel; Levin, Robert; Berney, Seth M; Chindalore, Vishala; Olsen, Nancy; Richman, Laura; Le, Chenxiong; Jallal, Bahija; White, Barbara

2011-11-01

Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets. Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE. received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days. Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014). Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.

The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given 'as needed' in mild asthma: study protocols for two randomised controlled trials.

PubMed

O'Byrne, Paul M; FitzGerald, J Mark; Zhong, Nanshan; Bateman, Eric; Barnes, Peter J; Keen, Christina; Almqvist, Gun; Pemberton, Kristine; Jorup, Carin; Ivanov, Stefan; Reddel, Helen K

2017-01-10

In many patients with mild asthma, the low frequency of symptoms and the episodic nature of exacerbations make adherence to regular maintenance treatment difficult. This often leads to over-reliance on short-acting β 2 -agonist (SABA) reliever medication and under-treatment of the underlying inflammation, with poor control of asthma symptoms and increased risk of exacerbations. The use of budesonide/formoterol 'as needed' in response to symptoms may represent an alternative treatment option for patients with mild asthma. The SYmbicort Given as needed in Mild Asthma (SYGMA) programme consists of two 52-week, double-blind, randomised, multicentre, parallel-group, phase 3 trials of patients aged 12 years and older with a clinical diagnosis of asthma for at least 6 months, who would qualify for treatment with regular inhaled corticosteroids (ICS). SYGMA1 aims to recruit 3750 patients who will be randomised to placebo twice daily (bid) plus as-needed budesonide/formoterol 160/4.5 μg, placebo bid plus as-needed terbutaline 0.4 mg, or budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the superiority of as-needed budesonide/formoterol over as-needed terbutaline for asthma control, as measured by well-controlled asthma weeks; a secondary objective is to establish the noninferiority of as-needed budesonide/formoterol versus maintenance budesonide plus as-needed terbutaline using the same outcome measure. SYGMA2 aims to recruit 4114 patients who will be randomised to placebo bid plus as-needed budesonide/formoterol 160/4.5 μg, or budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the noninferiority of as-needed budesonide/formoterol over budesonide bid plus as-needed terbutaline as measured by the annualised severe exacerbation rate. In both studies, use of all blinded study inhalers will be recorded electronically using Turbuhaler® Usage Monitors. Given the known risks of mild asthma, and known poor adherence with regular inhaled corticosteroids, the results of the SYGMA programme will help to determine the efficacy and safety of as-needed budesonide/formoterol therapy in mild asthma. Patient recruitment is complete, and completion of the phase 3 studies is planned in 2017. ClinicalTrials.gov identifiers: NCT02149199 SYGMA1 and NCT02224157 SYGMA2. Registered on 16 May 2014 and 19 August 2014, respectively.

Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial.

PubMed

Orban, Tihamer; Bundy, Brian; Becker, Dorothy J; DiMeglio, Linda A; Gitelman, Stephen E; Goland, Robin; Gottlieb, Peter A; Greenbaum, Carla J; Marks, Jennifer B; Monzavi, Roshanak; Moran, Antoinette; Raskin, Philip; Rodriguez, Henry; Russell, William E; Schatz, Desmond; Wherrett, Diane; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S

2011-07-30

The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes. In this multicentre, double-blind, randomised controlled trial, patients aged 6-45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer-generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375. 112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6·1-112) higher at 2 years with abatacept (n=73, 0·378 nmol/L) than with placebo (n=30, 0·238 nmol/L; p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months' delay (95% CI 3·47-15·6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]). Co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions. US National Institutes of Health. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial

PubMed Central

2014-01-01

Background Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. Methods In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20–65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. Results 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Conclusion Our study failed to demonstrate a statistically-significant protective effect of HFC vs. LFC consumption on skin sensitivity to UV radiation as measured by MED. Trial registration ClinicalTrials.gov identifier: NCT01444625 PMID:24970388

Effect of Arnica D30 in marathon runners. Pooled results from two double-blind placebo controlled studies.

PubMed

Tveiten, D; Bruset, S

2003-10-01

To examine whether the homeopathic medicine Arnica D30 has an effect on muscle soreness and cell damage after marathon running. The subjects were 82 marathon runners from two separate randomised double-blind placebo controlled trials participating in the Oslo Marathon in 1990 and 1995. Five pills of Arnica D30 or placebo were given morning and evening. Treatment started on the evening before the marathon and continued on day of the race and the three following days. The runners assessed muscular soreness on a visual analogue scale. Muscle enzymes, electrolytes and creatinine were measured before and after the marathon. Muscle soreness immediately after the marathon run was lower in the Arnica group than in the placebo group (P = 0.04). Cell damage measured by enzymes was similar in the Arnica and the placebo group. These pooled results suggest that Arnica D30 has a positive effect on muscle soreness after marathon running, but not on cell damage measured by enzymes.

Reflexology has an acute (immediate) haemodynamic effect in healthy volunteers: a double-blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2012-11-01

Reflexologists claim that massage to specific points of the feet increases blood supply to internal organs. This study measured changes in cardiovascular parameters in subjects receiving reflexology to areas of their feet thought to correspond to the heart (intervention) compared with other areas which are not (control). 16 reflexology-naive healthy volunteers received an active and control reflexology treatment in an RCT, double-blind repeated measures study. 'Beat-to-beat' continuous measurement of selected cardiovascular parameters, State Anxiety Inventory. Cardiac index decreased significantly in the intervention group during left foot treatment (LFT) (baseline mean 2.6; standard deviation (SD) 0.75; 95% CI ± 0.38 vs. LFT mean 2.45; SD 0.68; CI 0.35), effect size (p = 0.035, omega squared effect (w2) = 0.002; w = 0.045). Reflexology massage applied to the upper part of the left foot may have a modest specific effect on the cardiac index of healthy volunteers. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of local anaesthetic wound infiltration on chronic pain after lower limb joint replacement: A protocol for a double-blind randomised controlled trial

PubMed Central

2011-01-01

Background For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA. Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement. Trial registration Current Controlled Trials ISRCTN96095682 PMID:21352559

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

PubMed

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-05-05

Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. UMIN000018752. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M; Wing, Alan M; Tyson, Sarah F; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M

2015-01-01

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services. Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments. Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Clinicaltrials.gov NCT01600391.

Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from the phase III trial, MEASURE 2.

PubMed

Marzo-Ortega, Helena; Sieper, Joachim; Kivitz, Alan; Blanco, Ricardo; Cohen, Martin; Delicha, Evie-Maria; Rohrer, Susanne; Richards, Hanno

2017-01-01

Secukinumab treatment has previously been shown to significantly improve the signs and symptoms of active ankylosing spondylitis (AS), with responses sustained through 2 years. Here, we report the long-term (3 years) efficacy and safety of secukinumab in the MEASURE 2 study. MEASURE 2 (NCT01649375) is a 5-year phase III, randomised, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of subcutaneous loading and maintenance dosing of secukinumab in adult subjects with active AS. Subjects were randomised to receive subcutaneous secukinumab 150 mg, 75 mg or placebo at baseline, weeks 1, 2 and 3 and every 4 weeks from week 4. At week 16, placebo-treated subjects were rerandomised to receive secukinumab 150/75 mg. Retention rates were high during weeks 16-156 and were 86% and 76% for secukinumab 150 and 75 mg, respectively. Secukinumab 150 mg provided sustained improvements in the Assessment of Spondyloarthritis International Society ASAS 20/40 response rates at week 156 (70.1%/60.9%) compared with week 52 (74.2%/57.0%); however, there was a slight decrease for secukinumab 75 mg (54.3%/37.0% vs 62.5%/43.2%, respectively). Sustained improvements were observed in all other end points, including Bath Ankylosing Spondylitis Disease Activity Index, AS Disease Activity Score with C reactive protein inactive disease, ASAS 5/6, Short Form-36 Physical Component Summary and ASAS partial remission. Clinical benefits were observed regardless of prior exposure to anti-tumour necrosis factor agents. The safety profile remained favourable and was consistent with previous reports. This study showed sustained improvement through 3 years in signs, symptoms and physical function in subjects with AS. Retention rates were high and secukinumab was well tolerated, with a favourable safety profile.

Rabeprazole is equivalent to omeprazole in the treatment of erosive gastro-oesophageal reflux disease. A randomised, double-blind, comparative study of rabeprazole and omeprazole 20 mg in acute treatment of reflux oesophagitis, followed by a maintenance open-label, low-dose therapy with rabeprazole.

PubMed

Pace, F; Annese, V; Prada, A; Zambelli, A; Casalini, S; Nardini, P; Bianchi Porro, G

2005-10-01

Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones. To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis. Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks. After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p<0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse. Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.

A multi-centre, parallel group superiority trial of silk therapeutic clothing compared to standard care for the management of eczema in children (CLOTHES Trial): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor F; Haines, Rachel H; Cowdell, Fiona; Sach, Tracey H; Dean, Taraneh; Pollock, Ian; Burrows, Nigel P; Buckley, Hannah; Batchelor, Jonathan; Williams, Hywel C; Lawton, Sandra; Brown, Sara J; Bradshaw, Lucy E; Ahmed, Amina; Montgomery, Alan A; Mitchell, Eleanor J; Thomas, Kim S

2015-09-02

Eczema is a chronic, itchy skin condition that can have a large impact on the quality of life of patients and their families. People with eczema are often keen to try out non-pharmacological therapies like silk therapeutic garments that could reduce itching or the damage caused by scratching. However, the effectiveness and cost-effectiveness of these garments in the management of eczema has yet to be proven. The CLOTHES Trial will test the hypothesis that 'silk therapeutic garments plus standard eczema care' is superior to 'standard care alone' for children with moderate to severe eczema. Parallel group, observer-blind, pragmatic, multi-centre randomised controlled trial of 6 months' duration. Three hundred children aged 1 to 15 years with moderate to severe eczema will be randomised (1:1) to receive silk therapeutic garments plus standard eczema care, or standard eczema care alone. Primary outcome is eczema severity, as assessed by trained and blinded investigators at 2, 4 and 6 months (using the Eczema Area and Severity Index (EASI)). Secondary outcomes include: patient-reported eczema symptoms (collected weekly for 6 months to capture long-term control); global assessment of severity; quality of life of the child, family and main carer; use of standard eczema treatments (emollients, corticosteroids applied topically, calcineurin inhibitors applied topically and wet wraps); frequency of infections; and cost-effectiveness. The acceptability and durability of the clothing will also be assessed, as will adherence to wearing the garments. A nested qualitative study will assess the views of a subset of children wearing the garments and their parents, and those of healthcare providers and commissioners. Randomisation uses a computer-generated sequence of permuted blocks of randomly varying size, stratified by recruiting hospital and child's age (< 2 years; 2 to 5 years; > 5 years), and concealed using a secure web-based system. The sequence of treatment allocations will remain concealed until randomisation and data collection are complete. Recruitment is taking place from November 2013 to May 2015, and the trial will be completed in 2016. Full details of results will be published in the National Institute for Health Research Journal series. Current Controlled Trials ISRCTN77261365 (registered 11 November 2013).

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

Long-term effect of modification of dietary protein intake on the progression of diabetic nephropathy: a randomised controlled trial.

PubMed

Koya, D; Haneda, M; Inomata, S; Suzuki, Y; Suzuki, D; Makino, H; Shikata, K; Murakami, Y; Tomino, Y; Yamada, K; Araki, S I; Kashiwagi, A; Kikkawa, R

2009-10-01

There is currently insufficient evidence to recommend a low-protein diet for type 2 diabetic patients with diabetic nephropathy. We assessed whether a low-protein diet could prevent the progression of diabetic nephropathy. This was a multi-site parallel randomised controlled trial for prevention of diabetic nephropathy progression among 112 Japanese type 2 diabetic patients with overt nephropathy. It was conducted in Japan from 1 December 1997 to 30 April 2006. The participants were randomly assigned using a central computer-generated schedule to either low-protein diet (0.8 g kg(-1) day(-1)) and normal-protein diet (1.2 g kg(-1) day(-1)), and were followed for 5 years. The participants and investigators were not blinded to the assignment. The primary outcomes were the annual change in estimated GFR and creatinine clearance, the incidence of doubling of serum creatinine and the time to doubling of baseline serum creatinine. The study was completed by 47 (84%) of 56 participants in the low-protein diet group and 41 (73%) of 56 participants in the normal-diet group. During the study period, the difference in mean annual change in estimated GFR between the low-protein diet and the normal-protein diet groups was -0.3 ml min(-1) 1.73 m(-2) (95% CI -3.9, 4.4; p = 0.93). The difference in mean annual change in creatinine clearance between the low-protein diet and the normal-protein diet groups was -0.006 ml s(-1) 1.73 m(-2) (95% CI -0.089, 0.112; p = 0.80). A doubling of serum creatinine was reached in 16 patients of the low-protein group (34.0%), compared with 15 in the normal-protein group (36.6%), the difference between groups being -2.6% (95% CI -22.6, 17.5; p = 0.80). The time to doubling of serum creatinine was similar in both groups (p = 0.66). It is extremely difficult to get patients to follow a long-term low-protein diet. Although in the low-protein group overall protein intake was slightly (but not significantly) lower, it did not confer renoprotection. ClinicalTrials.gov NCT00448526. Research grant from the Ministry of Health, Labour and Welfare of Japan.

Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

PubMed Central

Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

2016-01-01

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

Ethical considerations in placebo-controlled randomised clinical trials.

PubMed

Kaufman, Kenneth R

2015-06-01

Ethical considerations in standard medical care and clinical research are underpinnings to quality medicine. Similarly, the placebo-controlled double-blind randomised clinical trial is the gold standard for medical research and fundamental to the development of evidence-based medicine. Researchers and clinicians are challenged by ethical concerns in the informed consent with a need to maximise understanding and minimise therapeutic misconception. This editorial expands on themes raised by Chen et al 's article 'Disclosing the Potential Impact of Placebo Controls in Antidepressant Trials' and serves as an invitation for further submissions to BJPsych Open on ethics, research design and informed consent. None. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial

USDA-ARS?s Scientific Manuscript database

As populations shift to include a larger proportion of older adults, the necessity of research targeting older populations is becoming increasingly apparent. Changes in motor coordination during ‘normal’ aging, in animals and humans, include decrements in balance and locomotion. Parallel to alterati...

The Handbook of Research Impact Assessment. Edition 7. Summer 1997.

DTIC Science & Technology

1997-01-01

Treatment of Patients with Chronic-Schizophrenia - A Multi-National, Multicenter, Double-Blind, Parallel-Group Study Versus Haloperidol ", BRITISH JOURNAL OF...34The Scientific Production and International Reputation of Travassos,Lauro", MEMORIAS DO INSTITUTO OSWALDO CRUZ,1992, Vol 87, Iss S1, pp R7-R10 Courtial

Effect of Piracetam on Dyslexic's Reading Ability.

ERIC Educational Resources Information Center

Wilsher, C.; And Others

1985-01-01

Forty-six dyslexic boys (aged eight to 13) were administered Piracetam or placebo in a double-blind, parallel experiment. Although, overall, there were no significant group effects, the within-subject design revealed improvements in reading speed and accuracy in Piracetam Ss. Dyslexics with higher reading ages improved significantly compared to…

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

PubMed

Wagenlehner, Florian M; Umeh, Obiamiwe; Steenbergen, Judith; Yuan, Guojun; Darouiche, Rabih O

2015-05-16

Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. Cubist Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study.

PubMed

Wade, C; Wang, L; Zhao, W J; Cardini, F; Kronenberg, F; Gui, S Q; Ying, Z; Zhao, N Q; Chao, M T; Yu, J

2016-01-05

To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. A Menstrual Disorder Centre at a public hospital in Shanghai, China. Chinese women aged 14-25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (-0.71, CI -1.37 to -0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic. NCT00104546; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study

PubMed Central

Wade, C; Wang, L; Zhao, W J; Cardini, F; Kronenberg, F; Gui, S Q; Ying, Z; Zhao, N Q; Chao, M T; Yu, J

2016-01-01

Objective To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. Setting A Menstrual Disorder Centre at a public hospital in Shanghai, China. Participants Chinese women aged 14–25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. Interventions A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. Primary and secondary outcome measures The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. Results Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (−0.71, CI −1.37 to −0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. Conclusions Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic. Trial registration number NCT00104546; Results. PMID:26733563

Persistent occiput posterior: OUTcomes following digital rotation: a pilot randomised controlled trial.

PubMed

Graham, Kathryn; Phipps, Hala; Hyett, Jon A; Ludlow, Joanne P; Mackie, Adam; Marren, Anthony; De Vries, Bradley

2014-06-01

To determine the feasibility of a multicentre randomised controlled trial (RCT) to investigate whether digital rotation of the fetal head from occiput posterior (OP) position in the second stage of labour reduces the risk of operative delivery (defined as caesarean section (CS) or instrumental delivery). We conducted the study between December 2010 and December 2011 in a tertiary referral hospital in Australia. A transabdominal ultrasound was performed early in the second stage of labour on women with cephalic, singleton pregnancies to determine the fetal position. Those women with a fetus in the OP position were randomised to either a digital rotation or a sham procedure. In all other ways, participants received their usual intrapartum care. Data regarding demographics, mode of delivery, labour, post natal period and neonatal outcomes were collected. One thousand and four women were consented, 834 achieved full dilatation, and 30 were randomised. An additional portable ultrasound scan and a blinded 'sham' digital rotation were acceptable to women and staff. Operative delivery rates were 13/15 in the digital rotation (four CS and nine instrumental) and 12/15 in the sham (three CS and nine instrumental) groups, respectively. A large double-blinded multicentre RCT would be feasible and acceptable to women and staff. Strategies to improve recruitment such as consenting women with an effective epidural in active labour should be considered. This would be the first RCT to answer a clinically important question which could significantly affect the operative delivery rate in Australia and internationally. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial.

PubMed

Fitton, A R; Ragbir, M; Milling, M A

1996-09-01

We report the results of a randomised, case matched, controlled, double blind study on 40 patients undergoing correction of their prominent ears, comparing efficacy of pH adjusted lignocaine to lignocaine alone in controlling operative pain. Each patient received commercial lignocaine in one ear and the same preparation reconstituted with 1 ml of 8.4% sodium bicarbonate in the other ear according to our randomisation protocol. 30 patients were studied to compare the difference between the buffered and commercial preparation infiltrated at room temperature. A further 10 patients were studied to assess the benefit the buffered preparation at room temperature had over commercial lignocaine warmed to body temperature. Linear analogue pain scores for discomfort at infiltration and during the operation itself were analysed. Buffered lignocaine imparts a significant reduction in pain on infiltration, compared to the commercial preparation at both room and body temperature. Both preparations were equally effective in obliterating pain during the operation itself.

Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial.

PubMed

Zenico, T; Cicero, A F G; Valmorri, L; Mercuriali, M; Bercovich, E

2009-04-01

Lepidium meyenii (Maca) is a cultivated root belonging to the brassica family used in the Andean region for its supposed aphrodisiac properties. We carried out a double-blind clinical trial on 50 Caucasian men affected by mild erectile dysfunction (ED), randomised to treatment with Maca dry extract, 2400 mg, or placebo. The treatment effect on ED and subjective well-being was tested administrating before and after 12 weeks the International Index of Erectile Function (IIEF-5) and the Satisfaction Profile (SAT-P). After 12 weeks of treatment, both Maca- and placebo-treated patients experienced a significant increase in IIEF-5 score (P < 0.05 for both). However, patients taking Maca experienced a more significant increase than those taking placebo (1.6 +/- 1.1 versus 0.5 +/- 0.6, P < 0.001). Both Maca- and placebo-treated subjects experienced a significant improvement in psychological performance-related SAT-P score, but the Maca group higher than that of placebo group (+9 +/- 6 versus +6 +/- 5, P < 0.05). However, only Maca-treated patients experienced a significant improvement in physical and social performance-related SAT-P score compared with the baseline (+7 +/- 6 and +7 +/- 6, both P < 0.05). In conclusion, our data support a small but significant effect of Maca supplementation on subjective perception of general and sexual well-being in adult patients with mild ED.

Does hydroxyapatite coating enhance ingrowth and improve longevity of a Zweymuller type stem? A double-blinded randomised RSA trial.

PubMed

Hoornenborg, Daniel; Sierevelt, Inger N; Spuijbroek, Joost A; Cheung, John; van der Vis, Harm M; Beimers, Lijkele; Haverkamp, Daniel

2017-09-11

An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem. 51 patients were randomly assigned to receive either an uncoated or a HA-coated femoral component during total hip replacement. RSA images were obtained direct postoperatively and at 6 weeks, 12 weeks, 6 months, 12 months and 24 months. HOOS scores were obtained preoperative and at final follow-up. RSA evaluation demonstrated significant migration up to 3 months postoperatively in both groups. After initial setting no significant migration was observed. There was no significant difference in migration between the HA-coated group and the uncoated group.Both Harris Hip Score (HHS) and HOOS domain scores (pain and ADL) significantly improved compared to baseline at 24 months after surgery in both treatment groups (p<0.001 for all comparisons). Improvement did not differ significantly between the 2 groups. At 2 years follow-up, the HA-coated and uncoated Zweymuller type, distal fitting stem do not show different migration patterns.

Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

PubMed Central

Grube, Barbara; Alt, Felix; Uebelhack, Ralf

2015-01-01

Background. Litramine (IQP-G-002AS) was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day) or a matching placebo. Primary endpoints were difference of mean body weight (kg) between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (−0.62 ± 1.55 kg versus 1.62 ± 1.48 kg, p < 0.001). More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387. PMID:26435849

Efficacy and safety of the topical application of tranexamic acid in primary cementless hip arthroplasty: prospective, randomised, double-blind and controlled study.

PubMed

Tavares Sánchez-Monge, F J; Aguado Maestro, I; Bañuelos Díaz, A; Martín Ferrero, M Á; García Alonso, M F

To evaluate the efficacy of topical tranexamic acid topical in cementless total hip arthroplasty from the point of view of bleeding, transfusion requirements and length of stay, and describe the complications of use compared to a control group. A prospective, randomised, double-blinded and controlled study including all patients undergoing cementless total hip arthroplasty in our centre between June 2014 and July 2015. Blood loss was estimated using the formula described by Nadler and Good. The final analysis included 119 patients. The decrease in haemoglobin after surgery was lower in the tranexamic acid group (3.28±1.13g/dL) than in the controls (4.03±1.27g/dL, P=.001) and estimated blood loss (1,216.75±410.46mL vs. 1,542.12±498.97mL, P<.001), the percentage of transfused patients (35.9% vs. 19.3%, P<.05) and the number of transfused red blood cell units per patient (0.37±0.77 vs. 0.98±1.77; P<.05). There were no differences between groups in the occurrence of complications or length of stay. The use of topical tranexamic acid in cementless total hip arthroplasty results in a decrease in bleeding and transfusion requirements without increasing the incidence of complications. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial.

PubMed

Pleguezuelos, Olga; Robinson, Stuart; Stoloff, Gregory A; Caparrós-Wanderley, Wilson

2012-06-29

Current Influenza vaccines elicit antibody mediated prophylactic immunity targeted to viral capsid antigens. Despite their global use these vaccines must be administered yearly to the population, cannot be manufactured until the circulating viral strain(s) have been identified and have limited efficacy. A need remains for Influenza vaccines addressing these issues and here we report the results of a Phase Ib trial of a novel synthetic Influenza vaccine (FLU-v) targeting T cell responses to NP, M1 and M2. Forty-eight healthy males aged 18-40 were recruited for this single-centre, randomised, double blind study. Volunteers received one single low (250 μg) or high (500 μg) dose of FLU-v, either alone or adjuvanted. Safety, tolerability and basic immunogenicity (IgG and IFN-γ responses) parameters were assessed pre-vaccination and for 21 days post-vaccination. FLU-v was found to be safe and well tolerated with no vaccine associated severe adverse events. Dose-dependent IFN-γ responses >2-fold the pre-vaccination level were detected in 80% and 100% of volunteers receiving, respectively, the low and high dose adjuvanted FLU-v formulations. No formulation tested induced any significant FLU-v antibody response. FLU-v is safe and induces a vaccine-specific cellular immunity. Cellular immune responses are historically known to control and mitigate infection and illness during natural infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients.

