The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Process evaluation results from the HEALTHY nutrition intervention to modify the total school food environment

USDA-ARS?s Scientific Manuscript database

The process evaluation of HEALTHY, a large multi-center trial to decrease type 2 diabetes mellitus in middle school children, monitored the implementation of the intervention to ascertain the extent that components were delivered and received as intended. The purpose of this article is to report the...

Efficacy and Safety of Frozen Blood for Transfusion in Trauma Patients - A Multi-Center Trial

DTIC Science & Technology

2015-04-01

threshold are based on a randomized controlled trial by Hébert et al . that showed that critically ill patients who are not actively bleeding should not...causes of increased morbidity and mortality in several studies [23-28]. In a large study, Malone et al . assessed the effect of blood transfusion on...strong independent predictor of mortality. Another study published by Murrell et al . did not find an association between the dose of aged blood and

Bone stimulation for fracture healing: What's all the fuss?

PubMed Central

Victoria, Galkowski; Petrisor, Brad; Drew, Brian; Dick, David

2009-01-01

Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of “bone growth stimulators.” This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods. PMID:19838359

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

PubMed

Lam, Ming Kai; Sen, Hanim; Tandjung, Kenneth; van Houwelingen, K Gert; de Vries, Arie G; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Löwik, Marije M; Linssen, Gerard C M; Ijzerman, Maarten J; van der Palen, Job; Doggen, Carine J M; von Birgelen, Clemens

2014-04-01

To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

PubMed Central

Wind, Jan; Hofland, Jan; Preckel, Benedikt; Hollmann, Markus W; Bossuyt, Patrick MM; Gouma, Dirk J; van Berge Henegouwen, Mark I; Fuhring, Jan Willem; Dejong, Cornelis HC; van Dam, Ronald M; Cuesta, Miguel A; Noordhuis, Astrid; de Jong, Dick; van Zalingen, Edith; Engel, Alexander F; Goei, T Hauwy; de Stoppelaar, I Erica; van Tets, Willem F; van Wagensveld, Bart A; Swart, Annemiek; van den Elsen, Maarten JLJ; Gerhards, Michael F; de Wit, Laurens Th; Siepel, Muriel AM; van Geloven, Anna AW; Juttmann, Jan-Willem; Clevers, Wilfred; Bemelman, Willem A

2006-01-01

Background Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. Methods/design The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. Discussion The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease. PMID:17134506

Participation of a coordinating center pharmacy in a multicenter international study.

PubMed

Jeon, Jihyun Esther; Mighty, Janet; Lane, Karen; McBee, Nichol; Majkowski, Ryan; Mayo, Steven; Hanley, Daniel

2016-11-15

The activities of a coordinating center pharmacy (CCP) supporting a multicenter, international clinical trial are described. Serving in a research support role comparable to that of a commercial clinical trial supply company, a CCP within the Johns Hopkins Hospital Investigational Drug Service (JHH IDS) uses its management expertise and infrastructure to support multicenter trials, such as the recently completed Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage, Phase III (CLEAR III) trial. The role of the CCP staff in supporting the CLEAR III trial was overall investigational product (IP) management through coordination of IP-related operations to ensure high-quality care for study participants at study sites in the United States and abroad. For the CLEAR III trial, the CCP coordinated IP supply activities; provided education to site pharmacists; developed study-specific documents, including pharmacy manuals; communicated with trial stakeholders, including third-party IP distributors; monitored treatment assignments; and performed quality assurance monitoring to ensure compliance with institutional, state, federal, and international regulations regarding IP procurement and storage. Acting as a CCP for a multicenter international study poses a number of operational challenges while providing opportunities for the CCP to contribute to research of global importance and enrich the skill sets of its personnel. The development and implementation of the CCP at JHH IDS for the CLEAR III trial included several responsibilities, such as IP supply management, communication, and database, regulatory, and finance management. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

PubMed Central

2014-01-01

Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Identifying and collecting pertinent medical records for centralized abstraction in a multi-center randomized clinical trial: the model used by the American College of Radiology arm of the National Lung Screening Trial.

PubMed

Gareen, Ilana F; Sicks, JoRean D; Jain, Amanda Adams; Moline, Denise; Coffman-Kadish, Nancy

2013-01-01

In clinical trials and epidemiologic studies, information on medical care utilization and health outcomes is often obtained from medical records. For multi-center studies, this information may be gathered by personnel at individual sites or by staff at a central coordinating center. We describe the process used to develop a HIPAA-compliant centralized process to collect medical record information for a large multi-center cancer screening trial. The framework used to select, request, and track medical records incorporated a participant questionnaire with unique identifiers for each medical provider. De-identified information from the questionnaires was sent to the coordinating center indexed by these identifiers. The central coordinating center selected specific medical providers for abstraction and notified sites using these identifiers. The site personnel then linked the identifiers with medical provider information. Staff at the sites collected medical records and provided them for central abstraction. Medical records were successfully obtained and abstracted to ascertain information on outcomes and health care utilization in a study with over 18,000 study participants. Collection of records required for outcomes related to positive screening examinations and lung cancer diagnosis exceeded 90%. Collection of records for all aims was 87.32%. We designed a successful centralized medical record abstraction process that may be generalized to other research settings, including observational studies. The coordinating center received no identifying data. The process satisfied requirements imposed by the Health Insurance Portability and Accountability Act and concerns of site institutional review boards with respect to protected health information. Copyright © 2012 Elsevier Inc. All rights reserved.

Identifying and collecting pertinent medical records for centralized abstraction in a multi-center randomized clinical trial: The model used by the American College of Radiology arm of the National Lung Screening Trial

PubMed Central

Gareen, Ilana F.; Sicks, JoRean; Adams, Amanda; Moline, Denise; Coffman-Kadish, Nancy

2012-01-01

Background In clinical trials and epidemiologic studies, information on medical care utilization and health outcomes is often obtained from medical records. For multi-center studies, this information may be gathered by personnel at individual sites or by staff at a central coordinating center. We describe the process used to develop a HIPAA-compliant centralized process to collect medical record information for a large multi-center cancer screening trial. Methods The framework used to select, request, and track medical records incorporated a participant questionnaire with unique identifiers for each medical provider. De-identified information from the questionnaires was sent to the coordinating center indexed by these identifiers. The central coordinating center selected specific medical providers for abstraction and notified sites using these identifiers. The site personnel then linked the identifiers with medical provider information. Staff at the sites collected medical records and provided them for central abstraction. Results Medical records were successfully obtained and abstracted to ascertain information on outcomes and health care utilization in a study with over 18,000 study participants. Collection of records required for outcomes related to positive screening examinations and lung cancer diagnosis exceeded 90%. Collection of records for all aims was 87.32%. Conclusions We designed a successful centralized medical record abstraction process that may be generalized to other research settings, including observational studies. The coordinating center received no identifying data. The process satisfied requirements imposed by the Health Insurance Portability and Accountability Act and concerns of site institutional review boards with respect to protected health information. PMID:22982342

Logistics and quality control for DNA sampling in large multicenter studies.

PubMed

Nederhand, R J; Droog, S; Kluft, C; Simoons, M L; de Maat, M P M

2003-05-01

To study associations between genetic variation and disease, large bio-banks need to be created in multicenter studies. Therefore, we studied the effects of storage time and temperature on DNA quality and quantity in a simulation experiment with storage up to 28 days frozen, at 4 degrees C and at room temperature. In the simulation experiment, the conditions did not influence the amount or quality of DNA to an unsatisfactory level. However, the amount of extracted DNA was decreased in frozen samples and in samples that were stored for > 7 days at room temperature. In a sample of patients from 24 countries of the EUROPA trial obtained by mail with transport times up to 1 month DNA yield and quality were adequate. From these results we conclude that transport of non-frozen blood by ordinary mail is usable and practical for DNA isolation for polymerase chain reaction in clinical and epidemiological studies.

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis

PubMed Central

Dorst, Johannes; Ludolph, Albert C.; Huebers, Annemarie

2017-01-01

In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important. Nutrition and ventilation are now an important focus of ALS therapy. Several studies have firmly established that noninvasive ventilation improves patients’ quality of life and prolongs survival. On the other hand, there is still no consensus regarding best nutritional management, but big multicenter trials addressing this issue are currently ongoing. Evidence regarding secondary symptoms like spasticity, muscle cramps or sialorrhea remains generally scarce, but some new insights will also be discussed. Growing evidence suggests that multidisciplinary care in specialized clinics improves survival. PMID:29399045

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

PubMed

Deschamps, Alain; Hall, Richard; Grocott, Hilary; Mazer, C David; Choi, Peter T; Turgeon, Alexis F; de Medicis, Etienne; Bussières, Jean S; Hudson, Christopher; Syed, Summer; Seal, Doug; Herd, Stuart; Lambert, Jean; Denault, André; Deschamps, Alain; Mutch, Alan; Turgeon, Alexis; Denault, Andre; Todd, Andrea; Jerath, Angela; Fayad, Ashraf; Finnegan, Barry; Kent, Blaine; Kennedy, Brent; Cuthbertson, Brian H; Kavanagh, Brian; Warriner, Brian; MacAdams, Charles; Lehmann, Christian; Fudorow, Christine; Hudson, Christopher; McCartney, Colin; McIsaac, Dan; Dubois, Daniel; Campbell, David; Mazer, David; Neilpovitz, David; Rosen, David; Cheng, Davy; Drapeau, Dennis; Dillane, Derek; Tran, Diem; Mckeen, Dolores; Wijeysundera, Duminda; Jacobsohn, Eric; Couture, Etienne; de Medicis, Etienne; Alam, Fahad; Abdallah, Faraj; Ralley, Fiona E; Chung, Frances; Lellouche, Francois; Dobson, Gary; Germain, Genevieve; Djaiani, George; Gilron, Ian; Hare, Gregory; Bryson, Gregory; Clarke, Hance; McDonald, Heather; Roman-Smith, Helen; Grocott, Hilary; Yang, Homer; Douketis, James; Paul, James; Beaubien, Jean; Bussières, Jean; Pridham, Jeremy; Armstrong, J N; Parlow, Joel; Murkin, John; Gamble, Jonathan; Duttchen, Kaylene; Karkouti, Keyvan; Turner, Kim; Baghirzada, Leyla; Szabo, Linda; Lalu, Manoj; Wasowicz, Marcin; Bautista, Michael; Jacka, Michael; Murphy, Michael; Schmidt, Michael; Verret, Michaël; Perrault, Michel-Antoine; Beaudet, Nicolas; Buckley, Norman; Choi, Peter; MacDougall, Peter; Jones, Philip; Drolet, Pierre; Beaulieu, Pierre; Taneja, Ravi; Martin, Rene; Hall, Richard; George, Ronald; Chun, Rosa; McMullen, Sarah; Beattie, Scott; Sampson, Sonia; Choi, Stephen; Kowalski, Stephen; McCluskey, Stuart; Syed, Summer; Boet, Sylvain; Ramsay, Tim; Saha, Tarit; Mutter, Thomas; Chowdhury, Tumul; Uppal, Vishal; Mckay, William

2016-04-01

Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

PROMISE of Coronary CT Angiography: Precise and Accurate Diagnosis and Prognosis in Coronary Artery Disease.

PubMed

Thomas, Dustin M; Branch, Kelley R; Cury, Ricardo C

2016-04-01

Coronary computed tomography angiography (CCTA) is a rapidly growing and powerful diagnostic test that offers a great deal of precision with respect to diagnosing coronary artery disease (CAD). Guideline statements for patients with stable ischemic heart disease have recommended CCTA for only a limited portion of intermediate-risk patients who have relative or absolute contraindications for exercise or vasodilator stress testing. The publication of two large, prospective randomized clinical trials, the Prospective Multicenter Imaging Study for Evaluation of Chest Pain and the Scottish Computed Tomography of the Heart Trial are likely to expand these indications. These new data from large trials, in addition to other studies, show that CCTA is highly sensitive for the detection of CAD, identifies high-risk patients for cardiac events based on extent or plaque morphology of CAD that would not be identified by other noninvasive means, and provides significantly greater diagnostic certainty for proper treatment, including referral for invasive coronary angiography with revascularization more appropriately. Superior diagnostic accuracy and prognostic data with CCTA, when compared with other functional stress tests, may result in a reduction in unnecessary downstream testing and cost savings. In addition, newer CCTA applications hold the promise of providing a complete evaluation of a patient's coronary anatomy as well as a per-vessel ischemic evaluation. This review focuses on the interval knowledge obtained from newer data on CCTA in patients with stable ischemic heart disease, primarily focusing on the contributions of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain and the Scottish Computed Tomography of the Heart Trial.

Advancing the evidence base in cancer: psychosocial multicenter trials

PubMed Central

2012-01-01

Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

Comparative effectiveness and cost-effectiveness of Chuna manual therapy versus conventional usual care for nonacute low back pain: study protocol for a pilot multicenter, pragmatic randomized controlled trial (pCRN study).

PubMed

Shin, Byung-Cheul; Kim, Me-Riong; Cho, Jae-Heung; Jung, Jae-Young; Kim, Koh-Woon; Lee, Jun-Hwan; Nam, Kibong; Lee, Min Ho; Hwang, Eui-Hyoung; Heo, Kwang-Ho; Kim, Namkwen; Ha, In-Hyuk

2017-01-17

While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce. This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment. This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial. Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016.

Safety and efficacy of a 10% intravenous immunoglobulin preparation in patients with immune thrombocytopenic purpura: results of two international, multicenter studies.

PubMed

Kovaleva, Lidia; Apte, Shashikant; Damodar, Sharat; Ramanan, Vijay; Loriya, Svetlana; Navarro-Puerto, Jordi; Khojasteh, Ali

2016-12-01

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma ® 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 9 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

PubMed Central

Papachristou, Georgios I.; Machicado, Jorge D.; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C.; Singh, Vikesh K.; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A.; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O.; Triantafyllou, Konstantinos; Barbu, Sorin T.; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A.; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch.; Nawaz, Haq; Park, Walter G.; de-Madaria, Enrique; Lee, Peter J.; Wu, Bechien U.; Greer, Phil J.; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials. PMID:28042246

Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

PubMed

Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

2017-01-01

The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P < .001). Radiologic devices are largely approved by multireader, multicenter studies, the recommended standard for assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

PubMed

Davis, Stephanie D; Ratjen, Felix; Brumback, Lyndia C; Johnson, Robin C; Filbrun, Amy G; Kerby, Gwendolyn S; Panitch, Howard B; Donaldson, Scott H; Rosenfeld, Margaret

2016-05-01

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada - baseline findings of a multicenter trial.

PubMed

Umeh, Chizoba C; Pérez, Adriana; Augustine, Erika F; Dhall, Rohit; Dewey, Richard B; Mari, Zoltan; Simon, David K; Wills, Anne-Marie A; Christine, Chadwick W; Schneider, Jay S; Suchowersky, Oksana

2014-01-01

Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy - the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease.

Statistical monitoring of data quality and consistency in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial.

PubMed

Timmermans, Catherine; Doffagne, Erik; Venet, David; Desmet, Lieven; Legrand, Catherine; Burzykowski, Tomasz; Buyse, Marc

2016-01-01

Data quality may impact the outcome of clinical trials; hence, there is a need to implement quality control strategies for the data collected. Traditional approaches to quality control have primarily used source data verification during on-site monitoring visits, but these approaches are hugely expensive as well as ineffective. There is growing interest in central statistical monitoring (CSM) as an effective way to ensure data quality and consistency in multicenter clinical trials. CSM with SMART™ uses advanced statistical tools that help identify centers with atypical data patterns which might be the sign of an underlying quality issue. This approach was used to assess the quality and consistency of the data collected in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, involving 1495 patients across 232 centers in Japan. In the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, very few atypical data patterns were found among the participating centers, and none of these patterns were deemed to be related to a quality issue that could significantly affect the outcome of the trial. CSM can be used to provide a check of the quality of the data from completed multicenter clinical trials before analysis, publication, and submission of the results to regulatory agencies. It can also form the basis of a risk-based monitoring strategy in ongoing multicenter trials. CSM aims at improving data quality in clinical trials while also reducing monitoring costs.

Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology.

PubMed

Simpson, Jennifer L; Melia, Michele; Yang, Michael B; Buffenn, Angela N; Chiang, Michael F; Lambert, Scott R

2012-04-01

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

["Notebook computer" in combination with WWW-technology in multicenter clinical trials and for chronic patient care].

PubMed

Koop, A; Gatermann, C; Mösges, R

2000-01-01

Our purpose was to determine conditions, under which the use of hand-held computers in the diagnosis and therapy of patients with chronic diseases seems to be handy. Two scenarios are presented showing the employment of these computers in a doctor's office and in multicenter clinical trials. Security-related aspects involved in transferring medical data via the internet are discussed.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

Hysterectomy for complications after uterine artery embolization for leiomyoma: results of a Canadian multicenter clinical trial.

PubMed

Pron, Gaylene; Mocarski, Eva; Cohen, Marsha; Colgan, Terence; Bennett, John; Common, Andrew; Vilos, George; Kung, Rose

2003-02-01

To determine the complication-related hysterectomy rate after uterine artery embolization (UAE) for symptomatic uterine leiomyomas. Prospective, multicenter, nonrandomized, single-arm clinical trial (Canadian Task Force classification II-2). Eight Ontario University-affiliated teaching and community hospitals. Five hundred fifty-five women. Polyvinyl alcohol particles were delivered through a catheter into uterine arteries under fluoroscopic guidance. Prospective follow-up investigations consisted of telephone interviews, ultrasound examinations, and reviews of pathology and surgery reports. Median follow-up was 8.1 months, and all but five patients had complete 3-month follow-up. At 3 months, eight women (1.5%, 95% CI 0.6-2.8) underwent complication-related hysterectomy. Half of the surgeries were performed at institutions other than where UAE had been performed. Indications for hysterectomies were infections (2), postembolization pain (4), vaginal bleeding (1), and prolapsed leiomyoma (1). The 3-month complication rate resulting in hysterectomy after UAE in a large cohort of women was low. Hysterectomy after UAE is an important measure of safety and a key outcome measure of this new therapy.

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

PubMed

Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

2017-06-23

Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study

PubMed Central

Carter, Rickey E; Sonne, Susan C; Brady, Kathleen T

2005-01-01

Background Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated. Methods This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development. Results Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period. Conclusion The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial. PMID:15796782

A multicenter, randomized, controlled trial of osteopathic manipulative treatment on preterms.

PubMed

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D'Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D'Incecco, Carmine; Barlafante, Gina

2015-01-01

Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants.

Accounting for center in the Early External Cephalic Version trials: an empirical comparison of statistical methods to adjust for center in a multicenter trial with binary outcomes.

PubMed

Reitsma, Angela; Chu, Rong; Thorpe, Julia; McDonald, Sarah; Thabane, Lehana; Hutton, Eileen

2014-09-26

Clustering of outcomes at centers involved in multicenter trials is a type of center effect. The Consolidated Standards of Reporting Trials Statement recommends that multicenter randomized controlled trials (RCTs) should account for center effects in their analysis, however most do not. The Early External Cephalic Version (EECV) trials published in 2003 and 2011 stratified by center at randomization, but did not account for center in the analyses, and due to the nature of the intervention and number of centers, may have been prone to center effects. Using data from the EECV trials, we undertook an empirical study to compare various statistical approaches to account for center effect while estimating the impact of external cephalic version timing (early or delayed) on the outcomes of cesarean section, preterm birth, and non-cephalic presentation at the time of birth. The data from the EECV pilot trial and the EECV2 trial were merged into one dataset. Fisher's exact method was used to test the overall effect of external cephalic version timing unadjusted for center effects. Seven statistical models that accounted for center effects were applied to the data. The models included: i) the Mantel-Haenszel test, ii) logistic regression with fixed center effect and fixed treatment effect, iii) center-size weighted and iv) un-weighted logistic regression with fixed center effect and fixed treatment-by-center interaction, iv) logistic regression with random center effect and fixed treatment effect, v) logistic regression with random center effect and random treatment-by-center interaction, and vi) generalized estimating equations. For each of the three outcomes of interest approaches to account for center effect did not alter the overall findings of the trial. The results were similar for the majority of the methods used to adjust for center, illustrating the robustness of the findings. Despite literature that suggests center effect can change the estimate of effect in multicenter trials, this empirical study does not show a difference in the outcomes of the EECV trials when accounting for center effect. The EECV2 trial was registered on 30 July 30 2005 with Current Controlled Trials: ISRCTN 56498577.

Challenges in the design and implementation of the Multicenter Uveitis Steroid Treatment (MUST) Trial--lessons for comparative effectiveness trials.

PubMed

Holbrook, Janet T; Kempen, John H; Prusakowski, Nancy A; Altaweel, Michael M; Jabs, Douglas A

2011-12-01

Randomized clinical trials (RCTs) are an important component of comparative effectiveness (CE) research because they are the optimal design for head-to-head comparisons of different treatment options. To describe decisions made in the design of the Multicenter Uveitis Steroid Treatment (MUST) Trial to ensure that the results would be widely generalizable. Review of design and implementation decisions and their rationale for the trial. The MUST Trial is a multicenter randomized controlled CE trial evaluating a novel local therapy (intraocular fluocinolone acetonide implant) versus the systemic therapy standard of care for noninfectious uveitis. Decisions made in protocol design in order to broaden enrollment included allowing patients with very poor vision and media opacity to enroll and including clinical sites outside the United States. The treatment protocol was designed to follow standard care. The primary outcome, visual acuity, is important to patients and can be evaluated in all eyes with uveitis. Other outcomes include patient-reported visual function, quality of life, and disease and treatment related complications. The trial population is too small for subgroup analyses that are of interest and the trial is being conducted at tertiary medical centers. CE trials require greater emphasis on generalizability than many RCTs but otherwise face similar challenges for design choices as any RCT. The increase in heterogeneity in patients and treatment required to ensure generalizability can be balanced with a rigorous approach to implementation, outcome assessment, and statistical design. This approach requires significant resources that may limit implementation in many RCTs, especially in clinical practice settings.

Hyperbaric oxygen for neurologic indications--action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus.

PubMed

Helms, A; Evans, A W; Chu, J; Sahgal, A; Ostrowski, R; Sosiak, T; Wolf, G; Gillett, J; Whelan, H

2011-01-01

The 2008 Toronto Hyperbaric Medicine Symposium was convened to discuss research into neurologic indications for hyperbaric oxygen therapy (HBO2T). Four topics were particularly addressed: acute ischemic stroke; acute traumatic brain injury; brain radiation necrosis; and status migrainosus. Four multicenter trials were designed and proposed to evaluate the efficacy of HBO2T for these indications and are presented here in addition to brief reviews of the rationale behind each.

Fluid Lavage of Open Wounds (FLOW): A Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures

DTIC Science & Technology

2013-10-01

Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures PRINCIPAL...Solutions and Pressures in Patients with Open Fractures 5b. GRANT NUMBER W81XWH-12-1-0530 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kyle J. Jeray...important initial step in preventing infection in open fractures . However, there is little clinical evidence as to the best irrigation methods and additives

Multicenter Trial of Sentinel Node Biopsy for Breast Cancer Using Both Technetium Sulfur Colloid and Isosulfan Blue Dye

PubMed Central

Tafra, Lorraine; Lannin, Donald R.; Swanson, Melvin S.; Van Eyk, Jason J.; Verbanac, Kathryn M.; Chua, Arlene N.; Ng, Peter C.; Edwards, Maxine S.; Halliday, Bradford E.; Henry, C. Alan; Sommers, Linda M.; Carman, Claire M.; Molin, Melinda R.; Yurko, John E.; Perry, Roger R.; Williams, Robert

2001-01-01

Objective To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). Summary Background Data Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. Methods Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. Results Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. Conclusions This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation. PMID:11141225

Clinical research in Finland in 2002 and 2007: quantity and type

PubMed Central

2013-01-01

Background Regardless of worries over clinical research and various initiatives to overcome problems, few quantitative data on the numbers and type of clinical research exist. This article aims to describe the volume and type of clinical research in 2002 and 2007 in Finland. Methods The research law in Finland requires all medical research to be submitted to regional ethics committees (RECs). Data from all new projects in 2002 and 2007 were collected from REC files and the characteristics of clinical projects (76% of all submissions) were analyzed. Results The number of clinical projects was large, but declining: 794 in 2002 and 762 in 2007. Drug research (mainly trials) represented 29% and 34% of the clinical projects; their total number had not declined, but those without a commercial sponsor had. The number of different principal investigators was large (630 and 581). Most projects were observational, while an experimental design was used in 43% of projects. Multi-center studies were common. In half of the projects, the main funder was health care or was done as unpaid work; 31% had industry funding as the main source. There was a clear difference in the type of research by sponsorship. Industry-funded research was largely drug research, international multi-center studies, with randomized controlled or other experimental design. The findings for the two years were similar, but a university hospital as the main research site became less common between 2002 and 2007. Conclusions Clinical research projects were common, but numbers are declining; research was largely funded by health care, with many physicians involved. Drug trials were a minority, even though most research promotion efforts and regulation concerns them. PMID:23680289

Clinical research in Finland in 2002 and 2007: quantity and type.

PubMed

Hemminki, Elina; Virtanen, Jorma; Veerus, Piret; Regushevskaya, Elena

2013-05-16

Regardless of worries over clinical research and various initiatives to overcome problems, few quantitative data on the numbers and type of clinical research exist. This article aims to describe the volume and type of clinical research in 2002 and 2007 in Finland. The research law in Finland requires all medical research to be submitted to regional ethics committees (RECs). Data from all new projects in 2002 and 2007 were collected from REC files and the characteristics of clinical projects (76% of all submissions) were analyzed. The number of clinical projects was large, but declining: 794 in 2002 and 762 in 2007. Drug research (mainly trials) represented 29% and 34% of the clinical projects; their total number had not declined, but those without a commercial sponsor had. The number of different principal investigators was large (630 and 581). Most projects were observational, while an experimental design was used in 43% of projects. Multi-center studies were common. In half of the projects, the main funder was health care or was done as unpaid work; 31% had industry funding as the main source. There was a clear difference in the type of research by sponsorship. Industry-funded research was largely drug research, international multi-center studies, with randomized controlled or other experimental design. The findings for the two years were similar, but a university hospital as the main research site became less common between 2002 and 2007. Clinical research projects were common, but numbers are declining; research was largely funded by health care, with many physicians involved. Drug trials were a minority, even though most research promotion efforts and regulation concerns them.

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

PubMed Central

Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2014-01-01

Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial: A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial.

PubMed

Rogers, Amy; Flynn, Robert Wv; McDonnell, Patrick; Mackenzie, Isla S; MacDonald, Thomas M

2016-12-01

Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial. A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee. To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed. The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large-scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system. © The Author(s) 2016.

A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

2015-01-01

Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

When Is It Appropriate to Use Glutamine in Critical Illness?

PubMed

Mundi, Manpreet S; Shah, Meera; Hurt, Ryan T

2016-08-01

Glutamine is a nonessential amino acid, which under trauma or critical illness can become essential. A number of historic small single-center randomized controlled trials (RCTs) have demonstrated positive treatment effects on clinical outcomes with glutamine supplementation. Meta-analyses based on these trials demonstrated a significant reduction in hospital mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS with intravenous (IV) glutamine. Similar results were not noted in 2 large multicenter RCTs (REDOXS and MetaPlus) assessing the efficacy of glutamine supplementation in ventilated ICU patients. The REDOXS trial of 40 ICUs randomized 1223 ventilated ICU patients to glutamine (IV and enteral), antioxidants, both glutamine and antioxidants, or placebo. The main conclusions were a trend toward increased 28-day mortality and significant increased hospital and 6-month mortality in those who received glutamine. The MetaPlus trial of 14 ICUs, which randomized 301 ventilated ICU patients to glutamine-enriched enteral vs an isocaloric diet, noted increased 6-month mortality in the glutamine-supplemented group. Newer RCTs have focused on specific populations and have demonstrated benefits in burn and elective surgery patients with glutamine supplementation. Whether larger studies will confirm these findings is yet to be determined. Recent American Society for Parenteral and Enteral Nutrition guidelines recommend that IV and enteral glutamine should not be used in the critical care setting based on the moderate quality of evidence available. We agree with these recommendations and would encourage larger multicenter studies to evaluate the risks and benefits of glutamine in burn and elective surgery patients. © 2016 American Society for Parenteral and Enteral Nutrition.