PubMed

Chan, W C; Lam, L C; Choy, C N; Leung, V P; Li, S W; Chiu, H F

2001-12-01

Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms. Copyright 2001 John Wiley & Sons, Ltd.

Ginkgo biloba special extract LI 1370 improves dual-task walking in patients with MCI: a randomised, double-blind, placebo-controlled exploratory study.

PubMed

Gschwind, Yves J; Bridenbaugh, Stephanie A; Reinhard, Sarah; Granacher, Urs; Monsch, Andreas U; Kressig, Reto W

2017-08-01

In patients with mild cognitive impairment (MCI), gait instability, particularly in dual-task situations, has been associated with impaired executive function and an increased fall risk. Ginkgo biloba extract (GBE) could be an effective mean to improve gait stability. This study investigated the effect of GBE on spatio-temporal gait parameters of MCI patients while walking under single and dual-task conditions. Fifty patients aged 50-85 years with MCI and associated dual-task-related gait impairment participated in this randomised, double-blind, placebo-controlled, exploratory phase IV drug trial. Intervention group (IG) patients received GBE (Symfona ® forte 120 mg) twice-daily for 6 months while control group (CG) patients received placebo capsules. A 6-month open-label phase with identical GBE dosage followed. Gait was quantified at months 0, 3, 6 and 12. After 6 months, dual-task-related cadence increased in the IG compared to the CG (p = 0.019, d = 0.71). No significant changes, but GBE-associated numerical non-significant trends were found after 6-month treatment for dual-task-related gait velocity and stride time variability. Findings suggest that 120 mg of GBE twice-daily for at least 6 months may improve dual-task-related gait performance in patients with MCI. The observed gait improvements add to the understanding of the self-reported unspecified improvements among MCI patients when treated with standardised GBE.

Naturalistic conversation improves daytime motorway driving performance under a benzodiazepine: a randomised, crossover, double-blind, placebo-controlled study.

PubMed

Moták, Ladislav; Bayssac, Laëtitia; Taillard, Jacques; Sagaspe, Patricia; Huet, Nathalie; Terrier, Patrice; Philip, Pierre; Daurat, Agnès

2014-06-01

The adverse effects of benzodiazepines on driving are widely recognised. The aims of this study were both to determine the impact of naturalistic conversation on the driving ability of drivers under a benzodiazepine, and to measure the accuracy of drivers' assessments of the joint effects of the benzodiazepine and conversation. Sixteen healthy male participants (29.69 ± 3.30 years) underwent a randomised, crossover, double-blind, placebo-controlled study with the benzodiazepine lorazepam (2mg). They drove 200 km (125 miles) on a motorway in the morning. We measured two driving ability-related variables (i.e., lane-keeping performance), and collected a set of self-assessed variables (i.e., self-assessment of driving performance) during two 10-min sequences of interest (no conversation vs. conversation). An analysis of variance revealed an interaction whereby lane-keeping performance under lorazepam was worse in the no-conversation condition than in the conversation condition. No such difference was detected under placebo. Pearson's correlation coefficients revealed that self-assessments were (i) not at all predictive of lane-keeping when performed before the drive, but (ii) moderately predictive of lane-keeping performance when performed during or after the drive. We conclude that conversation with a passenger may contribute to safer lane-keeping when driving under a benzodiazepine. Moreover, a degree of awareness may be attained after some experience of driving under the influence of this type of medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design.

PubMed

Malde, Marian K; Bügel, Susanne; Kristensen, Mette; Malde, Ketil; Graff, Ingvild E; Pedersen, Jan I

2010-07-20

Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Mean Ca absorption (+/- SEE) from the three different Ca sources were 21.9 +/- 1.7%, 22.5 +/- 1.7% and 27.4 +/- 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements.

Efficacy of actinidin-containing kiwifruit extract Zyactinase on constipation: a randomised double-blinded placebo-controlled clinical trial.

PubMed

Weir, Iona; Shu, Quan; Wei, Nengding; Wei, Chengkai; Zhu, Yi

2018-01-01

Zyactinase® is an extract of green kiwifruit, formulated into the consumer healthcare products marketed as Phloe® and Kivia, used to assist in the relief of the symptoms associated with a range of digestive system dysfunction, including constipation and Irritable Bowel Syndrome (IBS). A randomised, double-blind, placebo-controlled clinical trial was undertaken to determine the ef-fects of the kiwifruit extract on bowel movement, stool formation and IBS associated symptoms amongst a sub-ject group of generally healthy individuals experiencing a period of moderate constipation. Fifty-eight partici-pants were randomized to the kiwifruit extract (28) or placebo (30). Selection criterion was decreased number of bowel movements (<3/week), with increased faecal hardness and IBS associated symptoms. The study ran for three weeks, with participants first undergoing a seven-day wash out period, followed by a seven-day dosing pe-riod, and then a seven-day follow up period. There was a significant increase in the defecation frequency (p<0.001), with a significant improvement in faecal score (p<0.01). There was a significant difference in pain-ful defecation and abdominal pain between the two groups (p<0.01). No side effects, including diarrhoea, urgen-cy or abdominal pain, were observed during the trial. The green kiwifruit extract significantly in-duced normal bowel movements with no adverse effects. The kiwifruit extract relieved constipation and the symptoms of IBS such as bloating, flatulence and abdominal pain.

Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol

PubMed Central

Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; de la Rosa, Laura Alejandra; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

2017-01-01

Introduction In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Methods and analysis Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. Ethics and dissemination This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. Trial registration number ClinicalTrials.gov: NCT02837666. PMID:28645949

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design

PubMed Central

2010-01-01

Background Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Methods Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Results Mean Ca absorption (± SEE) from the three different Ca sources were 21.9 ± 1.7%, 22.5 ± 1.7% and 27.4 ± 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. Conclusion We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements. PMID:20646299

Propranolol reduces implicit negative racial bias.

PubMed

Terbeck, Sylvia; Kahane, Guy; McTavish, Sarah; Savulescu, Julian; Cowen, Philip J; Hewstone, Miles

2012-08-01

Implicit negative attitudes towards other races are important in certain kinds of prejudicial social behaviour. Emotional mechanisms are thought to be involved in mediating implicit "outgroup" bias but there is little evidence concerning the underlying neurobiology. The aim of the present study was to examine the role of noradrenergic mechanisms in the generation of implicit racial attitudes. Healthy volunteers (n = 36) of white ethnic origin, received a single oral dose of the β-adrenoceptor antagonist, propranolol (40 mg), in a randomised, double-blind, parallel group, placebo-controlled, design. Participants completed an explicit measure of prejudice and the racial implicit association test (IAT), 1-2 h after propranolol administration. Relative to placebo, propranolol significantly lowered heart rate and abolished implicit racial bias, without affecting the measure of explicit racial prejudice. Propranolol did not affect subjective mood. Our results indicate that β-adrenoceptors play a role in the expression of implicit racial attitudes suggesting that noradrenaline-related emotional mechanisms may mediate negative racial bias. Our findings may also have practical importance given that propranolol is a widely used drug. However, further studies will be needed to examine whether a similar effect can be demonstrated in the course of clinical treatment.

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial.

PubMed

Gauthier, Serge; Feldman, Howard H; Schneider, Lon S; Wilcock, Gordon K; Frisoni, Giovanni B; Hardlund, Jiri H; Moebius, Hans J; Bentham, Peter; Kook, Karin A; Wischik, Damon J; Schelter, Bjoern O; Davis, Charles S; Staff, Roger T; Bracoud, Luc; Shamsi, Kohkan; Storey, John M D; Harrington, Charles R; Wischik, Claude M

2016-12-10

Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31-7·34]: 75 mg LMTM twice a day [n=257] -0·02, -1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] -0·43, -2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [-8·22, 95% CI -9·63 to -6·82]: 75 mg LMTM twice a day -0·93, -3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day -0·34, -2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. TauRx Therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial

PubMed Central

Gauthier, Serge; Feldman, Howard H; Schneider, Lon S; Wilcock, Gordon K; Frisoni, Giovanni B; Hardlund, Jiri H; Moebius, Hans J; Bentham, Peter; Kook, Karin A; Wischik, Damon J; Schelter, Bjoern O; Davis, Charles S; Staff, Roger T; Bracoud, Luc; Shamsi, Kohkan; Storey, John M D; Harrington, Charles R; Wischik, Claude M

2016-01-01

Summary Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer’s disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer’s disease. Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer’s disease. Patients concomitantly using other medicines for Alzheimer’s disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer’s disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Alzheimer’s Disease Co-operative Study–Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31–7·34]: 75 mg LMTM twice a day [n=257] –0·02, –1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] –0·43, –2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [–8·22, 95% CI –9·63 to –6·82]: 75 mg LMTM twice a day –0·93, –3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day –0·34, –2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer’s disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer’s disease will be reported soon. Funding TauRx Therapeutics. PMID:27863809

Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hakama, Matti; Hemminki, Elina

2012-04-04

The Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT), with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001) received open-label HT or no treatment, participants in the blind trial (N = 777) remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes. Effect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial. The women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91) than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied.Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94) was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98). The results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events. [ISRCTN35338757].

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial.

PubMed

Valery, Patricia C; Morris, Peter S; Byrnes, Catherine A; Grimwood, Keith; Torzillo, Paul J; Bauert, Paul A; Masters, I Brent; Diaz, Abbey; McCallum, Gabrielle B; Mobberley, Charmaine; Tjhung, Irene; Hare, Kim M; Ware, Robert S; Chang, Anne B

2013-10-01

Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1-2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study. National Health and Medical Research Council (Australia) and Health Research Council (New Zealand). Copyright © 2013 Elsevier Ltd. All rights reserved.

Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial.

PubMed

Ludolph, Albert C; Schuster, Joachim; Dorst, Johannes; Dupuis, Luc; Dreyhaupt, Jens; Weishaupt, Jochen H; Kassubek, Jan; Weiland, Ulrike; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Schrank, Berthold; Boentert, Matthias; Emmer, Alexander; Hermann, Andreas; Zeller, Daniel; Prudlo, Johannes; Winkler, Andrea S; Grehl, Torsten; Heneka, Michael T; Wollebæk Johannesen, Siw; Göricke, Bettina

2018-06-18

Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the primary outcome, the survival probability at the end of the study was 0·43 (95% CI 0·25-0·59) in the rasagiline group (n=126) and 0·53 (0·43-0·62) in the placebo group (n=125). The estimated effect size (hazard ratio) was 0·91 (one-sided 97·5% CI -infinity to 1·34; p=0·31). Rasagiline was well tolerated, and most adverse events were due to amyotrophic lateral sclerosis disease progression rather than treatment; the most frequent of these were dysphagia (32 [25%] taking rasagiline vs 24 [19%] taking placebo) and respiratory failure (25 [20%] vs 31 [25%]). Frequency of adverse events were comparable between both groups. Rasagiline was safe in patients with amyotrophic lateral sclerosis. There was no difference between groups in the primary outcome of survival, although post-hoc analysis suggested that rasagiline might modify disease progression in patients with an initial slope of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised greater than 0·5 points per month at baseline. This should be confirmed in another clinical trial. Teva Pharmaceutical Industries. Copyright © 2018 Elsevier Ltd. All rights reserved.

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD.

PubMed

Kilfeather, S A; Ponitz, H H; Beck, E; Schmidt, P; Lee, A; Bowen, I; Hesse, Ch

2004-05-01

We performed a multicentre, randomised, double-blind (within-device), placebo- and active-controlled, parallel-group study to compare the efficacy and safety of ipratropium bromide plus fenoterol hydrobromide (IB/FEN; Berodual) delivered via the novel, propellant-free Respimat Soft Mist Inhaler (SMI) and from a chlorofluorocarbon (CFC)-metered-dose inhaler (MDI) in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. After 2-weeks' run-in (CFC-MDI [IB 20 microg/FEN 50 microg per actuation] two actuations q.i.d. [MDI 40/100]), 892 patients were randomised to Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50) or placebo (one actuation q.i.d.), or a CFC-MDI containing IB 20 microg/FEN 50 microg (MDI 40/100) or placebo (two actuations q.i.d.) for 12 weeks. Analysis of the primary endpoint (change in forced expiratory volume in 1 s [FEV1] in the first 60 min after dosing [area under the curve; AUC0-1h]) on day 85 showed that the efficacy of Respimat SMI 20/50 (but not Respimat SMI 10/25) was not inferior to that of MDI 40/100. The safety profile of Respimat SMI was comparable to CFC-MDI. Switching from MDI 40/100 to Respimat SMI was well tolerated. Respimat SMI enables a 50% reduction of the nominal inhaled dose of IB/FEN in COPD patients while offering similar therapeutic efficacy and safety to the CFC-MDI.

Efficacy evaluation of an anti-caries varnish: protocol for a phase II randomised controlled trial

PubMed Central

Tut, Ohnmar; Rothen, Marilynn; Mancl, Lloyd; Gallen, Marcelle; Tanzer, Jason M

2017-01-01

Introduction Dental caries (tooth decay) is a common disease in which the products of sugar metabolism by certain bacteria that populate the tooth surface induce the development and progression of lesions (cavities). This is a phase II single-centre randomised, double-blind, active-controlled, parallel-group trial to assess the efficacy of a combination povidone iodine and sodium fluoride dental varnish to determine if it is superior to a varnish containing only sodium fluoride in the prevention of new caries lesions. The objective of this report is to describe the rationale and protocol for the trial. Methods and analysis The study site is Pohnpei State, Federated States of Micronesia. The study population is 284 children 48–84 months old. The primary outcome will be the surface-level primary molar caries increment (d2-3mfs/DMFS) at 2 years post baseline. The incremental dental caries at 1 year will also be compared between the two interventions. The secondary outcome is the Facial Image Scale after the initial treatment and after the fifth treatment at 1 year that gauges the child’s response to the treatment. Ethics and dissemination The Western Institutional Review Board (designated IRB) and the Institutional Review Board of the College of Micronesia-FSM approved all study procedures. The US Food and Drug Administration (FDA) has issued IND 128835 covering this study. The study results will be published and submitted to the FDA in support of a new drug application. Trialregistration number NCT03082196. PMID:28667230

LDL-cholesterol lowering activity of a blend of rice bran oil and safflower oil (8:2) in patients with hyperlipidaemia: a proof of concept, double blind, controlled, randomised parallel group study.

PubMed

Malve, Harshad; Kerkar, Prafulla; Mishra, Nidheesh; Loke, Sanjita; Rege, N N; Marwaha-Jaspal, Ankita; Jainani, Kiran J

2010-11-01

Cardiovascular diseases have emerged as major health burden worldwide in recent times. Low density lipoprotein cholesterol (LDL-C) serves as the primary marker for cardiovascular diseases. Reports suggest that rice bran oil has antihyperlipidaemic properties. However, current evidence suggests that no single oil can provide the recommended dietary fat ratio. Hence the present study was undertaken in patients with hyperlipidaemia to study effects of substitution of the cooking oil with a blend of 80% rice bran oil and 20% safflower oil on LDL-C levels. The selected patients (n = 73) were randomly assigned either to the study oil group (blend under study) or control oil group (the oil which the patient was using before). The lipid profile was monitored monthly in these patients for 3 months during which they consumed the oil as per the randomisation. At each follow up, LDL-C levels showed a significant reduction from baseline in the study oil group and reduction was more than that observed in the control group. It was also observed that the percentage of the respondents was higher in the study oil group. At the end of the study period, 82% patients from this group had LDL levels less than 150 mg% as against 57% in the control group. Thus, the substitution of usual cooking oil with a blend of rice bran oil and safflower oil (8:2) was found to exert beneficial effects on the LDL-C levels shifting them to low-risk lipid category.

Comparative trial of Aloe vera/olive oil combination cream versus phenytoin cream in the treatment of chronic wounds.

PubMed

Panahi, Y; Izadi, M; Sayyadi, N; Rezaee, R; Jonaidi-Jafari, N; Beiraghdar, F; Zamani, A; Sahebkar, A

2015-10-01

Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream.

Weight loss effects from vegetable intake: a 12-month randomised controlled trial.

PubMed

Tapsell, L C; Batterham, M J; Thorne, R L; O'Shea, J E; Grafenauer, S J; Probst, Y C

2014-07-01

Direct evidence for the effects of vegetable intake on weight loss is qualified. The study aimed to assess the effect of higher vegetable consumption on weight loss. A single blind parallel controlled trial was conducted with 120 overweight adults (mean body mass index=29.98 kg/m(2)) randomised to two energy deficit healthy diet advice groups differing only by doubling the serving (portion) sizes of vegetables in the comparator group. Data were analysed as intention-to-treat using a linear mixed model. Spearmans rho bivariate was used to explore relationships between percentage energy from vegetables and weight loss. After 12 months, the study sample lost 6.5±5.2 kg (P<0.001 time) with no difference between groups (P>0.05 interaction). Both groups increased vegetable intake and lost weight in the first 3 months, and the change in weight was significantly correlated with higher proportions of energy consumed as vegetables (rho=-0.217, P=0.024). Fasting glucose, insulin and triglyceride levels decreased (P<0.001 time) and high-density lipoprotein cholesterol levels increased (P<0.001 time), with no difference between groups. Weight loss was sustained for 12 months by both groups, but the comparator group reported greater hunger satisfaction (P=0.005). Advice to consume a healthy low-energy diet leads to sustained weight loss, with reductions in cardiovascular disease risk factors regardless of an emphasis on more vegetables. In the short term, consuming a higher proportion of the dietary energy as vegetables may support a greater weight loss and the dietary pattern appears sustainable.

Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial

PubMed Central

Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N

2013-01-01

Introduction Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Methods and analysis Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m2) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. Ethics and dissemination The protocol was approved by the National Research Ethics Service (East Midlands—Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52 patients randomised. The treatment follow-up of LEAN participants is currently ongoing and is due to finish in July 2014. The findings of this trial will be disseminated through peer-reviewed publications and international presentations. Trial registration clinicaltrials.gov NCT01237119. PMID:24189085

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25%) in the placebo group had at least one serious adverse event (p=0·36). Rituximab is an effective and safe treatment for childhood-onset, complicated FRNS and SDNS. Japanese Ministry of Health, Labour and Welfare. Copyright © 2014 Elsevier Ltd. All rights reserved.

EFFECT of daily antiseptic body wash with octenidine on nosocomial primary bacteraemia and nosocomial multidrug-resistant organisms in intensive care units: design of a multicentre, cluster-randomised, double-blind, cross-over study.

PubMed

Meißner, Anne; Hasenclever, Dirk; Brosteanu, Oana; Chaberny, Iris Freya

2017-11-08

Nosocomial infections are serious complications that increase morbidity, mortality and costs and could potentially be avoidable. Antiseptic body wash is an approach to reduce dermal micro-organisms as potential pathogens on the skin. Large-scale trials with chlorhexidine as the antiseptic agent suggest a reduction of nosocomial infection rates. Octenidine is a promising alternative agent which could be more effective against Gram-negative organisms. We hypothesise that daily antiseptic body wash with octenidine reduces the risk of intensive care unit (ICU)-acquired primary bacteraemia and ICU-acquired multidrug-resistant organisms (MDRO) in a standard care setting. EFFECT is a controlled, cluster-randomised, double-blind study. The experimental intervention consists in using octenidine-impregnated wash mitts for the daily routine washing procedure of the patients. This will be compared with using placebo wash mitts. Replacing existing washing methods is the only interference into clinical routine.Participating ICUs are randomised in an AB/BA cross-over design. There are two 15-month periods, each consisting of a 3-month wash-out period followed by a 12-month intervention and observation period. Randomisation determines only the sequence in which octenidine-impregnated or placebo wash mitts are used. ICUs are left unaware of what mitts packages they are using.The two coprimary endpoints are ICU-acquired primary bacteraemia and ICU-acquired MDRO. Endpoints are defined based on individual ward-movement history and microbiological test results taken from the hospital information systems without need for extra documentation. Data on clinical symptoms of infection are not collected. EFFECT aims at recruiting about 45 ICUs with about 225 000 patient-days per year. The study was approved by the ethics committee of the University of Leipzig (number 340/16-ek) in November 2016. Findings will be published in peer-reviewed journals. DRKS-ID: DRKS00011282. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation.

PubMed

Miles, David; Cameron, David; Bondarenko, Igor; Manzyuk, Lyudmila; Alcedo, Juan Carlos; Lopez, Roberto Ivan; Im, Seock-Ah; Canon, Jean-Luc; Shparyk, Yaroslav; Yardley, Denise A; Masuda, Norikazu; Ro, Jungsil; Denduluri, Neelima; Hubeaux, Stanislas; Quah, Cheng; Bais, Carlos; O'Shaughnessy, Joyce

2017-01-01

MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m 2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-A high populations. Of 481 patients randomised (242 placebo-paclitaxel; 239 bevacizumab-paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51-0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo-paclitaxel versus 11.0 months with bevacizumab-paclitaxel) and 0.64 (96% confidence interval, 0.47-0.88; log-rank p = 0.0038) in the pVEGF-A high subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%). The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. ClinicalTrials.gov NCT01663727. Copyright © 2016. Published by Elsevier Ltd.

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study.

PubMed

Cohen, Stanley; Genovese, Mark C; Choy, Ernest; Perez-Ruiz, Fernando; Matsumoto, Alan; Pavelka, Karel; Pablos, Jose L; Rizzo, Warren; Hrycaj, Pawel; Zhang, Nan; Shergy, William; Kaur, Primal

2017-10-01

ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. NCT01970475; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.

PubMed

Pirotta, S; Kidgell, D J; Daly, R M

2015-01-01

Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.

PubMed

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-03-01

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary end points included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometrical mean ratio (GMR) of AUC inf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C max was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC inf and C max were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. EudraCT number 2012-000785-37; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.

PubMed

Auld, Fiona; Maschauer, Emily L; Morrison, Ian; Skene, Debra J; Riha, Renata L

2017-08-01

Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomised, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders. An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep wake syndrome in people who are blind, and rapid eye movement-behaviour disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep. A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomised and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p < 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo. These findings highlight the potential importance of melatonin in treating certain first degree sleep disorders. The development of large-scale, randomised, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.

PubMed

Wechsler, Michael E; Kunselman, Susan J; Chinchilli, Vernon M; Bleecker, Eugene; Boushey, Homer A; Calhoun, William J; Ameredes, Bill T; Castro, Mario; Craig, Timothy J; Denlinger, Loren; Fahy, John V; Jarjour, Nizar; Kazani, Shamsah; Kim, Sophia; Kraft, Monica; Lazarus, Stephen C; Lemanske, Robert F; Markezich, Amy; Martin, Richard J; Permaul, Perdita; Peters, Stephen P; Ramsdell, Joe; Sorkness, Christine A; Sutherland, E Rand; Szefler, Stanley J; Walter, Michael J; Wasserman, Stephen I; Israel, Elliot

2009-11-21

Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid. In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00200967. After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8-31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0-32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg-Gly/Gly] -0.1, -14.4 to 14.2; p=0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p<0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p=0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43-2.21, p=0.0038). Seven Arg/Arg participants (placebo, n=5; salmeterol, n=2) and six Gly/Gly participants (placebo, n=3; salmeterol, n=3) had an asthma exacerbation. Five serious adverse events were reported, one each during the pre-match and run-in phases on open-label inhaled corticosteroid, two during double-blind treatment with salmeterol/inhaled corticosteroid, and one during double-blind treatment with placebo/inhaled corticosteroid. None of the serious events was asthma-related or related to study drugs or procedures. In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine. National Institutes of Health.

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis

PubMed Central

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-01-01

Introduction Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. Methods and analysis The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Ethics and dissemination Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. PMID:28554913

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis.

PubMed

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-05-29

Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

PubMed Central

2010-01-01

Background The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression. Methods/Design The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm2 or >10 cm2. Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process. Discussion The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes. Trial Registration ACTRN12608000599370 PMID:20214822

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

2006-01-01

Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men.

PubMed

Cases, Julien; Romain, Cindy; Dallas, Constantin; Gerbi, Alain; Rouanet, Jean Max

2015-01-01

Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.

PubMed

2010-09-01

Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia. Copyright 2010 Elsevier Ltd. All rights reserved.

Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.

PubMed

Tilbrook, Helen; Forsythe, Rachael O; Rolfe, Debbie; Clark, Laura; Bland, Martin; Buckley, Hannah; Chetter, Ian; Cook, Liz; Dumville, Jo; Gabe, Rhian; Harding, Keith; Layton, Alison; Lindsay, Ellie; McDaid, Catriona; Moffatt, Christine; Phillips, Ceri; Stansby, Gerard; Vowden, Peter; Williams, Laurie; Torgerson, David; Hinchliffe, Robert J

2015-11-10

Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).

Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

PubMed Central

de Silva, H. Asita; Pathmeswaran, Arunasalam; Ranasinha, Channa D.; Jayamanne, Shaluka; Samarakoon, Senarath B.; Hittharage, Ariyasena; Kalupahana, Ranjith; Ratnatilaka, G. Asoka; Uluwatthage, Wimalasiri; Aronson, Jeffrey K.; Armitage, Jane M.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

Background Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized. Trial registration www.ClinicalTrials.gov NCT00270777 Please see later in the article for the Editors' Summary PMID:21572992

Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

PubMed Central

Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

2013-01-01

Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

[An experimental evaluation of the efficacy of 4 types of detergents for 3 types of dyes to which workers in color-printing plants are exposed].

PubMed

Terzaghi, G F; Settimi, L; Peverelli, C; Sevosi, L; Duca, P G

1996-01-01

The efficacy of 4 commercial cleansing products was tested with 3 colouring agents widely used in the dyeing industry in a randomised double blind trail involving 8 workers each time. A between-detergents statistically significant difference was observed; the interaction (detergents x colouring agents) was significant. The efficacy of type A detergent was higher for type I-III dyers, while the efficacy of type C detergent, which widely used was lowest.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

PubMed

Bhardwaj, Anjali K; Allsop, David J; Copeland, Jan; McGregor, Iain S; Dunlop, Adrian; Shanahan, Marian; Bruno, Raimondo; Phung, Nghi; Montebello, Mark; Sadler, Craig; Gugusheff, Jessica; Jackson, Melissa; Luksza, Jennifer; Lintzeris, Nicholas

2018-05-18

The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

PubMed

Verlaet, Annelies A J; Ceulemans, Berten; Verhelst, Helene; Van West, Dirk; De Bruyne, Tess; Pieters, Luc; Savelkoul, Huub F J; Hermans, Nina

2017-03-28

Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.

Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial

PubMed Central

Alam, S R; Lewis, S C; Zamvar, V; Pessotto, R; Dweck, M R; Krishan, A; Goodman, K; Oatey, K; Harkess, R; Milne, L; Thomas, S; Mills, N M; Moore, C; Semple, S; Wiedow, O; Stirrat, C; Mirsadraee, S; Newby, D E; Henriksen, P A

2015-01-01

Background Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. Methods and results In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI −207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI −235 to 711, p=0.320). Conclusions There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. Trial registration number (EudraCT 2010-019527-58, ISRCTN82061264). PMID:26310261

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial.

PubMed

Ali, Ather; Weiss, Theresa R; McKee, Douglas; Scherban, Alisa; Khan, Sumiya; Fields, Maxine R; Apollo, Damian; Mehal, Wajahat Z

2017-01-01

Patients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in patients with IBS guided by a leucocyte activation test. This is a parallel-group, double-blind, randomised controlled trial of 58 adults with IBS seen at an academic health centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte activation test; individual foods were reported to produce positive or negative results. Participants were randomised to a 4-week diet with either individualised guidance to eliminate foods with positive assay results and allow foods with negative assay results (intervention), or with individualised guidance, matched in rigour and complexity, to eliminate foods with negative assay results and allow foods with positive assay results (comparison). The primary outcome was between-group differences in the IBS Global Improvement Scale (GIS). Secondary outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An aptamer-based proteomic analysis was conducted in strong responders. The intervention group had significantly greater increases in mean GIS score after 4 weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had significantly greater reductions in mean SSS score at 4 weeks (-61.78 vs comparison; 95% CI -4.43 to -119.14; p=0.04) and 8 weeks (-66.42 vs comparison; 95% CI -5.75 to -127.09; p=0.03). There were no significant differences between intervention and comparison groups in mean AR or QOL scores. A reduction in neutrophil elastase concentration was associated with reduced symptoms. Elimination diets guided by leucocyte activation tests reduced symptoms. These findings could lead to insights into the pathophysiology of IBS. NCT02186743.

Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial.

PubMed

Chandra, Rampalli Viswa; Prabhuji, M L Venkatesh; Roopa, D Adinarayana; Ravirajan, Sandhya; Kishore, Hadal C

2007-01-01

The aim of the present study was to compare the effect of systemically administered lycopene (LycoRed) as a monotherapy and as an adjunct to scaling and root planing in gingivitis patients. Twenty systemically healthy patients showing clinical signs of gingivitis were involved in a randomised, double-blind, parallel, split-mouth study. The subjects were randomly distributed between the two treatment groups: experimental group (n = 10), 8 mg lycopene/day for 2 weeks; and controls (n = 10), placebo for 2 weeks. Quadrant allocation within each group was randomised with two quadrants treated with oral prophylaxis (OP) and two quadrants not receiving any form of treatment (non-OP). Bleeding index (SBI) and non-invasive measures of plaque (PI) and gingivitis (GI) were assessed at baseline, 1 and 2 weeks. Salivary uric acid levels were also measured. All the treatment groups demonstrated statistically significant reductions in the GI, SBI and PI. Treatment with OP-lycopene resulted in a statistically significant decrease in GI when compared with OP-placebo (p < 0.05) and non-OP-placebo (p < 0.01). Treatment with non-OP-lycopene resulted in a statistically significant decrease in GI when compared with non-OP-placebo (p < 0.01). The OP-lycopene group showed a statistically significant reduction in SBI values when compared with the non-OP-lycopene group (p < 0.05) and the non-OP-placebo group (p < 0.001). There was a strong negative correlation between the salivary uric acid levels and the percentage reduction in GI at 1 and 2 weeks in the OP-lycopene group (r = -0.852 and -0.802 respectively) and in the non-OP-lycopene group (r = -0.640 and -0.580 respectively). The results presented in this study suggest that lycopene shows great promise as a treatment modality in gingivitis. The possibility of obtaining an additive effect by combining routine oral prophylaxis with lycopene is also an exciting possibility, which deserves further study.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

PubMed Central

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

PubMed

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2013-09-01

Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0.53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. National Institute for Health Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

A multicentre double-blind randomised controlled trial evaluating the efficacy of daily use of antibacterial mouthwash against oropharyngeal gonorrhoea among men who have sex with men: the OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study protocol.

PubMed

Chow, Eric P F; Walker, Sandra; Hocking, Jane S; Bradshaw, Catriona S; Chen, Marcus Y; Tabrizi, Sepehr N; Howden, Benjamin P; Law, Matthew G; Maddaford, Kate; Read, Tim R H; Lewis, David A; Whiley, David M; Zhang, Lei; Grulich, Andrew E; Kaldor, John M; Cornelisse, Vincent J; Phillips, Samuel; Donovan, Basil; McNulty, Anna M; Templeton, David J; Roth, Norman; Moore, Richard; Fairley, Christopher K

2017-06-28

Gonorrhoea is one of the most common sexually transmissible infections in men who have sex with men (MSM). Gonorrhoea rates have increased substantially in recent years. There is concern that increasing gonorrhoea prevalence will increase the likelihood of worsening antibiotic resistance in Neisseria gonorrhoeae. A recent randomised controlled trial (RCT) demonstrated that a single-dose of mouthwash has an inhibitory effect against oropharyngeal gonorrhoea. We are conducting the first RCT to evaluate whether daily use of mouthwash could reduce the risk of acquiring oropharyngeal gonorrhoea. The OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study is a double-blind RCT and will be conducted at several sexual health clinics and high caseload General Practice (GP) clinics in Melbourne and Sydney, Australia. A total of 504 MSM attending the participating sites will be recruited. Participants will be randomised to either using 'Study mouthwash A' or 'Study mouthwash B' for 12 weeks. Study mouthwash A was inhibitory against N. gonorrhoeae in vitro, whereas study mouthwash B was not. Participants will be instructed to rinse and gargle the study mouthwash for 60 seconds every day. The primary outcome is the proportion of participants with oropharyngeal gonorrhoea detected by nucleic acid amplification test by 12 weeks. The results from this trial may provide a novel way to reduce gonorrhoea prevalence and transmission without the use of antibiotics that may be associated with development of resistance. If shown to be effective, the widespread use of mouthwash will reduce the prevalence of oropharyngeal gonorrhoea, which plays key role in driving the emergence of gonococcal antimicrobial resistance through DNA exchange with oral commensal bacteria. The anticipated net effect will be interruption of onward transmission of N. gonorrhoeae within high density sexual networks within MSM populations. Australian New Zealand Clinical Trials Registry ACTRN12616000247471 , registered on 23rd February 2016.

High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

PubMed Central

Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

2017-01-01

Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. Methods/design This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. Ethics and dissemination The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. Trial registration The trial has been registered at the ISRCTN (ISRTCN 63827758). PMID:28912191

Effect of a single prophylactic preoperative oral antibiotic dose on surgical site infection following complex dermatological procedures on the nose and ear: a prospective, randomised, controlled, double-blinded trial.

PubMed

Rosengren, Helena; Heal, Clare F; Buttner, Petra G

2018-04-19

There is limited published research studying the effect of antibiotic prophylaxis on surgical site infection (SSI) in dermatological surgery, and there is no consensus for its use in higher-risk cases. The objective of this study was to determine the effectiveness of a single oral preoperative 2 g dose of cephalexin in preventing SSI following flap and graft dermatological closures on the nose and ear. Prospective double-blinded, randomised, placebo-controlled trial testing for difference in infection rates. Primary care skin cancer clinics in North Queensland, Australia, were randomised to 2 g oral cephalexin or placebo 40-60 min prior to skin incision. 154 consecutive eligible patients booked for flap or graft closure following skin cancer excision on the ear and nose. 2 g dose of cephalexin administered 40-60 min prior to surgery. Overall 8/69 (11.6%) controls and 1/73 (1.4%) in the intervention group developed SSI (p=0.015; absolute SSI reduction 10.2%; number needed to treat (NNT) for benefit 9.8, 95% CI 5.5 to 45.5). In males, 7/44 controls and 0/33 in the intervention group developed SSI (p=0.018; absolute SSI reduction 15.9%; NNT for benefit 6.3, 95% CI 3.8 to 19.2). SSI was much lower in female controls (1/25) and antibiotic prophylaxis did not further reduce this (p=1.0). There was no difference between the study groups in adverse symptoms attributable to high-dose antibiotic administration (p=0.871). A single oral 2 g dose of cephalexin given before complex skin closure on the nose and ear reduced SSI. ANZCTR 365115; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo.

PubMed

Burgess, Ian F; Brunton, Elizabeth R; French, Rebecca; Burgess, Nazma A; Lee, Peter N

2014-05-30

To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations. Randomised, double-blind, cross-over, community study in Cambridgeshire, UK. 63 male and female schoolchildren aged 4-16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated. Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray. The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use. Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days. Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly. ISRCTN09524995. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial

PubMed Central

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-01-01

Background: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. Aims: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. Patients: One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. Methods: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children ⩾6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. Results: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. Conclusions: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation. PMID:15479678

Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.

PubMed

Eziefula, Alice Chijioke; Staedke, Sarah G; Yeung, Shunmay; Webb, Emily; Kamya, Moses; White, Nicholas J; Bousema, Teun; Drakeley, Chris

2013-03-26

For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status. In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine. These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.

Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial)

PubMed Central

Singa, Benson O; John-Stewart, Grace C; Richardson, Barbra A; Brander, Rebecca L; McGrath, Christine J; Tickell, Kirkby D; Amondi, Mary; Rwigi, Doreen; Babigumira, Joseph B; Kariuki, Sam; Nduati, Ruth; Walson, Judd L

2017-01-01

Introduction Child mortality due to infectious diseases remains unacceptably high in much of sub-Saharan Africa. Children who are hospitalised represent an accessible population at particularly high risk of death, both during and following hospitalisation. Hospital discharge may be a critical time point at which targeted use of antibiotics could reduce morbidity and mortality in high-risk children. Methods and analysis In this randomised, double-blind, placebo-controlled trial (Toto Bora Trial), 1400 children aged 1–59 months discharged from hospitals in Western Kenya, in Kisii and Homa Bay, will be randomised to either a 5-day course of azithromycin or placebo to determine whether a short course of azithromycin reduces rates of rehospitalisation and/or death in the subsequent 6-month period. The primary analysis will be modified intention-to-treat and will compare the rates of rehospitalisation or death in children treated with azithromycin or placebo using Cox proportional hazard regression. The trial will also evaluate the effect of a short course of azithromycin on enteric and nasopharyngeal infections and cause-specific morbidities. We will also identify risk factors for postdischarge morbidity and mortality and subpopulations most likely to benefit from postdischarge antibiotic use. Antibiotic resistance in Escherichia coli and Streptococcus pneumoniae among enrolled children and their primary caregivers will also be assessed, and cost-effectiveness analyses will be performed to inform policy decisions. Ethics and dissemination Study procedures were reviewed and approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington and the Kenyan Pharmacy and Poisons Board. The study is being externally monitored, and a data safety and monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. Trial registration number NCT02414399. PMID:29289941

Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: a double-blind, randomised controlled clinical trial.

PubMed

Ljunggren, Stefan; Hahn, Robert G; Nyström, Thomas

2014-06-01

Surgery initiates a series of physiological stress processes in the body, inducing transient insulin resistance. Preoperative carbohydrate treatment can reduce the latter phenomenon. We investigated the effects of carbohydrate loading on insulin sensitivity and beta-cell function after elective hip replacement. Twenty-three nondiabetic patients (mean age of 68 years) who underwent elective hip replacement surgery participated in this double-blind controlled study. The patients were randomised to a nutrition group, which ingested a carbohydrate-rich fluid (50 kcal/100 ml) (Preop(®)), or a control group (tap water flavoured with lemon) 800 ml + 400 ml before the surgery. The insulin response (beta-cell function) and the insulin sensitivity were measured with an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic euglycaemic glucose clamp, respectively, one day before and two days after the surgery. Insulin sensitivity decreased by 51% (median; 25-75th percentiles 35-61) after ingesting Preop(®) and by 39% (21-51) after ingesting in the control group (n.s.). The postoperative IVGTT in the nutrition group was followed by a significantly larger area under the curve (AUC) for plasma insulin (+54% versus the preoperative IVGTT) compared to the control group (+7%). This difference was already apparent during the first phase (0-10 min) of insulin secretion (+20 and -21%, respectively; P < 0.05). The patients randomised to the carbohydrate oral fluid or the water prior to the surgery demonstrated a significant but similar decrease in insulin sensitivity. The carbohydrates increased the beta-cell function as a compensatory response to the disposition index, resulting in a smaller reduction in surgery-induced insulin resistance compared to the tap water. The study was registered at http://www.clinicaltrials.gov (NCT01774084). Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Modafinil In Debilitating fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial.

PubMed

Lillicrap, Thomas; Krishnamurthy, Venkatesh; Attia, John; Nilsson, Michael; Levi, Christopher R; Parsons, Mark W; Bivard, Andrew

2016-08-17

Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient's self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life. MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke. The inclusion criteria will require an average score of 12 or more across all domains of the Multi-dimensional Fatigue Inventory (MFI-20) and the diagnosis of a stroke more than 6 months prior. Patients will be randomised 1:1 to receive either modafinil 200 mg daily or placebo for a period of 6 weeks, after which a crossover will occur where patients who are on modafinil will begin taking placebo and vice versa. The primary outcome will be improvement in fatigue as measured by the MFI-20. Secondary outcomes will include changes in the Fatigue Severity Scale, improved cognition measured using the Montreal Cognitive Assessment, improvement in mood as determined by the Depression, Anxiety and Stress Scale and improvement in each patient's stroke-specific quality of life score. All participants will also undergo magnetic resonance imaging (MRI) at baseline, crossover and study conclusion to measure cerebral blood flow on arterial spin labelling and brain activity on resting state functional MRI. This study will comply with the CONSORT guidelines. The projected sample size requirement is 36 participants in a crossover trial giving a power of 80 % and a type-1 error rate of 0.05. MIDAS seeks to enhance the quality of life in stroke survivors by assisting or resolving stroke-associated fatigue. ACTRN12615000350527 , registered on the 17 April 2015. Protocol version 3, approved 16 June 2015.

Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia.

PubMed

Amarapurkar, Deepak N; Rane, Priya

2004-12-01

Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly used in the management of functional dyspepsia. However, in a recently conducted international, multicentric study, efficacy of 3 different regimens of mosapride was shown to be comparable to placebo. The objective of this phase 4 randomised, double blind, prospective study was to compare the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia among patients attending the gastroenterology outpatient department of a tertiary care hospital. Ganaton 50 mg or mosapride citrate 5 mg three times daily before meals for a period of 2 weeks was administered orally. Thirty functional dyspepsia patients in each group (total = 60) were randomised to receive itopride hydrochloride or mosapride citrate treatment for 2 weeks. In itopride versus mosapride groups, global efficacy as judged by patients was excellent in 17 versus 9 (p < 0.05) and poor in 0 versus 3 (p < 0.05). In itopride versus mosapride group global efficacy as judged by physician was excellent in 24 (80%) versus 15 (50%) and poor in 0 (0%) versus 3 (10%) patients respectively. The global efficacy was rated as excellent to good in significantly (p < 0.05) more number of patients in itopride (93.3%) group as compared to mosapride (63.33 %) group. None of the patients reported any adverse events with itopride treatment. In the mosapride group 5 patients (16.7%) reported adverse events. Two patients (6.7%) were withdrawn from mosapride treatment due to adverse events. The physician rated global tolerability ofitopride versus mosapride treatment as excellent in 23 (76.7%) versus 8 (26.7%) (p < 0.05) and poor in 0 (0%) versus 6 (20%) patients respectively. It may be concluded that ganaton (itopride hydrochloride) is superior in efficacy and safety over mosapride citrate in the management of functional dyspepsia.

MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

PubMed Central

Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

2015-01-01

Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. Trial registration number NCT01023256 PMID:24534756

Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

PubMed

Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

2016-03-01

There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study.

PubMed

Sugano, Kentaro; Choi, Myung-Gyu; Lin, Jaw-Town; Goto, Shinya; Okada, Yasushi; Kinoshita, Yoshikazu; Miwa, Hiroto; Chiang, Chern-En; Chiba, Tsutomu; Hori, Masatsugu; Fukushima, Yasushi; Kim, Hyun-Soo; Chang, Chi-Yang; Date, Masataka

2014-07-01

To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia. In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81-324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer recurrence (Kaplan-Meier analysis). Efficacy findings are presented up to week 48, as per a planned interim analysis within the study protocol. A total of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set (esomeprazole, n=182; placebo, n=182). There was a statistically significant difference in the time to ulcer recurrence between esomeprazole and placebo (HR 0.09; 96.65% CI 0.02 to 0.41; p<0.001). The estimated ulcer-free rate at week 12 was 99.3% (esomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate for esomeprazole was maintained through to week 48 (98.3% vs. 81.2% of placebo-treated patients). No factors, other than female gender, reduced time to ulcer recurrence in addition to the effect of esomeprazole (p<0.001). Treatment with esomeprazole was generally well tolerated. Daily esomeprazole 20 mg is efficacious and well tolerated in reducing the recurrence of peptic ulcer in East-Asian patients with a history of ulcers who are taking low-dose ASA for cardiovascular protection. NCT01069939. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

PubMed

Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

2015-02-01

Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Heartburn treatment in primary care: randomised, double blind study for 8 weeks

PubMed Central

Hatlebakk, Jan G; Hyggen, Arild; Madsen, Per H; Walle, Per O; Schulz, Tom; Mowinckel, Petter; Bernklev, Tomm; Berstad, Arnold

1999-01-01

Objective To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. Design Randomised, double blind, placebo controlled study. Setting 65 primary care practices in Norway. Participants 483 untreated patients with complaints of heartburn ⩾3 days a week, with at most grade 1 reflux oesophagitis. Interventions Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. Main outcome measures Adequate control of heartburn, defined as ⩽1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. Results In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, P<0.0001; cisapride v placebo, non-significant). Results were comparable in patients with or without reflux oesophagitis. In patients treated with omeprazole only, symptom control was achieved significantly more often in patients positive for Helicobacter pylori. Antacid use was 2-3 times greater in patients taking cisapride or placebo than in those taking omeprazole. Relief of non-reflux symptoms did not significantly differ between the three groups. Significantly more patients taking cisapride reported adverse events than those taking omeprazole or placebo. Conclusions Omeprazole 20 mg once daily was highly effective in relieving heartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo. Key messagesIn primary care patients, heartburn is commonly treated empiricallyMost randomised clinical trials of treatment for heartburn have been conducted in specialist care, and documentation for empirical treatment is limitedOmeprazole was significantly more effective than cisapride or placebo in controlling heartburn and other symptoms of gastro-oesophageal reflux after 2, 4, and 8 weeks, whereas cisapride did not differ significantly from placeboOmeprazole should be considered as a first choice for empirical treatment of heartburn in primary care PMID:10463897

Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

PubMed

Blanco-Rojo, Ruth; Pérez-Granados, Ana M; Toxqui, Laura; González-Vizcayno, Carmen; Delgado, Marco A; Vaquero, M Pilar

2011-06-01

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P < 0·05) and became 80 % higher than in the P group after week 16 (P < 0·001), and transferrin decreased in the F group compared with the P group after week 4 (P < 0·001). RDW was higher at weeks 4 and 8 in the F group compared with the P group (P < 0·05). Transferrin saturation increased after week 8, and haematocrit, MCV and Hb increased after week 12, in the F group compared with the P group. Serum Fe did not change. sTfR and ZnPP decreased in the F group at week 16 (P < 0·05). Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial.

PubMed

Roll, Stephanie; Nocon, Marc; Willich, Stefan N

2011-01-01

Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18-65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

PubMed

Sweis, R; Kaufman, E; Anggiansah, A; Wong, T; Dettmar, P; Fried, M; Schwizer, W; Avvari, R K; Pal, A; Fox, M

2013-06-01

Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome. © 2013 Blackwell Publishing Ltd.

Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial.

PubMed

Avenell, Alison; Campbell, Marion K; Cook, Jonathan A; Hannaford, Philip C; Kilonzo, Mary M; McNeill, Geraldine; Milne, Anne C; Ramsay, Craig R; Seymour, D Gwyn; Stephen, Audrey I; Vale, Luke D

2005-08-06

To examine whether supplementation with multivitamins and multiminerals influences self reported days of infection, use of health services, and quality of life in people aged 65 or over. Randomised, placebo controlled trial, with blinding of participants, outcome assessors, and investigators. Communities associated with six general practices in Grampian, Scotland. 910 men and women aged 65 or over who did not take vitamins or minerals. Daily multivitamin and multimineral supplementation or placebo for one year. Primary outcomes were contacts with primary care for infections, self reported days of infection, and quality of life. Secondary outcomes included antibiotic prescriptions, hospital admissions, adverse events, and compliance. Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups. Routine multivitamin and multimineral supplementation of older people living at home does not affect self reported infection related morbidity. ISRCTN: 66376460.

Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial

PubMed Central

Ried-Larsen, Mathias; Hansen, Katrine B; Johansen, Mette Y; Pedersen, Maria; Zacho, Morten; Hansen, Louise S; Kofoed, Katja; Thomsen, Katja; Jensen, Mette S; Nielsen, Rasmus O; MacDonald, Chris; Langberg, Henning; Vaag, Allan A; Pedersen, Bente K; Karstoft, Kristian

2015-01-01

Introduction Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications. Methods and analysis The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment. Ethics and dissemination This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1–2014–114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences. Trial registration number NCT02417012. PMID:26656025

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial

PubMed Central

Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-01-01

Objective To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Design Parallel group randomised controlled trial. Setting Large public hospital in Brisbane during winter 2016. Participants 91 patients with systolic or diastolic heart failure who were over 50 years old. Intervention 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients’ data were available for the primary outcome which was collected blind to randomised group. Main outcome measures The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the ‘clo’. Monitors inside the participants’ homes recorded indoor temperatures throughout winter. Results The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference –1.2 days, 95% CI –4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. Conclusions There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. Trial registration number ACTRN12615001023549; Results. PMID:28993390

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial.