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): rationale and study design of a randomized multicenter trial in a Dutch all-comers population.

PubMed

Tandjung, Kenneth; Basalus, Mounir W Z; Sen, Hanim; Jessurun, Gillian A J; Danse, Peter W; Stoel, Martin; Linssen, Gerard C M; Derks, Anita; van Loenhout, Ton T; Nienhuis, Mark B; Hautvast, Raymond W M; von Birgelen, Clemens

2012-04-01

Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES. Copyright © 2012 Mosby, Inc. All rights reserved.

Endovascular vs medical management of acute ischemic stroke

PubMed Central

Ding, Dale; Starke, Robert M.; Mehndiratta, Prachi; Crowley, R. Webster; Liu, Kenneth C.; Southerland, Andrew M.; Worrall, Bradford B.

2015-01-01

Objective: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). Methods: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Results: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0–2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No difference was found for mortality at 90 days and sICH between endovascular therapy and medical management in all analyses and subgroup analyses. Conclusions: This meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO. PMID:26537058

Anchor Trial Launch

Cancer.gov

NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

Optimization of a whole blood phenotyping assay for enumeration of peripheral blood leukocyte populations in multicenter clinical trials.

PubMed

Hensley-McBain, Tiffany; Heit, Antje; De Rosa, Stephen C; McElrath, M Juliana; Andersen-Nissen, Erica

2014-09-01

Vaccination with viral vectors or adjuvants can induce early changes in circulating peripheral blood leukocytes that are predictive of a protective immune response. In this study, we define an 11-color whole blood antibody staining Trucount Panel (TP1) to enumerate and phenotype the major leukocyte populations in a human vaccine experimental medicine trial setting. TP1 can be prepared up to 8weeks prior to use, enabling bulk preparation at a central laboratory and distribution to clinical sites. Cells in whole blood must be stained within 4h of draw to accurately detect the major cell populations. Staining of cells with TP1 followed by storage and shipping at -80°C to a central laboratory has little to no effect on the cell concentrations observed. We also present data from an HIV vaccine multicenter clinical trial obtained using the optimized TP1 assay protocol and show that the data produced accurately correlates with complete blood count (CBC) data. Taken together, these data indicate the optimized TP1 panel assay can be used in a multicenter clinical trial setting to increase our understanding of systemic responses to vaccination or disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control, Multicenter Trial

DTIC Science & Technology

2015-01-01

control group; standard skin grafting with 1:1.5 meshing); Arm 2 (experimental group 1; wide 1:6 mesh graft with sprayed cells), and Arm 3...injured patient’s body and grafted over the wounded area to obtain a healed wound. These skin grafts are often “meshed” or flattened and spread out to...increase the size of the skin graft to better cover a large wound. Standard “meshing” increases the size of the donor graft by 1.5 times (1:1.5

Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control, Multicenter Trial

DTIC Science & Technology

2014-04-01

randomization design, after all patients are treated with dermal matrix, patients will be randomized to Arm 1 (control group; standard skin grafting with... grafts are often “meshed” or flattened and spread out to increase the size of the skin graft to better cover a large wound. Standard “meshing” increases...the size of the donor graft by 1.5 times (1:1.5). Problems with healing and skin irritation remain with such skin grafts when the injured areas are

Update on worldwide efforts to prevent type 1 diabetes.

PubMed

Skyler, Jay S

2008-12-01

This paper reviews worldwide efforts to interdict the type 1 diabetes (T1D) disease process, during the stage of evolution of the disease prior to the time of disease onset. The goal of intervention before disease onset is to arrest immune destruction and thus prevent or delay clinical disease. In this regard, there have been several large-scale multicenter randomized controlled clinical trials designed to prevent T1D. These have tested nicotinamide, parenteral insulin, oral insulin, nasal insulin, and the elimination of cow's milk from infant feeding.

Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN)

PubMed Central

English, Joey D.; Yavagal, Dileep R.; Gupta, Rishi; Janardhan, Vallabh; Zaidat, Osama O.; Xavier, Andrew R.; Nogueira, Raul G.; Kirmani, Jawad F.; Jovin, Tudor G.

2016-01-01

Five landmark multicenter, prospective, randomized, open-label, blinded end point clinical trials have recently demonstrated significant clinical benefit of endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS) patients presenting with proximal intracranial large vessel occlusions. The Society of Vascular and Interventional Neurology (SVIN) appointed an expert writing committee to summarize this new evidence and make recommendations on how these data should guide emergency endovascular therapy for AIS patients. PMID:27051410

Preserving cognition, quality of life, physical health and functional ability in Alzheimer's disease: the effect of physical exercise (ADEX trial): rationale and design.

PubMed

Hoffmann, Kristine; Frederiksen, Kristian S; Sobol, Nanna Aue; Beyer, Nina; Vogel, Asmus; Simonsen, Anja Hviid; Johannsen, Peter; Lolk, Annette; Terkelsen, Ole; Cotman, Carl W; Hasselbalch, Steen G; Waldemar, Gunhild

2013-01-01

Exercise is hypothesized to improve cognition, physical performance, functional ability and quality of life, but evidence is scarce. Previous studies were of short duration, often underpowered and involving home-based light exercise programs in patients with undefined dementia. The aim of the ADEX ('Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish whether aerobic exercise is effective in improving cognition as well as in reducing the prevalence of psychiatric symptoms among patients with Alzheimer's disease (AD). The ADEX study is a multicenter, single-blind, randomized trial with two arms: an intervention group attending 16 weeks of continuously supervised moderate-to-high intensity aerobic exercise and a control group receiving usual care. We plan to recruit 192 patients with mild AD. The primary outcome measure is change from baseline in cognitive performance at 16 weeks (as measured by the Symbol Digit Modalities test). To our knowledge this is the first large-scale controlled study to investigate the effects of supervised moderate aerobic exercise on cognition in patients with AD. Recruitment began in January 2012 and results are expected to be available in 2014. We summarize the methodological challenges we and other studies have faced in this type of complex multicenter intervention with unique challenges to study design. © 2013 S. Karger AG, Basel.

Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

PubMed

Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

2013-06-01

Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial (CE-MARC 2): A prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease

PubMed Central

Ripley, David P.; Brown, Julia M.; Everett, Colin C.; Bijsterveld, Petra; Walker, Simon; Sculpher, Mark; McCann, Gerry P.; Berry, Colin; Plein, Sven; Greenwood, John P.

2015-01-01

Background A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance. Trial Design CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance–guided care, single-photon emission computed tomography–guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines–based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed. Conclusions The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation. PMID:25497243

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of hematologic measurements between local and central laboratories: data from the BABY HUG trial.

PubMed

Kalpatthi, Ram; Thompson, Bruce; Lu, Ming; Wang, Winfred C; Patel, Niren; Kutlar, Abdullah; Howard, Thomas; Luchtman-Jones, Lori; Miller, Scott T

2013-02-01

To investigate the concordance of blood count indices measured locally and at a central laboratory. In a multi-center clinical trial of hydroxyurea therapy in infants with sickle cell anemia (BABY HUG), the concordance between blood count indices measured locally and at a central laboratory was investigated. Local laboratory measurements of neutrophil and monocyte counts were significantly higher (44% and 37%, respectively) compared to the central measurements (p<0.0001), and mean corpuscular volume (MCV) was higher centrally. Overnight shipping with processing delay causes spurious reductions in absolute neutrophil count (ANC) and absolute monocyte count (AMC) that may result in incorrect monitoring decisions in multicenter clinical trials. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

PubMed

Naslund, Thomas C; Becker, Stacey Y

2003-01-01

Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success.

Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents.

PubMed

March, John S; Klee, Brian J; Kremer, Charlotte M E

2006-01-01

The aim of this study was to examine the balance between the benefits of treatment and the risk of suicidality in children and adolescents in multicenter, randomized, controlled trials of sertraline versus placebo. The published literature was searched for multicenter, randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four trials were identified: Two (pooled) in pediatric major depressive disorder (MDD; Wagner 2003) and two in obsessive-compulsive disorder (OCD; March et al. 1998; POTS Team 2004). Using intent-to-treat (ITT) analysis populations, the authors calculated the number needed to treat (NNT) for response and remission and the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. NNTs ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for OCD than for MDD, and for adolescents as compared with children in MDD. No age effect was apparent for OCD. Suicidality was reported in 8 patients (5 assigned to sertraline and 3 assigned to placebo). All but 1 (a placebo-treated patient in the Pfizer OCD trial) were enrolled in the sertraline MDD trial. The NNH for suicidality in MDD was 64. Treatment emergent suicidality was more common in children (NNH 28.7) than in adolescents (NNH 706.3). Because no patient developed suicidality in sertraline-treated OCD patients, the NNH for sertraline in OCD approaches infinity. With the stipulation that doctor and patient preferences necessarily play a critical role in the choice of treatment, NNT to NNH ratios indicate a positive benefit-to-risk ratio for sertraline in adolescents with MDD and in patients of all ages with OCD.

The effect of static scanning and mobility training on mobility in people with hemianopia after stroke: A randomized controlled trial comparing standardized versus non-standardized treatment protocols

PubMed Central

2011-01-01

Background Visual loss following stroke impacts significantly on activities of daily living and is an independent risk factor for becoming dependent. Routinely, allied health clinicians provide training for visual field loss, mainly with eye movement based therapy. The effectiveness of the compensatory approach to rehabilitation remains inconclusive largely due to difficulty in validating functional outcome with the varied type and dosage of therapy received by an individual patient. This study aims to determine which treatment is more effective, a standardized approach or individualized therapy in patients with homonymous hemianopia post stroke. Methods/Design This study is a double-blind randomized controlled, multicenter trial. A standardised scanning rehabilitation program (Neuro Vision Technology (NVT) program) of 7 weeks at 3 times per week, is compared to individualized therapy recommended by clinicians. Discussion The results of the trial will provide information that could potentially inform the allocation of resources in visual rehabilitation post stroke. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000494033 PMID:21767413

A cooperative network of trained sites for the conduct of a complex clinical trial: a new concept in multicenter clinical research.

PubMed

Davidson, Robert M; McNeer, J Frederick; Logan, Leanne; Higginbotham, Michael B; Anderson, Jerome; Blackshear, Joseph; Chu, Alan; Hettleman, Bruce; McGrew, Frank; Meesse, Roderick; O'Connor, Christopher; Schneider, Ricky; Wagner, Galen S

2006-02-01

The purpose of this report is to present a model of physicians in full-time clinical practice participating as investigators in multicenter clinical trials, sponsored by a pharmaceutical or medical device company. This gas-exchange substudy was conducted as a pilot study to establish the feasibility of the 10-member EXERcise testing group of the Duke University Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex multicenter trial using cardiopulmonary exercise testing. An active interchange of information was established involving the principal investigator for the substudy, a dedicated full-time project coordinator, a medical director of the overall EXERDUCCS network site, the project coordinator for the sponsor, and all the participating EXERDUCCS investigators and coordinators. The sponsor set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met this goal. As a result of the successful enrollment and completion of the study and substudy by the EXERDUCCS sites, the sponsor subsequently increased the payment stipends to the sites to compensate for the extra work and expense incurred. This cooperative experience accomplished several goals: (1) it allowed a complex clinical trial to be successfully completed in a time frame which would not have been possible using only single unconnected sites; (2) it educated the physician-investigators (and their personnel) in exercise cardiopulmonary; and (3) it prepared the sites for future clinical trials involving this methodology.

Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES): a randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue.

PubMed

van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Sonke, Gabe S; Aaronson, Neil K

2010-12-07

Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs. This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up. This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy. This study is registered at the Netherlands Trial Register (NTR 2159).

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.

PubMed

Lentz, S R; Ehrenforth, S; Karim, F Abdul; Matsushita, T; Weldingh, K N; Windyga, J; Mahlangu, J N

2014-08-01

Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept(™) 2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg(-1) ) or rFVIIa (one to three doses at 90 μg kg(-1) ). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24-48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit-risk profile is unlikely to be achieved with vatreptacog alfa. © 2014 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial.

PubMed

Adabag, A Selcuk; Mithani, Salima; Al Aloul, Basel; Collins, Dorothea; Bertog, Stefan; Bloomfield, Hanna E

2009-05-01

Peroxisome proliferator-activated receptor alpha (PPARalpha) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease. We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor. A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 +/- 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 +/- 7.1 years. Over 4.4 +/- 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82). In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.

Translatability of helminth therapy in inflammatory bowel diseases

PubMed Central

Weinstock, Joel V; Elliott, David E.

2013-01-01

Modern hygienic lifestyles are associated with the emergence of inflammatory bowel disease (IBD) which now afflicts millions of people in highly-developed countries. Meticulous hygiene interrupts conduits of transmission required for ubiquitous exposure to parasitic worms (helminths). We proposed that loss of exposure to helminths permits development of IBD. Early clinical trials suggested that exposure to helminths such as Trichuris suis or Necator americanus can improve IBD. Over the last several years, processes to “medicinalize” T. suis have been developed and use of this helminth is now being studied in large multi-center clinical trials. Concurrently, we and others have identified some of the immune regulatory mechanisms elicited by helminth exposure that suppress inappropriate intestinal inflammation. These efforts could soon result in new therapies for patients with IBD. PMID:23178819

Adjusted regression trend test for a multicenter clinical trial.

PubMed

Quan, H; Capizzi, T

1999-06-01

Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

PubMed

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

PubMed Central

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-01-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity. PMID:21463120

Diagnostic performance of computed tomography coronary angiography (from the Prospective National Multicenter Multivendor EVASCAN Study).

PubMed

Gueret, Pascal; Deux, Jean-François; Bonello, Laurent; Sarran, Anthony; Tron, Christophe; Christiaens, Luc; Dacher, Jean-Nicolas; Bertrand, David; Leborgne, Laurent; Renard, Cedric; Caussin, Christophe; Cluzel, Philippe; Helft, Gerard; Crochet, Dominique; Vernhet-Kovacsik, Hélène; Chabbert, Valérie; Ferrari, Emile; Gilard, Martine; Willoteaux, Serge; Furber, Alain; Barone-Rochette, Gilles; Jankowski, Adrien; Douek, Philippe; Mousseaux, Elie; Sirol, Marc; Niarra, Ralph; Chatellier, Gilles; Laissy, Jean-Pierre

2013-02-15

Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity. Copyright © 2013 Elsevier Inc. All rights reserved.

Sensorimotor Assessment and Rehabilitative Apparatus

DTIC Science & Technology

2016-10-01

Support: Title: Tinnitus Retraining Treatment Trial Data Coordinating Center (TRTT) (GRANT RECENTLY ENDED) Grant Number/PI: U01 DC007422 (Scherer...Description of project’s goals: The Tinnitus Retraining Therapy Trial is a multi-center randomized controlled trial testing the efficacy of tinnitus ...retraining therapy versus usual care as a treatment for severe debilitating tinnitus in patients with functionally normal hearing. Title

Emergence times and airway reactions in general laryngeal mask airway anesthesia: study protocol for a randomized controlled trial.

PubMed

Stevanovic, Ana; Rossaint, Rolf; Keszei, András P; Fritz, Harald; Fröba, Gebhard; Pühringer, Friedrich; Coburn, Mark

2015-07-26

The use of a laryngeal mask airway (LMA) in appropriate patients supports fast-track anesthesia with a lower incidence of postoperative airway-connected adverse events. Data on the most favorable anesthetic in this context, with the lowest rate of upper airway complications and fast emergence times, are controversial and limited. Desflurane seems to match these criteria best, but large randomized controlled trials (RCTs) with a standardized study protocol are lacking. Therefore, we aim to compare desflurane with other commonly used anesthetics, sevoflurane and propofol, in a sufficiently powered RCT. We hypothesize that desflurane is noninferior regarding the frequency of upper airway events and superior regarding the emergence times to sevoflurane and propofol. A total of 351 patients undergoing surgery with an LMA will be included in this prospective, randomized, double-blind controlled, multicenter clinical trial. The patients will be randomly assigned to the three treatment arms: desflurane (n = 117), sevoflurane (n = 117), and propofol (n = 117). The emergence time (time to state the date of birth) will be the primary endpoint of this study. The secondary endpoints include further emergence times, such as time to open eyes, to remove LMA, to respond to command and to state name. Additionally, we will determine the frequency of cough and laryngospasm, measured intraoperatively and at emergence. We will assess the postoperative recovery on the first postoperative day via the Postoperative Quality Recovery Scale. Despite increasing importance of cost-effective and safe anesthesia application, we lack proof for the most advantageous anesthetic agent, when an LMA is used. There are only a few RCTs comparing desflurane to other commonly used anesthetics (sevoflurane, propofol and isoflurane) in patients with LMA. These RCTs were conducted with small sample sizes, huge interstudy variability, and some also showed strong biases. The present multicenter RCT will provide results from a large sample size with a standardized study protocol and minimized bias, which is feasible in the clinical routine. Furthermore, we will expand our knowledge regarding the most favorable recovery on the first postoperative day, which impacts patients' comfort after surgery. EudraCT Identifier: 2014-003810-96, 5 September 2014 ClinicalTrials.gov: NCT02322502, December 2014.

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT

PubMed Central

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-01-01

Purpose A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Materials and Methods Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. Results In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT’s safety profile. Conclusion The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC. PMID:25410761

The Adult Respiratory Distress Syndrome Cognitive Outcomes Study

PubMed Central

Christie, Jason D.; Lanken, Paul N.; Biester, Rosette C.; Thompson, B. Taylor; Bellamy, Scarlett L.; Localio, A. Russell; Demissie, Ejigayehu; Hopkins, Ramona O.; Angus, Derek C.

2012-01-01

Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment. Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post–hospital discharge. Measurements and Main Results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02). Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation. PMID:22492988

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT.

PubMed

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-07-01

A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT's safety profile. The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.

Update on mechanical cardiopulmonary resuscitation devices.

PubMed

Rubertsson, Sten

2016-06-01

The aim of this review is to update and discuss the use of mechanical chest compression devices in treatment of cardiac arrest. Three recently published large multicenter randomized trials have not been able to show any improved outcome in adult out-of-hospital cardiac arrest patients when compared with manual chest compressions. Mechanical chest compression devices have been developed to better deliver uninterrupted chest compressions of good quality. Prospective large randomized studies have not been able to prove a better outcome compared to manual chest compressions; however, latest guidelines support their use when high-quality manual chest compressions cannot be delivered. Mechanical chest compressions can also be preferred during transportation, in the cath-lab and as a bridge to more invasive support like extracorporeal membrane oxygenation.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Rationale of a novel study design for the BIOFLOW V study, a prospective, randomized multicenter study to assess the safety and efficacy of the Orsiro sirolimus-eluting coronary stent system using a Bayesian approach.

PubMed

Doros, Gheorghe; Massaro, Joseph M; Kandzari, David E; Waksman, Ron; Koolen, Jacques J; Cutlip, Donald E; Mauri, Laura

2017-11-01

Traditional study design submitted to the Food and Drug Administration to test newer drug-eluting stents (DES) for marketing approval is the prospective randomized controlled trial. However, several DES have extensive clinical data from trials conducted outside the United States that have led to utilization of a novel design using the Bayesian approach. This design was proposed for testing DES with bioresorbable polymer compared with DES most commonly in use today that use durable polymers for drug elution. This prospective, multicenter, randomized, controlled trial is designed to assess the safety and efficacy of the Orsiro bioresorbable polymer sirolimus-eluting stent (BP SES). Up to 1,334 subjects with up to 3 de novo or restenotic coronary artery lesions who qualify for percutaneous coronary intervention with stenting will be randomized 2:1 to the BP SES versus the Xience durable polymer everolimus-eluting stent (DP EES). Data from this trial will be combined with data from 2 similarly designed trials that also randomize subjects to BP SES and DP EES (BIOFLOW II, N=452 and BIOFLOW IV, N=579) by using a Bayesian approach. The primary end point is target lesion failure at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a test of noninferiority of the BP SES versus DP EES on the primary end point according to a noninferiority delta of 3.85%. Secondary end points include stent thrombosis and the individual components of target lesion failure. Subjects will be followed for 5 years after randomization. The BIOFLOW V trial offers an opportunity to assess clinical outcomes in patients treated with coronary revascularization using the Orsiro BP SES relative to a commonly used DP EES. The use of a Bayesian analysis combines a large randomized cohort of patients 2 two smaller contributing randomized trials to augment the efficiency of the comparison. Copyright © 2017 Elsevier Inc. All rights reserved.

Lifestyle interventions and independence for elders study: Recruitment and baseline characteristics

USDA-ARS?s Scientific Manuscript database

Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate...

Sweat Chloride as A Biomarker of CFTR Activity: Proof of Concept and Ivacaftor Clinical Trial Data

PubMed Central

Accurso, Frank J.; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J.; Dong, Qunming; Ordonez, Claudia L.; Rowe, Steven M.; Clancy, John Paul; Konstan, Michael W.; Hoch, Heather E.; Heltshe, Sonya L.; Ramsey, Bonnie W.; Campbell, Preston W.; Ashlock, Melissa A.

2014-01-01

Background We examined data from a Phase 2 trial {NCT00457821 } of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Methods Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing, and analysis was employed for the first time.. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Results Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Conclusions Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators. PMID:24660233

Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.

PubMed

Accurso, Frank J; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J; Dong, Qunming; Ordonez, Claudia L; Rowe, Steven M; Clancy, John Paul; Konstan, Michael W; Hoch, Heather E; Heltshe, Sonya L; Ramsey, Bonnie W; Campbell, Preston W; Ashlock, Melissa A

2014-03-01

We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Assessment of In-Stent Restenosis Using 64-MDCT: Analysis of the CORE-64 Multicenter International Trial

PubMed Central

Wykrzykowska, Joanna J.; Arbab-Zadeh, Armin; Godoy, Gustavo; Miller, Julie M.; Lin, Shezhang; Vavere, Andrea; Paul, Narinder; Niinuma, Hiroyuki; Hoe, John; Brinker, Jeffrey; Khosa, Faisal; Sarwar, Sheryar; Lima, Joao; Clouse, Melvin E.

2012-01-01

OBJECTIVE Evaluations of stents by MDCT from studies performed at single centers have yielded variable results with a high proportion of unassessable stents. The purpose of this study was to evaluate the accuracy of 64-MDCT angiography (MDCTA) in identifying in-stent restenosis in a multicenter trial. MATERIALS AND METHODS The Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography Using 64 Detectors (CORE-64) Multicenter Trial and Registry evaluated the accuracy of 64-MDCTA in assessing 405 patients referred for coronary angiography. A total of 75 stents in 52 patients were assessed: 48 of 75 stents (64%) in 36 of 52 patients (69%) could be evaluated. The prevalence of in-stent restenosis by quantitative coronary angiography (QCA) in this subgroup was 23% (17/75). Eighty percent of the stents were ≤ 3.0 mm in diameter. RESULTS The overall sensitivity, specificity, positive predictive value, and negative predictive value to detect 50% in-stent stenosis visually using MDCT compared with QCA was 33.3%, 91.7%, 57.1%, and 80.5%, respectively, with an overall accuracy of 77.1% for the 48 assessable stents. The ability to evaluate stents on MDCTA varied by stent type: Thick-strut stents such as Bx Velocity were assessable in 50% of the cases; Cypher, 62.5% of the cases; and thinner-strut stents such as Taxus, 75% of the cases. We performed quantitative assessment of in-stent contrast attenuation in Hounsfield units and correlated that value with the quantitative percentage of stenosis by QCA. The correlation coefficient between the average attenuation decrease and ≥ 50% stenosis by QCA was 0.25 (p = 0.073). Quantitative assessment failed to improve the accuracy of MDCT over qualitative assessment. CONCLUSION The results of our study showed that 64-MDCT has poor ability to detect in-stent restenosis in small-diameter stents. Evaluability and negative predictive value were better in large-diameter stents. Thus, 64-MDCT may be appropriate for stent assessment in only selected patients. PMID:20028909

Recommendations for Self-Report Outcome Measures in Vulvodynia Clinical Trials.

PubMed

Pukall, Caroline F; Bergeron, Sophie; Brown, Candace; Bachmann, Gloria; Wesselmann, Ursula

2017-08-01

Vulvodynia (idiopathic chronic vulvar pain) is a prevalent condition associated with significant and negative impacts in many areas of function. Despite the increased research interest in vulvodynia in recent years, recommendations for outcome measures for use in clinical trials are missing. The purpose of this paper, therefore, was to provide recommendations for outcome measures for vulvodynia clinical trials so that consistent measures are used across trials to facilitate between-study comparisons and the conduct of large multicenter trials, and to improve measurement of the multiple dimensions of vulvodynia. Given that provoked vestibulodynia (PVD)-characterized by provoked pain localized to the vaginal opening-is the most common subtype of vulvodynia and the current main focus of clinical trials, this paper focused on recommended outcome measures in PVD clinical trials. The framework used to guide the selection of outcome measures was based on the one proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). The IMMPACT framework provided a well-suited guideline for outcome measure recommendations in PVD clinical trials. However, given the provoked presentation of PVD and the significant impact it has on sexuality, modifications to some of the IMMPACT recommendations were made and specific additional measures were suggested. Measures that are specific to vulvovaginal pain are ideal for adoption in PVD clinical trials, and many such measures currently exist that allow the relevant IMMPACT domains to be captured.

Effects of a Psychological Intervention in a Primary Health Care Center for Caregivers of Dependent Relatives: A Randomized Trial

ERIC Educational Resources Information Center

Rodriguez-Sanchez, Emiliano; Patino-Alonso, Maria C.; Mora-Simon, Sara; Gomez-Marcos, Manuel A.; Perez-Penaranda, Anibal; Losada-Baltar, Andres; Garcia-Ortiz, Luis

2013-01-01

Purpose: To assess, in the context of Primary Health Care (PHC), the effect of a psychological intervention in mental health among caregivers (CGs) of dependent relatives. Design and Methods: Randomized multicenter, controlled clinical trial. The 125 CGs included in the trial were receiving health care in PHC. Inclusion criteria: Identifying…

Selective decontamination of the digestive tract in gastrointestinal surgery: useful in infection prevention? A systematic review.

PubMed

Abis, Gabor S A; Stockmann, Hein B A C; van Egmond, Marjolein; Bonjer, Hendrik J; Vandenbroucke-Grauls, Christina M J E; Oosterling, Steven J

2013-12-01

Gastrointestinal surgery is associated with a high incidence of infectious complications. Selective decontamination of the digestive tract is an antimicrobial prophylaxis regimen that aims to eradicate gastrointestinal carriage of potentially pathogenic microorganisms and represents an adjunct to regular prophylaxis in surgery. Relevant studies were identified using bibliographic searches of MEDLINE, EMBASE, and the Cochrane database (period from 1970 to November 1, 2012). Only studies investigating selective decontamination of the digestive tract in gastrointestinal surgery were included. Two randomized clinical trials and one retrospective case-control trial showed significant benefit in terms of infectious complications and anastomotic leakage in colorectal surgery. Two randomized controlled trials in esophageal surgery and two randomized clinical trials in gastric surgery reported lower levels of infectious complications. Selective decontamination of the digestive tract reduces infections following esophageal, gastric, and colorectal surgeries and also appears to have beneficial effects on anastomotic leakage in colorectal surgery. We believe these results provide the basis for a large multicenter prospective study to investigate the role of selective decontamination of the digestive tract in colorectal surgery.