PubMed

Barnett, Adrian Gerard; Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-10-08

To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Parallel group randomised controlled trial. Large public hospital in Brisbane during winter 2016. 91 patients with systolic or diastolic heart failure who were over 50 years old. 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients' data were available for the primary outcome which was collected blind to randomised group. The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the 'clo'. Monitors inside the participants' homes recorded indoor temperatures throughout winter. The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference -1.2 days, 95% CI -4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. ACTRN12615001023549; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A randomised controlled trial of complete denture impression materials.

PubMed

Hyde, T P; Craddock, H L; Gray, J C; Pavitt, S H; Hulme, C; Godfrey, M; Fernandez, C; Navarro-Coy, N; Dillon, S; Wright, J; Brown, S; Dukanovic, G; Brunton, P A

2014-08-01

There is continuing demand for non-implant prosthodontic treatment and yet there is a paucity of high quality Randomised Controlled Trial (RCT) evidence for best practice. The aim of this research was to provide evidence for best practice in prosthodontic impressions by comparing two impression materials in a double-blind, randomised, crossover, controlled, clinical trial. Eighty-five patients were recruited, using published eligibility criteria, to the trial at Leeds Dental Institute, UK. Each patient received two sets of dentures; made using either alginate or silicone impressions. Randomisations determined the order of assessment and order of impressions. The primary outcome was patient blinded preference for unadjusted dentures. Secondary outcomes were patient preference for the adjusted dentures, rating of comfort, stability and chewing efficiency, experience of each impression, and an OHIP-EDENT questionnaire. Seventy-eight (91.8%) patients completed the primary assessment. 53(67.9%) patients preferred dentures made from silicone impressions while 14(17.9%) preferred alginate impressions. 4(5.1%) patients found both dentures equally satisfactory and 7 (9.0%) found both equally unsatisfactory. There was a 50% difference in preference rates (in favour of silicone) (95%CI 32.7-67.3%, p<0.0001). There is significant evidence that dentures made from silicone impressions were preferred by patients. Given the strength of the clinical findings within this paper, dentists should consider choosing silicone rather than alginate as their material of choice for secondary impressions for complete dentures. ISRCTN 01528038. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

PubMed Central

Calzetti, S; Findley, L J; Gresty, M A; Perucca, E; Richens, A

1981-01-01

Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle. PMID:7031187

Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial.

PubMed

Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

2014-06-19

We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922.

Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

ERIC Educational Resources Information Center

Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

2012-01-01

Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

PubMed

Fox, Kim; Ford, Ian; Steg, P Gabriel; Tendera, Michal; Ferrari, Roberto

2008-09-06

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

Statins in hypercholesterolaemia: A dose-specific meta-analysis of lipid changes in randomised, double blind trials

PubMed Central

Edwards, Jayne E; Moore, R Andrew

2003-01-01

Background Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol. Review methods PubMed, the Cochrane Library, references lists of reports, and reviews were searched (September 2001) for randomised, double blind trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was calculated using pooled data for particular statins, and for particular doses of a statin. Pre-planned sensitivity analyses were used to determine the effects of initial concentration of total cholesterol, study duration, the effects of major trials, and effects in placebo versus active controlled trials. Information was not collected on adverse events. Results Different statins at a range of doses reduced total cholesterol by 17–35% and LDL-cholesterol by 24–49% from baseline. Lower doses of statins generally produced less cholesterol lowering, though for most statins in trials of 12 weeks or longer there was at best only a weak relationship between dose and cholesterol reduction. Duration of treatment and baseline total cholesterol concentration did not alter the amount of the benefit attained. Conclusions Statins are effective medicines and confer benefit to patients in terms of primary and secondary prevention of coronary heart disease. Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and rosuvastatin 5 mg and 10 mg. PMID:14969594

Homeopathic arnica therapy in patients receiving knee surgery: results of three randomised double-blind trials.

PubMed

Brinkhaus, B; Wilkens, J M; Lüdtke, R; Hunger, J; Witt, C M; Willich, S N

2006-12-01

We investigated the effectiveness of homeopathic Arnica montana on postoperative swelling and pain after arthroscopy (ART), artificial knee joint implantation (AKJ), and cruciate ligament reconstruction (CLR). Three randomised, placebo-controlled, double-blind, sequential clinical trials. Single primary care unit specialised in arthroscopic knee surgery. Patients suffering from a knee disease that necessitated arthroscopic surgery. Prior to surgery, patients were given 1 x 5 globules of the homeopathic dilution 30x (a homeopathic dilution of 1:10(30)) of arnica or placebo. Following surgery, 3 x 5 globules were administered daily. The primary outcome parameter was difference in knee circumference, defined as the ratio of circumference on day 1 (ART) or day 2 (CLR and AKJ) after surgery to baseline circumference. A total of 227 patients were enrolled in the ART (33% female, mean age 43.2 years;), 35 in the AKJ (71% female, 67.0 years), and 57 in the CLR trial (26% female; 33.4 years). The percentage of change in knee circumference was similar between the treatment groups for ART (group difference Delta=-0.25%, 95% CI: -0.85 to 0.41, p=0.204) and AKJ (Delta=-1.68%, -4.24 to 0.77, p=0.184) and showed homeopathic arnica to have a beneficial effect compared to placebo in CLR (Delta=-1.80%, -3.30 to -0.30, p=0.019). In all three trials, patients receiving homeopathic arnica showed a trend towards less postoperative swelling compared to patients receiving placebo. However, a significant difference in favour of homeopathic arnica was only found in the CLR trial.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

PubMed

Lockyer, Stacey; Corona, Giulia; Yaqoob, Parveen; Spencer, Jeremy P E; Rowland, Ian

2015-07-14

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

PubMed

Schmidt, Simone; Gocheva, Vanya; Zumbrunn, Thomas; Rubino-Nacht, Daniela; Bonati, Ulrike; Fischer, Dirk; Hafner, Patricia

2017-03-09

Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

A Randomised, Double-Blind, Controlled Efficacy Trial of the LiESP/QA-21 Vaccine in Naïve Dogs Exposed to Two Leishmania infantum Transmission Seasons

PubMed Central

Oliva, Gaetano; Nieto, Javier; Foglia Manzillo, Valentina; Cappiello, Silvia; Fiorentino, Eleonora; Di Muccio, Trentina; Scalone, Aldo; Moreno, Javier; Chicharro, Carmen; Carrillo, Eugenia; Butaud, Therese; Guegand, Laurie; Martin, Virginie; Cuisinier, Anne-Marie; McGahie, David; Gueguen, Sylvie; Cañavate, Carmen; Gradoni, Luigi

2014-01-01

Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum, where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply, but is also responsible for several of the pathological processes seen in this disease. Effective canine vaccines are therefore a highly desirable prevention tool. In this randomised, double-blinded, controlled trial, the efficacy of the LiESP/QA-21 vaccine (CaniLeish, Virbac, France) was assessed by exposing 90 naïve dogs to natural L. infantum infection during 2 consecutive transmission seasons, in two highly endemic areas of the Mediterranean basin. Regular PCR, culture, serological and clinical examinations were performed, and the infection/disease status of the dogs was classified at each examination. The vaccine was well-tolerated, and provided a significant reduction in the risk of progressing to uncontrolled active infection (p = 0.025) or symptomatic disease (p = 0.046), with an efficacy of 68.4% and a protection rate of 92.7%. The probability of becoming PCR positive was similar between groups, but the probability of returning to a PCR negative condition was higher in the vaccinated group (p = 0.04). In conclusion, we confirmed the interest of using this vaccine as part of a comprehensive control program for canine leishmaniasis, and validated the use of a protocol based on regular in-depth assessments over time to assess the efficacy of a canine leishmaniasis vaccine. PMID:25299614

Dietary supplements and prostate cancer: a systematic review of double-blind, placebo-controlled randomised clinical trials.

PubMed

Posadzki, Paul; Lee, Myeong Soo; Onakpoya, Igho; Lee, Hye Won; Ko, Byong Seob; Ernst, Edzard

2013-06-01

Dietary supplements are popular among patients with prostate cancer (PC). The objective of this systematic review was to critically examine double-blind, placebo-controlled randomised clinical trials (RCTs) of non-herbal dietary supplements and vitamins (NHDS) for evidence that prostate specific antigen (PSA) levels were reduced in PC patients. Five databases were searched from their inception through December 2012 to identify studies that met our inclusion criteria. Methodological quality was independently assessed by two reviewers using the Cochrane tool. Eight RCTs met the eligibility criteria and were of high methodological quality. The following supplements were tested: isoflavones (genistein, daidzein, and glycitein), minerals (Se) or vitamins (vitamin D) or a combination of antioxidants, bioflavonoids, carotenoids, lycopenes, minerals (Se, Zn, Cu, and Mg), phytoestrogens, phytosterols, vitamins (B2, B6, B9, B12, C, and E), and other substances (CoQ10 and n-acetyl-l cysteine). Five RCTs reported no significant effects compared with placebo. Two RCTs reported that a combination of antioxidants, isoflavones, lycopenes, minerals, plant oestrogens and vitamins significantly decreased PSA levels compared with placebo. One RCT did not report differences in PSA levels between the groups. In conclusion, the hypothesis that dietary supplements are effective treatments for PC patients is not supported by sound clinical evidence. There are promising data for only two specific remedies, which contained a mixture of ingredients, but even for these supplements, additional high quality evidence is necessary before firm recommendations would be justified. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

PubMed

Kirschner, J; Schorling, D; Hauschke, D; Rensing-Zimmermann, C; Wein, U; Grieben, U; Schottmann, G; Schara, U; Konrad, K; Müller-Felber, W; Thiele, S; Wilichowski, E; Hobbiebrunken, E; Stettner, G M; Korinthenberg, R

2014-02-01

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III. Copyright © 2013 Elsevier B.V. All rights reserved.

Eight weeks of omeprazole 20 mg significantly reduces both laryngopharyngeal reflux and comorbid chronic rhinosinusitis signs and symptoms: Randomised, double-blind, placebo-controlled trial.

PubMed

Anzić, S A; Turkalj, M; Župan, A; Labor, M; Plavec, D; Baudoin, T

2018-04-01

Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS). Double-blind randomised placebo-controlled trial. Eight weeks of treatment with omeprazole 20 mg once daily (OD). Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS. Significant reduction in signs and symptoms (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS) as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo. Secondary objectives were significant reduction in signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo and the association of the severity of signs and symptoms of LPR with the ones of CRS. RSI and RFS decreased significantly more in the active treatment group after 8 weeks compared to placebo (P < .001 for both). CRS and endoscopy scoring decreased both significantly more in the active group after 8 weeks compared to placebo (P < .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P = .015) but not with RFS (R = 0.199, P = .127). The results of our trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS, although in most patients still present at the end of the trial. © 2017 John Wiley & Sons Ltd.

Flurbiprofen microgranules for relief of sore throat: a randomised, double-blind trial

PubMed Central

Russo, Marc; Bloch, Mark; de Looze, Fred; Morris, Christopher; Shephard, Adrian

2013-01-01

Background Many people with sore throat seek, and are often inappropriately prescribed, antibiotics. Aim The objective of this study was to determine the analgesic efficacy of flurbiprofen 8.75 mg microgranules versus placebo. These microgranules are a possible alternative treatment for patients with sore throat due to upper respiratory tract infection (URTI). Design and setting Randomised, double-blind, placebo-controlled, multiple-dose study conducted at eight primary care sites in Australia. Method Participants with sore throat of onset within the past 4 days received either flurbiprofen 8.75 mg microgranules or non-medicated placebo microgranules. Throat soreness, difficulty in swallowing, sore throat pain intensity, sore throat relief, oral temperature, and treatment benefits were all assessed at regular intervals. Result Of 373 patients from eight centres, 186 received flurbiprofen 8.75 mg microgranules and 187 received placebo microgranules (intent-to-treat population). Throat soreness was significantly reduced over the first 2 hours after the first dose. Reductions in difficulty in swallowing were observed at all time points from 5 to 360 minutes after the first dose, after taking flurbiprofen microgranules versus placebo. Sore throat relief was also evident at 1 minute and lasted for at least 6 hours. The multiple-dose efficacy results showed reduction of difficulty in swallowing at the end of days 1–3 and sore throat relief at the end of day 1. Conclusion Microgranules containing flurbiprofen 8.75 mg provided fast and effective relief from sore throat due to URTI and represent an alternative treatment option to antibiotic therapy. PMID:23561694

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

PubMed

Hirayama, S; Terasawa, K; Rabeler, R; Hirayama, T; Inoue, T; Tatsumi, Y; Purpura, M; Jäger, R

2014-04-01

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects. PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study

PubMed Central

Ossoukhova, Anastasia; Owen, Lauren; Ibarra, Alvin; Pipingas, Andrew; He, Kan; Roller, Marc; Stough, Con

2010-01-01

Rationale Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. Objectives The availability of a highly standardised extract of P. quinquefolius (Cereboost™) led us to evaluate its neurocognitive properties in humans for the first time. Methods This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost™ (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. Results There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and ‘calmness’ were significantly improved by 100 mg. There were no changes in blood glucose levels. Conclusions This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile. PMID:20676609

Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study.

PubMed

Scheidtmann, K; Fries, W; Müller, F; Koenig, E

2001-09-08

Functional disability is generally caused by hemiplegia after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia. We did a prospective, randomised, placebo-controlled, double-blind study in which we enrolled 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. We quantitatively assessed motor function every week with Rivermead motor assessment (RMA). Six patients were excluded from analyses because of non-neurological complications. Motor recovery was significantly improved after 3 weeks of drug intervention in those on levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment (p<0.004). The advantage of the levodopa group was maintained at study endpoint 3 weeks after levodopa was stopped. At the end of the study the total RMA score gain for the levodopa group was 8.2 points compared with 5.7 in the placebo group (p=0.020). A single dose of levodopa is well tolerated and, when given in combination with physiotherapy, enhances motor recovery in patients with hemiplegia. In view of its minimal side-effects, levodopa will be a possible add- on during stroke rehabilitation.

Implant design influences patient outcome after total knee arthroplasty: a prospective double-blind randomised controlled trial.

PubMed

Hamilton, D F; Burnett, R; Patton, J T; Howie, C R; Moran, M; Simpson, A H R W; Gaston, P

2015-01-01

Total knee arthroplasty (TKA) is an established and successful procedure. However, the design of prostheses continues to be modified in an attempt to optimise the functional outcome of the patient. The aim of this study was to determine if patient outcome after TKA was influenced by the design of the prosthesis used. A total of 212 patients (mean age 69; 43 to 92; 131 female (62%), 81 male (32%)) were enrolled in a single centre double-blind trial and randomised to receive either a Kinemax (group 1) or a Triathlon (group 2) TKA. Patients were assessed pre-operatively, at six weeks, six months, one year and three years after surgery. The outcome assessments used were the Oxford Knee Score; range of movement; pain numerical rating scales; lower limb power output; timed functional assessment battery and a satisfaction survey. Data were assessed incorporating change over all assessment time points, using repeated measures analysis of variance longitudinal mixed models. Implant group 2 showed a significantly greater range of movement (p = 0.009), greater lower limb power output (p = 0.026) and reduced report of 'worst daily pain' (p = 0.003) over the three years of follow-up. Differences in Oxford Knee Score (p = 0.09), report of 'average daily pain' (p = 0.57) and timed functional performance tasks (p = 0.23) did not reach statistical significance. Satisfaction with outcome was significantly better in group 2 (p = 0.001). These results suggest that patient outcome after TKA can be influenced by the prosthesis used. ©2015 The British Editorial Society of Bone & Joint Surgery.

Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy.

PubMed

Candy, David C A; Edwards, Diane; Geraint, Mike

2006-07-01

To assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol) as oral monotherapy in the treatment of faecal impaction in children, and to compare PEG + E with lactulose as maintenance therapy in a randomised trial. An initial open-label study of PEG + E in the inpatient treatment of faecal impaction (phase 1), followed by a randomised, double-blind comparison between PEG + E and lactulose for maintenance treatment of constipation over a 3-month period (phase 2) in children aged 2 to 11 years with a clinical diagnosis of faecal impaction. Disimpaction on PEG + E was achieved in 58 (92%) of 63 of children (89% of 2-4 year olds and 94% of 5-11 year olds) without additional interventions. A maximum dose of 4 sachets (for 2-4 year olds) or 6 sachets (for 5-11 year olds) was required; median time to disimpaction was 6 days (range, 3-7 days). Seven children (23%) reimpacted whilst taking lactulose, whereas no children reimpacted while taking PEG + E (P = 0.011). The total incidence rate of adverse events seen was higher in the lactulose group (83%) than in the PEG + E group (64%). PEG + E is safe and highly effective in the management of childhood constipation. It allows a single orally administered laxative to be used for disimpaction without recourse to invasive interventions. It is significantly more effective than lactulose as maintenance therapy, both in efficacy in treating constipation and efficacy in preventing the recurrence of faecal impaction.

Randomised double blind placebo controlled trial of the effect of botulinum toxin on walking in cerebral palsy

PubMed Central

Ubhi, T; Bhakta, B; Ives, H; Allgar, V; Roussounis, S

2000-01-01

BACKGROUND—Cerebral palsy is the commonest cause of severe physical disability in childhood. For many years treatment has centred on the use of physiotherapy and orthotics to overcome the problems of leg spasticity, which interferes with walking and can lead to limb deformity. Intramuscular botulinum toxin (BT-A) offers a targeted form of therapy to reduce spasticity in specific muscle groups.
AIMS—To determine whether intramuscular BT-A can improve walking in children with cerebral palsy.
DESIGN—Randomised, double blind, placebo controlled trial.
METHODS—Forty patients with spastic diplegia or hemiplegia were enrolled. Twenty two received botulinum toxin and 18 received placebo. The primary outcome measure was video gait analysis and secondary outcome measures were gross motor function measure (GMFM), physiological cost index (PCI), and passive ankle dorsiflexion.
RESULTS—Video gait analysis showed clinically and statistically significant improvement in initial foot contact following BT-A at six weeks and 12 weeks compared to placebo. Forty eight per cent of BT-A treated children showed clinical improvement in VGA compared to 17% of placebo treated children. The GMFM (walking dimension) showed a statistically significant improvement in favour of the botulinum toxin treated group. Changes in PCI and passive ankle dorsiflexion were not statistically significant.
CONCLUSION—The study gives further support to the use of intramuscular botulinum toxin type A as an adjunct to conventional physiotherapy and orthoses to reduce spasticity and improve functional mobility in children with spastic diplegic or hemiplegic cerebral palsy.

 PMID:11087280

Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.

PubMed

Matthys, Heinrich; Pliskevich, Dina A; Bondarchuk, Oleksandr M; Malek, Fathi A; Tribanek, Michael; Kieser, Meinhard

2013-05-01

Preventing and managing exacerbations is one major component in COPD treatment. We investigated whether EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides, could prolong time to acute exacerbation in patients with COPD stage II/III. In this randomised, double-blind, placebo-controlled clinical trial, patients were randomly allocated to oral 24-week add-on therapy with 3 × 30 drops/day EPs 7630 (n = 99) or placebo (n = 101) to a standardised baseline-treatment. Primary endpoint was time to first exacerbation of COPD. Secondary endpoints were number of exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and tolerability. Median time to exacerbation was significantly prolonged with EPs 7630 compared to placebo (57 versus 43 days, Kaplan-Maier-estimate; p = 0.005, one-sided centre-stratified log-rank test). The superiority of EPs 7630 was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group. The results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use. Trial Registration No.: ISRCTN01681733. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

PubMed

Ball, Susan; Vickery, Jane; Hobart, Jeremy; Wright, Dave; Green, Colin; Shearer, James; Nunn, Andrew; Cano, Mayam Gomez; MacManus, David; Miller, David; Mallik, Shahrukh; Zajicek, John

2015-02-01

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS. There were three objectives in the CUPID study: (1) to evaluate whether or not Δ(9)-THC could slow the course of progressive MS; (2) to assess the long-term safety of Δ(9)-THC; and (3) to explore newer ways of conducting clinical trials in progressive MS. The CUPID trial was a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were randomised in a 2 : 1 ratio to Δ(9)-THC or placebo. Randomisation was balanced according to Expanded Disability Status Scale (EDSS) score, study site and disease type. Analyses were by intention to treat, following a pre-specified statistical analysis plan. A cranial magnetic resonance imaging (MRI) substudy, Rasch measurement theory (RMT) analyses and an economic evaluation were undertaken. Twenty-seven UK sites. Adults aged 18-65 years with primary or secondary progressive MS, 1-year evidence of disease progression and baseline EDSS 4.0-6.5. Oral Δ(9)-THC (maximum 28 mg/day) or matching placebo. Three and 6 months, and then 6-monthly up to 36 or 42 months. Primary outcomes were time to EDSS progression, and change in Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) 20-point physical subscale (MSIS-29phys) score. Various secondary patient- and clinician-reported outcomes and MRI outcomes were assessed. RMT analyses examined performance of MS-specific rating scales as measurement instruments and tested for a symptomatic or disease-modifying treatment effect. Economic evaluation estimated mean incremental costs and quality-adjusted life-years (QALYs). Effectiveness - recruitment targets were achieved. Of the 498 randomised patients (332 to active and 166 to placebo), 493 (329 active and 164 placebo) were analysed. no significant treatment effect; hazard ratio EDSS score progression (active : placebo) 0.92 [95% confidence interval (CI) 0.68 to 1.23]; and estimated between-group difference in MSIS-29phys score (active-placebo) -0.9 points (95% CI -2.0 to 0.2 points). Secondary clinical and MRI outcomes: no significant treatment effects. Safety - at least one serious adverse event: 35% and 28% of active and placebo patients, respectively. RMT analyses - scale evaluation: MSIS-29 version 2, MS Walking Scale-12 version 2 and MS Spasticity Scale-88 were robust measurement instruments. There was no clear symptomatic or disease-modifying treatment effect. Economic evaluation - estimated mean incremental cost to NHS over usual care, over 3 years £27,443.20 per patient. No between-group difference in QALYs. The CUPID trial failed to demonstrate a significant treatment effect in primary or secondary outcomes. There were no major safety concerns, but unwanted side effects seemed to affect compliance. Participants were more disabled than in previous studies and deteriorated less than expected, possibly reducing our ability to detect treatment effects. RMT analyses supported performance of MS-specific rating scales as measures, enabled group- and individual person-level examination of treatment effects, but did not influence study inferences. The intervention had significant additional costs with no improvement in health outcomes; therefore, it was dominated by usual care and not cost-effective. Future work should focus on determining further factors to predict clinical deterioration, to inform the development of new studies, and modifying treatments in order to minimise side effects and improve study compliance. The absence of disease-modifying treatments in progressive MS warrants further studies of the cannabinoid pathway in potential neuroprotection. Current Controlled Trials ISRCTN62942668. The National Institute for Health Research Health Technology Assessment programme, the Medical Research Council Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society and Multiple Sclerosis Trust. The report will be published in full in Health Technology Assessment; Vol. 19, No. 12. See the NIHR Journals Library website for further project information.

Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

PubMed Central

Bennell, Kim; Coburn, Sally; Wee, Elin; Green, Sally; Harris, Anthony; Forbes, Andrew; Buchbinder, Rachelle

2007-01-01

Background Chronic rotator cuff pathology (CRCP) is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI), average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36), Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, strength and stiffness, and manual muscle testing for shoulder strength using a handheld dynamometer. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor monthly. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Participant measures of perceived change will be compared between groups by calculating the relative risks and their 95% confidence intervals at each time point using log binomial regression. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of a physiotherapy program for the management of CRCP. Trial registration NIH Clinical Trials Registry # NCT00415441 PMID:17761004

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Greenway, Frank L; Fujioka, Ken; Plodkowski, Raymond A; Mudaliar, Sunder; Guttadauria, Maria; Erickson, Janelle; Kim, Dennis D; Dunayevich, Eduardo

2010-08-21

Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants. Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779. 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%]; naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo. A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity. Orexigen Therapeutics. Copyright 2010 Elsevier Ltd. All rights reserved.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand.

PubMed

Wilder-Smith, Annelies; Byass, Peter; Olanratmanee, Phanthip; Maskhao, Pongsri; Sringernyuang, Luechai; Logan, James G; Lindsay, Steve W; Banks, Sarah; Gubler, Duane; Louis, Valérie R; Tozan, Yesim; Kittayapong, Pattamaporn

2012-11-15

There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. clinicaltrial.gov. NCT01563640.

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial

PubMed Central

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-01-01

Introduction Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Methods and analysis Inclusion criteria are patients 7–15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). Ethics and dissemination This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. Trial registration number ClinicalTrials.gov NCT02084433. PMID:26163031

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial.

PubMed

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-07-10

Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Inclusion criteria are patients 7-15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. ClinicalTrials.gov NCT02084433. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Recovery characteristics of patients receiving either sugammadex or neostigmine and glycopyrrolate for reversal of neuromuscular block: a randomised controlled trial.

PubMed

Paech, M J; Kaye, R; Baber, C; Nathan, E A

2018-03-01

Sugammadex more rapidly and reliably reverses rocuronium-induced neuromuscular block compared with neostigmine, but it is not known if subsequent patient outcomes, including nausea, vomiting and other aspects of recovery are modified. In this study, we compared the recovery characteristics of sugammadex and neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a single-centre, randomised, blinded, parallel-group clinical trial in women undergoing elective day-surgical laparoscopic gynaecological surgery, with a standardised general anaesthesia regimen that included rocuronium. Neuromuscular block was reversed with either sugammadex 2 mg.kg -1 or neostigmine 40 μg.kg -1 and glycopyrrolate 400 μg. The primary outcome was the incidence of nausea and vomiting during the first six postoperative hours. Secondary outcomes included other measures of postoperative recovery such as patient symptoms and recovery scores. Three-hundred and four women were analysed by intention-to-treat (sugammadex n = 151, neostigmine n = 153), which included four major protocol violations. There was no significant difference between sugammadex and neostigmine groups in the incidence of early nausea and vomiting (49.0% vs. 51.0%, respectively; OR 0.92, 95%CI 0.59-1.45; p = 0.731). Double vision (11.5% vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median (IQR [range]) 0 (0-3 [0-10]) vs. 2 (0-4.[0-10]); p = 0.021). Twenty-four-hour recovery scores were not significantly different between groups. Reversal with sugammadex in this patient population did not reduce postoperative nausea or vomiting compared with neostigmine/glycopyrrolate. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Weight loss effects from vegetable intake: a 12-month randomised controlled trial

PubMed Central

Tapsell, L C; Batterham, M J; Thorne, R L; O'Shea, J E; Grafenauer, S J; Probst, Y C

2014-01-01

Background/Objectives: Direct evidence for the effects of vegetable intake on weight loss is qualified. The study aimed to assess the effect of higher vegetable consumption on weight loss. Subjects/Methods: A single blind parallel controlled trial was conducted with 120 overweight adults (mean body mass index=29.98 kg/m2) randomised to two energy deficit healthy diet advice groups differing only by doubling the serving (portion) sizes of vegetables in the comparator group. Data were analysed as intention-to-treat using a linear mixed model. Spearmans rho bivariate was used to explore relationships between percentage energy from vegetables and weight loss. Results: After 12 months, the study sample lost 6.5±5.2 kg (P<0.001 time) with no difference between groups (P>0.05 interaction). Both groups increased vegetable intake and lost weight in the first 3 months, and the change in weight was significantly correlated with higher proportions of energy consumed as vegetables (rho=–0.217, P=0.024). Fasting glucose, insulin and triglyceride levels decreased (P<0.001 time) and high-density lipoprotein cholesterol levels increased (P<0.001 time), with no difference between groups. Weight loss was sustained for 12 months by both groups, but the comparator group reported greater hunger satisfaction (P=0.005). Conclusions: Advice to consume a healthy low-energy diet leads to sustained weight loss, with reductions in cardiovascular disease risk factors regardless of an emphasis on more vegetables. In the short term, consuming a higher proportion of the dietary energy as vegetables may support a greater weight loss and the dietary pattern appears sustainable. PMID:24667750

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

PubMed

Lees, J; Michalopoulou, P G; Lewis, S W; Preston, S; Bamford, C; Collier, T; Kalpakidou, A; Wykes, T; Emsley, R; Pandina, G; Kapur, S; Drake, R J

2017-10-01

Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

Study protocol for a randomised controlled trial of ultrasound-guided pulsed radiofrequency of the genicular nerves in the treatment of patients with osteoarthritis knee pain

PubMed Central

Valentí, Pedro; Hernández, Beatriz; Mir, Bartolome; Aguilar, Jose Luis

2017-01-01

Introduction The goals for the management of patients with osteoarthritis (OA) of the knee are to control pain and to minimise disability. Because the number of patients will increase as the population ages, alternative approaches to alleviate their joint pain other than conventional treatments are necessary. The purpose of this article is to present a refined protocol to determine if there is long-term improvement in pain and function after ultrasound-guided pulsed radiofrequency treatment of the genicular nerves (GNs) in patients with chronic painful knee OA. Methods and analysis This study is a randomised, double-blind, placebo-controlled, parallel design trial. One hundred and forty-two outpatients with OA of the knee will be recruited from Mallorca, Spain. Participants will be randomly allocated into two groups: ultrasound-guided sham GN pulsed radiofrequency without active treatment and ultrasound-guided real GN pulsed radiofrequency. The primary outcome measures will be the observed changes from baseline pain intensity based on visual analogue scale (VAS). The possible changes in the secondary efficacy variables from the baseline as assessed by the Goldberg Anxiety and Depression Scale, pain medication use, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC subscales) and VAS pain intensity are also to be included in the study. These variables will be assessed at baseline, 1 month, 3 months, 6 months and 1 year after treatment. Ethics and dissemination The protocol was approved by the Research Ethic Committee of the Balearic Islands (IB 3223/16 PI). The results will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration Trial registration numberNCT02915120; Pre-results PMID:29102985

Efficacy of flurbiprofen 8.75 mg spray in patients with sore throat due to an upper respiratory tract infection: A randomised controlled trial.

PubMed

de Looze, Ferdinandus; Russo, Marc; Bloch, Mark; Montgomery, Barney; Shephard, Adrian; Smith, Gary; Aspley, Sue

2016-06-01

Viral infections cause most cases of pharyngitis (sore throat); consequently, antibiotics are generally not warranted. However, a treatment targeting pain and inflammation, e.g. a topical non-steroidal anti-inflammatory spray, may be helpful for patients. To evaluate the efficacy and safety of flurbiprofen 8.75 mg spray. This randomised, double-blind, parallel group study was conducted at six community-based clinical research centres in Australia and two in New Zealand. Adults with sore throat due to upper respiratory tract infection (onset ≤ four days) took one dose of flurbiprofen (n = 249) or placebo spray (n = 256); after six hours, they could re-dose every three-six hours as required, for three days (max. five doses/day). The primary endpoint was the area under the change from baseline curve in throat soreness from zero-two hours (AUC0-2h). The change from baseline in other sore throat symptoms also assessed efficacy. The mean AUC0-2h for throat soreness was significantly greater with flurbiprofen spray (-1.82; 95% CI: -1.98 to 1.65) compared with placebo (-1.13; 95% CI: -1.27 to 0.99) (P < 0.0001). Significantly greater reductions from baseline were observed with flurbiprofen spray compared with placebo from the first time-points assessed (five minutes for throat soreness/difficulty swallowing, 20 minutes for sore throat pain intensity and 30 minutes for swollen throat) for up to six hours (P < 0.05 for all). There was no significant difference in adverse events between treatment groups during the three-day study. Flurbiprofen spray provides rapid and long-lasting relief from sore throat symptoms, and is well-tolerated over three days.

Physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity: a nested mixed-methods randomised-controlled study.

PubMed

Boden, Ianthe; El-Ansary, Doa; Zalucki, Nadia; Robertson, Iain K; Browning, Laura; Skinner, Elizabeth H; Denehy, Linda

2018-06-01

To (1) assess memorability and treatment fidelity of pre-operative physiotherapy education prior to elective upper abdominal surgery and, (2) to explore patient opinions on pre-operative education. Mixed-methods analysis of a convenience sample within a larger parallel-group, double-blinded, randomised controlled trial with concealed allocation and intention-to-treat analysis. Tertiary Australian hospital. Twenty-nine patients having upper abdominal surgery attending pre-admission clinic within six-weeks of surgery. The control group received an information booklet about preventing pulmonary complications with early ambulation and breathing exercises. The experimental group received an additional face-to-face 30-minute physiotherapy education and training session on pulmonary complications, early ambulation, and breathing exercises. Primary outcome was proportion of participants who remembered the taught breathing exercises following surgery. Secondary outcomes were recall of information sub-items and attainment of early ambulation goals. These were measured using standardised scoring of a semi-scripted digitally-recorded interview on the 5th postoperative day, and the attainment of early ambulation goals over the first two postoperative days. Experimental group participants were six-times more likely to remember the breathing exercises (95%CI 1.7 to 22) and 11-times more likely (95%CI 1.6 to 70) to report physiotherapy as the most memorable part of pre-admission clinic. Participants reported physiotherapy education content to be detailed, interesting, and of high value. Some participants reported not reading the booklet and professed a preference for face-to-face information delivery. Face-to-face pre-operative physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity. ACTRN-12613000664741. Copyright © 2017 Chartered Society of Physiotherapy. All rights reserved.

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial

PubMed Central

Boyle, Robert J; Pedroletti, Christophe; Wickman, Magnus; Bjermer, Leif; Valovirta, Erkka; Dahl, Ronald; Von Berg, Andrea; Zetterström, Olof

2011-01-01

Objective To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. Design Randomised, double-blind, placebo-controlled, parallel-group trial. Setting Nineteen European asthma clinics. Participants 312 patients aged 7–70 with inadequately controlled persistent atopic asthma. Main outcome measure Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment. Results TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of −7.1 ppb (−13.6 to −0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. Conclusion Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma. Trial registration number Clinical Trials NCT00986323. PMID:22131290

EFFECT OF A DENTIFRICE CONTAINING ALOE VERA ON PLAQUE AND GINGIVITIS CONTROL. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

PubMed Central

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) – dentifrice containing Aloe vera - or the control group (n=15) – fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice. PMID:19089263

Effect of a dentifrice containing Aloe vera on plaque and gingivitis control. A double-blind clinical study in humans.

PubMed

de Oliveira, Sílvia Morgana Araújo; Torres, Ticiana Carneiro; Pereira, Sérgio Luís da Silva; Mota, Olívia Morais de Lima; Carlos, Márlio Ximenes

2008-01-01

The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized, parallel and double-blind clinical trial. Subjects were randomly allocated to the test group (n=15) - dentifrice containing Aloe vera - or the control group (n=15) - fluoridated dentifrice. Plaque index (PI) and gingival bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush their teeth with the control or test dentifrice, three times a day, during a 30-day period. There was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01). The dentifrice containing Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice.

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo].

PubMed

Halaska, M; Raus, K; Bĕles, P; Martan, A; Paithner, K G

1998-10-01

The aim of study presented here was to gather the data about the tolerability and efficacy of Vitex agnus castus (VACS) extract. The study was designed as double-blind, placebo controlled in two parallel groups (each 50 patients). Treatment phase lasted 3 consequent menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or placebo. Mastalgia during at least 5 days of the cycle before the treatment was the strict inclusion condition. For assessment of the efficacy visual analogue scale was used. Altogether 97 patients were included into the statistical analysis (VACS: n = 48, placebo: n = 49). Intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory. We found VACS to be useful in the treatment of cyclical breast pain in women.

Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II.

PubMed

Zapfe jun, G

2001-07-01

In a randomised, placebo-controlled, double-blind clinical study the clinical efficacy and safety of Crataegus extract WS 1442, standardised to 18.75% oligomeric procyanidines, were investigated in 40 female and male outpatients suffering from congestive heart failure NYHA class II. Following a wash-out period of up to seven days, the patients were randomised to be treated for 12 weeks with either WS 1442 (3 x 1 capsule) or placebo. The primary outcome variable was exercise tolerance determined with bicycle exercise testing; as a secondary outcome variable the difference of the double product was calculated. On average, the exercise tolerance increased by 66.3 W x min (10.8%) in the WS 1442 group while in the placebo group a reduction of 105.3 W x min (16.9%) was measured. This difference between the groups was borderline statistically significant (p = 0.06). During the three month therapy the difference of the double product (heart rate x systolic blood pressure x 10(-2)) decreased by 14.4 mmHg s(-1) (26.8%) in the WS 1442 group and by 1.3 mmHg s(-1) (2.7%) in the placebo group, respectively. Recording of laboratory parameters and adverse events showed that WS 1442 was safe and well tolerated. The data show that Crataegus extract WS 1442 is clinically effective in patients with congestive heart failure corresponding to NYHA class II.

Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

2011-01-01

Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Regular consumption of HolisFiit, a polyphenol-rich extract-based food supplement, improves mind and body well-being of overweight and slightly obese volunteers: a randomized, double-blind, parallel trial.

PubMed

Romain, Cindy; Alcaraz, Pedro Emilio; Chung, Linda Haiwon; Cases, Julien

2017-11-01

Modern lifestyles face growing demands for natural solutions to help improve general well-being. Accordingly, mind-body activities such as yoga have considerably grown. However, beneficial effects require regular workout. Besides, literature suggests that polyphenols may demonstrate positive effects on both mental and physical health. Overweight and obese volunteers, for which well-being might be perceived degraded, were included in a 16-week double-blind, randomized and parallel trial with a daily supplementation of HolisFiit ® , a polyphenol-rich food supplement. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) technology; well-being was evaluated with both, Athens Insomnia Scale (AIS) and components from Short Form-36 questionnaire (SF-36). Body composition significantly rebalanced by 7.7% (p = .019) of the lean-to-fat mass ratio. Also, sleep quality significantly improved by 43% (p = .00015) as well as both physical and mental components from SF-36, respectively by 10% (p = .004) and 7% (p = .021). These data altogether, suggest that regular consumption of HolisFiit ® , might significantly improve mind and body well-being.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial.

PubMed

Isiordia-Espinoza, M-A; Pozos-Guillen, A; Martinez-Rider, R; Perez-Urizar, J

2016-09-01

Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. According to the VAS and UAC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.

[Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review].

PubMed

Prado, J C; Ruilope, L M; Segura, J

Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

PubMed

Pandit, S; Biswas, S; Jana, U; De, R K; Mukhopadhyay, S C; Biswas, T K

2016-06-01

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. © 2015 The Authors. Andrologia Published by Blackwell Verlag GmbH.

Efficacy of wheat-based biscuits fortified with microcapsules containing ferrous sulfate and potassium iodate or a new hydrogen-reduced elemental iron: a randomised, double-blind, controlled trial in Kuwaiti women.

PubMed

Biebinger, Ralf; Zimmermann, Michael B; Al-Hooti, Suad N; Al-Hamed, Nawal; Al-Salem, Ebtehal; Zafar, Tasleem; Kabir, Yearul; Al-Obaid, I'nam; Petry, Nicolai; Hurrell, Richard F

2009-11-01

Adverse sensory changes prevent the addition of highly bioavailable ferrous sulfate (FeSO4) to most wheat flours. Poorly absorbable reduced Fe powders are commonly used. Encapsulation of FeSO4 can overcome these sensory changes, but the particle size of commercial compounds is too large to be used by flour mills. The first objective of the study was to measure the efficacy in wheat flour of two newly developed Fe compounds, an H-reduced Fe powder (NutraFine RS; North America Höganäs High Alloys LLC, Johnstown, PA, USA) and small particle-sized (40 microm) encapsulated FeSO4. As a second objective, the microcapsules were evaluated as a vehicle for iodine fortification. A randomised, double-blind controlled intervention trial was conducted in Kuwaiti women (n 279; aged 18-35 years) with low body Fe stores (serum ferritin (SF) < 25 microg/l) randomly assigned to one of three groups (20 mg Fe as NutraFine RS, 10 mg Fe as encapsulated FeSO4 and 150 microg iodine, or no fortification Fe) who consumed wheat-based biscuits 5 d per week. At baseline and 22 weeks, Hb, SF, transferrin receptor, urinary iodine and body Fe stores were measured. Relative to control, mean SF in the encapsulated FeSO4 group increased by 88 % (P < 0.001) and body Fe stores increased from - 0.96 to 2.24 mg/kg body weight (P < 0.001), while NutraFine RS did not significantly increase SF or body Fe stores. The median urinary iodine concentration increased from 140 to 213 microg/l (P < 0.01). NutraFine RS added at double the amount of Fe as FeSO4 was not efficacious in improving Fe status. The newly developed microcapsules were highly efficacious in improving both Fe stores and iodine status.

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

PubMed Central

Schlesinger, Naomi; Mysler, Eduardo; Lin, Hsiao-Yi; De Meulemeester, Marc; Rovensky, Jozef; Arulmani, Udayasankar; Balfour, Alison; Krammer, Gerhard; Sallstig, Peter; So, Alexander

2011-01-01

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. PMID:21540198

Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT).

PubMed

Carvajal, Richard D; Schwartz, Gary K; Mann, Helen; Smith, Ian; Nathan, Paul D

2015-06-10

Uveal melanoma is characterised by mutations in GNAQ and GNA11, resulting in Ras/Raf/MEK/ERK pathway activation. Treatment with selumetinib (AZD6244, ARRY-142886), a MEK1/2 inhibitor, results in antitumour effects in uveal melanoma pre-clinical models. A randomised phase II trial demonstrated improved progression-free survival (PFS) and response rate (RR) with selumetinib monotherapy versus chemotherapy with temozolomide or dacarbazine in patients with metastatic uveal melanoma. Pre-clinically, selumetinib in combination with alkylating agents enhanced antitumour activity compared with chemotherapy alone. We hypothesise that selumetinib in combination with dacarbazine will result in improved clinical outcomes in patients with metastatic uveal melanoma versus dacarbazine alone. SUMIT is a randomised, international, double-blind, placebo-controlled, phase III study assessing the efficacy and safety of selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma who have not received prior systemic therapy. Primary endpoint is PFS. Secondary endpoints include objective RR, duration of response, change in tumour size at Week 6, overall survival, safety and tolerability. Exploratory endpoints include efficacy in tumours with GNAQ or GNA11 mutations. Eligible patients must have: ≥1 lesion that can be accurately measured at baseline, and is suitable for accurate repeated measurements; ECOG performance status 0-1; life expectancy>12 weeks. Mutation status for GNAQ/GNA11 will be assessed retrospectively. An estimated 128 patients from approximately 50 sites globally will be randomised (3:1) to selumetinib 75 mg twice daily or placebo in combination with dacarbazine 1000 mg/m(2) on Day 1 of every 21-day cycle until objective disease progression, intolerable toxicity or occurrence of another discontinuation criterion. Randomisation will be stratified by the presence/absence of liver metastases. Tumours will be evaluated by RECIST v1.1 every 6 weeks. All patients have the option of receiving selumetinib with or without dacarbazine at disease progression. Study enrolment began in April 2014 and is expected to complete in early 2015. Treatment of patients with metastatic uveal melanoma represents an area of high unmet medical need. This study evaluating selumetinib in combination with dacarbazine was designed with input from the US FDA, and is the first potential registration trial to be conducted in patients with metastatic uveal melanoma. Clinicaltrials.gov (Date of registration, October 10, 2013) REGISTRATION NUMBER: NCT01974752 Trial abbreviation: SUMIT.

The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age.

PubMed

Kappelgaard, Anne-Marie; Kiyomi, Fumiaki; Horikawa, Reiko; Yokoya, Susumu; Tanaka, Toshiaki

2014-01-01

An examination of the effects of up to 260 weeks of growth hormone (GH) therapy on metabolic parameters in Japanese children born small for gestational age (SGA). Data were analysed from a 156-week extension of a 104-week multicentre, randomised, double-blind, parallel-group trial. Sixty-five children born SGA (age 3-<8 years) received 33 μg/kg/day (n = 31, 64.5% male) or 67 μg/kg/day (n = 34, 58.8% male) GH for 260 weeks. Changes in metabolic parameters - glucose, insulin, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol - were recorded. Alterations in weight, body mass index standard deviation score (BMI SDS) and vital signs were also evaluated. Over 260 weeks of GH treatment, a positive correlation between Δheight SDS and Δinsulin-like growth factor-I SDS was observed. Insulin and glucose levels were generally unaffected. Favourable changes in lipid profiles were recorded, which were maintained for the study duration. No adverse alterations in weight, BMI SDS or vital signs were noted. Long-term, continuous GH treatment in children born SGA appears to be efficacious, associated with potential benefits for several metabolic parameters and associated with no long-term safety concerns.

Novel, single-dose, topical treatment of tinea pedis using terbinafine: results of a dose-finding clinical trial.

PubMed

de Chauvin, Martine Feuilhade; Viguié-Vallanet, Claude; Kienzler, Jean-Luc; Larnier, Catherine

2008-01-01

Tinea pedis is the most common dermatophytosis requiring topical antifungals for at least 1-4 weeks. To determine the effectiveness of a novel topical single dose formulation of terbinafine (film forming solution-FFS) in the treatment of tinea pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria suffering from tinea pedis with possible extension to soles confirmed by mycological examination (direct and culture) were evaluated for efficacy of terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled parallel group dose finding study. Evaluations were carried out at baseline, 1 and 6 weeks after a single application of FFS. Effective treatment rate based on negative mycology (direct and culture) and minimal signs and symptoms (two or less with only mild recorded) was measured at week 6. Effective treatment rates at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with 18% with placebo. All three active preparations were shown to be significantly superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non-inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose for the treatment of tinea pedis. This novel product represents a significant advance with the enhanced compliance and convenience that it offers.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

PubMed

Thwaites, Guy E; Scarborough, Matthew; Szubert, Alexander; Nsutebu, Emmanuel; Tilley, Robert; Greig, Julia; Wyllie, Sarah A; Wilson, Peter; Auckland, Cressida; Cairns, Janet; Ward, Denise; Lal, Pankaj; Guleri, Achyut; Jenkins, Neil; Sutton, Julian; Wiselka, Martin; Armando, Gonzalez-Ruiz; Graham, Clive; Chadwick, Paul R; Barlow, Gavin; Gordon, N Claire; Young, Bernadette; Meisner, Sarah; McWhinney, Paul; Price, David A; Harvey, David; Nayar, Deepa; Jeyaratnam, Dakshika; Planche, Tim; Minton, Jane; Hudson, Fleur; Hopkins, Susan; Williams, John; Török, M Estee; Llewelyn, Martin J; Edgeworth, Jonathan D; Walker, A Sarah

2018-02-17

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. UK National Institute for Health Research Health Technology Assessment. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

PubMed

2017-10-01

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

PubMed

Dignass, Axel; Stoynov, Simeon; Dorofeyev, Andrey E; Grigorieva, Galina A; Tomsová, Eva; Altorjay, István; Tuculanu, Daniel; Bunganič, Ivan; Pokrotnieks, Juris; Kupčinskas, Limas; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2014-09-01

Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients

PubMed Central

Molloy, Alexander J; Clarke, France; Herridge, Margaret S; Koo, Karen K Y; Rudkowski, Jill; Seely, Andrew J E; Pellizzari, Joseph R; Tarride, Jean-Eric; Mourtzakis, Marina; Karachi, Timothy; Cook, Deborah J

2016-01-01

Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. Trial registration number NCT02377830; Pre-results. PMID:27059469

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

PubMed

López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

2018-06-01

Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. Laboratorios del Dr. Esteve, S.A.U.

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.

PubMed

Slykerman, R F; Hood, F; Wickens, K; Thompson, J M D; Barthow, C; Murphy, R; Kang, J; Rowden, J; Stone, P; Crane, J; Stanley, T; Abels, P; Purdie, G; Maude, R; Mitchell, E A

2017-10-01

Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. Australia NZ Clinical Trials Registry: ACTRN12612000196842. 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002). Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum. Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial.