Are orange lollies effective in preventing nausea and vomiting related to dimethyl sulfoxide? A multicenter randomized trial.

PubMed

Gonella, Silvia; Berchialla, Paola; Bruno, Benedetto; Di Giulio, Paola

2014-09-01

Nausea and vomiting (NV) related to DMSO affect patients undergoing auto-SCT despite antiemetic measures. Orange flavoring may reduce gastrointestinal symptoms. A multicenter, randomized, three-arm, open-label trial in four Italian large bone marrow transplant centers was conducted to assess the effectiveness of orange aroma in preventing NV related to DMSO. Patients were randomized to orange ice lollies, non-citrus ice lollies, and routine treatment (deep breaths) during reinfusion. Data on NV were collected up to 5 days after infusion; 69/98 patients were randomized: 23 to orange, 21 to non-citrus ice lollies, and 25 to routine treatment. Although 48 h after transplantation no differences were observed in controlled nausea (Numerical Rating Scale (NRS) 0-100, ≤25) or vomiting, significantly fewer patients had no episodes of vomiting, no antiemetic rescue therapy, and no nausea (NRS <5) in the deep breath vs lollies groups (P = 0.017). The intensity of nausea over time differed significantly between ice lollies vs routine care (P = 0.001) groups, but not between the orange and non-citrus groups (P = 0.428). The vasoconstrictive action of ice may prevent NV related to DMSO in the acute phase and reduce the need for rescue antiemetic therapy. Ice lollies offer a simple, noninvasive, and economic means for relieving nausea and vomiting related to this preservative.

Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG).

PubMed

Escolar, Diana M; Henricson, Erik K; Pasquali, Livia; Gorni, Ksenija; Hoffman, Eric P

2002-10-01

Progress in the development of rationally based therapies for Duchenne muscular dystrophy has been accelerated by encouraging multidisciplinary, multi-institutional collaboration between basic science and clinical investigators in the Cooperative International Research Group. We combined existing research efforts in pathophysiology by a gene expression profiling laboratory with the efforts of animal facilities capable of conducting high-throughput drug screening and toxicity testing to identify safe and effective drug compounds that target different parts of the pathophysiologic cascade in a genome-wide drug discovery approach. Simultaneously, we developed a clinical trial coordinating center and an international network of collaborating physicians and clinics where those drugs could be tested in large-scale clinical trials. We hope that by bringing together investigators at these facilities and providing the infrastructure to support their research, we can rapidly move new bench discoveries through animal model screening and into therapeutic testing in humans in a safe, timely and cost-effective setting.

A Paradox-based data collection and management system for multi-center randomized clinical trials.

PubMed

Abdellatif, Mazen; Reda, Domenic J

2004-02-01

We have developed a Paradox-based data collection and management system for large-scale multi-site randomized clinical trials. The system runs under Windows operating system and integrates Symantec pcAnywhere32 telecommunications software for data transmission and remote control sessions, PKZIP utility for the compression/decompression of transmitted data, and Stat/Transfer for exporting the centralized Paradox database for analyses. We initially developed this system for VA Cooperative Study #399 'The Effect of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation', which collects over 1000 variables on 706 patients at 20 sites. Patient intake for this 5-year study began in March of 1998. We have also developed an enhanced version of this system, which is being used in the NIH-funded 'Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)' that collects over 1200 variables on 1588 patients at 13 sites. Patient intake for this 4-year study began in October of 2000.

[A multicenter, large-sample, randomized clinical trial on improving the median survival time of advanced non-small cell lung cancer by combination of Ginseng Rg3 and chemotherapy].

PubMed

Zhang, Y; Wang, X Q; Liu, H; Liu, J; Hou, W; Lin, H S

2018-04-23

Objective: To observe the efficacy of the combination of chemotherapy and Ginseng Rg3 on advanced non-small cell lung cancer(NSCLC). Methods: In the multi-center, large-sample, randomized, double blind trial, 414 patients with Ⅲ-Ⅳ NSCLC were enrolled.199 were in the experimental group and 215 the control group. The patients in the experimental group were treated with the standard first-line chemotherapy combined with Ginseng Rg3. The patients in the control group were treated with the same chemotherapy combined with placebo. Median overall survival (OS), Karnofsky performance scale (KPS), Traditional Chinese Medicine (TCM) symptoms score and side effects of two groups were observed as main indexes. Results: The median OS were 12.03 months in the experimental group, which was significantly better than that in the control group (8.46 months, P <0.05). Hemoglobin and white blood cells were decreased after the first and second cycle of treatment in both groups. Both adverse events were significantly milder in the treatment group ( P <0.05). In addition, after two courses of treatment, the KPS of patients was 78.95±9.14 in the experimental group and 76.77±9.15 in the control group, while the TCM symptoms score was 2.45±1.73 in the experimental group and 2.92±2.06 in the control group, with significant difference ( P <0.05). Conclusions: Combination of TCM with Western medicine such as chemotherapy could prolong the survival of patients with advanced NSCLC. The combined therapy improved patients' symptoms and reduced chemotherapy induced myelosuppression.

Computerized Training of Working Memory in Children with ADHD-A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Klingberg, Torkel; Fernell, Elisabeth; Olesen, Pernille J.; Johnson, Mats; Gustafsson, Per; Dahlstrom, Kerstin; Gillberg, Christopher G.; Forssberg, Hans; Westerberg, Helena

2005-01-01

Objective: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic…

Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke.

PubMed

Saver, Jeffrey L; Goyal, Mayank; Bonafe, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Cohen, David J; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek; du Mesnil de Rochemont, Richard; Jahan, Reza

2015-04-01

Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2). © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

PubMed Central

Gao, Peng; Zhao, Zhenwei; Wang, Daming; Wu, Jian; Cai, Yiling; Li, Tianxiao; Wu, Wei; Shi, Huaizhang; He, Weiwen; Zhu, Fengshui; Ling, Feng

2015-01-01

Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers. PMID:25934656

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2015-09-01

multimodality therapy, but remain at exceedingly high risk for recurrence. The specific aim of this project is to conduct a multicenter, double...mskcc.org Table of Contents Page Introduction…………………………………………………………….………..….. 4 Body………………………………………………………………………………….. 4 Key Research...exceedingly high risk for recurrence. The specific aim of this project is to conduct a multicenter, double-blinded, randomized trial comparing treatment

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders.

PubMed

Loechelt, Brett J; Green, Michael; Gottlieb, Peter A; Blumberg, Emily; Weinberg, Adriana; Quinlan, Scott; Baden, Lindsey R

2015-09-01

Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases.

Quality expectations and tolerance limits of trial master files (TMF) – Developing a risk-based approach for quality assessments of TMFs

PubMed Central

Hecht, Arthur; Busch-Heidger, Barbara; Gertzen, Heiner; Pfister, Heike; Ruhfus, Birgit; Sanden, Per-Holger; Schmidt, Gabriele B.

2015-01-01

This article addresses the question of when a trial master file (TMF) can be considered sufficiently accurate and complete: What attributes does the TMF need to have so that a clinical trial can be adequately reconstructed from documented data and procedures? Clinical trial sponsors face significant challenges in assembling the TMF, especially when dealing with large, international, multicenter studies; despite all newly introduced archiving techniques it is becoming more and more difficult to ensure that the TMF is complete. This is directly reflected in the number of inspection findings reported and published by the EMA in 2014. Based on quality risk management principles in clinical trials the authors defined the quality expectations for the different document types in a TMF and furthermore defined tolerance limits for missing documents. This publication provides guidance on what type of documents and processes are most important, and in consequence, indicates on which documents and processes trial team staff should focus in order to achieve a high-quality TMF. The members of this working group belong to the CQAG Group (Clinical Quality Assurance Germany) and are QA (quality assurance) experts (auditors or compliance functions) with long-term experience in the practical handling of TMFs. PMID:26693218

Quality expectations and tolerance limits of trial master files (TMF) - Developing a risk-based approach for quality assessments of TMFs.

PubMed

Hecht, Arthur; Busch-Heidger, Barbara; Gertzen, Heiner; Pfister, Heike; Ruhfus, Birgit; Sanden, Per-Holger; Schmidt, Gabriele B

2015-01-01

This article addresses the question of when a trial master file (TMF) can be considered sufficiently accurate and complete: What attributes does the TMF need to have so that a clinical trial can be adequately reconstructed from documented data and procedures? Clinical trial sponsors face significant challenges in assembling the TMF, especially when dealing with large, international, multicenter studies; despite all newly introduced archiving techniques it is becoming more and more difficult to ensure that the TMF is complete. This is directly reflected in the number of inspection findings reported and published by the EMA in 2014. Based on quality risk management principles in clinical trials the authors defined the quality expectations for the different document types in a TMF and furthermore defined tolerance limits for missing documents. This publication provides guidance on what type of documents and processes are most important, and in consequence, indicates on which documents and processes trial team staff should focus in order to achieve a high-quality TMF. The members of this working group belong to the CQAG Group (Clinical Quality Assurance Germany) and are QA (quality assurance) experts (auditors or compliance functions) with long-term experience in the practical handling of TMFs.

MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

PubMed

Di Biase, Luigi; Tung, Roderick; Szili-Torok, Tamás; Burkhardt, J David; Weiss, Peter; Tavernier, Rene; Berman, Adam E; Wissner, Erik; Spear, William; Chen, Xu; Neužil, Petr; Skoda, Jan; Lakkireddy, Dhanunjaya; Schwagten, Bruno; Lock, Ken; Natale, Andrea

2017-04-01

Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia. The MAGNETIC VT trial will assess if VT ablation using the Niobe™ ES magnetic navigation system results in superior outcomes compared to a manual approach in subjects with ischemic scar VT and low ejection fraction. This is a randomized, single-blind, prospective, multicenter post-market study. A total of 386 subjects (193 per group) will be enrolled and randomized 1:1 between treatment with the Niobe ES system and treatment via a manual procedure at up to 20 sites. The study population will consist of patients with ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of ≤35% and implantable cardioverter defibrillator (ICD) who have sustained monomorphic VT. The primary study endpoint is freedom from any recurrence of VT through 12 months. The secondary endpoints are acute success; freedom from any VT at 1 year in a large-scar subpopulation; procedure-related major adverse events; and mortality rate through 12-month follow-up. Follow-up will consist of visits at 3, 6, 9, and 12 months, all of which will include ICD interrogation. The MAGNETIC VT trial will help determine whether substrate-based ablation of VT with RMN has clinical advantages over manual catheter manipulation. Clinicaltrials.gov identifier: NCT02637947.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial.

PubMed

Günter, Christina Irene; Bader, Augustinus; Dornseifer, Ulf; Egert, Silvia; Dunda, Sebastian; Grieb, Gerrit; Wolter, Thomas; Pallua, Norbert; von Wild, Tobias; Siemers, Frank; Mailänder, Peter; Thamm, Oliver; Ernert, Carsten; Steen, Michael; Sievers, Reiner; Reichert, Bert; Rahmanian-Schwarz, Afshin; Schaller, Hans; Hartmann, Bernd; Otte, Max; Kehl, Victoria; Ohmann, Christian; Jelkmann, Wolfgang; Machens, Hans-Günther

2013-05-03

Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824.

Measurement and Evaluation of Quantitative Performance of PET/CT Images before a Multicenter Clinical Trial.

PubMed

Zhu, Yanjia; Geng, Caizheng; Huang, Jia; Liu, Juzhen; Wu, Ning; Xin, Jun; Xu, Hao; Yu, Lijuan; Geng, Jianhua

2018-06-13

To ensure the reliability of the planned multi-center clinical trial, we assessed the consistence and comparability of the quantitative parameters of the eight PET/CT units that will be used in this trial. PET/CT images were scanned using a PET NEMA image quality phantom (Biodex) on the eight units of Discovery PET/CT 690 from GE Healthcare. The scanning parameters were the same with the ones to be used in the planned trial. The 18 F-NaF concentration in the background was 5.3 kBq/ml, while the ones in the spheres of diameter 37 mm, 22 mm, 17 mm and 10 mm were 8:1 as to that of the background and the ones in the spheres of diameter 28 mm and 13 mm were 0 kBq/ml. The consistency of hot sphere recovery coefficient (HRC), cold sphere recovery coefficient (CRC), hot sphere contrast (Q H ) and cold sphere contrast (Q c ) among these 8 PET/CTs was analyzed. The variation of the main quantitative parameters of the eight PET/CT systems was within 10%, which is acceptable for the clinical trial.

Study Design and Rationale of "A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus MOrphine in Acute Pulmonary Edema": MIMO Trial.

PubMed

Dominguez-Rodriguez, Alberto; Burillo-Putze, Guillermo; Garcia-Saiz, Maria Del Mar; Aldea-Perona, Ana; Harmand, Magali González-Colaço; Mirò, Oscar; Abreu-Gonzalez, Pedro

2017-04-01

Morphine has been used for several decades in cases of acute pulmonary edema (APE) due to the anxiolytic and vasodilatory properties of the drug. The non-specific depression of the central nervous system is probably the most significant factor for the changes in hemodynamics in APE. Retrospective studies have shown both negative and neutral effects in patients with APE and therefore some authors have suggested benzodiazepines as an alternative treatment. The use of intravenous morphine in the treatment of APE remains controversial. The MIdazolan versus MOrphine in APE trial (MIMO) is a multicenter, prospective, open-label, randomized study designed to evaluate the efficacy and safety of morphine in patients with APE. The MIMO trial will evaluate as a primary endpoint whether intravenous morphine administration improves clinical outcomes defined as in-hospital mortality. Secondary endpoint evaluation will be mechanical ventilation, cardiopulmonary resuscitation, intensive care unit admission rate, intensive care unit length of stay, and hospitalization length. In the emergency department, morphine is still used for APE in spite of poor scientific background data. The data from the MIMO trial will establish the effect-and especially the risk-when using morphine for APE.

Decreasing prematurity in twin gestations: predicaments and possibilities.

PubMed

Zork, Noelia; Biggio, Joseph; Tita, Alan; Rouse, Dwight; Gyamfi-Bannerman, Cynthia

2013-08-01

The twin birth rate has been steadily increasing in the United States over the past 10 years attributable in large part to the increased use of reproductive technologies. Despite advancements in the prevention of preterm labor for singletons, the overall rate of preterm birth has decreased only minimally. Several interventions to prevent preterm birth in twins have been studied, but none has proven effective. Inpatient bedrest has not been shown to be effective and can cause significant maternal morbidity. Although intramuscular 17α-hydroxyprogesterone caproate is effective in decreasing the risk of recurrent preterm delivery in singletons, neither it nor cerclage is effective in twin gestations, even in those with a short cervix. However, small trials, subgroup analyses, and a meta-analysis suggest that vaginal progesterone and the Arabin cervical pessary may reduce rates of preterm birth in twins of mothers with a short cervix. Given the current lack of effective therapies to prevent preterm birth in twins, large multicenter trials are needed to assess the effectiveness of vaginal progesterone and pessary in twins of mothers with a short cervix.

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience.

PubMed

Zielinski, Stephanie M; Viveiros, Helena; Heetveld, Martin J; Swiontkowski, Marc F; Bhandari, Mohit; Patka, Peter; Van Lieshout, Esther M M

2012-01-08

Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. ClinicalTrials.gov: NCT00761813.

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

[Cannabinoids in multiple sclerosis -- therapeutically reasonable?].

PubMed

Trebst, C; Stangel, M

2005-08-01

For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS. Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS. Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms. Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS. This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.

Interculturalism and Informed Consent: Respecting Cultural Differences without Breaching Human Rights.

PubMed

Ekmekci, Perihan Elif; Arda, Berna

2017-01-01

Interventions in medicine require multicenter clinical trials on a large rather than limited number of subjects from various genetic and cultural backgrounds. International guidelines to protect the rights and well-being of human subjects involved in clinical trials are criticized for the priority they place on Western cultural values. These discussions become manifest especially with regard to the content and methodology of the informed consent procedure. The ethical dilemma emerges from the argument that there are fundamental differences about the concept of respect for the autonomy of individuals in different cultures and religions. Some communities prioritize the consent of community leaders or the head of family - usually men - over the voluntary and free consent of the individual. The aim of this work is to discuss this ethical dilemma to determine a base for a consensus that satisfies the sensibilities of different cultures without damaging the rights and autonomy of human subjects.

Interculturalism and Informed Consent: Respecting Cultural Differences without Breaching Human Rights

PubMed Central

Ekmekci, Perihan Elif; Arda, Berna

2018-01-01

Interventions in medicine require multicenter clinical trials on a large rather than limited number of subjects from various genetic and cultural backgrounds. International guidelines to protect the rights and well-being of human subjects involved in clinical trials are criticized for the priority they place on Western cultural values. These discussions become manifest especially with regard to the content and methodology of the informed consent procedure. The ethical dilemma emerges from the argument that there are fundamental differences about the concept of respect for the autonomy of individuals in different cultures and religions. Some communities prioritize the consent of community leaders or the head of family – usually men – over the voluntary and free consent of the individual. The aim of this work is to discuss this ethical dilemma to determine a base for a consensus that satisfies the sensibilities of different cultures without damaging the rights and autonomy of human subjects. PMID:29645014

Characterizing stroke lesions using digital templates and lesion quantification tools in a web-based imaging informatics system for a large-scale stroke rehabilitation clinical trial

NASA Astrophysics Data System (ADS)

Wang, Ximing; Edwardson, Matthew; Dromerick, Alexander; Winstein, Carolee; Wang, Jing; Liu, Brent

2015-03-01

Previously, we presented an Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) imaging informatics system that supports a large-scale phase III stroke rehabilitation trial. The ePR system is capable of displaying anonymized patient imaging studies and reports, and the system is accessible to multiple clinical trial sites and users across the United States via the web. However, the prior multicenter stroke rehabilitation trials lack any significant neuroimaging analysis infrastructure. In stroke related clinical trials, identification of the stroke lesion characteristics can be meaningful as recent research shows that lesion characteristics are related to stroke scale and functional recovery after stroke. To facilitate the stroke clinical trials, we hope to gain insight into specific lesion characteristics, such as vascular territory, for patients enrolled into large stroke rehabilitation trials. To enhance the system's capability for data analysis and data reporting, we have integrated new features with the system: a digital brain template display, a lesion quantification tool and a digital case report form. The digital brain templates are compiled from published vascular territory templates at each of 5 angles of incidence. These templates were updated to include territories in the brainstem using a vascular territory atlas and the Medical Image Processing, Analysis and Visualization (MIPAV) tool. The digital templates are displayed for side-by-side comparisons and transparent template overlay onto patients' images in the image viewer. The lesion quantification tool quantifies planimetric lesion area from user-defined contour. The digital case report form stores user input into a database, then displays contents in the interface to allow for reviewing, editing, and new inputs. In sum, the newly integrated system features provide the user with readily-accessible web-based tools to identify the vascular territory involved, estimate lesion area, and store these results in a web-based digital format.

A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2)

PubMed Central

2012-01-01

Background Computed tomography (CT) scanning has become essential in the early diagnostic phase of trauma care because of its high diagnostic accuracy. The introduction of multi-slice CT scanners and infrastructural improvements made total-body CT scanning technically feasible and its usage is currently becoming common practice in several trauma centers. However, literature provides limited evidence whether immediate total-body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total-body CT scanning in trauma patients. Methods/design The REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. Patients in whom direct scanning will hamper necessary cardiopulmonary resuscitation or who require an immediate operation because of imminent death (both as judged by the trauma team leader) are excluded. Randomization will be computer assisted. The intervention group will receive a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness. Discussion The REACT-2 trial is a multicenter randomized clinical trial that will provide evidence on the value of immediate total-body CT scanning during the primary survey of severely injured trauma patients. If immediate total-body CT scanning is found to be the best imaging strategy in severely injured trauma patients it could replace conventional imaging supplemented with CT in this specific group. Trial Registration ClinicalTrials.gov: (NCT01523626). PMID:22458247

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

PubMed

Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence

PubMed Central

Pruett, Amanda E; Lee, Amanda K; Patterson, Herbert; Schwartz, Todd A; Glotzer, Jana M; Adams, Jr, Kirkwood F

2015-01-01

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple thera-pies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides pro-vide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syn-drome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key as-pects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively estab-lish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical. PMID:24251462

Information on center characteristics as costs' determinants in multicenter clinical trials: is modeling center effect worth the effort?

PubMed

Petrinco, Michele; Pagano, Eva; Desideri, Alessandro; Bigi, Riccardo; Ghidina, Marco; Ferrando, Alberto; Cortigiani, Lauro; Merletti, Franco; Gregori, Dario

2009-01-01

Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the PRO-CTCAE in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

PubMed Central

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O’Mara, Ann; Denicoff, Andrea; Minasian, Lori; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-01-01

Purpose To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials Patients enrolled in Trial XXXX (XXXX) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly x4 during treatment; 12-weeks post-treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results Among 226 study sites participating in Trial XXXX, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients of which 34 (43%) required tablet computers to be provided. All 152 patients in Trial XXXX agreed to self-report using the PRO-CTCAE (median age 66; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range 30–240), and median time for CRAs to teach a patient to self-report was 10 minutes (range 2–60). Compliance was high, particularly during active treatment when patients self-reported at 86% of expected time points, although compliance was lower post-treatment (72%). Common reasons for non-compliance were institutional errors such as forgetting to provide computers to participants; patients missing clinic visits; internet connectivity; and patients feeling “too sick”. Conclusions Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic adverse events at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between-visits, and by employing central compliance monitoring. These approaches are being incorporated into ongoing studies. PMID:28463161

Clinical Decision Support for a Multicenter Trial of Pediatric Head Trauma

PubMed Central

Swietlik, Marguerite; Deakyne, Sara; Hoffman, Jeffrey M.; Grundmeier, Robert W.; Paterno, Marilyn D.; Rocha, Beatriz H.; Schaeffer, Molly H; Pabbathi, Deepika; Alessandrini, Evaline; Ballard, Dustin; Goldberg, Howard S.; Kuppermann, Nathan; Dayan, Peter S.

2016-01-01

Summary Introduction For children who present to emergency departments (EDs) due to blunt head trauma, ED clinicians must decide who requires computed tomography (CT) scanning to evaluate for traumatic brain injury (TBI). The Pediatric Emergency Care Applied Research Network (PECARN) derived and validated two age-based prediction rules to identify children at very low risk of clinically-important traumatic brain injuries (ciTBIs) who do not typically require CT scans. In this case report, we describe the strategy used to implement the PECARN TBI prediction rules via electronic health record (EHR) clinical decision support (CDS) as the intervention in a multicenter clinical trial. Methods Thirteen EDs participated in this trial. The 10 sites receiving the CDS intervention used the Epic® EHR. All sites implementing EHR-based CDS built the rules by using the vendor’s CDS engine. Based on a sociotechnical analysis, we designed the CDS so that recommendations could be displayed immediately after any provider entered prediction rule data. One central site developed and tested the intervention package to be exported to other sites. The intervention package included a clinical trial alert, an electronic data collection form, the CDS rules and the format for recommendations. Results The original PECARN head trauma prediction rules were derived from physician documentation while this pragmatic trial led each site to customize their workflows and allow multiple different providers to complete the head trauma assessments. These differences in workflows led to varying completion rates across sites as well as differences in the types of providers completing the electronic data form. Site variation in internal change management processes made it challenging to maintain the same rigor across all sites. This led to downstream effects when data reports were developed. Conclusions The process of a centralized build and export of a CDS system in one commercial EHR system successfully supported a multicenter clinical trial. PMID:27437059

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

Guidelines for quality assurance in multicenter trials: a position paper.

PubMed

Knatterud, G L; Rockhold, F W; George, S L; Barton, F B; Davis, C E; Fairweather, W R; Honohan, T; Mowery, R; O'Neill, R

1998-10-01

In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. Franca Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O'Neill) to serve on the subcommittee. The subcommittee considered "how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often." During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected.

Multicenter clinical trials in sepsis: understanding the big picture and building a successful operation at your hospital.

PubMed

Dellinger, R Phillip; Schorr, Christa; Trzeciak, Stephen

2011-03-01

Only through adequately designed and adequately conducted clinical trials can new treatments be found for the benefit of the septic patient. Over the past 20 years, tens of thousands of patients have been enrolled in sepsis clinical trials with little success. These efforts, however, have not been without worth. Much has been learned and the knowledge gained has changed our approach to trial design in this very difficult field. Animal studies are better designed to match the clinical picture of severe sepsis. Phase II studies are more carefully engineered to answer questions about the most suitable target population and end points. Trial conduct likely benefits from use of CROs and a CCC. The future of clinical trials may include more standardization of sepsis management across investigative sites. Before the decision is made to become an investigative site in a multicenter industry-sponsored clinical trial in sepsis or severe sepsis, it is important to recognize what is required to succeed. Once these key-to-success elements are in place, members of the investigative team are more likely to realize the satisfaction and career growth from becoming a successful site. The most professional satisfaction comes from the knowledge of contributing to original science in the field of the sepsis. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

PubMed Central

Margolis, Karen L.; Davis, Barry R.; Baimbridge, Charles; Ciocon, Jerry O.; Cuyjet, Aloysius B.; Dart, Richard A.; Einhorn, Paula T.; Ford, Charles E.; Gordon, David; Hartney, Thomas J; Haywood, L. Julian; Holtzman, Jordan; Mathis, David E.; Oparil, Suzanne; Probstfield, Jeffrey L.; Simpson, Lara M.; Stokes, John D.; Wiegmann, Thomas B.; Williamson, Jeff D.

2015-01-01

A randomized, controlled, multicenter trial assigned well-controlled hypertensive participants ≥55 years, with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4-8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for total follow-up of 8-13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. Primary outcome was all-cause mortality; secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin versus usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03), or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in Blacks (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant over the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in Blacks. PMID:23889716

Controlled multicenter trial of laparoscopic transabdominal preperitoneal hernioplasty vs Shouldice herniorrhaphy. Early results.

PubMed

Tschudi, J; Wagner, M; Klaiber, C; Brugger, J; Frei, E; Krähenbühl, L; Inderbitzi, R; Hüsler, J; Hsu Schmitz, S

1996-08-01

In February 1993 a prospective randomized multicenter trial was initiated to compare laparoscopic transabdominal preperitoneal hernioplasty to Shouldice herniorrhaphy as performed by surgeons of nonspecialized clinics. Until January 1994, 87 patients with 108 hernias took part in the trial (43 Shouldice and 44 laparoscopic repairs). The laparoscopic procedure took significantly longer than did the open operation but caused less pain as measured by pain analogue score and consumption of paracetamol and narcotics. The postoperative complication rate was 26% in the open and 16% in the laparoscopic group. The patients in the laparoscopic group were discharged earlier and their convalescence was shorter than after open hernia repair. There has been one early recurrence in the laparoscopic and two in the open group to date with a mean follow-up of 201 days. Laparoscopic hernia repair causes less pain than the conventional operation and enables the patient to return to full work and usual activities earlier. The recurrence rate will not be known for 5 years.

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

PubMed

Li, Yan; Ma, Hongli; Zhang, Yuehui; Kuang, Hongying; Ng, Ernest Hung Yu; Hou, Lihui; Wu, Xiaoke

2013-07-18

Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. We postulate that women with PCOS will have improved insulin resistance following berberine administration. This study is registered at ClinicalTrials.gov, NCT01138930.

Multicenter Evaluation of a New Shortened Peptide Nucleic Acid Fluorescence In Situ Hybridization Procedure for Species Identification of Select Gram-Negative Bacilli from Blood Cultures▿

PubMed Central

Morgan, Margie; Marlowe, Elizabeth; Della-Latta, Phyllis; Salimnia, Hossein; Novak-Weekley, Susan; Wu, Fann; Crystal, Benjamin S.