PubMed

Rice, Andrew S C; Dworkin, Robert H; McCarthy, Tom D; Anand, Praveen; Bountra, Chas; McCloud, Philip I; Hill, Julie; Cutter, Gary; Kitson, Geoff; Desem, Nuket; Raff, Milton

2014-05-10

Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 receptor (AT2R) is a new target for neuropathic pain. EMA401, a highly selective AT2R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22-89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22-28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores -2.29 [SD 1.75] vs -1.60 [1.66]; difference of adjusted least square means -0.69 [SE 0.25]; 95% CI -1.19 to -0.20; p=0.0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients. Spinifex Pharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

PubMed

Raal, Frederick J; Santos, Raul D; Blom, Dirk J; Marais, A David; Charng, Min-Ji; Cromwell, William C; Lachmann, Robin H; Gaudet, Daniel; Tan, Ju L; Chasan-Taber, Scott; Tribble, Diane L; Flaim, Joann D; Crooke, Stanley T

2010-03-20

Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins. ISIS Pharmaceuticals and Genzyme Corporation. Copyright 2010 Elsevier Ltd. All rights reserved.

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

PubMed

Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

2015-12-10

Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

PubMed

le Roux, Carel W; Astrup, Arne; Fujioka, Ken; Greenway, Frank; Lau, David C W; Van Gaal, Luc; Ortiz, Rafael Violante; Wilding, John P H; Skjøth, Trine V; Manning, Linda Shapiro; Pi-Sunyer, Xavier

2017-04-08

Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m 2 , or at least 27 kg/m 2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13-0·34). Liraglutide induced greater weight loss than placebo at week 160 (-6·1 [SD 7·3] vs -1·9% [6·3]; estimated treatment difference -4·3%, 95% CI -4·9 to -3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Novo Nordisk, Denmark. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparison of two treatments for childhood apraxia of speech: methods and treatment protocol for a parallel group randomised control trial

PubMed Central

2012-01-01

Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds (articulation) and melody (prosody) of speech. These difficulties may persist through life and are detrimental to academic, social, and vocational development. A number of published single subject and case series studies of speech treatments are available. There are currently no randomised control trials or other well designed group trials available to guide clinical practice. Methods/Design A parallel group, fixed size randomised control trial will be conducted in Sydney, Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech: 1) Rapid Syllable Transition Treatment and the 2) Nuffield Dyspraxia Programme – Third edition. Eligible children will be English speaking, aged 4–12 years with a diagnosis of suspected CAS, normal or adjusted hearing and vision, and no comprehension difficulties or other developmental diagnoses. At least 20 children will be randomised to receive one of the two treatments in parallel. Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals. Treatment will be administered in 1-hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week, 1 month and 4 months post-treatment. All post assessments will be completed by blinded assessors. Our hypotheses are: 1) treatment effects at 1 week post will be similar for both treatments, 2) maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3) generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment. This protocol was approved by the Human Research Ethics Committee, University of Sydney (#12924). Discussion This will be the first randomised control trial to test treatment for CAS. It will be valuable for clinical decision-making and providing evidence-based services for children with CAS. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12612000744853 PMID:22863021

Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomised, multicentre study.

PubMed

Giles, Thomas D; Weber, Michael A; Basile, Jan; Gradman, Alan H; Bharucha, David B; Chen, Wei; Pattathil, Manoj

2014-05-31

The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating β blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension. We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites. Participants (age ≥18 years) with hypertension but with blood pressure less than 180/110 mm Hg were randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo. Doses were doubled in weeks 5-8; results are reported according to the final dose. Participants and research staff were masked to treatment allocation. The primary and key secondary endpoints were changes from baseline to week 8 in diastolic and systolic blood pressure, respectively. The primary statistical comparison was between the highest fixed-dose combination dose and the highest monotherapy doses; lower doses were then compared if this comparison was positive (Hochberg method for multiple testing). Efficacy analyses were by intention to treat. Safety assessments included monitoring of adverse events. Continuous efficacy parameters were analysed using an ANCOVA model; binary outcomes were analysed using a logistic regression model. This study is registered with ClinicalTrials.gov, NCT01508026. Between Jan 6, 2012, and March 15, 2013, 4161 patients were randomly assigned (277 to placebo and 554-555 to each active comparator group), 4118 of whom were included in the primary analysis. At week 8, the fixed-dose combination 20 and 320 mg/day group had significantly greater reductions in diastolic blood pressure from baseline than both nebivolol 40 mg/day (least-squares mean difference -1·2 mm Hg, 95% CI -2·3 to -0·1; p=0·030) and valsartan 320 mg/day (-4·4 mm Hg, -5·4 to -3·3; p<0·0001); all other comparisons were also significant, favouring the fixed-dose combinations (all p<0·0001). All systolic blood pressure comparisons were also significant (all p<0·01). At least one treatment-emergent adverse event was experienced by 30-36% of participants in each group. Nebivolol and valsartan fixed-dose combination is an effective and well-tolerated treatment option for patients with hypertension. Forest Research Institute. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial.

PubMed

Rajasekaran, S; Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Maheswaran, Anupama; Shetty, Janardhan Yerram

2016-06-01

To evaluate the effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy using clinical parameters and DTI analysis. Early cervical myelopathy cases with MJOA scores ≥13, were recruited for the double-blinded, placebo-controlled randomised control trial. Thirty cases with fifteen cases each in the test and placebo group were studied. Analysis was done using diffusion tensor imaging (DTI) and clinical evaluation, pre- and post-institution of sodium channel blocker Riluzole for a period of 1 month (50 mg twice daily). Placebo group was treated with Vitamin B complex tablets. Diffusion co-efficient fractional anisotrophy (FA), apparent diffusion co-efficient (ADC), volume ratio (VR), relative anisotrophy (RA) and Eigen vectors were calculated. Outcomes analysis was based on clinical scores of MJOA, Nurick grading, SF-12, NDI, and statistical analysis of DTI datametrics. The mean MJOA score was 15.6 (13-17) with no significant change in the test and control groups. The mean ADC, FA values were 1533.36 (1238-1779) and 494.36 (364-628) and changed to 1531.57 (1312-2091) and 484.86 (294-597), respectively, in the Riluzole group. However, the changes in the values of ADC, FA, and other co-efficients including VR, RA and eigenvectors in the two groups were not statistically significant. The functional scores in the SF-12 and NDI questionnaires did not change significantly. Our study did not show a significant change in the clinical outcome and DTI Indices with the use of Riluzole as a standalone pharmacotherapeutic agent for early cervical myelopathy. More studies may be needed to confirm the usefulness of Riluzole as a treatment option for cervical myelopathy.

Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial.

PubMed

Weeks, Andrew D; Alia, Godfrey; Vernon, Gillian; Namayanja, Annette; Gosakan, Radhika; Majeed, Tayyaba; Hart, Anna; Jafri, Hussain; Nardin, Juan; Carroli, Guillermo; Fairlie, Fiona; Raashid, Yasmin; Mirembe, Florence; Alfirevic, Zarko

2010-01-09

Retained placenta is associated with post-partum haemorrhage. Meta-analysis has suggested that umbilical injection of oxytocin could increase placental expulsion without the need for a surgeon or anaesthetic. We assessed the effect of high-dose umbilical vein oxytocin as a treatment for retained placenta. In this double-blind, placebo-controlled trial, haemodynamically stable women with a retained placenta for more than 30 min were recruited from 13 sites in the UK, Uganda, and Pakistan. 577 women were randomly assigned by a computer-generated randomisation list stratified by centre to 30 mL saline containing either 50 IU oxytocin (n=292) or 5 mL water (n=285), which was injected into the placenta through an umbilical vein catheter. All trial participants, study workers, and data handlers were masked to individual allocations. The primary outcome was the need for manual removal of the placenta. Analysis was by intention to treat. This study is registered, number ISRCTN 13204258. The primary outcome was recorded for all participants. We detected no difference between the groups in the need for manual removal of placenta (oxytocin 179/292 [61.3%] vs placebo 177/285 [62.1%]; relative risk 0.98, 95% CI 0.87-1.12; p=0.84). The need for manual removal was higher in the UK (overall 250/361 [69%]) than in Uganda (90/190 [47%]) or Pakistan (16/26 [62%]). Adverse events did not differ between the two groups. Umbilical oxytocin has no clinically significant effect on the need for manual removal for women with retained placenta. WHO, WellBeing of Women, Pakistan Higher Education Commission. Copyright 2010 Elsevier Ltd. All rights reserved.

Total hip arthroplasty and perioperative oral carbohydrate treatment: a randomised, double-blind, controlled trial.

PubMed

Harsten, Andreas; Hjartarson, Hjörtur; Toksvig-Larsen, Sören

2012-06-01

Perioperative oral carbohydrate intake is beneficial to general surgery patients. Total hip arthroplasty is a common surgical procedure, and even a moderate improvement in patient outcome could have a significant effect on the resources needed for these patients. However, few studies have focused on the effects of carbohydrate intake on orthopaedic patients. The purpose of this study was to investigate if perioperative oral carbohydrate intake alters the postoperative course for patients undergoing total hip arthroplasty. The primary hypothesis was that pain scores would be lower in patients treated with carbohydrate. A randomised, double-blind, controlled trial. This study was carried out between September 2009 and April 2011 at a district Swedish hospital that specialises in orthopaedic surgery. Sixty ASA physical status I-III patients scheduled for elective total hip arthroplasty were included. Exclusion criteria were obesity, diabetes, prior hip surgery to the same hip, ongoing infection, immunological deficiency or age less than 50 or more than 80 years. Patients were given 400 ml of either an oral 12.5% carbohydrate solution or a placebo beverage (flavoured water) 1.5 h before and 2 h after surgery. Visual analogue scales were used to score six discomfort parameters. Immediately prior to surgery, the carbohydrate-treated patients were less hungry (median score 9.5 vs. 22 mm) and experienced less nausea (0 vs. 1.5 mm) (P< 0.05). Postoperatively, patients in the carbohydrate group experienced less pain at 12, 16 and 20 h (median scores 20, 30 and 34 vs. 7, 5 and 0 mm; P<0.05). This study shows that there is limited benefit from administering oral carbohydrate prior to total hip arthroplasty.

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

PubMed

Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

2016-05-23

Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial.

PubMed

Ulven, Stine M; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob J; Telle-Hansen, Vibeke H; Skjetne, Anne J; Raael, Ellen; Sheikh, Navida A; Holck, Marianne; Torvik, Kristin; Lamglait, Amandine; Thyholt, Kari; Byfuglien, Marte G; Granlund, Linda; Andersen, Lene F; Holven, Kirsten B

2016-10-01

The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25-70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was -9 and -11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.

Treating hypertension with a device that slows and regularises breathing: a randomised, double-blind controlled study.

PubMed

Schein, M H; Gavish, B; Herz, M; Rosner-Kahana, D; Naveh, P; Knishkowy, B; Zlotnikov, E; Ben-Zvi, N; Melmed, R N

2001-04-01

To examine the efficacy of a new device, which slows and regularises breathing, as a non-pharmacological treatment of hypertension and thus to evaluate the contribution of breathing modulation in the blood pressure (BP) reduction. Randomised, double-blind controlled study, carried out in three urban family practice clinics in Israel. Sixty-five male and female hypertensives, either receiving antihypertensive drug therapy or unmedicated. Four patients dropped out at the beginning of the study. Self treatment at home, 10 minutes daily for 8 consecutive weeks, using either the device (n = 32), which guides the user towards slow and regular breathing using musical sound patterns, or a Walkman, with which patients listened to quiet music (n = 29). Medication was unchanged 2 months prior to and during the study period. Systolic BP, diastolic BP and mean arterial pressure (MAP) changes from baseline. BP reduction in the device group was significantly greater than a predetermined 'clinically meaningful threshold' of 10.0, 5.0 and 6.7 mm Hg for the systolic BP, diastolic BP and MAP respectively (P = 0.035, P = 0.0002 and P = 0.001). Treatment with the device reduced systolic BP, diastolic BP and MAP by 15.2, 10.0 and 11.7 mm Hg respectively, as compared to 11.3, 5.6 and 7.5 mm Hg (P = 0.14, P = 0.008, P = 0.03) with the Walkman. Six months after treatment had stopped, diastolic BP reduction in the device group remained greater than the 'threshold' (P < 0.02) and also greater than in the walkman group (P = 0.001). The device was found to be efficacious in reducing high BP during 2 months of self-treatment by patients at home. Breathing pattern modification appears to be an important component in this reduction.

Clinical improvement of patients with osteoarthritis using thermal mineral water at Szigetvár Spa—results of a randomised double-blind controlled study

NASA Astrophysics Data System (ADS)

Hanzel, Adrienn; Horvát, Krisztina; Molics, Bálint; Berényi, Károly; Németh, Balázs; Szendi, Katalin; Varga, Csaba

2018-02-01

Since 1966, Szigetvár in Hungary is well recognised as a thermal spa. Many patients suffering from rheumatic diseases are treated with its thermal mineral water. Our objective was to investigate the effects of a 3-week-long outpatient balneotherapy-based rehabilitation program on patients suffering from osteoarthritis of the hips and the knees. During the treatment period, patients received a 30-min underwater jet massage in a bath tub, five times a week. One patient group received jet massage in a bath tub containing mineral water; the other group received the same treatment in tap water. Primary outcomes were measured by range of movement of the involved joints and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Visual analogue scale (VAS) was applied to measure current severity of pain. Furthermore, quality of life was assessed using the Short Form 36 questionnaire (SF-36). Range of movement (ROM) score, Western Ontario and McMaster University Osteoarthritis Index and visual analogue scale were determined before the first treatment, after the last treatment and 3 months after the last treatment. SF-36 questionnaire was filled in before the first and after the last treatment. Fifty patients (17 male, 33 female mean age 66.7 ± 4.79 years) were enrolled. After randomisation, patients were divided into two groups: tap water n = 24 and mineral water n = 26. Treatment with the thermal mineral water of Szigetvár significantly improved ROM, WOMAC scores, and SF-36-scored quality of life of the patients. Our double-blind study provided evidence for the beneficial health effects of another Hungarian thermal mineral water masking the colour, odour and pH of the tap water and mineral water.

Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study.

PubMed

Brown, Alexander J M; Lang, Chim; McCrimmon, Rory; Struthers, Allan

2017-08-23

Patients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively. The exact mechanism (s) responsible for these effects remain (s) unclear. One potential mechanism is regression of Left ventricular hypertrophy (LVH). The DAPA-LVH trial is a prospective, double-blind, randomised, placebo-controlled 'proof of concept' single-centre study that has been ongoing since January 2017. It is designed specifically to assess whether the SGLT2 inhibitor dapagliflozin regresses left ventricular [LV] mass in patients with diabetes and left ventricular hypertrophy [LVH]. We are utilising cardiac and abdominal magnetic resonance imaging [MRI] and ambulatory blood pressure monitoring to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard care over a 1 year observation period. The primary endpoint is to detect the changes in LV mass. The secondary outcomes are to assess the changes in, LV volumes, blood pressure, weight, visceral and subcutaneous fat. This trial will be able to determine if SGLT2 inhibitor therapy reduces LV mass in patient with diabetes and LVH thereby strengthening their position as oral hypoglycaemic agents with cardioprotective benefits. Clinical Trials.gov: NCT02956811 . Registered November 2016.

Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.

PubMed

Impey, Lawrence; Pandit, Meghana

2005-05-01

External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. Randomised, double-blinded, placebo-controlled trial. UK teaching hospital. One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV. Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat. Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity. The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged. The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.

Multimodal infiltration of local anaesthetic in total knee arthroplasty; is posterior capsular infiltration worth the risk? a prospective, double-blind, randomised controlled trial.

PubMed

Pinsornsak, P; Nangnual, S; Boontanapibul, K

2017-04-01

Multimodal infiltration of local anaesthetic provides effective control of pain in patients undergoing total knee arthroplasty (TKA). There is little information about the added benefits of posterior capsular infiltration (PCI) using different combinations of local anaesthetic agents. Our aim was to investigate the effectiveness of the control of pain using multimodal infiltration with and without infiltration of the posterior capsule of the knee. In a double-blind, randomised controlled trial of patients scheduled for unilateral primary TKA, 86 were assigned to be treated with multimodal infiltration with (Group I) or without (Group II) PCI. Routine associated analgesia included the use of bupivacaine, morphine, ketorolac and epinephrine. All patients had spinal anaesthesia and patient-controlled analgesia (PCA) post-operatively. A visual analogue scale (VAS) for pain and the use of morphine were recorded 24 hours post-operatively. Side effects of the infiltration, blood loss, and length of stay in hospital were recorded. There were no statistically significant differences between the groups in relation to: VAS pain scores in the first 24 hours post-operatively (p = 0.693), the use of morphine in the PCA (p = 0.647), blood loss (p = 0.625), and length of stay (p = 0.17). There were no neurovascular complications in either group. The multimodal infiltration of local anaesthetic with infiltration of the posterior capsule did not provide significant added analgesic benefits or reduce the use of morphine after TKA. Multimodal infiltration is a satisfactory technique for the management of pain in these patients without the attendant risks of PCI. Cite this article: Bone Joint J 2017; 99-B:483-8. ©2017 The British Editorial Society of Bone & Joint Surgery.

A double blind randomised controlled clinical trial comparing a novel anti-stain and calculus reducing dentifrice with a standard fluoride dentifrice.

PubMed

Jowett, Adrian K; Marlow, Ian; Rawlinson, Andrew

2013-04-01

This clinical trial tested the anti-stain efficacy at 3 and 6 months of a novel, sodium polyaspartate-containing, anti-stain dentifrice. In addition, the efficacy of the new dentifrice in controlling gingival inflammation and inhibition of calculus deposition was tested. Participants were recruited to this double blind randomised control clinical trial, and allocated to either test or control groups. The presence of stain and calculus were entry criteria. Measurements of stain, calculus and gingival inflammation were recorded using the Shaw and Murray Stain score, Volpe-Manhold Calculus score and the Modified Gingival Index respectively. Measurements were made at baseline, prior to the removal of stain and calculus, and after 3 and 6 months. Missing data were imputed by and the outcomes were analysed using univariate analysis. At three months, toothpaste containing sodium polyaspartate was better (difference of mean 1.13 with SEM 0.57) than control for the control of dental stain (p<0.05). Stain scores also showed a trend in favour of the test product (difference of mean 1.03 with SEM 0.78) at six months (p>0.05). There was no difference between toothpastes with respect to calculus deposition or gingival inflammation. Toothpaste containing sodium polyaspartate was more effective than a control toothpaste at preventing deposition of dental stain for 3 months after professional tooth cleaning but showed no significant effect at 6 months. Sodium polyaspartate toothpaste was more effective than a control toothpaste at preventing dental stain formation and maybe helpful in controlling staining between episodes of scaling and polishing. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bioavailability of astaxanthin stereoisomers from wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon in healthy men: a randomised, double-blind study.

PubMed

Rüfer, Corinna E; Moeseneder, Jutta; Briviba, Karlis; Rechkemmer, Gerhard; Bub, Achim

2008-05-01

The objective of the present study was to investigate the bioavailability and the configurational isomer distribution of the carotenoid astaxanthin (AST) in human plasma after ingestion of wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon. In a randomised and double-blind trial, twenty-eight healthy men consumed 250 g wild or aquacultured salmon daily for 4 weeks which provided 5 mug AST/g salmon flesh. The plasma AST concentrations as well as the isomer distribution were measured by HPLC using a reversed and a chiral stationary phase. After 6 d of intervention with salmon, plasma AST concentrations reached a plateau of 39 nmol/l after consumption of wild salmon and of 52 nmol/l after administration of aquacultured salmon. At days 3, 6, 10 and 14 -- but not at day 28 -- the AST concentrations in human plasma were significantly greater after ingestion of aquacultured salmon. After administration of wild salmon, the (3S,3'S) isomer predominated in plasma (80 %), whereas after intake of aquacultured salmon the meso form (3R,3'S) prevailed (48 %). Therefore, the AST isomer pattern in human plasma resembles that of the ingested salmon. However, after consumption of both wild and aquacultured salmon for 28 d the relative proportion of the (3S,3'S) isomer was slightly higher and the (3R,3'R) form lower in human plasma compared with the isomer distribution in salmon flesh. A selective process of isomer absorption could be responsible for the observed differences in the relative proportions of the (3S,3'S) and (3R,3'R) isomers in human plasma compared with salmon flesh.

The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.

PubMed

Black, R Neil A; Ennis, Cieran N; Young, Ian S; Hunter, Steven J; Atkinson, A Brew; Bell, Patrick M

2014-01-01

Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus. Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or atorvastatin 10mg daily followed by the alternate drug in the second period. Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution. Weight, physical activity and other medications did not change. Total cholesterol (mean +/- standard error) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively, p<0.05. LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L, p<0.05 and triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L, p<0.05. Insulin-stimulated whole-body glucose disposal (35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min) and nadir endogenous glucose production (6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min) revealed no significant differences in effects of the treatments. In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin. This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses. Copyright © 2014 Elsevier Inc. All rights reserved.

Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial.

PubMed

Zhou, Shao J; Sullivan, Thomas; Gibson, Robert A; Lönnerdal, Bo; Prosser, Colin G; Lowry, Dianne J; Makrides, Maria

2014-05-01

The safety and nutritional adequacy of goat milk infant formulas have been questioned. The primary aim of the present study was to compare the growth and nutritional status of infants fed a goat milk infant formula with those of infants fed a typical whey-based cow milk infant formula. The secondary aim was to examine a range of health- and allergy-related outcomes. A double-blind, randomised controlled trial with 200 formula-fed term infants randomly assigned to receive either goat or cow milk formula from 2 weeks to at least 4 months of age was conducted. A cohort of 101 breast-fed infants was included for comparison. Weight, length and head circumference were measured at 2 weeks and 1, 2, 3, 4, 6 and 12 months of age. Nutritional status was assessed from serum albumin, urea, creatinine, Hb, ferritin, and folate and plasma amino acid concentrations at 4 months. Z-scores for weight, length, head circumference and weight for length were not different between the two formula-fed groups. There were differences in the values of some amino acids and blood biomarkers between the formula-fed groups, but the mean values for biomarkers were within the normal reference range. There were no differences in the occurrence of serious adverse events, general health, and incidence of dermatitis or medically diagnosed food allergy. The incidence of parentally reported blood-stained stools was higher in the goat milk formula-fed group, although this was a secondary outcome and its importance is unclear. Goat milk formula provided growth and nutritional outcomes in infants that did not differ from those provided by a standard whey-based cow milk formula.

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

PubMed Central

Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

2005-01-01

Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

Butorphanol pre-treatment prevents myoclonus induced by etomidate: a randomised, double-blind, controlled clinical trial.

PubMed

He, Liang; Ding, Ying; Chen, Huiyu; Qian, Yanning; Li, Zhong

2014-01-01

Myoclonic movements are common problems during induction of anaesthesia with etomidate. The myoclonus occurring after etomidate administration may represent a form of seizure. Agonistic modulation of the κ opiate receptor may reduce seizures, and butorphanol acts in such a manner. The aim of this randomised, double-blind, placebo-controlled clinical trial was to test our hypothesis that pre-treatment with butorphanol might reduce the incidence and severity of myoclonus induced by etomidate. Patients (108) with American Society of Anaesthesiologists physical status I or II were randomly assigned to one of two groups to receive either 0.015 mg/kg of butorphanol (n = 54) or saline (n = 54) intravenously. At two minutes after infusion of butorphanol or saline, 0.3 mg/kg etomidate was given. The occurrence and severity (observational score of 0-3) of myoclonus was assessed during 2 minutes after administration of etomidate. For each patient, blood pressure (BP), saturation of peripheral oxygen (SpO₂), and heart rate (HR) were measured. The incidence of myoclonus was significantly lower in Group Butorphanol than in Group Saline (13.0% vs 79.6%; RR = 0.163, 95%CI: 0.081-0.329; χ² = 48.265, p <0.0001). The severity levels of myoclonic movement were also significantly lower in Group Butorphanol than in Group Saline (p <0.0001). Throughout the procedure, changes of BP, SpO₂, and HR did not differ between the groups. There were no problems with bradycardia or hypotension. Infusion of 0.015 mg/kg butorphanol 2 minutes before etomidate administration is effective for suppressing myoclonus induced by etomidate during induction of general anaesthesia.

Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome.

PubMed

Fodor, Anthony A; Pimentel, Mark; Chey, William D; Lembo, Anthony; Golden, Pamela L; Israel, Robert J; Carroll, Ian M

2018-04-30

Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon.

PubMed

Hill, N; Lenglet, A; Arnéz, A M; Carneiro, I

2007-11-17

To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening. A double blind, placebo controlled cluster-randomised clinical study. Rural villages and peri-urban districts in the Bolivian Amazon. 4008 individuals in 860 households. All individuals slept under treated nets; one group also used a plant based insect repellent each evening, a second group used placebo. Episodes of Plasmodium falciparum or P vivax malaria confirmed by rapid diagnostic test or blood slide, respectively. We analysed 15,174 person months at risk and found a highly significant 80% reduction in episodes of P vivax in the group that used treated nets and repellent (incidence rate ratio 0.20, 95% confidence interval 0.11 to 0.38, P<0.001). Numbers of P falciparum cases during the study were small and, after adjustment for age, an 82% protective effect was observed, although this was not significant (0.18, 0.02 to 1.40, P=0.10). Reported episodes of fever with any cause were reduced by 58% in the group that used repellent (0.42, 0.31 to 0.56, P<0.001). Insect repellents can provide protection against malaria. In areas where vectors feed in the early evening, effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime. This has important implications in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents, as advocated for most tourists travelling to high risk areas, is fully justified. NCT 00144716.

A Double-Blind, Randomised Study Comparing the Skin Hydration and Acceptability of Two Emollient Products in Atopic Eczema Patients with Dry Skin.

PubMed

Djokic-Gallagher, Jasmina; Rosher, Phil; Oliveira, Gabriela; Walker, Jennine

2017-09-01

Healthcare professionals tend to recommend emollients based primarily on patient/consumer preference and cost, with cheaper options assumed to be therapeutically equivalent. The aim of this study was therefore to compare the effects on skin hydration of two emollients prescribed in the UK, Doublebase Dayleve™ gel (DELP) and a cheaper alternative, Zerobase Emollient™ cream (ZBC). This was a single-centre, randomised, double-blind, concurrent bi-lateral (within-patient) comparison in 18 females with atopic eczema and dry skin on their lower legs. DELP gel and ZBC cream were each applied to one lower leg twice daily for 4 days and on the morning only on day 5. The efficacy of both products was assessed by hydration measurements using a Corneometer CM825 probe (Courage-Khazaka Electronic). The measurements were made three times daily on days 1 to 5. The primary efficacy variable was the area under the curve (AUC) of the change from baseline corneometer readings over the 5 days. Skin hydration using DELP gel was significantly higher than using ZBC cream (p < 0.0001). The cumulative increase in skin hydration observed for DELP gel was substantial and long lasting. In contrast, for ZBC cream, there was no significant improvement of the cumulative skin hydration as measured by the AUC (p = 0.22). DELP gel achieved substantial, long-lasting and cumulative skin hydration, whilst ZBC cream achieved no measurable improvement in skin hydration compared to before treatment. Healthcare professionals should be aware that different emollients can perform differently. Dermal Laboratories Ltd. EudraCT number:2014-001026-16.

Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial.

PubMed

Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

2013-01-01

To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle. VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash. It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.

Efficacy of Bacillus coagulans Unique IS2 in treatment of irritable bowel syndrome in children: a double blind, randomised placebo controlled study.

PubMed

Sudha, M Ratna; Jayanthi, N; Aasin, M; Dhanashri, R D; Anirudh, T

2018-06-15

The efficacy of the probiotic strain, Bacillus coagulans Unique IS2 in the treatment of Irritable Bowel Syndrome (IBS) was evaluated in children. A total of 141 children of either sex in the age group 4-12 years, diagnosed with IBS according to the Rome III criteria, participated in the double-blind randomised controlled trial. Children received either B. coagulans Unique IS2 chewable tablets or placebo once daily for eight weeks followed by a two week follow-up period. Reduction in pain intensity as well as other symptoms associated with Irritable Bowel Syndrome like abdominal discomfort, bloating, distension, sense of incomplete evacuation, straining at stool, urgency of bowel movement, passage of gas and mucus, and bowel habit satisfaction were assessed. B. coagulans Unique IS2 treated group showed a greater reduction in pain scores as evaluated by a weekly pain intensity scale. There was a significant reduction (P<0.0001) in pain intensity in the probiotic treated group (7.6±0.98) as compared to the placebo group (4.2±1.41) by the end of the treatment period (8 weeks). There was also a significant improvement in stool consistency as well as reduction in abdominal discomfort, bloating, staining, urgency, incomplete evacuation and passage of gas. Bowel habit satisfaction and global assessment of relief was also observed in the B. coagulans Unique IS2 treated group as compared to the placebo group. This study demonstrates the efficacy of B. coagulans Unique IS2 in reducing the symptoms of Irritable Bowel Syndrome in children in the age group of 4-12 years.

A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine.

PubMed

Montgomery, Stuart A; Nielsen, Rebecca Z; Poulsen, Lis H; Häggström, Lars

2014-09-01

This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine(10-20 mg/day) versus agomelatine (25-50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI) monotherapy. Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale). Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence. Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated.

Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

PubMed

Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

2018-01-01

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (P<0·001) and Faecalibacterium (P=0·010) and decreases in Coprococcus (P=0·010), Dorea (P=0·043) and Ruminococcus (Lachnospiraceae family) (P=0·032). This study demonstrates that those with HDF intakes have a greater gut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

PubMed

Rees, Dinka; Holtrop, Grietje; Chope, Gemma; Moar, Kim M; Cruickshank, Morven; Hoggard, Nigel

2018-03-01

The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour. Compared with controls, GS subjects had a favourable cardiovascular lipid profile - lower LDL (4·0 (sem 0·3) v. 2·8 (sem 0·2) mmol/l; P=0·008) and LDL:HDL ratio (3·2 (sem 0·4) v. 1·8 (sem 0·2); P=0·005) and modified haematological profile. The majority of the GS subjects followed a low-gluten lifestyle, which helps to reduce the gastrointestinal (GI) symptoms severity. The low-gluten lifestyle does not have any effect on the quality of life, fatigue or mental state of this population. Consumption of normal wheat bread increased GI symptoms in GS subjects compared with their habitual diet. ANPEP lowered the immunogenic gluten in the treated bread by approximately 40 %. However, when compared with the control bread for inducing GI symptoms, no treatment effects were apparent. ANPEP can be applied in the production of bread with taste, texture and appearance comparable with standard bread.

Effect of addition of dexamethasone to ropivacaine on post-operative analgesia in ultrasonography-guided transversus abdominis plane block for inguinal hernia repair: A prospective, double-blind, randomised controlled trial.

PubMed

Sharma, Uma Datt; Prateek; Tak, Himani

2018-05-01

Ultrasonography (USG)-guided transversus abdominis plane (TAP) block is an abdominal field block with high efficacy. This study was undertaken with the aim of determining the effect of the addition of dexamethasone to 0.5% ropivacaine on post-operative analgesia in USG-guided TAP block for inguinal hernia repair. A double-blind randomised control study was conducted on sixty patients posted for inguinal hernia repair with the American Society of Anesthesiologists physical Status I or II, who were allocated two groups of 30 each. Patients in Group RS received 0.5% ropivacaine (20 ml) and normal saline (2 ml) whereas patients in Group RD received 0.5% ropivacaine (20 ml) and dexamethasone (2 ml, i.e., 8 mg), in USG-guided TAP Block on the same side, after repair of inguinal hernia under spinal anaesthesia. Visual analogue scale (VAS) scores, time for request of first analgesia and total tramadol consumption in first 24 h were compared. Unpaired Student's t -test and Mann-Whitney U-test were performed using SPSS 23 Software. Patients in Group RD had significantly lower VAS scores as compared to Group RS from 4 th to 12 th h, postoperatively. Duration of analgesia was significantly more in Group RD (547.50 [530,530] min) when compared with Group RS (387.50 [370,400] min) ( P < 0.001). The demand for intravenous tramadol was significantly low in Group RD (223.33 ± 56.83 mg) as compared to Group RS (293.33 ± 25.71 mg) ( P < 0.001). Addition of dexamethasone to ropivacaine in USG-guided TAP block significantly reduces post-operative pain and prolongs the duration of post-operative analgesia, thereby reducing analgesic consumption.

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

PubMed

O'Scanaill, P; Keane, S; Wall, V; Flood, G; Buggy, D J

2018-04-01

Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h -1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. AUC moving was mean (SD) 71 (34) mm h -1 vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. NCT 03024697. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Sildenafil citrate as a medical expulsive therapy for distal ureteric stones: A randomised double-blind placebo-controlled study.

PubMed

Shokeir, Ahmed A; Tharwat, Mohamed A; Abolazm, Ahmed Elhussein; Harraz, Ahmed

2016-03-01

To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18-65 years, normal renal function, and a single radiopaque unilateral DUS of 5-10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P < 0.001). A multivariable Cox proportional hazards model showed that receiving sildenafil citrate was the only independent factor that had a significant impact on stone passage with a hazard ratio of 2.7 (95% confidence interval 1.5-4.8; P < 0.001). Sildenafil citrate enhances spontaneous passage of 5-10 mm DUS.

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

PubMed

Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

2017-09-01

Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The dose-response relationship between pseudoephedrine ingestion and exercise performance.

PubMed

Pritchard-Peschek, Kellie R; Jenkins, David G; Osborne, Mark A; Slater, Gary J; Taaffe, Dennis R

2014-09-01

The purpose of the present study was to examine a possible dose-response between pre-exercise pseudoephedrine intake and cycling time trial performance. Randomised, double-blind, crossover trial. Ten trained male endurance cyclists (26.5 ± 6.2 years, 75.1 ± 5.9 kg, 70.6 ± 6.8 mL kg(-1)min(-1)) undertook three cycling time trials in which a fixed amount of work (7 kJ kg(-1) body mass) was completed in the shortest possible time. Sixty minutes before the start of exercise, subjects orally ingested either 2.3 mg kg(-1) or 2.8 mg kg(-1) body mass of pseudoephedrine or a placebo in a randomised and double-blind manner. Venous blood was sampled at baseline, pre- and post-warm up and post-exercise for the analysis of pH and lactate and glucose concentrations; plasma catecholamine and pseudoephedrine concentrations were measured at all times except post-warm up. Cycling time trial performance (∼ 30 min) was not enhanced by pseudoephedrine ingestion. Plasma pseudoephedrine concentration increased from pre-warm up to post-exercise in both treatment conditions, with the 2.8 mg kg(-1) body mass dose producing the highest concentration at both time points (2.8 mg kg(-1)>2.3 mg kg(-1)>placebo; p<0.001). There was large individual variation in plasma pseudoephedrine concentration between subjects following pseudoephedrine administration. A number of factors clearly influence the uptake and appearance of pseudoephedrine in the blood and these are not yet fully understood. Combined with subsequent differences in plasma pseudoephedrine between individuals, this may partially explain the present findings and also the inconsistencies in performance following pseudoephedrine administration in previous studies. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial

PubMed Central

Serisier, David J; Bilton, Diana; De Soyza, Anthony; Thompson, Philip J; Kolbe, John; Greville, Hugh W; Cipolla, David; Bruinenberg, Paul; Gonda, Igor

2013-01-01

Background The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery. Methods Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation—after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study. Results DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs −0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events. Conclusions Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population. PMID:23681906

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

PubMed

Martinez de Tejada, B; Karolinski, A; Ocampo, M C; Laterra, C; Hösli, I; Fernández, D; Surbek, D; Huespe, M; Drack, G; Bunader, A; Rouillier, S; López de Degani, G; Seidenstein, E; Prentl, E; Antón, J; Krähenmann, F; Nowacki, D; Poncelas, M; Nassif, J C; Papera, R; Tuma, C; Espoile, R; Tiberio, O; Breccia, G; Messina, A; Peker, B; Schinner, E; Mol, B W; Kanterewicz, L; Wainer, V; Boulvain, M; Othenin-Girard, V; Bertolino, M V; Irion, O

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour. © 2014 Royal College of Obstetricians and Gynaecologists.

Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate-to-severe erosive oesophagitis - the results of two double-blind studies.

PubMed

Laine, L; Katz, P O; Johnson, D A; Ibegbu, I; Goldstein, M J; Chou, C; Rossiter, G; Lu, Y

2011-01-01

Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition. To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate-severe erosive oesophagitis. Patients with LA grade C or D oesophagitis were randomised to rabeprazole-ER 50 mg or esomeprazole 40 mg once daily in two identical 8-week double-blind trials (N = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole-ER non-inferior to esomeprazole (non-inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole-ER superior to esomeprazole (P < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks. Rabeprazole-ER was non-inferior to esomeprazole in week-8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week-4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole-ER vs. esomeprazole differences in week-8 healing = 10.4% (95% CI: -1.4%, 22.2%) and week-4 healing = 12.0% (P = 0.048). Rabeprazole-ER is as effective as esomeprazole in healing moderate-severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775). © 2010 Blackwell Publishing Ltd.

Double blind randomised controlled trial of two different breathing techniques in the management of asthma

PubMed Central

Slader, C A; Reddel, H K; Spencer, L M; Belousova, E G; Armour, C L; Bosnic‐Anticevich, S Z; Thien, F C K; Jenkins, C R

2006-01-01

Background Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non‐specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. Methods After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Results Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Conclusion Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non‐specific upper body exercises. PMID:16517572

Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

PubMed Central

Takeuchi, Tsutomu; Tanaka, Yoshiya; Iwasaki, Manabu; Ishikura, Hiroaki; Saeki, Satoshi; Kaneko, Yuichiro

2016-01-01

Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results. PMID:26672064

Pain management after laparoscopic cholecystectomy-a randomized prospective trial of low pressure and standard pressure pneumoperitoneum.

PubMed

Singla, Sanjeev; Mittal, Geeta; Raghav; Mittal, Rajinder K

2014-02-01

Abdominal pain and shoulder tip pain after laparoscopic cholecystectomy are distressing for the patient. Various causes of this pain are peritoneal stretching and diaphragmatic irritation by high intra-abdominal pressure caused by pneumoperitoneum . We designed a study to compare the post operative pain after laparoscopic cholecystectomy at low pressure (7-8 mm of Hg) and standard pressure technique (12-14 mm of Hg). Aim : To compare the effect of low pressure and standard pressure pneumoperitoneum in post laparoscopic cholecystectomy pain . Further to study the safety of low pressure pneumoperitoneum in laparoscopic cholecystectomy. A prospective randomised double blind study. A prospective randomised double blind study was done in 100 ASA grade I & II patients. They were divided into two groups -50 each. Group A patients underwent laparoscopic cholecystectomy with low pressure pneumoperitoneum (7-8 mm Hg) while group B underwent laparoscopic cholecystectomy with standard pressure pneumoperitoneum (12-13 mm Hg). Both the groups were compared for pain intensity, analgesic requirement and complications. Demographic data and intraoperative complications were analysed using chi-square test. Frequency of pain, intensity of pain and analgesics consumption was compared by applying ANOVA test. Post-operative pain score was significantly less in low pressure group as compared to standard pressure group. Number of patients requiring rescue analgesic doses was more in standard pressure group . This was statistically significant. Also total analgesic consumption was more in standard pressure group. There was no difference in intraoperative complications. This study demonstrates the use of simple expedient of reducing the pressure of pneumoperitoneum to 8 mm results in reduction in both intensity and frequency of post-operative pain and hence early recovery and better outcome.This study also shows that low pressure technique is safe with comparable rate of intraoperative complications.

Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol.

PubMed

Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; Rosa, Laura Alejandra de la; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

2017-06-23

In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima ) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. ClinicalTrials.gov: NCT02837666. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

PubMed Central

Cohen, S; Moreland, L; Cush, J; Greenwald, M; Block, S; Shergy, W; Hanrahan, P; Kraishi, M; Patel, A; Sun, G; Bear, M

2004-01-01

Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). Methods: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. Results: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). Conclusions: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone. PMID:15082469

Postoperative symbiotic in patients with head and neck cancer: a double-blind randomised trial.

PubMed

Lages, Priscilla C; Generoso, Simone V; Correia, Maria Isabel T D

2018-01-01

Studies on the 'gut origin of sepsis' have suggested that stressful insults, such as surgery, can affect intestinal permeability, leading to bacterial translocation. Symbiotics have been reported to be able to improve gut permeability and modulate the immunologic system, thereby decreasing postoperative complications. Therefore we aimed to evaluate the postoperative use of symbiotics in head and neck cancer surgical patients for intestinal function and permeability, as well as the postoperative outcomes. Patients were double-blind randomised into the symbiotic (n 18) or the control group (n 18). Samples were administered twice a day by nasoenteric tube, starting on the 1st postoperative day until the 5th to 7th day, and comprised 109 colony-forming units/ml each of Lactobacillus paracasei, L. rhamnosus, L. acidophilus, and Bifidobacterium lactis plus 6 g of fructo-oligosaccharides, or a placebo (6 g of maltodextrin). Intestinal function (day of first evacuation, total stool episodes, stool consistency, gastrointestinal tract symptoms and gut permeability by diamine oxidase (DAO) enzyme) and postoperative complications (infectious and non-infectious) were assessed. Results of comparison of the pre- and postoperative periods showed that the groups were similar for all outcome variables. In all, twelve patients had complications in the symbiotic group v. nine in the control group (P>0·05), and the preoperative-postoperative DAO activity ranged from 28·5 (sd 15·4) to 32·7 (sd 11·0) ng/ml in the symbiotic group and 35·2 (sd 17·7) to 34·1 (sd 12·0) ng/ml in the control group (P>0·05). In conclusion, postoperative symbiotics did not impact on intestinal function and postoperative outcomes of head and neck surgical patients.

Double blind randomised controlled trial of two different breathing techniques in the management of asthma.

PubMed

Slader, C A; Reddel, H K; Spencer, L M; Belousova, E G; Armour, C L; Bosnic-Anticevich, S Z; Thien, F C K; Jenkins, C R

2006-08-01

Previous studies have shown that breathing techniques reduce short acting beta(2) agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises.

The effects of dexmedetomidine and magnesium sulphate in adult patients undergoing endoscopic transnasal transsphenoidal resection of pituitary adenoma: A double-blind randomised study

PubMed Central

Soliman, Rabie; Fouad, Eman

2017-01-01

Background and Aim: Transnasal transsphenoidal resection of pituitary tumours is associated with blood loss and wide fluctuations in haemodynamic parameters. The aim of the present study was to compare the effect of dexmedetomidine and magnesium sulphate during the transsphenoidal resection of pituitary tumours. Methods: The study was a double-blind, randomised study and included 152 patients classified randomly into two groups: Group D: Dexmedetomidine was given as a loading dose 1 μg/kg over 10 min before induction followed by an infusion at 0.5 μg/kg/h during the surgery. Group M: Magnesium sulphate was given as loading dose of 50 mg/kg over 10 min followed by an infusion at 15 mg/kg/h during the surgery. The systolic, diastolic and mean arterial blood pressures, in addition to the amount of blood loss were measured at specific timepoints. Data were described in terms of mean ± standard deviation, median, frequencies, 95% confidence of interval of mean and percentages. Results: Mean bleeding score was lower in Group D than Group M (1.36 ± 0.48 vs. 3.05 ± 0.65, respectively; P = 0.002). Mean blood loss was lower in Group D (157.43 ± 48.79 ml vs.299.47 ± 77.28 ml in Group M; P < 0.001)Heart rate, mean arterial pressure, fentanyl requirements, end-tidal sevoflurane concentration, and extubation and emergence times were lower, while incidence of bradycardia and hypotension were higher in Group D. Conclusions: During transsphenoidal pituitary resection, dexmedetomidine, compared to magnesium, is associated with lower blood loss and better operating conditions but with more hypotension and bradycardia PMID:28584351

Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude.

PubMed

Martin, Daniel S; Gilbert-Kawai, Edward T; Meale, Paula M; Fernandez, Bernadette O; Cobb, Alexandra; Khosravi, Maryam; Mitchell, Kay; Grocott, Michael P W; Levett, Denny Z H; Mythen, Michael G; Feelisch, Martin

2013-11-01

The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients. © 2013. Published by Elsevier Inc. All rights reserved.

Vibrating vaginal balls to improve pelvic floor muscle performance in women after childbirth: a protocol for a randomised controlled feasibility trial.

PubMed

Oblasser, Claudia; McCourt, Christine; Hanzal, Engelbert; Christie, Janice

2016-04-01

This paper presents a feasibility trial protocol the purpose of which is to prepare for a future randomised controlled trial to determine the effectiveness of vibrating vaginal pelvic floor training balls for postpartum pelvic floor muscle rehabilitation. Vibrating vaginal pelvic floor training balls are available in Austria to enhance women's pelvic floor muscles and thus prevent or treat urinary incontinence and other pelvic floor problems following childbirth. Nonetheless, there is currently little empirical knowledge to substantiate their use or assess their relative effectiveness in comparison to current standard care, which involves pelvic floor muscle exercises. Single blind, randomised controlled feasibility trial with two parallel groups. It is planned to recruit 56 postpartum women in Vienna, who will be randomised into one of two intervention groups to use either vibrating vaginal balls or a comparator pelvic floor muscle exercises for 12 weeks. As this is a feasibility study, study design features (recruitment, selection, randomisation, intervention concordance, data collection methods and tools) will be assessed and participants' views and experiences will be surveyed. Tested outcome measures, collected before and after the intervention, will be pelvic floor muscle performance as reported by participants and measured by perineometry. Descriptive and inferential statistics and content analysis will serve the preparation of the future trial. The results of this feasibility trial will inform the design and conduct of a full randomised controlled trial and provide insight into the experiences of women regarding the interventions and study participation. © 2015 John Wiley & Sons Ltd.

Clinical Investigation Program Report.

DTIC Science & Technology

1983-10-01

metastatic to liver. (0) H-83-63. Double-blind, randomized parallel comparison of two different dosage regimens of naproxen sodium in patients with...different dosage regimens of naproxen sodium in patients with bone pain due to m etastatic cancer. Start Date: May 83 Est Comp Date: Indefinite Principal...Investigator: Facility: LTC D Gandara, MD LAMC CPT R Mansour, MD D ept/Svc: Associate Investigators: Hematology-Oncology Key Words: naproxen sodium

Forecasting Three-Month Outcomes in a Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR) and Atomoxetine (Strattera) in School-Aged Children with ADHD

ERIC Educational Resources Information Center

Faraone, Stephen V.; Wigal, Sharon B.; Hodgkins, Paul

2007-01-01

Objective: Compare observed and forecasted efficacy of mixed amphetamine salts extended release (MAS-XR; Adderall) with atomoxetine (Strattera) in ADHD children. Method: The authors analyze data from a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study of children ages 6 to 12 with ADHD combined…

A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN® administered orally.

PubMed

Solomon, Todd M; Leech, Jarrett; deBros, Guy B; Murphy, Cynthia A; Budson, Andrew E; Vassey, Elizabeth A; Solomon, Paul R

2016-03-01

Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study. Copyright © 2016 John Wiley & Sons, Ltd.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy.

PubMed Central

Gillham, R A; Blacklaw, J; McKee, P J; Brodie, M J

1993-01-01

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation. PMID:8270925

Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial

PubMed Central

Eichenseer, M.; Johansen, C.; Mueller, R. S.