2010-01-01

A shortened protocol for two peptide nucleic acid fluorescence in situ hybridization (PNA FISH) assays for the detection of Gram-negative bacilli from positive blood cultures was evaluated in a multicenter trial. There was 100% concordance between the two protocols for each assay (368 of 368 and 370 of 370 results) and 99.7% (367 of 368 and 369 of 370 results) agreement with routine laboratory techniques. PMID:20357212

The MOSAIC study - comparison of the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with anorexia nervosa or eating disorder not otherwise specified, anorexia nervosa type: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Anorexia nervosa (AN) is a biologically based serious mental disorder with high levels of mortality and disability, physical and psychological morbidity and impaired quality of life. AN is one of the leading causes of disease burden in terms of years of life lost through death or disability in young women. Psychotherapeutic interventions are the treatment of choice for AN, but the results of psychotherapy depend critically on the stage of the illness. The treatment response in adults with a chronic form of the illness is poor and drop-out from treatment is high. Despite the seriousness of the disorder the evidence-base for psychological treatment of adults with AN is extremely limited and there is no leading treatment. There is therefore an urgent need to develop more effective treatments for adults with AN. The aim of the Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC) is to evaluate the efficacy and cost effectiveness of two outpatient treatments for adults with AN, Specialist Supportive Clinical Management (SSCM) and the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA). Methods/Design 138 patients meeting the inclusion criteria are randomly assigned to one of the two treatment groups (MANTRA or SSCM). All participants receive 20 once-weekly individual therapy sessions (with 10 extra weekly sessions for those who are severely ill) and four follow-up sessions with monthly spacing thereafter. There is also optional access to a dietician and extra sessions involving a family member or a close other. Body weight, eating disorder- related symptoms, neurocognitive and psychosocial measures, and service use data are measured during the course of treatment and across a one year follow up period. The primary outcome measure is body mass index (BMI) taken at twelve months after randomization. Discussion This multi-center study provides a large sample size, broad inclusion criteria and a follow-up period. However, the study has to contend with difficulties directly related to running a large multi-center randomized controlled trial and the psychopathology of AN. These issues are discussed. Trial Registration Current Controlled Trials ISRCTN67720902 - A Maudsley outpatient study of treatments for anorexia nervosa and related conditions. PMID:23721562

Venlafaxine ER for the Treatment of Pediatric Subjects with Depression: Results of Two Placebo-Controlled Trials

ERIC Educational Resources Information Center

Emslie, Graham J.; Findling, Robert L.; Yeung, Paul P.; Kunz, Nadia R.; Li, Yunfeng

2007-01-01

Objective: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. Method: Participants received venlafaxine ER (flexible dose,…

Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

PubMed

Nakanishi, Rine; Post, Wendy S; Osawa, Kazuhiro; Jayawardena, Eranthi; Kim, Michael; Sheidaee, Nasim; Nezarat, Negin; Rahmani, Sina; Kim, Nicholas; Hathiramani, Nicolai; Susarla, Shriraj; Palella, Frank; Witt, Mallory; Blaha, Michael J; Brown, Todd T; Kingsley, Lawrence; Haberlen, Sabina A; Dailing, Christopher; Budoff, Matthew J

2018-01-01

The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.

PubMed

Merhi, Basma; Shireman, Theresa; Carpenter, Myra A; Kusek, John W; Jacques, Paul; Pfeffer, Marc; Rao, Madhumathi; Foster, Meredith C; Kim, S Joseph; Pesavento, Todd E; Smith, Stephen R; Kew, Clifton E; House, Andrew A; Gohh, Reginald; Weiner, Daniel E; Levey, Andrew S; Ix, Joachim H; Bostom, Andrew

2017-09-01

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. Cohort study. The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54). We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted. Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort

PubMed Central

Merhi, Basma; Shireman, Theresa; Carpenter, Myra A.; Kusek, John W.; Jacques, Paul; Pfeffer, Marc; Rao, Madhumathi; Foster, Meredith C.; Kim, S. Joseph; Pesavento, Todd E.; Smith, Stephen R.; Kew, Clifton E.; House, Andrew A.; Gohh, Reginald; Weiner, Daniel E.; Levey, Andrew S.; Ix, Joachim H.; Bostom, Andrew

2017-01-01

Background Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. Study Design Cohort study. Setting & Participants The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B–based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Predictor Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. Results During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92–1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15–1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04–1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00–1.31), transplant failure (HR, 1.72; 95% CI, 1.46–2.01), and mortality (HR, 1.34; 95% CI, 1.15–1.54). Limitations We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Conclusions Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted. PMID:28579423

Video-Only Cardiopulmonary Resuscitation Education for High-Risk Families Before Hospital Discharge: A Multicenter Pragmatic Trial

PubMed Central

Blewer, Audrey L.; Putt, Mary E.; Becker, Lance B.; Riegel, Barbara J.; Li, Jiaqi; Leary, Marion; Shea, Judy A.; Kirkpatrick, James N.; Berg, Robert A.; Nadkarni, Vinay M.; Groeneveld, Peter W.; Abella, Benjamin S.

2016-01-01

Background CPR training rates in the US are low, highlighting the need to develop CPR educational approaches that are simpler, with broader dissemination potential. The minimum training required to ensure long-term skill retention remains poorly characterized. We compared CPR skill retention among laypersons randomized to training with video-only (VO; no manikin) to those trained with a video self-instruction kit (VSI; with manikin). We hypothesized that VO training would be non-inferior to the VSI approach with respect to chest compression (CC) rate. Methods and Results We performed a prospective cluster randomized trial of CPR education for family members of high-risk cardiac patients on hospital cardiac units, using a multicenter pragmatic design. Eight hospitals were randomized to offer either VO or VSI training before discharge using volunteer trainers. CPR skills were assessed six months post-training. Mean CC rate among those trained with VO compared to VSI was assessed with a non-inferiority margin set at 8 CC per min (cpm); as a secondary outcome, mean differences in CC depth were assessed. From 2/2012 to 5/2015, 1464 subjects were enrolled and 522 subjects completed a skills assessment. The mean CC rates were 87.7(VO) cpm and 89.3 (VSI) cpm; we concluded non-inferiority for VO based on a mean difference of −1.6 (90% CI: −5.2, 2.1). The mean CC depth was 40.2 mm (VO) and 45.8 mm (VSI) with a mean difference of −5.6 (95% CI: −7.6, −3.7). Results were similar after multivariate regression adjustment. Conclusions In this large prospective trial of CPR skill retention, VO training yielded a non-inferior difference in CC rate compared to VSI training. CC depth was greater in the VSI group. These findings suggest a potential trade-off in efforts for broad dissemination of basic CPR skills; VO training might allow for greater scalability and dissemination, but with a potential reduction in CC depth. Clinical Trial Registration URL: ClinicalTrials.gov, Identifier: NCT01514656. PMID:27703033

Transanal hemorrhoidal dearterialization with mucopexy versus open hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized control trials.

PubMed

Xu, L; Chen, H; Lin, G; Ge, Q; Qi, H; He, X

2016-12-01

The aim of this study was to analyse the outcomes of transanal hemorrhoidal dearterialization with mucopexy (THDm) versus open hemorrhoidectomy (OH) in the management of hemorrhoids. Randomized controlled trials in English were found by searching PubMed, Web of science, EMBASE, and the Cochrane Library database. Trials that compared THDm with OH were identified. Data were extracted independently for each study, and a meta-analysis was performed using fixed and random effects models. Four trials, including 316 patients, met the inclusion criteria. No statistically significant differences were noted in either total complications or postoperative bleeding, incontinence, recurrent prolapse, and urinary retention rate. Operative time was significantly longer for THDm with Doppler guidance than for THDm without Doppler guidance. Patients returned to normal activities faster after THDm than after OH. No statistically significant differences between THDm and OH were noted with regard to recurrence and reoperation rates. Our meta-analysis shows that THDm and OH are equally effective and can be attempted for the management of hemorrhoids. However, for THDm with Doppler guidance, more instruments and a longer operative time are required. Future large-scale, high-quality, multicenter trials with long-term outcomes are needed to prove these results and determine whether Doppler guidance in THD is truly necessary or not.

Testing homogeneity of proportion ratios for stratified correlated bilateral data in two-arm randomized clinical trials.

PubMed

Pei, Yanbo; Tian, Guo-Liang; Tang, Man-Lai

2014-11-10

Stratified data analysis is an important research topic in many biomedical studies and clinical trials. In this article, we develop five test statistics for testing the homogeneity of proportion ratios for stratified correlated bilateral binary data based on an equal correlation model assumption. Bootstrap procedures based on these test statistics are also considered. To evaluate the performance of these statistics and procedures, we conduct Monte Carlo simulations to study their empirical sizes and powers under various scenarios. Our results suggest that the procedure based on score statistic performs well generally and is highly recommended. When the sample size is large, procedures based on the commonly used weighted least square estimate and logarithmic transformation with Mantel-Haenszel estimate are recommended as they do not involve any computation of maximum likelihood estimates requiring iterative algorithms. We also derive approximate sample size formulas based on the recommended test procedures. Finally, we apply the proposed methods to analyze a multi-center randomized clinical trial for scleroderma patients. Copyright © 2014 John Wiley & Sons, Ltd.

Defibrillator implantations for primary prevention in the United States: Inappropriate care or inadequate documentation: Insights from the National Cardiovascular Data ICD Registry.

PubMed

Kaiser, Daniel W; Tsai, Vivian; Heidenreich, Paul A; Goldstein, Mary K; Wang, Yongfei; Curtis, Jeptha; Turakhia, Mintu P

2015-10-01

Prior studies have reported that more than 20% of implantable cardioverter-defibrillator (ICD) implantations in the United States do not adhere to trial-based criteria. We sought to investigate the patient characteristics associated with not meeting the inclusion criteria of the clinical trials that have demonstrated the efficacy of primary prevention ICDs. Using data from the National Cardiovascular Data Registry's ICD Registry, we identified patients who received ICDs for primary prevention from January 2006 to December 2008. We determined whether patients met the inclusion criteria of at least 1 of the 4 ICD primary prevention trials: Multicenter Automatic Defibrillator Implantation Trial (MADIT), MADIT-II, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), and the Multicenter Unsustained Tachycardia Trial (MUSTT). Among 150,264 patients, 86% met criteria for an ICD implantation based on trial data. The proportion of patients who did not meet trial-based criteria increased as age decreased. In multivariate analysis, the significant predictors for not meeting trial criteria included prior cardiac transplantation (odds ratio [OR] 2.1), pediatric electrophysiology operator (OR 2.0), and high-grade atrioventricular conduction disease (OR 1.4). Among National Cardiovascular Data Registry registrants receiving first-time ICDs for primary prevention, the majority met trial-based criteria. Multivariate analyses suggested that many patients who did not meet the trial-based criteria may have had clinical circumstances that warranted ICD implantation. These findings caution against the use of trial-based indications to determine site quality metrics that could penalize sites that care for younger patients. The planned incorporation of appropriate use criteria into the ICD registry may better characterize patient- and site-level quality and performance. Published by Elsevier Inc.

PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial.

PubMed

Douglas, Pamela S; Hoffmann, Udo; Lee, Kerry L; Mark, Daniel B; Al-Khalidi, Hussein R; Anstrom, Kevin; Dolor, Rowena J; Kosinski, Andrzej; Krucoff, Mitchell W; Mudrick, Daniel W; Patel, Manesh R; Picard, Michael H; Udelson, James E; Velazquez, Eric J; Cooper, Lawton

2014-06-01

Suspected coronary artery disease (CAD) is one of the most common, potentially life-threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials have been performed to guide the selection of diagnostic strategies for these patients. The PROMISE study is a prospective, randomized trial comparing the effectiveness of 2 initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either (1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram) or (2) anatomical testing with ≥64-slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians, and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core laboratory quality and completeness assessment. All subjects are followed up for ≥1 year. The primary end point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis, and renal failure), or hospitalization for unstable angina. More than 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care, and anesthesiology sites. Multispecialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. The PROMISE trial will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomical testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost-effectiveness, and radiation exposure will be assessed. Copyright © 2014 Mosby, Inc. All rights reserved.

PROspective Multicenter Imaging Study for Evaluation of Chest Pain: Rationale and Design of the PROMISE Trial

PubMed Central

Douglas, Pamela S.; Hoffmann, Udo; Lee, Kerry L.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Anstrom, Kevin; Dolor, Rowena J.; Kosinski, Andrzej; Krucoff, Mitchell W.; Mudrick, Daniel W.; Patel, Manesh R.; Picard, Michael H.; Udelson, James E.; Velazquez, Eric J.; Cooper, Lawton

2014-01-01

Background Suspected coronary artery disease (CAD) is one of the most common, potentially life threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials have been performed to guide the selection of diagnostic strategies for these patients. Methods The PROMISE study is a prospective, randomized trial comparing the effectiveness of two initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either: 1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram); or 2) anatomic testing with >=64 slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core lab quality and completeness assessment. All subjects are followed for ≥1 year. The primary end-point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis and renal failure) or hospitalization for unstable angina. Results Over 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care and anesthesiology sites. Conclusion Multi-specialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. PROMISE will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomic testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost effectiveness and radiation exposure will be assessed. Clinical trials.gov identifier NCT01174550 PMID:24890527

Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders

PubMed Central

Loechelt, Brett J.; Green, Michael; Gottlieb, Peter A.; Blumberg, Emily; Weinberg, Adriana; Quinlan, Scott; Baden, Lindsey R.

2015-01-01

Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases. PMID:26336066

Randomized controlled trial comparing retroperitoneal laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for the treatment of large renal pelvic calculi: a pilot study.

PubMed

Li, Sheng; Liu, Tong-Zu; Wang, Xing-Huan; Zeng, Xian-Tao; Zeng, Guang; Yang, Zhong-Hua; Weng, Hong; Meng, Zhe; Huang, Jing-Yu

2014-08-01

To evaluate the efficacy and safety of retroperitoneal laparoscopic pyelolithotomy (RLP) versus percutaneous nephrolithotomy (PCNL) for large renal pelvic calculi using a randomized controlled trial. Patients with large renal pelvic calculi were prospectively randomized using matched-pair analysis (1:1 scenario) into either the RLP group or the PCNL group. The patients in each group underwent the procedure accordingly. Treatment efficacy, safety, and complications were evaluated after surgery. Finally, 178 eligible patients were included and the demographics and mean stone size of two groups were similar. We found no significant differences in the mean postoperative hospital stay (4.5±2.3 vs. 4.3±1.3 days), rate of blood transfusion (0% vs. 1.1%), conversion rate (0% vs. 3.4%), and rate of total postoperative complication (p>0.05). The procedural duration and mean drop in hemoglobin levels were significantly lower in the RLP group as compared with the PCNL group (90.87±33.4 vs. 116.8±44.4 minutes, p<0.001; 0.9±0.5 vs. 1.7±1.3 g/dL, p<0.001, respectively). Significant differences were also observed in the stone-free rate (98% vs. 90%, p=0.03) and postoperative fever rate (3.4% vs. 13.5%, p=0.02). Current evidence suggests that PCNL and RLP are both effective and safe for the treatment of large renal pelvic calculi. Our study shows that, compared with the PCNL approach, RLP for large renal pelvic stone resulted in shorter operative time, less bleeding, less postoperative fever, and a higher stone-free rate. Data from larger, multicenter randomized controlled trials of high quality are needed to further confirm our findings.

Patient-Reported Outcomes and Socioeconomic Status as Predictors of Clinical Outcomes after Hematopoietic Stem Cell Transplantation: A Study from the Blood and Marrow Transplant Clinical Trials Network 0902 Trial.

PubMed

Knight, Jennifer M; Syrjala, Karen L; Majhail, Navneet S; Martens, Michael; Le-Rademacher, Jennifer; Logan, Brent R; Lee, Stephanie J; Jacobsen, Paul B; Wood, William A; Jim, Heather S L; Wingard, John R; Horowitz, Mary M; Abidi, Muneer H; Fei, Mingwei; Rawls, Laura; Rizzo, J Douglas

2016-12-01

This secondary analysis of a large, multicenter Blood and Marrow Transplant Clinical Trials Network randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes, including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pretransplantation Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores of the Short-Form 36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (P < .01 considered significant given multiple testing). Lower attained education was associated with increased distress (P = .002), lower income was related to worse physical functioning (P = .005) and increased distress (P = .008), lack of employment before transplantation was associated with worse physical functioning (P < .01), and unmarried status was associated with worse sleep (P = .003). In this large heterogeneous cohort of HCT recipients, although PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Sponsors meet scientists to speed pediatric medicines development.

PubMed

Davis, Jonathan M; Smoyer, William E; Connor, Edward M; Huskins, W Charles; Pastern, Cindy; Purucker, Mary; Schrader, Elisabeth C; Jackson, Cynthia R; Kaskel, Frederick J; Hirschfeld, Steven

2015-03-18

The Point-Person Project, a child-health research initiative, enables rapid response to opportunities for participation in multicenter pediatric clinical trials. Copyright © 2015, American Association for the Advancement of Science.

Use of a remote clinical decision support service for a multicenter trial to implement prediction rules for children with minor blunt head trauma.

PubMed

Goldberg, Howard S; Paterno, Marilyn D; Grundmeier, Robert W; Rocha, Beatriz H; Hoffman, Jeffrey M; Tham, Eric; Swietlik, Marguerite; Schaeffer, Molly H; Pabbathi, Deepika; Deakyne, Sara J; Kuppermann, Nathan; Dayan, Peter S

2016-03-01

To evaluate the architecture, integration requirements, and execution characteristics of a remote clinical decision support (CDS) service used in a multicenter clinical trial. The trial tested the efficacy of implementing brain injury prediction rules for children with minor blunt head trauma. We integrated the Epic(®) electronic health record (EHR) with the Enterprise Clinical Rules Service (ECRS), a web-based CDS service, at two emergency departments. Patterns of CDS review included either a delayed, near-real-time review, where the physician viewed CDS recommendations generated by the nursing assessment, or a real-time review, where the physician viewed recommendations generated by their own documentation. A backstopping, vendor-based CDS triggered with zero delay when no recommendation was available in the EHR from the web-service. We assessed the execution characteristics of the integrated system and the source of the generated recommendations viewed by physicians. The ECRS mean execution time was 0.74 ±0.72 s. Overall execution time was substantially different at the two sites, with mean total transaction times of 19.67 and 3.99 s. Of 1930 analyzed transactions from the two sites, 60% (310/521) of all physician documentation-initiated recommendations and 99% (1390/1409) of all nurse documentation-initiated recommendations originated from the remote web service. The remote CDS system was the source of recommendations in more than half of the real-time cases and virtually all the near-real-time cases. Comparisons are limited by allowable variation in user workflow and resolution of the EHR clock. With maturation and adoption of standards for CDS services, remote CDS shows promise to decrease time-to-trial for multicenter evaluations of candidate decision support interventions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials.

PubMed

Kimberly, Michael B; Hoehn, K Sarah; Feudtner, Chris; Nelson, Robert M; Schreiner, Mark

2006-05-01

To systematically compare standards for compensation and child participant assent in informed permission, assent, and consent forms (IP-A-CFs) approved by 55 local institutional review boards (IRBs) reviewing 3 standardized multicenter research protocols. Sixty-nine principal investigators participating in any of 3 national, multicenter clinical trials submitted standardized research protocols for their trials to their local IRBs for approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to an academic clinical research organization. This collection of IRB-approved forms allowed for a quasiexperimental retrospective evaluation of the variation in informed permission, assent, and consent standards operationalized by the local IRBs. Standards for compensation and child participant assent varied substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering compensation, monetary compensation was offered by 33 as reimbursement for travel, parking, or food expenses, whereas monetary or material compensation was offered by 22 for subject inconvenience and by 13 for subject time. Compensation ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that included a form of assent documentation, 33 included a line for assent on the informed permission or consent form, whereas 35 included a separate form written in simplified language. Of the IP-A-CFs that stipulated the documentation of assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission or consent forms were addressed either to parents or child participants. In response to identical clinical trial protocols, local IRBs generate IP-A-CFs that vary considerably regarding compensation and child participant assent.

Evaluation of a multi-center randomised clinical trial on prophylactic transfusion of fresh frozen plasma: implications for future trials.

PubMed

Müller, M C A; de Haan, R J; Vroom, M B; Juffermans, N P

2014-10-01

Prophylactic use of fresh frozen plasma (FFP) in critically ill patients with a coagulopathy is common. However, a lack of evidence of efficacy has resulted in a call for trials on the benefit of FFP in these patients. To date, conducting a trial on this subject has not been successful. Recently, a multi-center randomised trial was stopped prematurely due to slow inclusion. To assess clinicians' opinions regarding a trial on prophylactic administration of FFP in coagulopathic critically ill patients who need to undergo an intervention. A survey among 55 intensivists who all participated in a randomised trial on the risks and benefits of FFP in critically ill patients. Response rate was 84%. Majority of respondents indicated that international normalised ratio (INR) should be assessed before insertion of a central venous catheter (CVC) (61%), chest tube (89%) or tracheostomy (91%). Reasons to withhold transfusion of FFP to non-bleeding critically ill patients are risk of transfusion-related acute lung injury (TRALI) (46%), fluid overload (39%) and allergic reaction (24%). Although, the majority of respondents expressed the opinion that the trial was clinically relevant, 56% indicated that ≥1 patient subgroups should have been excluded from participation. Intensivists express the need for more evidence on the prophylactic use of FFP in coagulopathic critically ill patients. However, lack of knowledge about FFP and personal beliefs about the preferable transfusion strategy among clinicians, resulted in premature termination of a clinical trial on this topic. © 2014 British Blood Transfusion Society.

Informatics in neurocritical care: new ideas for Big Data.

PubMed

Flechet, Marine; Grandas, Fabian Güiza; Meyfroidt, Geert

2016-04-01

Big data is the new hype in business and healthcare. Data storage and processing has become cheap, fast, and easy. Business analysts and scientists are trying to design methods to mine these data for hidden knowledge. Neurocritical care is a field that typically produces large amounts of patient-related data, and these data are increasingly being digitized and stored. This review will try to look beyond the hype, and focus on possible applications in neurointensive care amenable to Big Data research that can potentially improve patient care. The first challenge in Big Data research will be the development of large, multicenter, and high-quality databases. These databases could be used to further investigate recent findings from mathematical models, developed in smaller datasets. Randomized clinical trials and Big Data research are complementary. Big Data research might be used to identify subgroups of patients that could benefit most from a certain intervention, or can be an alternative in areas where randomized clinical trials are not possible. The processing and the analysis of the large amount of patient-related information stored in clinical databases is beyond normal human cognitive ability. Big Data research applications have the potential to discover new medical knowledge, and improve care in the neurointensive care unit.

A Multicenter, Randomized Clinical Trial of a Cognitive Remediation Program for Childhood Survivors of a Pediatric Malignancy

ERIC Educational Resources Information Center

Butler, Robert W.; Copeland, Donna R.; Fairclough, Diane L.; Mulhern, Raymond K.; Katz, Ernest R.; Kazak, Anne E.; Noll, Robert B.; Patel, Sunita K.; Sahler, Olle Jane Z.

2008-01-01

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35%…

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial.

PubMed

Liu, Zhishun; Wang, Yang; Xu, Huanfang; Wu, Jiani; He, Liyun; Jiang, John Yi; Yan, Shiyan; Du, Ruosang; Liu, Baoyan

2014-06-21

Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

Understanding clinical development of chimeric antigen receptor T cell therapies.

PubMed

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2017-06-01

In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype with promising efficacy in cancer treatment which are tested in many clinical trials, but have not yet received MAA. We generated an overview of the characteristics of CAR T-cell clinical development in the United States, Canada and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell products that proceeded to a subsequent clinical trial, used as a proxy for success, were compared with those that did not proceed. From the U.S. and European Union clinical trial databases, 106 CAR T-cell trials were selected, from which 49 were linked to a subsequent trial and 57 were not. The majority of the trials had an academic sponsor from which most did not proceed, whereas most commercially sponsored trials were followed by another clinical trial. Furthermore, trials with a subsequent trial more frequently recruited large patient cohorts and were more often multicenter compared with trials that were not followed up. These characteristics can be used by investigators to better design clinical trials with CAR T cells. We encourage sponsors to plan clinical development ahead for a higher efficiency of product development and thereby achieving a higher success rate of development towards MAA. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

Patient-reported outcomes and socioeconomic status as predictors of clinical outcomes following hematopoietic stem cell transplantation: A study from the BMT CTN 0902 trial

PubMed Central

Knight, Jennifer M; Syrjala, Karen L; Majhail, Navneet S; Martens, Michael; Le-Rademacher, Jennifer; Logan, Brent R; Lee, Stephanie J; Jacobsen, Paul B; Wood, William A; Jim, Heather SL; Wingard, John R; Horowitz, Mary M; Abidi, Muneer H; Fei, Mingwei; Rawls, Laura; Rizzo, J Douglas

2016-01-01

This secondary analysis of a large, multi-center Blood and Marrow Transplant Clinical Trials Network (BMT CTN) randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pre-transplant Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores (MCS and PCS) of the SF-36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (p<.01 considered significant given multiple testing). Lower attained education was associated with increased distress (p=.002); lower income was related to worse physical functioning (p=.005) and increased distress (p=.008); lack of employment pre-transplant was associated with worse physical functioning (p<.01); unmarried status was associated with worse sleep (p=.003). In this large heterogeneous cohort of HCT recipients, while PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage. PMID:27565521

Current evidence for the safety and efficacy of the bio-engineered dual therapy COMBO stent.

PubMed

Kalkman, Deborah N; Chandrasekhar, Jaya; de Winter, Robbert J; Mehran, Roxana

2018-06-01

The novel dual-therapy COMBO stent aims to promote vessel healing after percutaneous coronary intervention (PCI) in patients with coronary artery disease. The pro-healing technique consists of an anti-CD34+ antibody layer that attracts circulating endothelial progenitor cells (EPCs), which bind to the stent surface and allow rapid endothelialization by differentiation of the EPCs into normal endothelial cells. The COMBO stent combines this pro-healing technique with an abluminal drug elution of sirolimus. The promise of this dual-therapy stent is that it may safely allow a shortened duration of dual-antiplatelet therapy (DAPT) after stent placement. Moreover, with a mature endothelial layer, lower rates of in-stent restenosis may be expected. Clinical outcomes after COMBO stent implantation have been recently evaluated in both randomized trials and large, prospective, multicenter registries, showing low clinical event rates of in-stent restenosis and stent thrombosis. Randomized clinical trials (HARMONEE and RECOVERY) have demonstrated the non-inferiority of COMBO versus "first in class" second generation and newer generation drug-eluting stents. Safety and efficacy of 3 months of DAPT after COMBO stent placement in patients presenting with acute coronary syndrome has been evaluated in the large REDUCE randomized controlled trial, showing non-inferiority to standard duration of 12-month DAPT. In this review we provide an overview of the current pre-clinical and clinical evidence for the performance of the COMBO stent.

Application of computerized exercise ECG digitization. Interpretation in large clinical trials.

PubMed

Caralis, D G; Shaw, L; Bilgere, B; Younis, L; Stocke, K; Wiens, R D; Chaitman, B R

1992-04-01

The authors report on a semiautomated program that incorporates both visual identification of fiducial points and digital determination of the ST-segment at 60 ms and 80 ms from the J point, ST slope, changes in R wave, and baseline drift. The off-line program can enhance the accuracy of detecting electrocardiographic (ECG) changes, as well as reproducibility of the exercise and postexercise ECG, as a marker of myocardial ischemia. The analysis program is written in Microsoft QuickBASIC 2.0 for an IBM personal computer interfaced to a Summagraphics mm1201 microgrid II digitizer. The program consists of the following components: (1) alphanumeric data entry, (2) ECG wave form digitization, (2) calculation of test results, (4) physician overread, and (5) editor function for remeasurements. This computerized exercise ECG digitization-interpretation program is accurate and reproducible for the quantitative assessment of ST changes and requires minimal time allotment for physician overread. The program is suitable for analysis and interpretation of large volumes of exercise tests in multicenter clinical trials and is currently utilized in the TIMI II, TIMI III, and BARI studies sponsored by the National Institutes of Health.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

PubMed

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Hossein Ahmadi, Zargham; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdol Hosein; Baharvand, Hossein; Aghdami, Nasser

2018-10-01

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. Copyright© by Royan Institute. All rights reserved.

EX-MET study: exercise in prevention on of metabolic syndrome - a randomized multicenter trial: rational and design.

PubMed

Tjønna, Arnt Erik; Ramos, Joyce S; Pressler, Axel; Halle, Martin; Jungbluth, Klaus; Ermacora, Erika; Salvesen, Øyvind; Rodrigues, Jhennyfer; Bueno, Carlos Roberto; Munk, Peter Scott; Coombes, Jeff; Wisløff, Ulrik

2018-04-02

Metabolic syndrome substantially increases risk of cardiovascular events. It is therefore imperative to develop or optimize ways to prevent or attenuate this condition. Exercise training has been long recognized as a corner-stone therapy for reducing individual cardiovascular risk factors constituting the metabolic syndrome. However, the optimal exercise dose and its feasibility in a real world setting has yet to be established. The primary objective of this randomized trial is to investigate the effects of different volumes of aerobic interval training (AIT) compared to the current exercise guideline of moderate-intensity continuous training (MICT) on the composite number of cardiovascular disease risk factors constituting the metabolic syndrome after a 16 week, 1-year, and 3-year follow-up. This is a randomized international multi-center trial including men and women aged ≥30 years diagnosed with the metabolic syndrome according to the International Diabetes Federation criteria. Recruitment began in August 2012 and concluded in December 2016. This trial consists of supervised and unsupervised phases to evaluate the efficacy and feasibility of different exercise doses on the metabolic syndrome in a real world setting. This study aims to include and randomize 465 participants to 3 years of one of the following training groups: i) 3 times/week of 4 × 4 min AIT at 85-95% peak heart rate (HRpeak); ii) 3 times/week of 1 × 4 min AIT at 85-95% HRpeak; or iii) 5-7 times/week of ≥30 min MICT at 60-70% HRpeak. Clinical examinations, physical tests and questionnaires are administered to all participants during all testing time points (baseline, 16 weeks and after 1-, and 3-years). This multi-center international trial indeed aims to ease the burden in healthcare/economic cost arising from treating end-stage CVD related conditions such as stroke and myocardial infarction, that could eventually emerge from the metabolic syndrome condition. Clinical registration number: NCT01676870 , ClinicalTrials.gov (August 31, 2012).

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project

PubMed Central

Freyer Karn, Catharine; Fox, Kristen

2015-01-01

Abstract Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. PMID:26176343

An automated diagnostic process (PDA) in clinical psychopharmacology. An exemplification of its use in a sulpiride versus haloperidol comparative trial.

PubMed

Castrogiovanni, P; Cassano, G B; Conti, L; Maggini, C; Bonollo, L; Sarteschi, P

1976-01-01

One of the main unsolved problems, and one which produces divergent results in clinical psychopharmacology, is that concerning the selection of patients and their diagnostic definition. An automated diagnostic procedure (PDA) was set up in order to classify each patient into one nosographic category on the basis of a cross-sectional examination of his mental state. Such diagnostic procedure appears particularly suitable for multicenter drug trials, since it gives a profile and a diagnostic definition of patients, assessed by investigators from different areas and with different cultural, and clinical backgrounds. In a multicenter trial (sulpiride versus haloperidol) PDA offered a chance to re-examine and analyze the characteristics of each patient and therefore to control the criteria followed for the sample selection in the various experimental settings. The agreement between clinician and computer diagnosis was 78.9%; this agreement rises to 85.5% if the computerlabelled schizo-affective syndromes are considered within the schizophrenic group. Moreover, and attempt has been made to relate psychopathological patterns to drug responses.

Noteworthy Articles in 2015 for the Cardiothoracic Anesthesiologist.

PubMed

Varelmann, Dirk J; Muehlschlegel, J Daniel

2016-03-01

Large multicenter, randomized controlled trials published in reputable journals had a large impact on the world of cardiothoracic anesthesia in 2015. We as cardiac anesthesiologists pride ourselves as being experts in applied physiology, physics, ultrasonography, and pharmacology/pharmacotherapy. The selected studies added to our knowledge in the fields of echocardiography, pharmacology, molecular biology, and genetics. Outcome studies shine a light on important topics that are relevant to all cardiac anesthesiologists: does surgical atrial fibrillation ablation during mitral valve surgery reduce the recurrence of atrial fibrillation at 1 year after surgery? Does remote ischemic preconditioning live up to its promise to reduce postoperative major cardiac and cerebral events? Although we still do not have the answer to all the questions, the year 2015 has been a great step toward the goal of understanding molecular mechanisms of ischemic myocardial injury and toward providing evidence-based medicine for improving patient outcome. © The Author(s) 2016.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

PubMed

Colì, Luigi; La Manna, Gaetano; Comai, Giorgia; Ursino, Mauro; Ricci, Davide; Piccari, Matteo; Locatelli, Francesco; Di Filippo, Salvatore; Cristinelli, Luciano; Bacchi, Massimo; Balducci, Alessandro; Aucella, Filippo; Panichi, Vincenzo; Ferrandello, Francesco Paolo; Tarchini, Renzo; Lambertini, Domenica; Mura, Carlo; Marinangeli, Giancarlo; Di Loreto, Ermanno; Quarello, Francesco; Forneris, Giacomo; Tancredi, Maurizio; Morosetti, Massimo; Palombo, Giuditta; Di Luca, Marina; Martello, Mauro; Emiliani, Giuseppe; Bellazzi, Roberto; Stefoni, Sergio

2011-07-01

Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. A noncontrolled (single arm), multicenter, prospective, clinical trial. 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. A noncontrolled (single arm) study, no crossover from AASD to standard treatment. This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Internet-delivered cognitive-behavioral treatment for adolescents with chronic pain and their parents: a randomized controlled multicenter trial.

PubMed

Palermo, Tonya M; Law, Emily F; Fales, Jessica; Bromberg, Maggie H; Jessen-Fiddick, Tricia; Tai, Gabrielle

2016-01-01

Internet-delivered interventions are emerging as a strategy to address barriers to care for individuals with chronic pain. This is the first large multicenter randomized controlled trial of Internet-delivered cognitive-behavioral therapy (CBT) for pediatric chronic pain. Participants included were 273 adolescents (205 females and 68 males), aged 11 to 17 years with mixed chronic pain conditions and their parents, who were randomly assigned in a parallel-group design to Internet-delivered CBT (n = 138) or Internet-delivered Education (n = 135). Assessments were completed before treatment, immediately after treatment, and at 6-month follow-up. All data collection and procedures took place online. The primary analysis used linear growth models. Results demonstrated significantly greater reduction on the primary outcome of activity limitations from baseline to 6-month follow-up for Internet CBT compared with Internet education (b = -1.13, P = 0.03). On secondary outcomes, significant beneficial effects of Internet CBT were found on sleep quality (b = 0.14, P = 0.04), on reducing parent miscarried helping (b = -2.66, P = 0.007) and protective behaviors (b = -0.19, P = 0.001), and on treatment satisfaction (P values < 0.05). On exploratory outcomes, benefits of Internet CBT were found for parent-perceived impact (ie, reductions in depression, anxiety, self-blame about their adolescent's pain, and improvement in parent behavioral responses to pain). In conclusion, our Internet-delivered CBT intervention produced a number of beneficial effects on adolescent and parent outcomes, and could ultimately lead to wide dissemination of evidence-based psychological pain treatment for youth and their families.

Gender indexing in publications of clinical trials: 1991-2008.

PubMed

Drye, Lea T; Meinert, Jill L; Meinert, Curtis L

2010-12-01

In 1993 Congress passed the NIH Revitalization Act, which instructed the Director of the NIH to ensure that phase III clinical trials are 'designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect females or members of minority groups, as the case may be, differently than other subjects in the trial.' The purpose of this article is to track the PubMed indexing of gender in clinical trial publications since 1991 with a view toward assessing the impact of the legislation on the number of gender specific trials. We searched PubMed for full-length publications from years 1991 to 2008 of research on humans indexed as publication type 'clinical trial', 'randomized clinical trial' and multicenter randomized trial ('multicenter study' AND 'randomized clinical trial'), and counted the number of trials indexed as male-only, female-only, male and female, and gender unknown in PubMed. The majority of trial publications were indexed in PubMed as including both genders. The proportion of publications indexed as including both genders has increased while the number of publications not indexed with respect to gender and the number of publications indexed as male-only have decreased. In 2005, approximately 13% of NIH expenditures were for female specific or related research compared to 6% for male specific or related research. The proportion of clinical trial publications that were indexed in PubMed as including females began to increase before the legislation so it is difficult to conclude that changes in the number of female-only or male-only trials are due to the legislation. PubMed listings do not include gender enrollment, so female and male enrollment totals could not be compared. The NIH policy should be rewritten to be made gender neutral to bring it in line with the principle of justice as embodied in the Belmont Report.

Mechanical Thrombectomy for Minor and Mild Stroke Patients Harboring Large Vessel Occlusion in the Anterior Circulation: A Multicenter Cohort Study.

PubMed

Dargazanli, Cyril; Arquizan, Caroline; Gory, Benjamin; Consoli, Arturo; Labreuche, Julien; Redjem, Hocine; Eker, Omer; Decroix, Jean-Pierre; Corlobé, Astrid; Mourand, Isabelle; Gaillard, Nicolas; Ayrignac, Xavier; Charif, Mahmoud; Duhamel, Alain; Labeyrie, Paul-Emile; Riquelme, Carlos; Ciccio, Gabriele; Smajda, Stanislas; Desilles, Jean-Philippe; Gascou, Grégory; Lefèvre, Pierre-Henri; Mantilla-García, Daniel; Cagnazzo, Federico; Coskun, Oguzhan; Mazighi, Mikael; Riva, Roberto; Bourdain, Frédéric; Labauge, Pierre; Rodesch, Georges; Obadia, Michael; Bonafé, Alain; Turjman, Francis; Costalat, Vincent; Piotin, Michel; Blanc, Raphaël; Lapergue, Bertrand

2017-12-01

Proximal large vessel occlusion (LVO) is present in up to 30% of minor strokes. The effectiveness of mechanical thrombectomy (MT) in the subgroup of minor stroke with LVO in the anterior circulation is still open to debate. Data about MT in this subgroup of patients are sparse, and their optimal management has not yet been defined. The purpose of this multicenter cohort study was to evaluate the effectiveness of MT in patients experiencing acute ischemic stroke (AIS) because of LVO in the anterior circulation, presenting with minor-to-mild stroke symptoms (National Institutes of Health Stroke Scale score of <8). Multicenter cohort study involving 4 comprehensive stroke centers having 2 therapeutic approaches (urgent thrombectomy associated with best medical treatment [BMT] versus BMT first and MT if worsening occurs) about management of patients with minor and mild acute ischemic stroke harboring LVO in the anterior circulation. An intention-to-treat analysis was conducted. The primary end point was the rate of excellent outcome defined as the achievement of a modified Rankin Scale score of 0 to 1 at 3 months. Three hundred one patients were included, 170 with urgent MT associated with BMT, and 131 with BMT alone as first-line treatment. Patients treated with MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.0%) in the medical group had rescue MT because of neurological worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the 2 groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size. Minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT. There is thus an urgent need for randomized trials to define the effectiveness of MT in this patient subgroup. © 2017 American Heart Association, Inc.

77 FR 54582 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Multi-Center Clinical Trial Review. Date... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes...

Conducting multicenter research in healthcare simulation: Lessons learned from the INSPIRE network.

PubMed

Cheng, Adam; Kessler, David; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay M; Hunt, Elizabeth A; Duval-Arnould, Jordan; Lin, Yiqun; Pusic, Martin; Auerbach, Marc

2017-01-01

Simulation-based research has grown substantially over the past two decades; however, relatively few published simulation studies are multicenter in nature. Multicenter research confers many distinct advantages over single-center studies, including larger sample sizes for more generalizable findings, sharing resources amongst collaborative sites, and promoting networking. Well-executed multicenter studies are more likely to improve provider performance and/or have a positive impact on patient outcomes. In this manuscript, we offer a step-by-step guide to conducting multicenter, simulation-based research based upon our collective experience with the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE). Like multicenter clinical research, simulation-based multicenter research can be divided into four distinct phases. Each phase has specific differences when applied to simulation research: (1) Planning phase , to define the research question, systematically review the literature, identify outcome measures, and conduct pilot studies to ensure feasibility and estimate power; (2) Project Development phase , when the primary investigator identifies collaborators, develops the protocol and research operations manual, prepares grant applications, obtains ethical approval and executes subsite contracts, registers the study in a clinical trial registry, forms a manuscript oversight committee, and conducts feasibility testing and data validation at each site; (3) Study Execution phase , involving recruitment and enrollment of subjects, clear communication and decision-making, quality assurance measures and data abstraction, validation, and analysis; and (4) Dissemination phase , where the research team shares results via conference presentations, publications, traditional media, social media, and implements strategies for translating results to practice. With this manuscript, we provide a guide to conducting quantitative multicenter research with a focus on simulation-specific issues.

Quality of life in preoperative patients with sacroiliac joint dysfunction is at least as depressed as in other lumbar spinal conditions.

PubMed

Cher, Daniel Joseph; Reckling, W Carlton

2015-01-01

Pain from the sacroiliac joint (SIJ) is an under-recognized cause of low back pain. The degree to which SIJ pain decreases quality of life has not been directly compared to other more familiar conditions of the lumbar spine. Multivariate regression analysis of individual patient data from two prospective multicenter clinical trials of SIJ fusion and three prospective multicenter clinical trials of surgical treatments for degenerative lumbar spine conditions. Controlling for baseline demographic parameters as well as a validated disability score, quality of life scores (EuroQOL 5-D and SF-36) were, in most cases, lower in the SIJ cohorts compared to the three other spine surgery cohorts. Patients with SIJ dysfunction considering surgery have decrements in quality of life as or more severe compared to patients with degenerative spondylolisthesis, spinal stenosis, and intervertebral disc herniation.

Multicenter trial of the proficiency of smart quantitative sensation tests.

PubMed

Dyck, Peter J; Argyros, Barbara; Russell, James W; Gahnstrom, Linde E; Nalepa, Susan; Albers, James W; Lodermeier, Karen A; Zafft, Andrew J; Dyck, P James B; Klein, Christopher J; Litchy, William J; Davies, Jenny L; Carter, Rickey E; Melton, L Joseph

2014-05-01

We assessed proficiency (accuracy and intra- and intertest reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic sensorimotor polyneuropathy (DSPN). Technologists from 3 medical centers using different but identical QSTs independently assessed 6 modalities of sensation of the foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intraclass correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra- or intertest differences were observed. These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra- or intertest differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length-dependent sensorimotor polyneuropathies. Copyright © 2013 Wiley Periodicals, Inc.

A Multicenter Trial of the Proficiency of Smart Quantitative Sensation Tests

PubMed Central

Dyck, Peter J.; Argyros, Barbara; Russell, James W.; Gahnstrom, Linde E.; Nalepa, Susan; Albers, James W.; Lodermeier, Karen A.; Zafft, Andrew J.; Dyck, P. James B.; Klein, Christopher J.; Litchy, William J.; Davies, Jenny L.; Carter, Rickey E.; Melton, L. Joseph

2014-01-01

Introduction We assessed proficiency (accuracy and intra- and inter-test reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic polyneuropathy (DSPN). Methods Technologists from 3 medical centers using different but identical QSTs assessed independently 6 modalities of sensation of foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. Results Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intra-class correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra- or inter-test differences were observed. Discussion These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra- or inter-test differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length-dependent sensorimotor polyneuropathies. PMID:23929701

Role of corticosteroid as a prophylactic measure in fat embolism syndrome: a literature review.

PubMed

Sen, Ramesh K; Tripathy, Sujit K; Krishnan, Vibhu

2012-06-01

Despite a number of studies on steroid therapy as a prophylactic measure in fat embolism syndrome (FES), there is no universal agreement about its role in this critical situation. The present article attempts to search the available literature, and provides a more lucid picture to the readers on this issue. Seven articles (total 483 patients) were reviewed and analyzed. Total of 223 patients received steroid (methyl prednisolone sodium succinate), while the remaining 260 patients formed the control population. Among these subjects, 9 patients in steroid-receiving group and 60 patients in the control group developed FES (P < 0.05). The lack of uniformities in these studies, variable dose and single-center trial are the principal limitations and confuses the surgeons to have definite conclusion. Large-scale, more uniformly designed, multi-centered, randomized, prospective trials are needed to determine the correct situations and dosage in which steroids provide the maximum benefit (with the least possible risk).

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies.

PubMed

Ho, V T; Revta, C; Richardson, P G

2008-02-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication.

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

PubMed

Chen, Lifang; Fang, Jianqiao; Ma, Ruijie; Froym, Ronen; Gu, Xudong; Li, Jianhua; Chen, Lina; Xu, Shouyu; Ji, Conghua

2014-06-08

Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

Mortality in two recent reports of clinical trials on patients with congestive heart failure compared with mortality in three previous clinical trials.

PubMed

Singer, R B

2000-01-01

Several clinical trials of drug treatment of patients with congestive heart failure (CHF) have previously been reported as Mortality Abstracts in the Journal of Insurance Medicine. Results are presented here for two similar clinical trials reported in September 1999 and compared with the previous results. In a recent international multicenter clinical trial, excess mortality in terms of excess death rates (EDRs) was reduced from 195 per 1000 per year in the placebo group to 139 in the group treated with Spironolactone. There was no significant reduction in the Danish multicenter study of Dofetilide to convert the atrial fibrillation (AF) to a normal rhythm in the 25% of the CHF patients who had AF (EDR was 224 in the placebo group and 216 in the Dofetilide group). In both of these studies, there were more patients with severe CHF than in the previous studies and the EDR values were higher. Results from the Danish study by severity according to the New York Heart Association (NYHA) classification show a progressive increase in EDR from 173 in class 2 to 237 in class 3 to 392 in class 4. Excess mortality in symptomatic CHF is far outside the issue limits for individual life insurance, but these results are of potential utility for the underwriting of such cases for structured settlement annuities.

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

A randomized study comparing outcomes of stapled and hand-sutured anastomoses in patients undergoing open gastrointestinal surgery.

PubMed

Chandramohan, S M; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L; Waggoner, Jason R; Tatla, Daljit

2013-08-01

Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospective, randomized, interventional, parallel, multicenter, controlled trial. Randomization was assigned in a 1:1 ratio between the hand-sutured group (n = 138) and the stapled group (n = 142). Anastomosis time, surgery time, and time to bowel activity were collected and compared as primary endpoints. A total of 280 subjects were enrolled from April 2009 to September 2010. Only the time of anastomosis was significantly different between the two arms: 17.6 ± 1.90 min (stapled) and 20.6 ± 1.90 min (hand-sutured). This difference was deemed not clinically or economically meaningful. Safety outcomes and other secondary endpoints were similar between the two arms. Mechanical stapling is faster than hand-suturing for the construction of gastrointestinal anastomoses. Apart from this, stapling and hand-suturing are similar with respect to the outcomes measured in this trial.

Demonstration of Nonlinearity Bias in the Measurement of the Apparent Diffusion Coefficient in Multicenter Trials

PubMed Central

Malyarenko, Dariya; Newitt, David; Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G.; Arlinghaus, Lori R.; Jacobs, Michael A.; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E.; Huang, Wei; Chenevert, Thomas L.

2015-01-01

Purpose Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Methods Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ±150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients and eddy currents were assessed independently. The observed bias errors were compared to numerical models. Results The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between −55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (±5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image co-registration of individual gradient directions. Conclusion The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. PMID:25940607

Demonstration of nonlinearity bias in the measurement of the apparent diffusion coefficient in multicenter trials.

PubMed

Malyarenko, Dariya I; Newitt, David; J Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G; Arlinghaus, Lori R; Jacobs, Michael A; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E; Huang, Wei; Chenevert, Thomas L

2016-03-01

Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ± 150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients, and eddy currents were assessed independently. The observed bias errors were compared with numerical models. The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between -55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (± 5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image coregistration of individual gradient directions. The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. © 2015 Wiley Periodicals, Inc.

Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

PubMed Central

Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

2017-01-01

Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

Factors predicting survival in ALS: a multicenter Italian study.

PubMed

Calvo, Andrea; Moglia, Cristina; Lunetta, Christian; Marinou, Kalliopi; Ticozzi, Nicola; Ferrante, Gianluca Drago; Scialo, Carlo; Sorarù, Gianni; Trojsi, Francesca; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Chiò, Adriano; Sansone, Valeria Ada; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Monsurrò, Maria Rosaria; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fini, Nicola; Mandrioli, Jessica

2017-01-01

The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

[Utilization of multimodal therapy concepts in stomach carcinoma in Germany].

PubMed

Bösing, N M; Heise, J W; Röher, H D

2000-01-01

In view of disappointing results after surgery alone multimodal therapeutic regimes are used to improve long-term prognosis in locally advanced gastric carcinomas. In presence of many reports about encouraging results ("down staging", improved R0-resection rates) but simultaneously missing evidence of efficiency of neoadjuvant therapies in respect to long-term survival (large randomized multicenter trials do not exist until today) and the herewith related uncertainties, we started an inquiry among many surgical units with the intention to evaluate the clinical practice of multimodal treatment for gastric cancer patients in Germany today. In a questionnaire (3/99) we asked among 97 surgical units (41 university hospitals, 56 big community hospitals) in Germany for the management of gastric cancer patients with special interest to practice and state of adjuvant and neoadjuvant therapeutic strategies. Further we analyzed all resected gastric cancer patients (1986-1995) without neoadjuvant treatment in advanced stage of disease (pT3/4NxMx; stage III/IV (UICC'92) in respect to R0-resection rate and long-term prognosis (Kaplan-Meier). Overall feedback amounted to 78% (76/97) and was higher in university hospitals (90%) than in big community hospitals (70%). Today, neoadjuvant therapies are of more interest than adjuvant therapeutic regimes. But also neoadjuvant therapy is only used in 32% as a rule (in 16% with, in 16% without study conditions). 25% of all surgical units do not employ any neoadjuvant therapy in locally advanced gastric cancer until today. In all other surgical units neoadjuvant treatment is performed more individually and sporadically (43%) only in some patients. Neoadjuvant therapies are practiced by haematooncologists in 50%, gastroenterologists in 32% and surgeons in 27%. The predominant neoadjuvant therapeutic strategy is chemotherapy alone (84%). Many surgical units in Germany are interested to participate in a multicenter trial with more interest in neoadjuvant than adjuvant therapy. 185 of 309 resected gastric cancer patients (60%) were classified as stage IIIa, stage IIIb or stage IV patients. R0-resection rate of these advanced gastric cancer patients amounted to 37%; only 24% of them survived 5 years or more. Considering the missing evidence that multimodal therapies are able to prolong long-term survival in advanced gastric cancer patients, its use without study conditions is questionable. Conclusions, taken from data of clinical trials regarding carcinomas of the esophagus and esophagealgastric junction, are inconsistent in respect to long-term prognosis and results are not transferable to gastric carcinomas. A prospective randomized multicenter trial in advanced gastric cancer patients is of great importance. Following our data, in Germany a high readiness to participate in the forthcoming EORTC-study is present.

The Radical Extent of lymphadenectomy - D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) trial: study protocol for a randomized controlled trial.

PubMed

Lu, Jun-Yang; Xu, Lai; Xue, Hua-Dan; Zhou, Wei-Xun; Xu, Tao; Qiu, Hui-Zhong; Wu, Bin; Lin, Guo-Le; Xiao, Yi

2016-12-08

The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy. The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes). The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety. ClinicalTrials.gov: NCT02619942 . Registered on 29 November 2015.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Yamada, Atsuo; Doyama, Hisashi; Shiratori, Yasutoshi; Nishida, Tsutomu; Kiyotoki, Shu; Yada, Tomoyuki; Fujita, Tomoki; Sumiyoshi, Tetsuya; Hasatani, Kenkei; Mikami, Tatsuya; Honda, Tetsuro; Mabe, Katsuhiro; Hara, Kazuo; Yamamoto, Katsumi; Takeda, Mariko; Takata, Munenori; Tanaka, Mototsugu; Shinozaki, Tomohiro; Fujishiro, Mitsuhiro; Koike, Kazuhiko

2018-04-03

The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression.

PubMed

Durkalski, Valerie; Wenle Zhao; Dillon, Catherine; Kim, Jaemyung

2010-04-01

Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost. To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression. The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems. The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports. Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is increased and the value of using this system for other trials is reduced. Web-based central computerized systems offer time-saving, secure options for managing clinical trial data. The choice of a commercially available system or an internally developed system is determined by the requirements of the study and users. Pros and cons to both approaches were discussed. If the intention is to use the system for various trials (single and multi-center, phases I-III) across various therapeutic areas, then the overall design should be a generic structure that simplifies the general application with minimal loss of functionality.

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. Methods This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. Discussion This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival. Trial registration Clinicaltrials.gov: NCT01785290. EudraCT number: 2012-004012-66. PMID:24261644

Enumeration of major peripheral blood leukocyte populations for multicenter clinical trials using a whole blood phenotyping assay.

PubMed

Hensley, Tiffany R; Easter, Austin B; Gerdts, Sarah E; De Rosa, Stephen C; Heit, Antje; McElrath, M Juliana; Andersen-Nissen, Erica

2012-09-16

Cryopreservation of peripheral blood leukocytes is widely used to preserve cells for immune response evaluations in clinical trials and offers many advantages for ease and standardization of immunological assessments, but detrimental effects of this process have been observed on some cell subsets, such as granulocytes, B cells, and dendritic cells. Assaying fresh leukocytes gives a more accurate picture of the in vivo state of the cells, but is often difficult to perform in the context of large clinical trials. Fresh cell assays are dependent upon volunteer commitments and timeframes and, if time-consuming, their application can be impractical due to the working hours required of laboratory personnel. In addition, when trials are conducted at multiple centers, laboratories with the resources and training necessary to perform the assays may not be located in sufficient proximity to clinical sites. To address these issues, we have developed an 11-color antibody staining panel that can be used with Trucount tubes (Becton Dickinson; San Jose, CA) to phenotype and enumerate the major leukocyte populations within the peripheral blood, yielding more robust cell-type specific information than assays such as a complete blood count (CBC) or assays with commercially-available panels designed for Trucount tubes that stain for only a few cell types. The staining procedure is simple, requires only 100 μl of fresh whole blood, and takes approximately 45 minutes, making it feasible for standard blood-processing labs to perform. It is adapted from the BD Trucount tube technical data sheet (version 8/2010). The staining antibody cocktail can be prepared in advance in bulk at a central assay laboratory and shipped to the site processing labs. Stained tubes can be fixed and frozen for shipment to the central assay laboratory for multicolor flow cytometry analysis. The data generated from this staining panel can be used to track changes in leukocyte concentrations over time in relation to intervention and could easily be further developed to assess activation states of specific cell types of interest. In this report, we demonstrate the procedure used by blood-processing lab technicians to perform staining on fresh whole blood and the steps to analyze these stained samples at a central assay laboratory supporting a multicenter clinical trial. The video details the procedure as it is performed in the context of a clinical trial blood draw in the HIV Vaccine Trials Network (HVTN).