2013-01-01

Antihistaminic drugs are commonly used as symptomatic therapy of atopic dermatitis in dogs. Unfortunately, their clinical benefit is largely unsubstantiated. In a double-blinded, placebo-controlled, cross-over trial, the influence of dimetinden and of a combination of chlorpheniramine and hydroxyzine on pruritus and lesions was evaluated in 19 dogs. They were treated with either product or a placebo orally for 14 days, each time followed by a 14-day washout period. Before and after each period, the dogs were examined and the Canine Atopic Dermatitis Extent and Severity Index (CADESI) determined by a clinician, and the pruritus and general condition by the owner. Dimetinden improved the pruritus significantly (P=0.014) but not the CADESI (P=0.087), the combination of hydroxyzine and chlorpheniramine improved the CADESI (P=0.049) and pruritus (P=0.05) significantly. Ten of 17 dogs improved by more than 25 per cent in pruritus with the combination of hydroxyzine and chlorpheniramine, 12 of 18 with dimetindenmaleate and only 2 of 19 with placebo. Antihistamines can help to reduce pruritus in atopic dogs, but in most cases, the improvement is limited and additional treatment may be needed. PMID:24114734

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

PubMed

Moulin, D E; Kreeft, J H; Murray-Parsons, N; Bouquillon, A I

1991-02-23

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

PubMed

Momeni, A Z; Jalayer, T; Emamjomeh, M; Khamesipour, A; Zicker, F; Ghassemi, R L; Dowlati, Y; Sharifi, I; Aminjavaheri, M; Shafiei, A; Alimohammadian, M H; Hashemi-Fesharki, R; Nasseri, K; Godal, T; Smith, P G; Modabber, F

1999-02-05

Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

Effects of orally administered lavender essential oil on responses to anxiety-provoking film clips.

PubMed

Bradley, Belinda F; Brown, Stephen L; Chu, Simon; Lea, Robert W

2009-06-01

Lavender odour is commonly used to alleviate mild anxiety. Double blind studies are difficult to conduct with odours, and there are few reliable investigations of lavender's efficacy. Orally administered lavender capsules (placebo, 100, 200 microl) were tested in a randomised between-subjects (n = 97) double-blind study. Film clips were used to elicit anxiety. Measures included anxiety, State Trait Anxiety Inventory (STAI), mood, positive and negative affect scale (PANAS), heart rate (HR), galvanic skin response (GSR), and heart rate variation (HRV). Following baseline measurements capsules were administered. Participants viewed a neutral film clip, then an anxiety-provoking and light-hearted recovery film clip. For the 200 microl lavender dose during the neutral film clip there was a trend towards reduced state anxiety, GSR and HR and increased HRV. In the anxiety-eliciting film, lavender was mildly beneficial in females but only on HRV measures. In males sympathetic arousal increased during the anxiety film (GSR). HRV significantly increased at 200 microl during all three film clips in females, suggesting decreased anxiety. These findings suggest that lavender has anxiolytic effects in humans under conditions of low anxiety, but these effects may not extend to conditions of high anxiety.

Emollient efficacy and acceptability in the treatment of eczematous dry skin: A double-blind, randomised comparison of two UK-marketed products

PubMed Central

Djokic-Gallagher, Jasmina; Rosher, Philip; Walker, Jennine; Sykes, Krystyna; Hart, Valerie

2016-01-01

Abstract Objective: The aim of this study was to compare the moisturising efficacy and acceptability of physical characteristics of two commonly prescribed emollients licenced in the UK, Doublebase Dayleve gel (DELP) and Diprobase cream (DIPC). Methods: The study was a double-blind, concurrent bi-lateral comparison in female eczema subjects with dry skin. Results: In Part 1, comparing the area under the curve (AUC) change from baseline corneometer readings over 24 h following single applications of the emollients to the volar forearms of 34 subjects, the AUC for DELP was more than three times that seen for DIPC (p < 0.0001). In Part 2, comparing the same outcome measured over 5 days of twice daily applications to the lower legs in 36 subjects, the AUC for DELP was approximately five times that for DIPC (p < 0.0001). 69% of subjects “Like Slightly” or “Like Strongly” DELP compared to 33% for DIPC (p = 0.025). 72% indicated they would use DELP again compared to 33% for DIPC (p = 0.033). 75% of subjects preferred DELP, 17% preferred DIPC and 8% expressed no preference (p = 0.0004). PMID:26864095

The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults.

PubMed

Auclair, S; Chironi, G; Milenkovic, D; Hollman, P C H; Renard, C M G C; Mégnien, J-L; Gariepy, J; Paul, J-L; Simon, A; Scalbert, A

2010-10-01

Epidemiological studies suggest that apple consumption is associated with a reduction in cardiovascular disease risk. Apple polyphenols may contribute to explain these effects. Endothelial dysfunction has been associated with early stage of atherosclerosis and polyphenols from various dietary sources have been shown to reverse it. The aim of the present study was to investigate the effect of the consumption of a polyphenol-rich apple on endothelial function. In all, 30 hypercholesterolemic volunteers were included in a double-blind, randomized crossover trial. They successively consumed 40 g of two lyophilized apples, polyphenol-rich and polyphenol-poor, providing respectively 1.43 and 0.21 g polyphenols per day during two 4-week periods separated by a 4-week washout period. Brachial artery flow-mediated vasodilation (FMD) was assessed at the beginning and at the end of each intervention period. FMD did not differ between the polyphenol-rich and the polyphenol-poor apples, neither did the other cardiovascular disease risk factors (plasma lipids, homocysteine, antioxidant capacity). These data suggest that over a 4-week period, the consumption of a polyphenol-rich apple does not improve vascular function in hypercholesterolemic patients.

The effects of an Ayurvedic medicinal toothpaste on clinical, microbiological and oral hygiene parameters in patients with chronic gingivitis: a double-blind, randomised, placebo-controlled, parallel allocation clinical trial.

PubMed

Howshigan, J; Perera, K; Samita, S; Rajapakse, P S

2015-12-01

Plant derived preparations have been essential components for maintenance of oral hygiene and the treatment of oral diseases globally since ancient times. Acacia chundra Willd, Adhatoda vasica Nees., Mimusops elengi L., Piper nigrum L., Pongamia pinnate L. Pirerre, Quercus infectoria Olivier., Syzygium aromaticum L., Terminalia chebula Retz., Zingiber offici-nale Roscoe., individually or in combination, have been used for this purpose because of their beneficial effects. To study the efficacy of an Ayurvedic toothpaste containing these herbs in patients with chronic gingivitis. Otherwise healthy males and non-pregnant females (n=80) aged 18-35 years with ≥20 teeth were randomly assigned to Group 1 (herbal toothpaste) and Group 2 (placebo toothpaste). Quigley Hein plaque index (PS), bleeding on probing (BOP) and probing pocket depth (PPD), were recorded for all teeth at six sites, and one ml of resting saliva was collected to ascertain anaerobic and aerobic bacterial counts at baseline, and at 4, 8, 12 and 24 weeks. Full-mouth prophylaxis was performed and instructions for brushing with the allocated toothpaste for 6 months were given at baseline. Sixty-six participants, 34 in Group 1 and 32 in Group 2 completed the study. Clinical examinations were performed by the same examiner blinded to group allocation. Linear mixed model analysis revealed significant reductions of PS, BOP, PPD (p<0.0001) and total salivary anaerobic counts (p<0.05) in Group 1 at all prescribed visits compared to Group 2. Moreover the reduction increased overtime. No unpleasant effects of toothpaste use were reported. This study provides robust evidence of the beneficial antiplaque and antigingivitis effects of the test herbal toothpaste Sudantha® on patients with chronic gingivitis.

Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

PubMed

Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

2015-12-03

This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p < 0.05) compared with placebo; AV relapse was delayed by up to 76 % (p < 0.05). Probiotic use also reduced and maintained low vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in patients with recurrent BV/AV and improved clinical and microbiological parameters. NCT01993524 ; 20 November 2013.

High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial.

PubMed

Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

2017-09-14

Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. The trial has been registered at the ISRCTN (ISRTCN 63827758). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

PubMed

Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

2013-12-01

Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation.

PubMed

van Bodegraven, Ad A; Bravenboer, Nathalie; Witte, Birgit I; Dijkstra, Gerard; van der Woude, C Janneke; Stokkers, Pieter C M; Russel, Maurice G; Oldenburg, Bas; Pierik, Marieke; Roos, Jan C; van Hogezand, Ruud A; Dik, Vincent K; Oostlander, Angela E; Netelenbos, J Coen; van de Langerijt, Lex; Hommes, Daniel W; Lips, Paul

2014-09-01

Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients. This double-blind, placebo-controlled randomised trial of risedronate with calcium and vitamin D supplementation was performed in osteopenic Crohn's disease patients. Patients were treated for 2 years with follow-up after 3 and after every 6 months. Disease characteristics and activity and bone turnover markers were assessed at all visits; dual x-ray absorptiometry was performed at baseline, 12 and 24 months; radiographs of the spine at baseline and 24 months. Of 132 consenting patients, 131 were randomised (67 placebo and 64 risedronate). Patient characteristics were similar in both groups, although the risedronate group was slightly heavier (body mass index 24.3 vs 23.0 kg/m(2)). Bone mineral density at lumbar spine increased 0.04 g/cm(2) on average in the risedronate group versus 0.01 g/cm(2) in the placebo group (p=0.007). The mean increase in total hip bone mineral density was 0.03 versus 0.01 g/cm(2), respectively (p=0.071). Fracture prevalence and incidence were similar. Change of T-scores and concentrations of bone turnover markers were consistent with a beneficial effect of risedronate when compared with placebo. The effect of risedronate was primarily demonstrated in the first 12 months of treatment. No serious unexpected suspected adverse events were observed. A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

PubMed

Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

2018-04-30

Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation < 95% was 49% in the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is always required. EUDRACT number 2013-003040-23.

Balanced versus chloride-rich solutions for fluid resuscitation in brain-injured patients: a randomised double-blind pilot study

PubMed Central

2013-01-01

Introduction We sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury. Methods We conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours. Results Forty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387). Conclusions This study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint, intracranial pressure did not appear different between groups. Trial registration EudraCT 2008-004153-15 and NCT00847977 The work in this trial was performed at Nantes University Hospital in Nantes, France. PMID:23601796

MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial.

PubMed

Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

2015-06-01

To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. NCT01023256. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double-blind randomised controlled trial.

PubMed

de Betue, Carlijn T; van Waardenburg, Dick A; Deutz, Nicolaas E; van Eijk, Hans M; van Goudoever, Johannes B; Luiking, Yvette C; Zimmermann, Luc J; Joosten, Koen F

2011-09-01

The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPE(Phe)). This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1 ± 0.3 g protein/kg/24 h, 119 ± 25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7 ± 0.2 g protein/kg/24 h, 84 ± 15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPE(Phe). Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73 ± 0.5 vs S-formula: 0.02 ± 0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6 ± 4.4, S-formula: 5.2 ± 2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9 ± 4.3, S-formula: 5.2 ± 2.6 g/kg/24 h). SPE(Phe) was not statistically different between the two groups (PE-formula: 39.8 ± 18.3%, S-formula: 52.4 ± 13.6%). Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants. Dutch Trial Register number: NTR 515.

Herbst appliance with skeletal anchorage versus dental anchorage in adolescents with Class II malocclusion: study protocol for a randomised controlled trial.

PubMed

Batista, Klaus Barretto Dos Santos Lopes; Lima, Tatiana; Palomares, Nathália; Carvalho, Felipe de Assis; Quintão, Cátia; Miguel, José Augusto Mendes; Lin, Yin-Ling; Su, Ting-Li; O'Brien, Kevin

2017-11-25

The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be implemented by the secretary of the Department of Orthodontics of Rio de Janeiro State University before the beginning of the study. The patients and the orthodontists who will treat the patients cannot be blinded, as they will know the type of appliance used. The technician who will take the CBCT image and the data analyst will be blinded to patients' group allocation. If this new intervention is effective, the findings can change orthodontic practice and may also be relevant to other forms of treatment in which appliances are fixed to the bones of the jaws. However, if the bone anchoring is not effective, the trial will provide much needed information on the use of this comparatively new development. ClinicalTrials.gov, protocol ID: NCT0241812 . Registered on 26 March 2015.

Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

Oral versus intravenous antibiotic treatment for bone and joint infections (OVIVA): study protocol for a randomised controlled trial.

PubMed

Li, Ho Kwong; Scarborough, Matthew; Zambellas, Rhea; Cooper, Cushla; Rombach, Ines; Walker, A Sarah; Lipsky, Benjamin A; Briggs, Andrew; Seaton, Andrew; Atkins, Bridget; Woodhouse, Andrew; Berendt, Anthony; Byren, Ivor; Angus, Brian; Pandit, Hemant; Stubbs, David; McNally, Martin; Thwaites, Guy; Bejon, Philip

2015-12-21

Bone and joint infection in adults arises most commonly as a complication of joint replacement surgery, fracture fixation and diabetic foot infection. The associated morbidity can be devastating to patients and costs the National Health Service an estimated £20,000 to £40,000 per patient. Current standard of care in most UK centres includes a prolonged course (4-6 weeks) of intravenous antibiotics supported, if available, by an outpatient parenteral antibiotic therapy service. Intravenous therapy carries with it substantial risks and inconvenience to patients, and the antibiotic-related costs are approximately ten times that of oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes. We hypothesise that, by selecting oral agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, key outcomes in patients managed primarily with oral therapy are non-inferior to those in patients treated by intravenous therapy. The OVIVA trial is a parallel group, randomised (1:1), un-blinded, non-inferiority trial conducted in thirty hospitals across the UK. Eligible participants are adults (>18 years) with a clinical syndrome consistent with a bone, joint or metalware-associated infection who have received ≤7 days of intravenous antibiotic therapy from the date of definitive surgery (or the start of planned curative therapy in patients treated without surgical intervention). Participants are randomised to receive either oral or intravenous antibiotics, selected by a specialist infection physician, for the first 6 weeks of therapy. The primary outcome measure is definite treatment failure within one year of randomisation, as assessed by a blinded endpoint committee, according to pre-defined microbiological, histological and clinical criteria. Enrolling 1,050 subjects will provide 90 % power to demonstrate non-inferiority, defined as less than 7.5 % absolute increase in treatment failure rate in patients randomised to oral therapy as compared to intravenous therapy (one-sided alpha of 0.05). If our results demonstrate non-inferiority of orally administered antibiotic therapy, this trial is likely to facilitate a dramatically improved patient experience and alleviate a substantial financial burden on healthcare services. ISRCTN91566927 - 14/02/2013.

RANDOMISED ASPIRIN ASSIGNMENT AND RISK OF ADULT-ONSET ASTHMA IN THE WOMEN'S HEALTH STUDY

PubMed Central

Kurth, Tobias; Barr, R. Graham; Gaziano, J. Michael; Buring, Julie E.

2008-01-01

Rationale Randomised data in men showed a small but significant reduction in risk of adult-onset asthma among those assigned to aspirin. Results from an observational study in women suggest that frequent use of aspirin decreased the risk of adult-onset asthma. Randomised data in women are lacking. Objective To test the effect of 100 mg of aspirin on alternate days or placebo on the risk of adult-onset asthma in the Women's Health Study. Methods Post-hoc analyses from a randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E in apparently healthy US women with no indication or contraindication to aspirin therapy and free of a history of asthma at study entry. Measurements Female health professionals could self-report an asthma diagnosis on yearly questionnaires. Results Among 37,270 women without reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new reports of asthma diagnosis in the aspirin group and 963 in the placebo group (hazard ratio=0.90; 95% confidence interval=0.82−0.99; P=0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, indicating no effect among women with a body mass index of ≥30 kg/m2. There was no significant effect modification by age, smoking status, exercise levels, postmenopausal hormone use, or randomised vitamin E assignment. Conclusions In this large, randomised clinical trial of apparently healthy adult women, assignment of 100 mg of aspirin on alternate days reduced the relative risk of newly reported diagnosis of asthma. PMID:18339679

Bupropion and Naltrexone for Smoking Cessation: A Double-Blind Randomized Placebo-Controlled Clinical Trial

PubMed Central

Mooney, Marc E.; Schmitz, Joy M.; Allen, Sharon; Grabowski, John; Pentel, Paul; Oliver, Andrew; Hatsukami, Dorothy K.

2016-01-01

Combination of non-nicotine pharmacotherapies has been under-examined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + Placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically-verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP+NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP+NTX, 54.1%; BUP+PBO, 33.3%), p = 0.0210, but not at 6-month follow-up (BUP+NTX, 27.9%; BUP+PBO, 15.0%), p = 0.09. Continuous abstinence rates did not differ, p = 0.0740 (BUP+NTX, 26.2%; BUP+PBO, 13.3%). Those receiving BUP+NTX reported reduced nicotine withdrawal, p = 0.0364. The BUP+NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups. PMID:27213949

Quantitative research.

PubMed

Watson, Roger

2015-04-01

This article describes the basic tenets of quantitative research. The concepts of dependent and independent variables are addressed and the concept of measurement and its associated issues, such as error, reliability and validity, are explored. Experiments and surveys – the principal research designs in quantitative research – are described and key features explained. The importance of the double-blind randomised controlled trial is emphasised, alongside the importance of longitudinal surveys, as opposed to cross-sectional surveys. Essential features of data storage are covered, with an emphasis on safe, anonymous storage. Finally, the article explores the analysis of quantitative data, considering what may be analysed and the main uses of statistics in analysis.

Study protocol--metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: a randomised, placebo-controlled, double-blind vitamin D intervention.

PubMed

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-07-31

The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome. Registered clinical. Registered clinical trial--Registration No. ACTRN12607000642482.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand

PubMed Central

2012-01-01

Background There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. Methods A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7–18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Discussion Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. Trial registration clinicaltrial.gov. Registration number: NCT01563640 PMID:23153360

Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention

PubMed Central

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-01-01

Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482 PMID:18667086

Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)

PubMed Central

Adrion, Christine; Fischer, Carolin Simone; Wagner, Judith; Gürkov, Robert; Mansmann, Ulrich

2016-01-01

Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms. What this study adds Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere’s disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere’s disease. Funding, competing interests, data sharing Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668. PMID:26797774

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

PubMed

Wickens, Kristin L; Barthow, Christine A; Murphy, Rinki; Abels, Peter R; Maude, Robyn M; Stone, Peter R; Mitchell, Edwin A; Stanley, Thorsten V; Purdie, Gordon L; Kang, Janice M; Hood, Fiona E; Rowden, Judy L; Barnes, Phillipa K; Fitzharris, Penny F; Crane, Julian

2017-03-01

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques.

PubMed

Conaghan, Philip G; Østergaard, Mikkel; Bowes, Michael A; Wu, Chunying; Fuerst, Thomas; van der Heijde, Désirée; Irazoque-Palazuelos, Fedra; Soto-Raices, Oscar; Hrycaj, Pawel; Xie, Zhiyong; Zhang, Richard; Wyman, Bradley T; Bradley, John D; Soma, Koshika; Wilkinson, Bethanie

2016-06-01

To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. NCT01164579. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

PubMed

Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

2017-02-03

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

Fixed-pressure CPAP versus auto-adjusting CPAP: comparison of efficacy on blood pressure in obstructive sleep apnoea, a randomised clinical trial.

PubMed

Pépin, J L; Tamisier, R; Baguet, J P; Lepaulle, B; Arbib, F; Arnol, N; Timsit, J F; Lévy, P

2016-08-01

Millions of individuals with obstructive sleep apnoea (OSA) are treated by CPAP aimed at reducing blood pressure (BP) and thus cardiovascular risk. However, evidence is scarce concerning the impact of different CPAP modalities on BP evolution. This double-blind, randomised clinical trial of parallel groups of patients with OSA indicated for CPAP treatment compared the efficacy of fixed-pressure CPAP (FP-CPAP) with auto-adjusting CPAP (AutoCPAP) in reducing BP. The primary endpoint was the change in office systolic BP after 4 months. Secondary endpoints included 24 h BP measurements. Patients (322) were randomised to FP-CPAP (n=161) or AutoCPAP (n=161). The mean apnoea+hypopnoea index (AHI) was 43/h (SD, 21); mean age was 57 (SD, 11), with 70% of males; mean body mass index was 31.3 kg/m(2) (SD, 6.6) and median device use was 5.1 h/night. In the intention-to-treat analysis, office systolic blood pressure decreased by 2.2 mm Hg (95% CI -5.8 to 1.4) and 0.4 mm Hg (-4.3 to 3.4) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.3 mm Hg (95% CI -4.1 to 1.5); p=0.37, adjusted for baseline BP values). 24 h diastolic BP (DBP) decreased by 1.7 mm Hg (95% CI -3.9 to 0.5) and 0.5 mm Hg (95% CI -2.3 to 1.3) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.4 mm Hg (95% CI -2.7 to -0.01); p=0.048, adjusted for baseline BP values). The result was negative regarding the primary outcome of office BP, while FP-CPAP was more effective in reducing 24 h DBP (a secondary outcome). NCT01090297. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study.

PubMed

Cohen, Stanley B; Alonso-Ruiz, Alberto; Klimiuk, Piotr A; Lee, Eric C; Peter, Nuala; Sonderegger, Ivo; Assudani, Deepak

2018-06-01

To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira. Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24. Further efficacy and safety endpoints and immunogenicity were assessed up to week 58. 645 patients were randomised. At week 12, 67.0% and 61.1% (90% CI -0.9 to 12.7) of patients receiving BI 695501 (n=324) and Humira (n=321), respectively, achieved ACR20; at week 24 the corresponding values were 69.0% and 64.5% (95% CI -3.4 to 12.5). These differences were within prespecified margins (week 12: 90% CI (-12% to 15%); week 24: 95% CI (-15% to 15%)), demonstrating therapeutic bioequivalence. 593 patients were rerandomised at week 24. Up to week 48, mean change from baseline in Disease Activity Score 28-erythrocyte sedimentation rate and ACR20/ACR50/ACR70 response rates were similar across the switched (n=147), continuous BI 695501 (n=298) and continuous Humira (n=148) groups. Similar immunogenicity (antidrug antibodies (ADAs), ADA titres and neutralising antibodies) was seen between BI 695501 and Humira (to week 24) and across rerandomised groups (to week 48). Safety and tolerability profiles were similar between groups. BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira; switch from Humira to BI 695501 had no impact on efficacy, safety and immunogenicity. NCT02137226, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Randomised, controlled trial of avocado-soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study.

PubMed

Maheu, Emmanuel; Cadet, Christian; Marty, Marc; Moyse, Dominique; Kerloch, Isabelle; Coste, Philippe; Dougados, Maxime; Mazières, Bernard; Spector, Tim D; Halhol, Hafid; Grouin, Jean-Marie; Lequesne, Michel

2014-02-01

To assess the ability of avocado-soybean unsaponifiable-Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of 'progressors' (JSW loss≥0.5 mm) between groups. 399 patients were randomised (345 kept in the FAS), aged 62 (35-84) years, 54% women, mean body mass index 27 (SD 4) kg/m(2), mean symptom duration 4 (SD 5) years, 0-100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (-0.638 mm vs -0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment.

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial

PubMed Central

Ali, Ather; Weiss, Theresa R; McKee, Douglas; Scherban, Alisa; Khan, Sumiya; Fields, Maxine R; Apollo, Damian; Mehal, Wajahat Z

2017-01-01

Background Patients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in patients with IBS guided by a leucocyte activation test. Methods This is a parallel-group, double-blind, randomised controlled trial of 58 adults with IBS seen at an academic health centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte activation test; individual foods were reported to produce positive or negative results. Participants were randomised to a 4-week diet with either individualised guidance to eliminate foods with positive assay results and allow foods with negative assay results (intervention), or with individualised guidance, matched in rigour and complexity, to eliminate foods with negative assay results and allow foods with positive assay results (comparison). The primary outcome was between-group differences in the IBS Global Improvement Scale (GIS). Secondary outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An aptamer-based proteomic analysis was conducted in strong responders. Results The intervention group had significantly greater increases in mean GIS score after 4 weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had significantly greater reductions in mean SSS score at 4 weeks (–61.78 vs comparison; 95% CI –4.43 to –119.14; p=0.04) and 8 weeks (–66.42 vs comparison; 95% CI –5.75 to –127.09; p=0.03). There were no significant differences between intervention and comparison groups in mean AR or QOL scores. A reduction in neutrophil elastase concentration was associated with reduced symptoms. Conclusions Elimination diets guided by leucocyte activation tests reduced symptoms. These findings could lead to insights into the pathophysiology of IBS. Trial registration number NCT02186743. PMID:29018540