Cognitive-Behavioral and Psychodynamic Therapy in Adolescents with Social Anxiety Disorder: A Multicenter Randomized Controlled Trial.

PubMed

Salzer, Simone; Stefini, Annette; Kronmüller, Klaus-Thomas; Leibing, Eric; Leichsenring, Falk; Henningsen, Peter; Peseschkian, Hamid; Reich, Günter; Rosner, Rita; Ruhl, Uwe; Schopf, Yvonne; Steinert, Christiane; Vonderlin, Eva; Steil, Regina

2018-06-12

Although social anxiety disorder (SAD) has an early onset and is frequently found in adolescence, evidence for psychotherapeutic treatments of SAD in adolescents is rather scarce. Within the Social Phobia Psychotherapy Research Network (SOPHO-NET), we examined the efficacy of cognitive-behavioral (CBT) and psychodynamic therapy (PDT) compared to a waiting list (WL) in these patients. In a multicenter randomized controlled superiority trial, 107 patients, aged 14-20 years, were randomized to CBT (n = 34), PDT (n = 34), or WL (n = 39). Assessments were made at baseline, at the end of treatment, and 6 and 12 months after termination. The Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA) applied by raters masked to the treatment condition was used as the primary outcome. As secondary outcomes, rates of response and remission and the Social Phobia Anxiety Inventory (SPAI) were used. Both treatments were superior to WL in the LSAS-CA (CBT: p = 0.0112, d = 0.61, 95% CI 0.14-1.08; PDT: p = 0.0261, d = 0.53, 95% CI 0.06-1.00). At the end of treatment, response rates were 66, 54, and 20% for CBT, PDT, and WL. The corresponding remission rates were 47, 34, and 6%, respectively. CBT and PDT were significantly superior to WL regarding remission (CBT: p = 0.0009, h = 1.0; PDT: p = 0.0135, h = 0.74), response (CBT: p = 0.0004, h = 0.97; PDT: p = 0.0056, h = 0.72), and the SPAI (CBT: p = 0.0021, d = 0.75, 95% CI 0.27-1.22; PDT: p = 0.0060, d = 0.66, 95% CI 0.19-1.13). Treatment effects were stable at 6- and 12-month follow-ups. These results are comparable to the large SOPHO-NET trial in adults (n = 495). Early treatments for social anxiety are needed in order to prevent chronic manifestation of SAD. © 2018 S. Karger AG, Basel.

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants

PubMed Central

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel

2017-01-01

ABSTRACT Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences (P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.) PMID:29061746

Acupuncture lowering blood pressure for secondary prevention of stroke: a study protocol for a multicenter randomized controlled trial.

PubMed

Du, Yu-Zheng; Gao, Xin-Xin; Wang, Cheng-Ting; Zheng, Hai-Zhen; Lei, Yun; Wu, Meng-Han; Shi, Xue-Min; Ban, Hai-Peng; Gu, Wen-Long; Meng, Xiang-Gang; Wei, Mao-Ti; Hu, Chun-Xiao

2017-09-15

Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants.

PubMed

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel; Bassat, Quique

2018-01-01

Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences ( P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.). Copyright © 2017 Gargano et al.

Factors influencing medical student attrition and their implications in a large multi-center randomized education trial.

PubMed

Kalet, A; Ellaway, R H; Song, H S; Nick, M; Sarpel, U; Hopkins, M A; Hill, J; Plass, J L; Pusic, M V

2013-08-01

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the opportunity to observe institutional and student factors linked to attrition from a study and the ways in which they altered the participation profile. The data is from a randomized controlled trial conducted at seven US medical schools investigating the educational impact of different instructional designs for computer-based learning modules for surgical clerks. All students undertaking their surgical clerkships at the participating schools were invited participate and those that consented were asked to complete five study measures during their surgery clerkship. Variations in study attrition rates were explored by institution and by participants' self-regulation, self-efficacy, perception of task value, and mastery goal orientation measured on entry to the study. Of the 1,363 invited participants 995 (73 %) consented to participate and provided baseline data. There was a significant drop in the rate of participation at each of the five study milestones with 902 (94 %) completing at least one of two module post-test, 799 (61 %) both module post-tests, 539 (36 %) the mid-rotation evaluation and 252 (25 %) the final evaluation. Attrition varied between institutions on survival analysis (p < 0.001). Small but statistically significant differences in self-regulation (p = 0.01), self-efficacy (p = 0.02) and task value (p = 0.04) were observed but not in mastery or performance goal orientation measures (p = NS). Study attrition was correlated with lower achievement on the National Board of Medical Examiners subject exam. The results of education trials should be interpreted with the understanding that students who persist may be somewhat more self-regulated, self-efficacious and higher achievers than their peers who drop out and as such do not represent the class as a whole.

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

PubMed

Qu, Jianhui; Yu, Zujiang; Li, Qin; Chen, Yongping; Xiang, Dedong; Tan, Lin; Lei, Chunliang; Bai, Wenlin; Li, Hongyan; Shang, Qinghua; Chen, Liang; Hu, Xiaoyu; Lu, Wei; Li, Zhiqin; Chen, Da; Wang, Xiaodong; Zhang, Changjiang; Xiao, Guangming; Qi, Xun; Chen, Jing; Zhou, Li; Chen, Guofeng; Li, Yonggang; Zeng, Zhen; Rong, Guanghua; Dong, Zheng; Chen, Yan; Lou, Min; Wang, Chunping; Lu, Yinying; Zhang, Cuihong; Yang, Yongping

2014-11-10

Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Azoulay, Elie; Lemiale, Virginie; Mokart, Djamel; Nseir, Saad; Argaud, Laurent; Pène, Frédéric; Kontar, Loay; Bruneel, Fabrice; Klouche, Kada; Barbier, François; Reignier, Jean; Stoclin, Anabelle; Louis, Guillaume; Constantin, Jean-Michel; Mayaux, Julien; Wallet, Florent; Kouatchet, Achille; Peigne, Vincent; Perez, Pierre; Girault, Christophe; Jaber, Samir; Oziel, Johanna; Nyunga, Martine; Terzi, Nicolas; Bouadma, Lila; Lebert, Christine; Lautrette, Alexandre; Bigé, Naike; Raphalen, Jean-Herlé; Papazian, Laurent; Rabbat, Antoine; Darmon, Michael; Chevret, Sylvie; Demoule, Alexandre

2018-03-05

Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO 2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO 2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. Via the inhibition of inflammatory reactions and of apoptosis, stem cell recruitment, advancement of angiogenesis and growth factor release, EPO enhances healing and thus restitutio ad integrum after trauma. Human skin contains EPO receptors and is able to synthesize EPO. We therefore hypothesize that EPO is able to optimize wound healing in thermally injured patients. Methods/Design This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. Discussion We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. Trial registration EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824. PMID:23782555

Optimal management of subfertility in polycystic ovary syndrome

PubMed Central

Berger, Joshua J; Bates, G Wright

2014-01-01

The purpose of this paper is to provide a stepwise approach to treating the infertility/subfertility associated with polycystic ovary syndrome. Defining polycystic ovary syndrome in a patient requires first investigating other possible causes for polycystic ovary morphology, acne, hirsutism, obesity, and the metabolic derangements that often accompany polycystic ovary syndrome. Beginning with lifestyle modification and use of metformin, the progressive inclusion of more intensive therapies for induction of ovulation is described. Second-line treatments are discussed and the new findings from a large multicenter trial are discussed in the context of evidence-based treatment strategies for first-line agents. Finally, monofollicular development as a treatment goal and in vitro fertilization are discussed for those with recalcitrant disease. PMID:24966697

Combination therapy for non-small cell lung cancer studied in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is slow growing and can affect smokers and non-smokers alike. David S. Schrump, M.D., Surgical Chief of the Thoracic and Gastrointestinal Oncology Branch, is leading the NCI’s participation in a multicenter trial of a combination drug therapy in patients with NSCLC. Read more...

Study of Tranexamic Acid During Air Medical Prehospital Transport (STAAMP) Trial

DTIC Science & Technology

2017-10-01

Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an...ABSTRACT Multi-center, prospective, randomized, blinded, controlled interventional trial focusing on patients with concern for bleeding who are ...retraining scenarios were provided and are currently being converted into a quiz for distribution to the pre-hospital crews). 4. KEY RESEARCH

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice.

PubMed

Guarracino, Fabio; Heringlake, Matthias; Cholley, Bernard; Bettex, Dominique; Bouchez, Stefaan; Lomivorotov, Vladimir V; Rajek, Angela; Kivikko, Matti; Pollesello, Piero

2018-01-01

Levosimendan is a calcium sensitizer and adenosine triphosphate-dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project.

PubMed

Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine

2012-05-18

There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

PubMed Central

2012-01-01

Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection. PMID:22607233

Comparison of Characteristics and Outcomes of Trial Participants and Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 Trial.

PubMed

Khera, Nandita; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Aljurf, Mahmoud D; Akpek, Görgün; Atsuta, Yoshiko; Beattie, Sara; Bredeson, Christopher N; Burns, Linda J; Dalal, Jignesh D; Freytes, César O; Gupta, Vikas; Inamoto, Yoshihiro; Lazarus, Hillard M; LeMaistre, Charles F; Steinberg, Amir; Szwajcer, David; Wingard, John R; Wirk, Baldeep; Wood, William A; Joffe, Steven; Hahn, Theresa E; Loberiza, Fausto R; Anasetti, Claudio; Horowitz, Mary M; Lee, Stephanie J

2015-10-01

Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and nonparticipants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Integrating Comparative Effectiveness Design Elements and Endpoints Into a Phase III, Randomized Clinical Trial (SWOG S1007) Evaluating OncotypeDX-Guided Management for Women With Breast Cancer Involving Lymph Nodes

PubMed Central

Ramsey, Scott D.; Barlow, William E.; Gonzalez-Angulo, Ana M.; Tunis, Sean; Baker, Laurence; Crowley, John; Deverka, Patricia; Veenstra, David; Hortobagyi, Gabriel N.

2012-01-01

Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1–3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups. PMID:23000081

Technology Insight: Combined external-beam radiation therapy and brachytherapy in the management of prostate cancer.

PubMed

Hurwitz, Mark D

2008-11-01

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

PubMed

Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

2004-01-01

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

PubMed

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-11-15

The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

PubMed Central

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.

PubMed

Sheth, Kevin N; Elm, Jordan J; Beslow, Lauren A; Sze, Gordon K; Kimberly, W Taylor

2016-02-01

Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies.

Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial.

PubMed

Kacmarek, Robert M; Villar, Jesús; Sulemanji, Demet; Montiel, Raquel; Ferrando, Carlos; Blanco, Jesús; Koh, Younsuck; Soler, Juan Alfonso; Martínez, Domingo; Hernández, Marianela; Tucci, Mauro; Borges, Joao Batista; Lubillo, Santiago; Santos, Arnoldo; Araujo, Juan B; Amato, Marcelo B P; Suárez-Sipmann, Fernando

2016-01-01

The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. A prospective, multicenter, pilot, randomized controlled trial. A network of 20 multidisciplinary ICUs. Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.

Quality of Reporting Randomized Controlled Trials in Five Leading Neurology Journals in 2008 and 2013 Using the Modified "Risk of Bias" Tool.

PubMed

Zhai, Xiao; Cui, Jin; Wang, Yiran; Qu, Zhiquan; Mu, Qingchun; Li, Peiwen; Zhang, Chaochao; Yang, Mingyuan; Chen, Xiao; Chen, Ziqiang; Li, Ming

2017-03-01

To examine the risk of bias of methodological quality of reporting randomized clinical trials (RCTs) in major neurology journals before and after the update (2011) of Cochrane risk of bias tool. RCTs in 5 leading neurology journals in 2008 and 2013 were searched systematically. Characteristics were extracted based on the list of the modified Cochrane Collaboration's tool. Country, number of patients, type of intervention, and funding source also were examined for further analysis. A total of 138 RCTs were enrolled in this study. The rates of following a trial plan were 61.6% for the allocation generation, 52.9% for the allocation concealment, 84.8% for the blinding of the participants or the personnel, 34.8% for the blinding of outcome assessment, 78.3% for the incomplete outcome data, and 67.4% for the selective reporting. A significant setback was found in "the selective reporting" in 2013 than that in 2008. Trials performed by multi-centers and on a large scale had significantly more "low risk of bias" trials. Not only the number of surgical trials (5.8%) was much less than that of trials using drugs (73.9%), but also the reporting quality of surgical trials were worse (P = 0.008). Finally, only 17.4% trials met the criterion of "low risk of bias." The modified "risk of bias" tool is an improved version for assessment. Methodological quality of reporting RCTs in the 5neurology journals is unsatisfactory, especially that for surgical RCTs, and it could be further improved. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical trials: bringing research to the bedside.

PubMed

Arvay, C A

1991-02-01

Over the years, clinical trials with their structured treatment plans and multicenter involvement have been instrumental in developing new treatments and establishing standard of care therapy. While clinical trials strive to advance medical knowledge, they provide scientifically sound, state of the art care and their use should be increased. The Brain Tumor Cooperative Group, one such NCI-sponsored cooperative group, has been the primary group for the treatment of malignant gliomas. As the field of neuro-oncology expands, the neuroscience nurse needs to develop an understanding of clinical trials and their operation. The nurse is in an optimal position to support medical research and the research participant.

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Crotalidae polyvalent immune Fab: in patients with North American crotaline envenomation.

PubMed

Keating, Gillian M

2011-04-01

Crotalidae polyvalent immune Fab is an antivenom comprising purified, sheep-derived, Fab IgG fragments and is indicated for use in patients with North American crotaline envenomation. Crotalidae polyvalent immune Fab is produced using four North American snake venoms: Crotalus atrox, Crotalus adamanteus, Crotalus scutulatus, and Agkistrodon piscivorus. Intravenous crotalidae polyvalent immune Fab was effective in patients aged ≥10 years who had minimal or moderate envenomation by a North American crotaline, who presented within 6 hours of the snakebite, and who had progression of the envenomation syndrome, according to the results of two prospective trials. One trial was a noncomparative, multicenter pilot study and the other trial was a randomized, open-label, multicenter trial in which patients received scheduled or 'as needed' administration of crotalidae polyvalent immune Fab after initial control had been achieved. A prospective, postmarketing trial demonstrated the efficacy of crotalidae polyvalent immune Fab in confirmed Crotalus viridis helleri envenomation (indicating cross-protection against a venom not used in its production). Results of these prospective trials are supported by the findings of additional (mainly retrospective) studies demonstrating the efficacy of crotalidae polyvalent immune Fab in patients with crotaline envenomation, including patients with severe envenomation, pediatric patients, and patients with symptoms of neurotoxicity. Despite treatment with crotalidae polyvalent immune Fab, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab was generally well tolerated; acute hypersensitivity reactions (e.g. urticaria, rash, pruritus) were the most commonly occurring adverse event. © 2011 Adis Data Information BV. All rights reserved.

[Design of a multicenter study for assessing the effectiveness of extracorporeal shockwave therapy in epicondylitis humeri radialis].

PubMed

Haake, M; Jensen, K; Prinz, H; Willenberg, T

2000-01-01

Previously published studies concerning, extracorporeal shock-wave therapy (ESWT) in the treatment of lateral epicondylitis do not fulfil the biometric standards of modern clinical research. The objective of the trial is to show that ESWT is effective in the treatment of chronic LE. A prospective, randomized, placebo-controlled, single-blinded, multicenter trial with an independent blinded observer was designed. The effectiveness of ESWT is evaluated by comparison with a control group in which sham-ESWT is performed, both under local anaesthesia. Outcome is determined on the basis of the Roles/Maudsley-Score. Inclusion criteria are a history of at least 6 months of LE and failure of conventional treatment. The therapy includes 3 sessions of low energy ESWT with 2000 impulses (energy flux density 0.07-0.09 mJ/mm2). Sample size is 272 patients. Randomisation started in October 1998 and is planned over a period of two and a half years. Only a randomised clinical trial with adequate control of placebo effects and observer bias can provide the required evidence for the efficiency of ESWT in the treatment of lateral epicondylitis of the elbow.

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project.

PubMed

McGovern, Kathleen; Karn, Catharine Freyer; Fox, Kristen

2015-10-01

Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. © 2015 Wiley Periodicals, Inc.

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

PubMed

Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

2012-01-01

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.

PubMed

Ferrando, Carlos; Soro, Marina; Canet, Jaume; Unzueta, Ma Carmen; Suárez, Fernando; Librero, Julián; Peiró, Salvador; Llombart, Alicia; Delgado, Carlos; León, Irene; Rovira, Lucas; Ramasco, Fernando; Granell, Manuel; Aldecoa, César; Diaz, Oscar; Balust, Jaume; Garutti, Ignacio; de la Matta, Manuel; Pensado, Alberto; Gonzalez, Rafael; Durán, M Eugenia; Gallego, Lucia; Del Valle, Santiago García; Redondo, Francisco J; Diaz, Pedro; Pestaña, David; Rodríguez, Aurelio; Aguirre, Javier; García, Jose M; García, Javier; Espinosa, Elena; Charco, Pedro; Navarro, Jose; Rodríguez, Clara; Tusman, Gerardo; Belda, Francisco Javier

2015-04-27

Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. Registered on 5 June 2014 with identification no. NCT02158923 .

A hybrid method in combining treatment effects from matched and unmatched studies.

PubMed

Byun, Jinyoung; Lai, Dejian; Luo, Sheng; Risser, Jan; Tung, Betty; Hardy, Robert J

2013-12-10

The most common data structures in the biomedical studies have been matched or unmatched designs. Data structures resulting from a hybrid of the two may create challenges for statistical inferences. The question may arise whether to use parametric or nonparametric methods on the hybrid data structure. The Early Treatment for Retinopathy of Prematurity study was a multicenter clinical trial sponsored by the National Eye Institute. The design produced data requiring a statistical method of a hybrid nature. An infant in this multicenter randomized clinical trial had high-risk prethreshold retinopathy of prematurity that was eligible for treatment in one or both eyes at entry into the trial. During follow-up, recognition visual acuity was accessed for both eyes. Data from both eyes (matched) and from only one eye (unmatched) were eligible to be used in the trial. The new hybrid nonparametric method is a meta-analysis based on combining the Hodges-Lehmann estimates of treatment effects from the Wilcoxon signed rank and rank sum tests. To compare the new method, we used the classic meta-analysis with the t-test method to combine estimates of treatment effects from the paired and two sample t-tests. We used simulations to calculate the empirical size and power of the test statistics, as well as the bias, mean square and confidence interval width of the corresponding estimators. The proposed method provides an effective tool to evaluate data from clinical trials and similar comparative studies. Copyright © 2013 John Wiley & Sons, Ltd.

Pregnancy after uterine artery embolization for leiomyomata: the Ontario multicenter trial.

PubMed

Pron, Gaylene; Mocarski, Eva; Bennett, John; Vilos, George; Common, Andrew; Vanderburgh, Leslie

2005-01-01

To report on pregnancies and deliveries occurring in a large cohort of women who underwent uterine artery embolization instead of surgery for symptomatic leiomyomata. A total of 555 women underwent uterine embolization in a multicenter clinical trial. The primary embolic agent was 355-500 microm polyvinyl alcohol particles with treatment end-point as bilateral stasis in the uterine arteries. Women desiring pregnancy were informed of the uncertain effect of embolization on fertility and pregnancy. Average age at embolization was 43 years (range 18-59 years). Thirty-one percent were younger than age 40 years. Women were followed up prospectively by telephone, and obstetric records of the women who conceived were reviewed. Twenty-one women of average age 34 years (range 27-42 years) conceived, (3 of these twice), and 13 women were nulliparous. Twenty-three of the 24 pregnancies were conceived spontaneously (1 woman had in vitro fertilization). There were 4 spontaneous abortions (16.7%, 95% confidence interval 5.4-41.9%) and 2 elective pregnancy terminations. Fourteen of the 18 live births were full term and 4 were preterm. There were 9 vaginal deliveries and 9 cesarean deliveries, 4 of which were elective. Abnormal placentation occurred in 3 cases, all nulliparas (12.5% 95% confidence interval 3.1-36.3%). Two cases developed placenta previa (1 had a clinical partial accreta) and the third developed a placenta membranacea with accreta resulting in cesarean hysterectomy. Three postpartum hemorrhages all secondary to placental abnormalities occurred. Four newborns were small for gestational age (< or = 5th percentile); 2 of these pregnancies were complicated by gestational hypertension. Women are able to achieve pregnancies after uterine artery embolization, and most resulted in term deliveries and appropriately grown newborns. Close monitoring of placental status, however, is recommended.

Internet-delivered cognitive-behavioral treatment for adolescents with chronic pain and their parents: a randomized controlled multicenter trial

PubMed Central

Palermo, Tonya M.; Law, Emily F.; Fales, Jessica; Bromberg, Maggie H.; Jessen-Fiddick, Tricia; Tai, Gabrielle

2016-01-01

Internet-delivered interventions are emerging as a strategy to address barriers to care for individuals with chronic pain. This is the first large multicenter randomized controlled trial of Internet-delivered cognitive-behavioral therapy (CBT) for pediatric chronic pain. Participants included were 273 adolescents (205 females and 68 males), aged 11 to 17 years with mixed chronic pain conditions and their parents, who were randomly assigned in a parallel-group design to Internet-delivered CBT (n = 138) or Internet-delivered Education (n = 135). Assessments were completed before treatment, immediately after treatment, and at 6-month follow-up. All data collection and procedures took place online. The primary analysis used linear growth models. Results demonstrated significantly greater reduction on the primary outcome of activity limitations from baseline to 6-month follow-up for Internet CBT compared with Internet education (b = −1.13, P = 0.03). On secondary outcomes, significant beneficial effects of Internet CBT were found on sleep quality (b = 0.14, P = 0.04), on reducing parent miscarried helping (b = −2.66, P = 0.007) and protective behaviors (b = −0.19, P = 0.001), and on treatment satisfaction (P values < 0.05). On exploratory outcomes, benefits of Internet CBT were found for parent-perceived impact (ie, reductions in depression, anxiety, self-blame about their adolescent’s pain, and improvement in parent behavioral responses to pain). In conclusion, our Internet-delivered CBT intervention produced a number of beneficial effects on adolescent and parent outcomes, and could ultimately lead to wide dissemination of evidence-based psychological pain treatment for youth and their families. PMID:26335910

Design considerations and rationale of a multi-center trial to sustain weight loss: the Weight Loss Maintenance Trial.

PubMed

Brantley, Phillip; Appel, Lawrence; Hollis, Jack; Stevens, Victor; Ard, Jamy; Champagne, Catherine; Elmer, Patricia; Harsha, David; Myers, Valerie; Proschan, Michael; William, Vollmer; Svetkey, Laura

2008-01-01

The Weight Loss Maintenance Trial (WLM) is a multi-center, randomized, controlled trial that compares the effects of two 30-month maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology (IT) to a self-directed usual care control group (SD), in overweight or obese individuals who are at high risk for cardiovascular disease. This paper provides an overview of the design and methods, and design considerations and lessons learned from this trial. All participants received a 6-month behavioral weight loss program consisting of weekly group sessions. Participants who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC condition provided monthly contacts with an interventionist primarily via telephone and quarterly face-to-face visits. The IT condition provided frequent, individualized contact through a tailored, website system. Both the PC and IT maintenance programs encouraged the DASH dietary pattern and employed theory-based behavioral techniques to promote maintenance. Design considerations included choice of study population, frequency and type of intervention visits, and choice of primary outcome. Overweight or obese persons with CVD risk factors were studied. The pros and cons of studying this population while excluding others are presented. We studied intervention contact strategies that made fewer demands on participant time and travel, while providing frequent opportunities for interaction. The primary outcome variable for the trial was change in weight from randomization to end of follow-up (30 months). Limits to generalizability are discussed. Individuals in need of weight loss strategies may have been excluded due to barriers associated with internet use. Other participants may have been excluded secondary to a comorbid condition. This paper highlights the design and methods of WLM and informs readers of discussions of critical issues and lessons learned from the trial.

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study.

PubMed

Yan, Cunling; Yang, Jia; Wei, Lianhua; Hu, Jian; Song, Jiaqi; Wang, Xiaoqin; Han, Ruilin; Huang, Ying; Zhang, Wei; Soh, Andrew; Beshiri, Agim; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-02-01

Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study (ClinicalTrials.gov Identifier: NCT03047603). This analysis included a total of 530 participants (41.43±12.14years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0-7.07ng/mL (LOQ- 97.5th percentiles). The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Prolonged Follow-Up of Patients in the U.S. Multicenter Trial of Ursodeoxycholic Acid for Primary Biliary Cirrhosis

PubMed Central

Combes, Burton; Luketic, Velimir A.; Peters, Marion G.; Zetterman, Rowen K.; Garcia-Tsao, Guadalupe; Munoz, Santiago J.; Lin, Danyu; Flye, Nancy; Carithers, Robert L.

2013-01-01

OBJECTIVE Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation. METHODS In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial. RESULTS No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization. CONCLUSIONS Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC. PMID:15046215

Generalizability of EXCEL and NOBLE results to a large registry population with unprotected left main coronary artery disease.

PubMed

Lee, Pil Hyung; Kang, Se Hun; Han, Seungbong; Ahn, Jung-Min; Bae, Jae Seok; Lee, Cheol Hyun; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-12-01

The aim of this study was to determine how trial-based findings of EXCEL and NOBLE might be interpreted and generalizable in 'real-world' settings with comparison of data from the large-scaled, all-comer Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. We compared baseline clinical and procedural characteristics and also determined how the relative treatment effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) was different in EXCEL and NOBLE, compared with those of the multicenter, IRIS-MAIN registry (n=2481). The primary outcome for between-study comparison was a composite of death, myocardial infarction (MI), or stroke. There were between-study differences in patient risk profiles (age, BMI, diabetes, and clinical presentation), lesion complexities, and procedural characteristics (stent type, the use of off-pump surgery, and radial artery); the proportion of diabetes and acute coronary syndrome was particularly lower in NOBLE than in other studies. Although there was interstudy heterogeneity for the protocol definition of MI, the risks for serious composite outcome of death, MI, or stroke were similar between PCI and CABG in EXCEL [hazard ratio (HR): 1.00; 95% confidence interval (CI): 0.79-1.26; P=0.98] and in the matched cohort of IRIS-MAIN (HR: 1.08; 95%CI: 0.85-1.38; P=0.53), whereas it was significantly higher after PCI than after CABG in NOBLE (HR: 1.47; 95%CI: 1.06-2.05; P=0.02), which was driven by more common MI and stroke after PCI. In the comparison of a large-sized, all-comer registry, the EXCEL trial might represent better generalizability with respect to baseline characteristics and observed clinical outcomes compared with the NOBLE trial.

Effect of structured physical activity on respiratory outcomes in sedentary elderly adults with mobility limitations

USDA-ARS?s Scientific Manuscript database

OBJECTIVES: To evaluate the effect of structured physical activity on respiratory outcomes in community dwelling elderly adults with mobility limitations. DESIGN: Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over...

Clinical impact of 8 prospective, randomized, multicenter glaucoma trials.

PubMed

Panarelli, Joseph F; Banitt, Michael R; Sidoti, Paul A; Budenz, Donald L; Singh, Kuldev

2015-01-01

To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

Dual sensory loss: development of a dual sensory loss protocol and design of a randomized controlled trial

PubMed Central

2013-01-01

Background Dual sensory loss (DSL) has a negative impact on health and wellbeing and its prevalence is expected to increase due to demographic aging. However, specialized care or rehabilitation programs for DSL are scarce. Until now, low vision rehabilitation does not sufficiently target concurrent impairments in vision and hearing. This study aims to 1) develop a DSL protocol (for occupational therapists working in low vision rehabilitation) which focuses on optimal use of the senses and teaches DSL patients and their communication partners to use effective communication strategies, and 2) describe the multicenter parallel randomized controlled trial (RCT) designed to test the effectiveness and cost-effectiveness of the DSL protocol. Methods/design To develop a DSL protocol, literature was reviewed and content was discussed with professionals in eye/ear care (interviews/focus groups) and DSL patients (interviews). A pilot study was conducted to test and confirm the DSL protocol. In addition, a two-armed international multi-center RCT will evaluate the effectiveness and cost-effectiveness of the DSL protocol compared to waiting list controls, in 124 patients in low vision rehabilitation centers in the Netherlands and Belgium. Discussion This study provides a treatment protocol for rehabilitation of DSL within low vision rehabilitation, which aims to be a valuable addition to the general low vision rehabilitation care. Trial registration Netherlands Trial Register (NTR) identifier: NTR2843 PMID:23941667

Patient Recruitment into a Multicenter Randomized Clinical Trial 
for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT)

PubMed Central

Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J.; Al‐Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey‐Mims, Marva

2012-01-01

Abstract We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open‐label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web‐based anonymous survey of site investigators revealed site‐related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start‐up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. Clin Trans Sci 2013; Volume 6: 13–20 PMID:23399084

Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

PubMed

Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

2013-02-01

We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. © 2013 Wiley Periodicals, Inc.

Multicenter Evaluation of the Cepheid Xpert Methicillin-Resistant Staphylococcus aureus (MRSA) Test as a Rapid Screening Method for Detection of MRSA in Nares▿

PubMed Central

Wolk, D. M.; Picton, E.; Johnson, D.; Davis, T.; Pancholi, P.; Ginocchio, C. C.; Finegold, S.; Welch, D. F.; de Boer, M.; Fuller, D.; Solomon, M. C.; Rogers, B.; Mehta, M. S.; Peterson, L. R.

2009-01-01

The first U.S. multicenter clinical trial to assess the performance of the Cepheid Xpert MRSA assay (Xpert MRSA) was conducted. The assay is a qualitative test designed for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nares swabs. This novel test combines integrated nucleic acid extraction and automated real-time PCR for the detection of a MRSA-specific signature sequence. A total of 1,077 nares specimens were collected from seven geographically distinct health care sites across the United States with prevalence rates ranging from 5.2% to 44%. Nares specimens were tested by (i) the Xpert MRSA assay, (ii) direct culture on CHROMagar MRSA medium (direct CM culture), and (iii) broth-enriched culture (Trypticase soy broth with 6.5% sodium chloride) followed by plating onto CHROMagar MRSA medium (broth-enriched CM culture). When direct CM culture was designated the reference method, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA assay were 94.3%, 93.2%, 73.0%, and 98.8%, respectively. When broth-enriched CM culture was used as the reference method, the clinical sensitivity, specificity, PPV, and NPV of the Xpert MRSA assay were 86.3%, 94.9%, 80.5%, and 96.6%, respectively. The BD GeneOhm MRSA (BDGO) assay was performed as a comparative molecular method. No statistical performance differences were observed between the Xpert MRSA and BDGO assays when they were compared to culture methods. From this large-scale, multicenter clinical comparison, we conclude that the Xpert MRSA assay is a simple, rapid, and accurate method for performing active surveillance for MRSA in a variety of health care populations. PMID:19129414

Follow-up of colorectal cancer patients after resection with curative intent-the GILDA trial.

PubMed

Grossmann, Erik M; Johnson, Frank E; Virgo, Katherine S; Longo, Walter E; Fossati, Rolando

2004-01-01

Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA). Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%). Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004. This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

Earlier Endpoints Are Required for Hemorrhagic Shock Trials among Severely Injured Patients

PubMed Central

Fox, Erin E.; Holcomb, John B.; Wade, Charles E.; Bulger, Eileen M.; Tilley, Barbara C.

2016-01-01

Background Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-hour and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints. Methods The goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data. Results Recent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0-2.6 hours. Approximately 85% of hemorrhagic deaths occur within 6 hours. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour post-enrollment to 1% per hour at 6 hours to <0.1% per hour by 9 hours and thereafter. Early primary endpoints (within 6 hours) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective. Conclusions Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 hours is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 hour and 30 day all-cause mortality as well as the customary safety endpoints. PMID:28207628

A systematic review of randomized controlled trials using music therapy for children.

PubMed

Mrázová, Marcela; Celec, Peter

2010-10-01

Music therapy is a promising approach widening the potential applications of psychotherapy. Music influences both, psychologic and physiologic parameters, and children are especially responsive to this form of therapy. Many aspects of its action mechanisms remain to be elucidated, underscoring the need for evidence-based medicine (EBM) for clinical use of music therapy. This review seeks to highlight some of the issues of music therapy research and to initiate a discussion about the need for international multicenter cooperation to bring scientifically sound evidence of the benefits of music therapy in pediatric patients. Scientific bibliographic databases were searched for randomized controlled trials on use of music therapy for children. Identified articles were evaluated according to criteria for scientific quality. Twenty-eight studies were identified. Most of the trials were biased by the number of participants, and some trials showed the need to improve design of control groups. Indeed, the novelty of this area of study has produced a large number of different studies (with variability in diagnoses, interventions, control groups, duration, and/or outcome parameters), and there is a need for a more homogeneous and systematic approach. Available studies highlight the need to address reproducibility issues. This analysis identifies the need for a subsequent series of clinical studies on the efficacy of music in the pediatric population, with more focus on eligibility criteria with respect to EBM and reproducibility.

The child and adolescent psychiatry trials network (CAPTN): infrastructure development and lessons learned

PubMed Central

Shapiro, Mark; Silva, Susan G; Compton, Scott; Chrisman, Allan; DeVeaugh-Geiss, Joseph; Breland-Noble, Alfiee; Kondo, Douglas; Kirchner, Jerry; March, John S

2009-01-01

Background In 2003, the National Institute of Mental Health funded the Child and Adolescent Psychiatry Trials Network (CAPTN) under the Advanced Center for Services and Intervention Research (ACSIR) mechanism. At the time, CAPTN was believed to be both a highly innovative undertaking and a highly speculative one. One reviewer even suggested that CAPTN was "unlikely to succeed, but would be a valuable learning experience for the field." Objective To describe valuable lessons learned in building a clinical research network in pediatric psychiatry, including innovations intended to decrease barriers to research participation. Methods The CAPTN Team has completed construction of the CAPTN network infrastructure, conducted a large, multi-center psychometric study of a novel adverse event reporting tool, and initiated a large antidepressant safety registry and linked pharmacogenomic study focused on severe adverse events. Specific challenges overcome included establishing structures for network organization and governance; recruiting over 150 active CAPTN participants and 15 child psychiatry training programs; developing and implementing procedures for site contracts, regulatory compliance, indemnification and malpractice coverage, human subjects protection training and IRB approval; and constructing an innovative electronic casa report form (eCRF) running on a web-based electronic data capture system; and, finally, establishing procedures for audit trail oversight requirements put forward by, among others, the Food and Drug Administration (FDA). Conclusion Given stable funding for network construction and maintenance, our experience demonstrates that judicious use of web-based technologies for profiling investigators, investigator training, and capturing clinical trials data, when coupled to innovative approaches to network governance, data management and site management, can reduce the costs and burden and improve the feasibility of incorporating clinical research into routine clinical practice. Having successfully achieved its initial aim of constructing a network infrastructure, CAPTN is now a capable platform for large safety registries, pharmacogenetic studies, and randomized practical clinical trials in pediatric psychiatry. PMID:19320979

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

An evaluation of the completeness of safety reporting in reports of complementary and alternative medicine trials

PubMed Central

2011-01-01

Background Adequate reporting of safety in publications of randomized controlled trials (RCTs) is a pre-requisite for accurate and comprehensive profile evaluation of conventional as well as complementary and alternative medicine (CAM) treatments. Clear and concise information on the definition, frequency, and severity of adverse events (AEs) is necessary for assessing the benefit-harm ratio of any intervention. The objectives of this study are to assess the quality of safety reporting in CAM RCTs; to explore the influence of different trial characteristics on the quality of safety reporting. Methods Survey of safety reporting in RCTs published in 2009 across 15 widely used CAM interventions identified from the Cochrane Collaboration's CAM Field specialized register of trials. Primary outcome measures, the adequacy of reporting of AEs; was defined and categorized according to the CONSORT for harms extension; the percentage of words devoted to the reporting of safety in the entire report and in the results section. Results Two-hundred and five trials were included in the review. Of these, 15% (31/205) reported that no harms were observed during the trial period. Of the remaining 174 trials reporting any safety information, only 21% (36/174) had adequate safety reporting. For all trials, the median percentage of words devoted to the reporting of safety in the results section was 2.6. Moreover, 69% (n = 141) of all trials devoted a lesser or equal percentage of words to safety compared to author affiliations. Of the predictor variables used in regression analysis, multicenter trials had more words devoted to safety in the results section than single centre trials (P = 0.045). Conclusions An evaluation of safety reporting in the reports of CAM RCTs across 15 different CAM interventions demonstrated that the reporting of harms was largely inadequate. The quality of reporting safety information in primary reports of CAM randomized trials requires improvement. PMID:21859470

Managing Multi-Center Recruitment in the PLCO Cancer Screening Trial.

PubMed

Gohagan, John K; Broski, Karen; Gren, Lisa H; Fouad, Mona N; Higgins, Darlene; Lappe, Karen; Ogden, Sheryl; Shambaugh, Vicki; Pinsky, Paul F; O'Brien, Barbara; Yurgalevich, Susan; Riley, Tom; Wright, Patrick; Prorok, Philip C

2015-01-01

There were significant recruitment challenges specific to the PLCO Cancer Screening Trial. Large numbers of participants were to be randomized from ten catchment areas nationwide within time and budgetary constraints. The eligible population was elderly and had to meet health and behavioral thresholds. Informed consent was required to participate and be randomized to screening for three cancers at periodic clinic visits or to a usual care arm that included no clinical visits. Consenting required special efforts to fully explain the trial and its potential scientific benefit to future patients with potentially no benefits but possible harms to PLCO participants. Participation would include continued follow-up for at least 13 years after randomization. Strong collaborative investments were required by the NCI and screening centers (SCs) to assure timely recruitment and appropriate racial participation. A trial-wide pilot phase tested recruitment and protocol follow through at SCs and produced a vanguard population of 11,406 participants. NCI announced the trial nationally in advance of the pilot and followed with an even more intense collaborative role with SCs for the main phase to facilitate trial-wide efficient and timely recruitment. Special efforts to enhance recruitment in the main phase included centralized and local monitoring of progress, cross-linking SCs to share experiences in problem solving, centralized training, substantial additional funding dedicated to recruitment and retention, including specialized programs for minority recruitment, obtaining national endorsement by the American Cancer Society, launching satellite recruitment and screening centers, including minority focused satellites, and adding a new SC dedicated to minority recruitment.

Plasma-Generating Glucose Monitor Accuracy Demonstrated in an Animal Model

PubMed Central

Magarian, Peggy; Sterling, Bernhard

2009-01-01

Introduction Four randomized controlled trials have compared mortality and morbidity of tight glycemic control versus conventional glucose for intensive care unit (ICU) patients. Two trials showed a positive outcome. However, one single-center trial and a large multicenter trial had negative results. The positive trials used accurate portable lab analyzers. The negative trial allowed the use of meters. The portable analyzer measures in filtered plasma, minimizing the interference effects. OptiScan Biomedical Corporation is developing a continuous glucose monitor using centrifuged plasma and mid-infrared spectroscopy for use in ICU medicine. The OptiScanner draws approximately 0.1 ml of blood every 15 min and creates a centrifuged plasma sample. Internal quality control minimizes sample preparation error. Interference adjustment using this technique has been presented at the Society of Critical Care Medicine in separate studies since 2006. Method A good laboratory practice study was conducted on three Yorkshire pigs using a central venous catheter over 6 h while performing a glucose challenge. Matching Yellow Springs Instrument glucose readings were obtained. Results Some 95.7% of the predicted values were in the Clarke Error Grid A zone and 4.3% in the B zone. Of those in the B zone, all were within 3.3% of the A zone boundaries. The coefficient of determination (R2) was 0.993. The coefficient of variance was 5.02%. Animal necropsy and blood panels demonstrated safety. Conclusion The OptiScanner investigational device performed safely and accurately in an animal model. Human studies using the device will begin soon. PMID:20144396

Rationale, design and methods of the HEALTHY study behavior intervention component

USDA-ARS?s Scientific Manuscript database

HEALTHY was a multi-center primary prevention trial designed to reduce risk factors for type 2 diabetes in adolescents. Seven centers each recruited six middle schools that were randomized to either intervention or control. The HEALTHY intervention integrated multiple components in nutrition, physic...

Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences.

PubMed

Meyer, Sascha; Gortner, Ludwig

2017-09-01

The aim of the NeoVitaA Trial is to assess the role of postnatal additional high-dose oral vitamin A supplementation for 28 days in reducing Bronchopulmonary dysplasia (BPD) or death in extremely low birth weight (ELBW) infants at 36 weeks postmenstrual age (PMA). All infants (both intervention and control group) will be provided with basic vitamin A (1000 IU/kg/day) in addition to trial intervention.In this short communication, we will give an up-date on obstacles, challenges as well as perspectives and potential solutions when putting into place a multicenter, double-blind, randomized trial in this cohort of extremely susceptible infants.

From "Gut Feeling" to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability.

PubMed

Watson, Christopher J E; Jochmans, Ina

2018-01-01

The purpose of this review was to summarise how machine perfusion could contribute to viability assessment of donor livers. In both hypothermic and normothermic machine perfusion, perfusate transaminase measurement has allowed pretransplant assessment of hepatocellular damage. Hypothermic perfusion permits transplantation of marginal grafts but as yet has not permitted formal viability assessment. Livers undergoing normothermic perfusion have been investigated using parameters similar to those used to evaluate the liver in vivo. Lactate clearance, glucose evolution and pH regulation during normothermic perfusion seem promising measures of viability. In addition, bile chemistry might inform on cholangiocyte viability and the likelihood of post-transplant cholangiopathy. While the use of machine perfusion technology has the potential to reduce and even remove uncertainty regarding liver graft viability, analysis of large datasets, such as those derived from large multicenter trials of machine perfusion, are needed to provide sufficient information to enable viability parameters to be defined and validated .

Process evaluation results from the HEALTHY nutrition intervention to modify the total school food environment

PubMed Central

Volpe, S. L.; Hall, W. J.; Steckler, A.; Schneider, M.; Thompson, D.; Mobley, C.; Pham, T.; El ghormli, L.

2013-01-01

The process evaluation of HEALTHY, a large multi-center trial to decrease type 2 diabetes mellitus in middle school children, monitored the implementation of the intervention to ascertain the extent that components were delivered and received as intended. The purpose of this article is to report the process evaluation findings concerning the extent to which the HEALTHY nutrition intervention was implemented during the HEALTHY trial. Overall, the observed fidelity of implementing nutrition strategies improved from baseline to the end of the study. By the last semester, all but two nutrition process evaluation goals were met. The most challenging goal to implement was serving high fiber foods, including grain-based foods and legumes. The easiest goals to implement were lowering the fat content of foods offered and offering healthier beverages. The most challenging barriers experienced by research dietitians and food service staff were costs, availability of foods and student acceptance. Forming strong relationships between the research dietitians and food service staff was identified as a key strategy to meet HEALTHY nutrition goals. PMID:24107856

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Design Features of the Diabetes and Periodontal Therapy Trial (DPTT): A Multicenter Randomized Single-Masked Clinical Trial Testing the Effect of Non-surgical Periodontal Therapy on Glycosylated Hemoglobin (HbA1c) Levels in Subjects with Type 2 Diabetes and Chronic Periodontitis

PubMed Central

2013-01-01

Background Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. Purpose The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. Methods DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. Conclusion Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other. PMID:24080100

Safety and effectiveness of the INVATEC MO.MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial.

PubMed

Ansel, Gary M; Hopkins, L Nelson; Jaff, Michael R; Rubino, Paolo; Bacharach, J Michael; Scheinert, Dierk; Myla, Subbarao; Das, Tony; Cremonesi, Alberto

2010-07-01

The multicenter ARMOUR (ProximAl PRotection with the MO.MA Device DUring CaRotid Stenting) trial evaluated the 30-day safety and effectiveness of the MO.MA Proximal Cerebral Protection Device (Invatec, Roncadelle, Italy) utilized to treat high surgical risk patients undergoing carotid artery stenting (CAS). Distal embolic protection devices (EPD) have been traditionally utilized during CAS. The MO.MA device acts as a balloon occlusion "endovascular clamping" system to achieve cerebral protection prior to crossing the carotid stenosis. This prospective registry enrolled 262 subjects, 37 roll-in and 225 pivotal subjects evaluated with intention to treat (ITT) from September 2007 to February 2009. Subjects underwent CAS using the MO.MA device. The primary endpoint, myocardial infarction, stroke, or death through 30 days (30-day major adverse cardiac and cerebrovascular events [MACCE]) was compared to a performance goal of 13% derived from trials utilizing distal EPD. For the ITT population, the mean age was 74.7 years with 66.7% of the cohort being male. Symptomatic patients comprised 15.1% and 28.9% were octogenarians. Device success was 98.2% and procedural success was 93.2%. The 30-day MACCE rate was 2.7% [95% CI (1.0-5.8%)] with a 30-day major stroke rate of 0.9%. No symptomatic patient suffered a stroke during this trial. The ARMOUR trial demonstrated that the MO.MA(R) Proximal Cerebral Protection Device is safe and effective for high surgical risk patients undergoing CAS. The absence of stroke in symptomatic patients is the lowest rate reported in any independently adjudicated prospective multicenter registry trial to date. (c) 2010 Wiley-Liss, Inc.

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

PubMed

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2012-03-01

The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Challenges and Potential Solutions to Meeting Accrual Goals in a Phase II Chemoprevention Trial for Prostate Cancer

PubMed Central

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2011-01-01

Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. PMID:22101219

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.

PubMed

Bluth, T; Teichmann, R; Kiss, T; Bobek, I; Canet, J; Cinnella, G; De Baerdemaeker, L; Gregoretti, C; Hedenstierna, G; Hemmes, S N; Hiesmayr, M; Hollmann, M W; Jaber, S; Laffey, J G; Licker, M J; Markstaller, K; Matot, I; Müller, G; Mills, G H; Mulier, J P; Putensen, C; Rossaint, R; Schmitt, J; Senturk, M; Serpa Neto, A; Severgnini, P; Sprung, J; Vidal Melo, M F; Wrigge, H; Schultz, M J; Pelosi, P; Gama de Abreu, M

2017-04-28

Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m 2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH 2 O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH 2 O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Effect of Contract Research Organization Bureaucracy in Clinical Trial Management: A Model From Lung Cancer.

PubMed

Gobbini, Elisa; Pilotto, Sara; Pasello, Giulia; Polo, Valentina; Di Maio, Massimo; Arizio, Francesca; Galetta, Domenico; Petrillo, Patrizia; Chiari, Rita; Matocci, Roberta; Di Costanzo, Alessandro; Di Stefano, Teresa Severina; Aglietta, Massimo; Cagnazzo, Celeste; Sperduti, Isabella; Bria, Emilio; Novello, Silvia

2018-03-01

Contract research organization (CRO) support is largely included in clinical trial management, although its effect in terms of time savings and benefit has not yet been quantified. We performed a retrospective multicenter analysis of lung cancer trials to explore differences in term of trial activation timelines and accrual for studies with and without CRO involvement. Results regarding study timelines from feasibility data to first patient enrollment were collected from 7 Italian thoracic oncology departments. The final accruals (screened/enrolled patients) are reported. We considered CRO/sponsor-administered and CRO-free trials according to who was responsible for the management of the crucial setup phases. Of 113 trials, 62 (54.9%) were CRO-administered, 34 (30.1%) were sponsor-administered, and 17 (15.0%) were CRO-free. The median time from feasibility invitation to documentation obtainment was 151 days in the CRO-administered trials versus 128 in the sponsor-administered and 120 in the CRO-free trials. The time from document submission to contract signature was 142 days in the CRO-administered versus 128 in the sponsor-administered and 132 in the CRO-free trials. The time from global accrual opening to first patient enrollment was 247 days for the CRO-administered versus 194 in the sponsor-administered and 151 in the CRO-free trials. No significant differences were observed in terms of the median overall timeline: 21 months in the CRO-administered, 15 in the sponsor-administered, and 18 months in the CRO-free studies (P = .29). Although no statistically significant differences were identified, the results of our analysis support the idea that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies. This bureaucratic delay could negatively affect Italian patients' screening and enrollment compared with other countries. Copyright © 2017 Elsevier Inc. All rights reserved.

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

Cardiac biomarkers in youth with type 2 diabetes mellitus: Results from the Today Study

USDA-ARS?s Scientific Manuscript database

To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 ...

Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

DTIC Science & Technology

2014-10-01

Evaluation Research (CDER), the Center for Biologics Evaluation Research (CBER), and the Center for Devices and Radiological Health ( CDRH ) to clarify...submitting a new application to the CDRH for a new product. This new product is the material that is produced in the validated manufacturing facility

Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

DTIC Science & Technology

2012-10-01

Drug Evaluation Research (CDER), the Center for Biologics E valuation Research (CBER), and the Center for Devices and Radiological Health ( CDRH ) on May...Research (CBER) , and the Center for Devices and Radiological Health ( CDRH ) to clar ify the designation of the keratin hydrogel. During this m eeting

[Qilin Pills for idiopathic oligoasthenospermia: A multi-centered randomized double-blind controlled clinical trial].

PubMed

Mao, Jia-Ming; Jiang, Hui; Wang, Chuan-Hang; Ning, Ke-Qin; Liu, Ji-Hong; Yang, Shu-Wen; Li, Hai-Song; Zhou, Shao-Hu; Zhang, Zhi-Chao; Xu, Ji-Xiu; Huang, Yong-Han

2017-03-01

To evaluate the clinical efficacy and safety of Qilin Pills in the treatment of oligoasthenospermia in infertile men. This multi-centered randomized double-blind controlled clinical trial included 216 infertile males with oligoasthenospermia, 108 in the trial group and the other 108 in the control, the former treated with Qilin Pills at the dose of 6 g tid while the latter with Wuziyanzong Pills at 6 g bid, both for 12 weeks. We examined the total sperm count, sperm motility and the count of progressively motile sperm of the patients before and at 4, 8 and 12 weeks after medication and evaluated the safety of the drug based on the adverse events and the laboratory results of blood and urine routine examinations and liver and kidney function tests. Compared with the baseline, the patients in the trial group showed a significant time-dependent improvement after 4, 8 and 12 weeks of medication in sperm motility (21.75% vs 27.54%, 29.04% and 32.95%, P <0.05), total sperm count (156.27 ×106 vs 177.33, 188.18 and 205.44 ×106, P <0.05), and the count of progressively motile sperm (32.08 ×10⁶/ml vs 46.33, 50.98 and 61.10 ×10⁶/ml, P <0.05). The three parameters above were also improved in the controls, but more significantly in the trial group (P <0.05). Qilin Pills can evidently improve the semen quality of oligoasthenospermia patients with no obvious adverse events.

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run.

PubMed

Kirisits, Christian; Federico, Mario; Nkiwane, Karen; Fidarova, Elena; Jürgenliemk-Schulz, Ina; de Leeuw, Astrid; Lindegaard, Jacob; Pötter, Richard; Tanderup, Kari

2015-12-01

Upfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). EMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1-10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. Overall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. The comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma.

PubMed

Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L; Gerstner, Elizabeth R; Colman, Howard; de Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J; Alexander, Brian M; Colen, Rivka; Taylor, Jennie W; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y; Pope, Whitney B; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y; Cloughesy, Timothy F

2018-04-05

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

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 C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial

PubMed Central

2012-01-01

Background Anastomotic leakage is a major complication in colorectal surgery and with an incidence of 11% the most common cause of morbidity and mortality. In order to reduce the incidence of anastomotic leakage the C-seal is developed. This intraluminal biodegradable drain is stapled to the anastomosis with a circular stapler and prevents extravasation of intracolonic content in case of an anastomotic dehiscence. The aim of this study is to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses, as assessed by anastomotic leakage leading to invasive treatment within 30 days postoperative. Methods The C-seal trial is a prospective multi-center randomized controlled trial with primary endpoint, anastomotic leakage leading to re-intervention within 30 days after operation. In this trial 616 patients will be randomized to the C-seal or control group (1:1), stratified by center, anastomotic height (proximal or distal of peritoneal reflection) and the intention to create a temporary deviating ostomy. Interim analyses are planned after 50% and 75% of patient inclusion. Eligible patients are at least 18 years of age, have any colorectal disease requiring a colorectal anastomosis to be made with a circular stapler in an elective setting, with an ASA-classification < 4. Oral mechanical bowel preparation is mandatory and patients with signs of peritonitis are excluded. The C-seal student team will perform the randomization procedure, supports the operating surgeon during the C-seal application and achieves the monitoring of the trial. Patients are followed for one year after randomization en will be analyzed on an intention to treat basis. Discussion This Randomized Clinical trial is designed to evaluate the effectiveness of the C-seal in preventing clinical anastomotic leakage. Trial registration NTR3080 PMID:23153188

Study design of the CLOSURE I Trial: a prospective, multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex septal closure system versus best medical therapy in patients with stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale.

PubMed

Furlan, Anthony J; Reisman, Mark; Massaro, Joseph; Mauri, Laura; Adams, Harold; Albers, Gregory W; Felberg, Robert; Herrmann, Howard; Kar, Saibal; Landzberg, Michael; Raizner, Albert; Wechsler, Lawrence

2010-12-01

Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke. This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I. This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

Surgical site infection after surgery to repair femoral neck fracture: a French multicenter retrospective study.

PubMed

Merrer, Jacques; Girou, Emmanuelle; Lortat-Jacob, Alain; Montravers, Philippe; Lucet, Jean-Christophe

2007-10-01

Femoral neck fracture is the most frequent orthopedic emergency among elderly persons. Despite a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in this population, no multicenter study of antibiotic prophylaxis practices and the rate and microbiological characteristics of surgical site infection (SSI) has been performed in France. Retrospective, multicenter cohort study. Twenty-two university and community hospitals in France. Each center provided data on 25 consecutive patients who underwent surgery for femoral neck fracture during the first quarter of 2005. Demographic, clinical, and follow-up characteristics were recorded, and most patients had a follow-up office visit or were involved in a telephone survey 1 year after surgery. These 22 centers provided data on 541 patients, 396 (73%) of whom were followed up 1 year after surgery. Of 504 (93%) patients for whom antibiotic prophylaxis was recorded, 433 (86%) received a cephalosporin. Twenty-two patients had an SSI, for a rate of 5.6% (95% confidence interval, 3.7-8.0). SSI was reported for 15 (6.9%) of patients who had a prosthesis placed and for 7 (3.9%) who underwent osteosynthesis (P=.27). SSI was diagnosed a median of 30 days after surgery (interquartile range, 21-41 days); 7 (32%) of these SSIs were superficial infections, and 15 (68%) were deep or organ-space infections. MRSA caused 7 SSIs (32%), Pseudomonas aeruginosa caused 5 (23%), other staphylococci caused 4 (18%), and other bacteria caused 2 (9%); the etiologic pathogen was unknown in 4 cases (18%). Reoperation was performed for 14 patients with deep or organ-space SSI, including 6 of 7 patients with MRSA SSI. The mortality rate 1 year after surgery was 20% overall but 50% among patients with SSI. In univariate analysis, only the National Nosocomial Infections Surveillance System risk index score was significantly associated with SSI (P=.006). SSI after surgery for femoral neck fracture is severe, and MRSA is the most frequently encountered etiologic pathogen. A large, multicenter prospective trial is necessary to determine whether the use of antibiotic prophylaxis effective against MRSA would decrease the SSI rate in this population.

Stable Atlas-based Mapped Prior (STAMP) machine-learning segmentation for multicenter large-scale MRI data.

PubMed

Kim, Eun Young; Magnotta, Vincent A; Liu, Dawei; Johnson, Hans J

2014-09-01

Machine learning (ML)-based segmentation methods are a common technique in the medical image processing field. In spite of numerous research groups that have investigated ML-based segmentation frameworks, there remains unanswered aspects of performance variability for the choice of two key components: ML algorithm and intensity normalization. This investigation reveals that the choice of those elements plays a major part in determining segmentation accuracy and generalizability. The approach we have used in this study aims to evaluate relative benefits of the two elements within a subcortical MRI segmentation framework. Experiments were conducted to contrast eight machine-learning algorithm configurations and 11 normalization strategies for our brain MR segmentation framework. For the intensity normalization, a Stable Atlas-based Mapped Prior (STAMP) was utilized to take better account of contrast along boundaries of structures. Comparing eight machine learning algorithms on down-sampled segmentation MR data, it was obvious that a significant improvement was obtained using ensemble-based ML algorithms (i.e., random forest) or ANN algorithms. Further investigation between these two algorithms also revealed that the random forest results provided exceptionally good agreement with manual delineations by experts. Additional experiments showed that the effect of STAMP-based intensity normalization also improved the robustness of segmentation for multicenter data sets. The constructed framework obtained good multicenter reliability and was successfully applied on a large multicenter MR data set (n>3000). Less than 10% of automated segmentations were recommended for minimal expert intervention. These results demonstrate the feasibility of using the ML-based segmentation tools for processing large amount of multicenter MR images. We demonstrated dramatically different result profiles in segmentation accuracy according to the choice of ML algorithm and intensity normalization chosen. Copyright © 2014 Elsevier Inc. All rights reserved.

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

PubMed Central

Macchi, Zachary; Wang, Yunxia; Moore, Dan; Katz, Jonathan; Saperstein, David; Walk, David; Simpson, Ericka; Genge, Angela; Bertorini, Tulio; Fernandes, J Americo; Swenson, Andrea; Elman, Lauren; Dimachkie, Mazen; Herbelin, Laura; Miller, Joann; Lu, Jianghua; Wilkins, Heather; Swerdlow, Russell H; Statland, Jeffrey; Barohn, Richard

2015-01-01

OBJECTIVE Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. METHODS We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. RESULTS Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, P=0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, P<0.0001). CONCLUSION Engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial. PMID:25832828

A manual-based individual therapy to improve metacognition in schizophrenia: protocol of a multi-center RCT

PubMed Central

2014-01-01

Background Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. Methods/Design MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). Discussion If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. Trial registration Current Controlled Trials: ISRCTN16659871. PMID:24490942

Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials

PubMed Central

Stevens, Wendy; Kamali, Anatoli; Karita, Etienne; Anzala, Omu; Sanders, Eduard J.; Jaoko, Walter; Kaleebu, Pontiano; Mulenga, Joseph; Dally, Len; Fast, Pat; Gilmour, Jill; Farah, Bashir; Birungi, Josephine; Hughes, Peter; Manigart, Olivier; Stevens, Gwynn; Yates, Sarah; Thomson, Helen; von Lieven, Andrea; Krebs, Marietta; Price, Matt A.; Stoll-Johnson, Lisa; Ketter, Nzeera

2008-01-01

Background An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. Methods Asymptomatic persons, aged 18–60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). Results and Conclusions Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons. PMID:18446196

Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial.

PubMed

Lanza, E; Schatzkin, A; Daston, C; Corle, D; Freedman, L; Ballard-Barbash, R; Caan, B; Lance, P; Marshall, J; Iber, F; Shike, M; Weissfeld, J; Slattery, M; Paskett, E; Mateski, D; Albert, P

2001-09-01

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel. Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients. Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample). Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group. Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period.

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

PubMed Central

Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Background Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. Methods A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated. Results At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Conclusion Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Trial Registration Chinese Clinical Trial Register ChiCTR-TRC-13003159 PMID:26098833

Quality control and assurance for validation of DOS/I measurements

NASA Astrophysics Data System (ADS)

Cerussi, Albert; Durkin, Amanda; Kwong, Richard; Quang, Timothy; Hill, Brian; Tromberg, Bruce J.; MacKinnon, Nick; Mantulin, William W.

2010-02-01

Ongoing multi-center clinical trials are crucial for Biophotonics to gain acceptance in medical imaging. In these trials, quality control (QC) and assurance (QA) are key to success and provide "data insurance". Quality control and assurance deal with standardization, validation, and compliance of procedures, materials and instrumentation. Specifically, QC/QA involves systematic assessment of testing materials, instrumentation performance, standard operating procedures, data logging, analysis, and reporting. QC and QA are important for FDA accreditation and acceptance by the clinical community. Our Biophotonics research in the Network for Translational Research in Optical Imaging (NTROI) program for breast cancer characterization focuses on QA/QC issues primarily related to the broadband Diffuse Optical Spectroscopy and Imaging (DOS/I) instrumentation, because this is an emerging technology with limited standardized QC/QA in place. In the multi-center trial environment, we implement QA/QC procedures: 1. Standardize and validate calibration standards and procedures. (DOS/I technology requires both frequency domain and spectral calibration procedures using tissue simulating phantoms and reflectance standards, respectively.) 2. Standardize and validate data acquisition, processing and visualization (optimize instrument software-EZDOS; centralize data processing) 3. Monitor, catalog and maintain instrument performance (document performance; modularize maintenance; integrate new technology) 4. Standardize and coordinate trial data entry (from individual sites) into centralized database 5. Monitor, audit and communicate all research procedures (database, teleconferences, training sessions) between participants ensuring "calibration". This manuscript describes our ongoing efforts, successes and challenges implementing these strategies.

Study protocol of a multicenter randomized controlled trial of mindfulness training to reduce burnout and promote quality of life in police officers: the POLICE study.

PubMed

Trombka, Marcelo; Demarzo, Marcelo; Bacas, Daniel Campos; Antonio, Sonia Beira; Cicuto, Karen; Salvo, Vera; Claudino, Felipe Cesar Almeida; Ribeiro, Letícia; Christopher, Michael; Garcia-Campayo, Javier; Rocha, Neusa Sica

2018-05-25

Police officers experience a high degree of chronic stress. Policing ranks among the highest professions in terms of disease and accident rates. Mental health is particularly impacted, evidenced by elevated rates of burnout, anxiety and depression, and poorer quality of life than the general public. Mindfulness training has been shown to reduce stress, anxiety, burnout and promote quality of life in a variety of settings, although its efficacy in this context has yet to be systematically evaluated. Therefore, this trial will investigate the efficacy of a mindfulness-based intervention versus a waitlist control in improving quality of life and reducing negative mental health symptoms in police officers. This multicenter randomized controlled trial has three assessment points: baseline, post-intervention, and six-month follow-up. Active police officers (n = 160) will be randomized to Mindfulness-Based Health Promotion (MBHP) or waitlist control group at two Brazilian major cities: Porto Alegre and São Paulo. The primary outcomes are burnout symptoms and quality of life. Consistent with the MBHP conceptual model, assessed secondary outcomes include perceived stress, anxiety and depression symptoms, and the potential mechanisms of resilience, mindfulness, decentering, self-compassion, spirituality, and religiosity. Findings from this study will inform and guide future research, practice, and policy regarding police offer health and quality of life in Brazil and globally. ClinicalTrials.gov NCT03114605 . Retrospectively registered on March 21, 2017.

A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study): Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness

PubMed Central

Kim, Jinyoung; Cho, Jae-Heung

2017-01-01

This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD), in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere's disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale) and frequency of dizziness, balance function (Berg Balance Scale), fatigue (Fatigue Severity Scale) and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire) levels, and depression (Korean version of Beck's Depression Inventory) and anxiety (State-Trait Anxiety Inventory) levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions' questionnaire) and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided). This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017. PMID:29387128

Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial

PubMed Central

van Bakelen, N. B.; Buijs, G. J.; Jansma, J.; de Visscher, J. G. A. M.; Hoppenreijs, Th. J. M.; Bergsma, J. E.; van Minnen, B.; Stegenga, B.; Bos, R. R. M.

2017-01-01

Background Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. Aim The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. Materials and methods The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). Results After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05–3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. Conclusion In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. Trial registration http://controlled-trials.com ISRCTN44212338. PMID:28493922

Video-Only Cardiopulmonary Resuscitation Education for High-Risk Families Before Hospital Discharge: A Multicenter Pragmatic Trial.

PubMed

Blewer, Audrey L; Putt, Mary E; Becker, Lance B; Riegel, Barbara J; Li, Jiaqi; Leary, Marion; Shea, Judy A; Kirkpatrick, James N; Berg, Robert A; Nadkarni, Vinay M; Groeneveld, Peter W; Abella, Benjamin S

2016-11-01

Cardiopulmonary resuscitation (CPR) training rates in the United States are low, highlighting the need to develop CPR educational approaches that are simpler, with broader dissemination potential. The minimum training required to ensure long-term skill retention remains poorly characterized. We compared CPR skill retention among laypersons randomized to training with video-only (VO; no manikin) with those trained with a video self-instruction kit (VSI; with manikin). We hypothesized that VO training would be noninferior to the VSI approach with respect to chest compression (CC) rate. We performed a prospective, cluster randomized trial of CPR education for family members of patients with high-risk cardiac conditions on hospital cardiac units, using a multicenter pragmatic design. Eight hospitals were randomized to offer either VO or VSI training before discharge using volunteer trainers. CPR skills were assessed 6 months post training. Mean CC rate among those trained with VO compared with those trained with VSI was assessed with a noninferiority margin set at 8 CC per min; as a secondary outcome, mean differences in CC depth were assessed. From February 2012 to May 2015, 1464 subjects were enrolled and 522 subjects completed a skills assessment. The mean CC rates were 87.7 (VO) CC per min and 89.3 (VSI) CC per min; we concluded noninferiority for VO based on a mean difference of -1.6 (90% confidence interval, -5.2 to 2.1). The mean CC depth was 40.2 mm (VO) and 45.8 mm (VSI) with a mean difference of -5.6 (95% confidence interval, -7.6 to -3.7). Results were similar after multivariate regression adjustment. In this large, prospective trial of CPR skill retention, VO training yielded a noninferior difference in CC rate compared with VSI training. CC depth was greater in the VSI group. These findings suggest a potential trade-off in efforts for broad dissemination of basic CPR skills; VO training might allow for greater scalability and dissemination, but with a potential reduction in CC depth. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01514656. © 2016 American Heart Association, Inc.

Cognitive Behavioral Analysis System of Psychotherapy as group psychotherapy for chronically depressed inpatients: a naturalistic multicenter feasibility trial.

PubMed

Sabaß, Lena; Padberg, Frank; Normann, Claus; Engel, Vera; Konrad, Carsten; Helmle, Kristina; Jobst, Andrea; Worlitz, Andrew; Brakemeier, Eva-Lotta

2017-09-27

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is a relatively new approach in the treatment of chronic depression (CD). Adapted as group psychotherapy for inpatients, CBASP is attracting increasing attention. In this naturalistic multicenter trial, we investigated its feasibility after 10 sessions of CBASP group therapy over a treatment time of at least 5 to a maximum of 10 weeks. Treatment outcome was additionally assessed. Across four centers, 116 inpatients with CD (DSM-IV-TR) attended CBASP group psychotherapy. Feasibility was focused on acceptance, and evaluated for patients and therapists after five (t1) and ten sessions (t2) of group psychotherapy. Observer- and self-rating scales (Hamilton Depression Rating Scale-24 items, HDRS 24 ; Beck Depression Inventory-II, BDI-II; World Health Organization Quality of Life assessment, WHOQOL-BREF) were applied before group psychotherapy (t0) and at t2. Dropouts were low (10.3%). Patients' evaluation improved significantly from t1 to t2 with a medium effect size (d = 0.60). Most of the patients stated that the group had enriched their treatment (75.3%), that the size (74.3%) and duration (72.5%) were 'optimal' and 37.3% wished for a higher frequency. Patients gave CBASP group psychotherapy an overall grade of 2 ('good'). Therapists' evaluation was positive throughout, except for size of the group. Outcome scores of HDRS 24 , BDI-II, and WHOQOL-BREF were significantly reduced from t0 to t2 with medium to large effect sizes (d = 1.48; d = 1.11; d = 0.67). In this naturalistic open-label trial, CBASP, when applied as inpatient group psychotherapy, was well accepted by patients and therapists. The results point towards a clinically meaningful effect of inpatient treatment with CBASP group psychotherapy on depression and quality of life. Other potential factors that could have promoted symptom change were discussed. A future controlled study could investigate the safety and efficacy of CBASP group psychotherapy for inpatients.

Effectiveness and cost-effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders: design of a multicenter randomized controlled trial.

PubMed

Zoun, Maringa H H; Koekkoek, Bauke; Sinnema, Henny; Muntingh, Anna D T; van Balkom, Anton J L M; Schene, Aart H; Smit, Filip; Spijker, Jan

2016-07-07

Many patients with anxiety or depressive disorders achieve no remission of their symptoms after evidence-based treatment algorithms. They develop a chronic course of the disorder. Current care for these patients usually consists of long-term supportive contacts with a community psychiatric nurse and pharmacological management by a psychiatrist. Data on the effectiveness of these treatments is lacking. A psychosocial rehabilitation approach, where self-management is an increasingly important part, could be more suitable. It focuses on the restoration of functioning and enhancement of patients' autonomy and responsibility. Treatment with this focus, followed by referral to primary care, may be more (cost-)effective. A multicenter randomized controlled trial is designed for twelve participating specialized outpatient mental health services in the Netherlands. Patients with chronic and treatment resistant anxiety or depressive disorders, currently receiving supportive care in specialized outpatient mental health care, are asked to participate. After inclusion, patients receive the baseline questionnaire and are randomized to the intervention group or the usual care control group. The intervention focuses on rehabilitation and self-management and is provided by a trained community psychiatric nurse, followed by referral to primary care. Measurements take place at 6, 12, and 18 months after baseline. This study evaluates both the effectiveness (on quality of life, symptom severity, and empowerment), and cost-effectiveness of the intervention compared to usual care. In addition, a questionnaire is designed to get insight in which self-management strategies patients use to manage their disorder, and in the experiences of patients with the change of care setting. In this study we evaluate the effectiveness and cost-effectiveness of a self-management intervention for patients with chronic and treatment resistant anxiety or depressive disorders in specialized outpatient mental health care. The results of this study may provide a first 'proof-of-concept' in this under-researched but important field, and might be relevant for a large group of patients in the context of a transition of the Dutch health care system. Netherlands Trial Register: NTR3335 , registered 7 March 2012.

Design of a placebo-controlled, randomized study of the efficacy of repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus.

PubMed

Landgrebe, Michael; Binder, Harald; Koller, Michael; Eberl, Yvonne; Kleinjung, Tobias; Eichhammer, Peter; Graf, Erika; Hajak, Goeran; Langguth, Berthold

2008-04-15

Chronic tinnitus is a frequent condition, which can have enormous impact on patient's life and which is very difficult to treat. Accumulating data indicate that chronic tinnitus is related to dysfunctional neuronal activity in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method which allows to focally modulate neuronal activity. An increasing amount of studies demonstrate reduction of tinnitus after repeated sessions of low-frequency rTMS and indicate that rTMS might represent a new promising approach for the treatment of tinnitus. However available studies have been mono-centric and are characterized by small sample sizes. Therefore, this multi-center trial will test the efficacy of rTMS treatment in a large sample of chronic tinnitus patients. This is a randomized, placebo-controlled, double-blind multi-center trial of two weeks 1 Hz rTMS-treatment in chronic tinnitus patients. Eligible patients will be randomized to either 2 weeks real or sham rTMS treatment. Main eligibility criteria: male or female individuals aged 18-70 years with chronic tinnitus (duration > 6 months), tinnitus-handicap-inventory-score > or = 38, age-adjusted normal sensorineural hearing (i.e. not more than 5 dB below the 10% percentile of the appropriate age and gender group (DIN EN ISO 7029), conductive hearing loss < or = 15dB. The primary endpoint is a change of tinnitus severity according to the tinnitus questionnaire of Goebel and Hiller (baseline vs. end of treatment period). A total of 138 patients are needed to detect a clinical relevant change of tinnitus severity (i.e. 5 points on the questionnaire of Goebel and Hiller; alpha = 0.05; 1-beta = 0.80). Assuming a drop-out rate of less than 5% until the primary endpoint, 150 patients have to be randomized to guarantee the target number of 138 evaluable patients. The study will be conducted by otorhinolaryngologists and psychiatrists of 7 university hospitals and 1 municipal hospital in Germany. This study will provide important information about the efficacy of rTMS in the treatment of chronic tinnitus. Current Controlled Trials ISRCTN89848288.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Run-up to participation in ATACH II in Japan

PubMed Central

Toyoda, K; Sato, S; Koga, M; Yamamoto, H; Nakagawara, J; Furui, E; Shiokawa, Y; Hasegawa, Y; Okuda, S; Sakai, N; Kimura, K; Okada, Y; Yoshimura, S; Hoshino, H; Uesaka, Y; Nakashima, T; Itoh, Y; Ueda, T; Nishi, T; Gotoh, J; Nagatsuka, K; Arihiro, S; Yamaguchi, T; Minematsu, K

2012-01-01

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial. PMID:23230457

Interrelationships between glutamine and citrulline metabolism.

PubMed

Marini, Juan C

2016-01-01

This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter randomized controlled trial resulted in increased mortality in the glutamine-supplemented group. Within this context, defining the contribution of glutamine to the production of citrulline, and thus to de-novo arginine synthesis, has become a pressing issue. The beneficial effects of glutamine supplementation may be partially mediated by the effects of glutamine on citrulline synthesis by the gut and the de-novo synthesis of arginine by the kidney and other tissues. Although there is no strong evidence to support that glutamine is a major precursor for citrulline synthesis in humans, glutamine has the potential to increase overall gut function and in this way increase citrulline production.

Effectiveness of the head CT choice decision aid in parents of children with minor head trauma: study protocol for a multicenter randomized trial

PubMed Central

2014-01-01

Background Blunt head trauma is a common cause of death and disability in children worldwide. Cranial computed tomography (CT), the reference standard for the diagnosis of traumatic brain injury (TBI), exposes children to ionizing radiation which has been linked to the development of brain tumors, leukemia, and other cancers. We describe the methods used to develop and test the effectiveness of a decision aid to facilitate shared decision-making with parents regarding whether to obtain a head CT scan or to further observe their child at home. Methods/Design This is a protocol for a multicenter clinician-level parallel randomized trial to compare an intervention group receiving a decision aid, ‘Head CT Choice’, to a control group receiving usual care. The trial will be conducted at five diverse emergency departments (EDs) in Minnesota and California. Clinicians will be randomized to decision aid or usual care. Parents visiting the ED with children who are less than 18-years-old, have experienced blunt head trauma within 24 hours, and have one or two risk factors for clinically-important TBI (ciTBI) from the Pediatric Emergency Care Applied Research Network head injury clinical prediction rules will be eligible for enrollment. We will measure the effect of Head CT Choice on: (1) parent knowledge regarding their child’s risk of ciTBI, the available diagnostic options, and the risks of radiation exposure associated with a cranial CT scan (primary outcome); (2) parent engagement in the decision-making process; (3) the degree of conflict parents experience related to feeling uninformed; (4) patient and clinician satisfaction with the decision made; (5) the rate of ciTBI at seven days; (6) the proportion of patients in whom a cranial CT scan is obtained; and (7) seven-day healthcare utilization. To capture these outcomes, we will administer parent and clinician surveys immediately after each clinical encounter, obtain video recordings of parent-clinician discussions, administer parent healthcare utilization diaries, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. Discussion This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in parents of children with minor head trauma in five diverse EDs. Trial registration ClinicalTrials.gov registration number: NCT02063087. Registration date February 13, 2014. PMID:24965659

Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial.

PubMed

Brenner, Thorsten; Decker, Sebastian O; Grumaz, Silke; Stevens, Philip; Bruckner, Thomas; Schmoch, Thomas; Pletz, Mathias W; Bracht, Hendrik; Hofer, Stefan; Marx, Gernot; Weigand, Markus A; Sohn, Kai

2018-02-01

Sepsis remains a major challenge, even in modern intensive care medicine. The identification of the causative pathogen is crucial for an early optimization of the antimicrobial treatment regime. In this context, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care, although they are associated with relevant limitations. Accordingly, culture-independent molecular diagnostic procedures might be of help for the identification of the causative pathogen in infected patients. The concept of an unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) has recently been identified to be a promising diagnostic platform for critically ill patients suffering from bloodstream infections. Although this new approach might be more sensitive and specific than culture-based state-of-the-art technologies, additional clinical trials are needed to exactly define the performance as well as clinical value of a NGS-based approach. Next GeneSiS is a prospective, observational, noninterventional, multicenter study to assess the diagnostic performance of a NGS-based approach for the detection of relevant infecting organisms in patients with suspected or proven sepsis [according to recent sepsis definitions (sepsis-3)] by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard (culture-based) microbiological diagnostics. The clinical value of this NGS-based approach will be estimated by a panel of independent clinical specialists, retrospectively identifying potential changes in patients' management based on NGS results. Further subgroup analyses will focus on the clinical value especially for patients suffering from a failure of empiric treatment within the first 3 days after onset [as assessed by death of the patient or lack of improvement of the patient's clinical condition (in terms of an inadequate decrease of SOFA-score) or persistent high procalcitonin levels]. This prospective, observational, noninterventional, multicenter study for the first time investigates the performance as well as the clinical value of a NGS-based approach for the detection of bacteremia in patients with sepsis and may therefore be a pivotal step toward the clinical use of NGS in this indication. DRKS-ID: DRKS00011911 (registered October 9, 2017) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011911; ClinicalTrials.gov Identifier: NCT03356249 (registered November 29, 2017) https://clinicaltrials.gov/ct2/show/NCT03356249.

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.

PubMed

Jüttler, Eric; Schwab, Stefan; Schmiedek, Peter; Unterberg, Andreas; Hennerici, Michael; Woitzik, Johannes; Witte, Steffen; Jenetzky, Ekkehart; Hacke, Werner

2007-09-01

Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23). DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

PubMed

Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

2016-03-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

PubMed Central

Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

2015-01-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

A randomized controlled trial of acupuncture and moxibustion to treat Bell's palsy according to different stages: design and protocol.

PubMed

Chen, Xiaoqin; Li, Ying; Zheng, Hui; Hu, Kaming; Zhang, Hongxing; Zhao, Ling; Li, Yan; Liu, Lian; Mang, Lingling; Yu, Shuyuan

2009-07-01

Acupuncture to treat Bell's palsy is one of the most commonly used methods in China. There are a variety of acupuncture treatment options to treat Bell's palsy in clinical practice. Since Bell's palsy has three different path-stages (acute stage, resting stage and restoration stage), so whether acupuncture is effective in the different path-stages and which acupuncture treatment is the best method are major issues in acupuncture clinical trials about Bell's palsy. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with acupuncture. There are five acupuncture groups, with four according to different path-stages and one not. In total, 900 patients with Bell's palsy are enrolled in this study. These patients are randomly assigned to receive one of the following four treatment groups according to different path-stages, i.e. 1) staging acupuncture group, 2) staging acupuncture and moxibustion group, 3) staging electro-acupuncture group, 4) staging acupuncture along yangming musculature group or non-staging acupuncture control group. The outcome measurements in this trial are the effect comparison achieved among these five groups in terms of House-Brackmann scale (Global Score and Regional Score), Facial Disability Index scale, Classification scale of Facial Paralysis, and WHOQOL-BREF scale before randomization (baseline phase) and after randomization. The result of this trial will certify the efficacy of using staging acupuncture and moxibustion to treat Bell's palsy, and to approach a best acupuncture treatment among these five different methods for treating Bell's palsy.

Improved quality monitoring of multi-center acupuncture clinical trials in China

PubMed Central

2009-01-01

Background In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). Methods A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. Results and discussion The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. Conclusions Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture. PMID:20035630

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

PubMed

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

Hormonal regulators of muscle and metabolism in aging (HORMA): Design and conduct of a complex, double-masked, multicenter trial

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Older persons often lose muscle mass, strength, and physical function. This report describes the challenges of conducting a complex clinical investigation assessing the effects of anabolic hormones on body composition, physical function, and metabolism during aging. METHODS: HORMA is a m...

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

USDA-ARS?s Scientific Manuscript database

Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. Our aim was to test the effect of soy isoflav...

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

Enhancing HIV Communication between Parents and Children: Efficacy of the Parents Matter! Program

ERIC Educational Resources Information Center

Miller, Kim S.; Lin, Carol Y.; Poulsen, Melissa N.; Fasula, Amy; Wyckoff, Sarah C.; Forehand, Rex; Long, Nicholas; Armistead, Lisa

2011-01-01

We examine efficacy of the Parents Matter! Program (PMP), a program to teach African-American parents of preadolescents sexual communication and HIV-prevention skills, through a multicenter, randomized control trial. A total of 1115 parent-child participants were randomized to one of three intervention arms (enhanced, brief, control). Percentages…

The Treatment for Adolescents with Depression Study (TADS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

n/a; n/a

2005-01-01

Objective: The Treatment for Adolescents With Depression Study is a multicenter, randomized clinical trial sponsored by the NIMH. This study is designed to evaluate the short- and long-term effectiveness of four treatments for adolescents with major depressive disorder: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely,…

A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study.

PubMed

Mattos, Paulo; Louzã, Mário Rodrigues; Palmini, André Luís Fernandes; de Oliveira, Irismar Reis; Rocha, Fábio Lopes

2013-07-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. To assess the effectiveness of methylphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. A 12-week, multicenter, open-label trial involving 60 patients was used. The measures used were Adult Self-Rating Scale, Adult ADHD Quality of Life Scale (AAQoL), State and Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI), and safety measures. A significance statistic level of 5% was adopted. Analyses included 60 patients (66.7% male; M age = 31.1 years) for safety and 58 patients for effectiveness. All AAQoL subscales improved from baseline to Week 12 (p < .0001), as well as the Total AAQoL (p < .0001). A significant reduction on Clinical Global Impression-Improvement (CGI-I), HAM-D, STAI, and ASRS scores was observed (p < .0001). No serious adverse event was reported. Treatment of adult ADHD patients with OROS MPH improves QoL.

Development of quality control and instrumentation performance metrics for diffuse optical spectroscopic imaging instruments in the multi-center clinical environment

NASA Astrophysics Data System (ADS)

Keene, Samuel T.; Cerussi, Albert E.; Warren, Robert V.; Hill, Brian; Roblyer, Darren; Leproux, AnaÑ--s.; Durkin, Amanda F.; O'Sullivan, Thomas D.; Haghany, Hosain; Mantulin, William W.; Tromberg, Bruce J.

2013-03-01

Instrument equivalence and quality control are critical elements of multi-center clinical trials. We currently have five identical Diffuse Optical Spectroscopic Imaging (DOSI) instruments enrolled in the American College of Radiology Imaging Network (ACRIN, #6691) trial located at five academic clinical research sites in the US. The goal of the study is to predict the response of breast tumors to neoadjuvant chemotherapy in 60 patients. In order to reliably compare DOSI measurements across different instruments, operators and sites, we must be confident that the data quality is comparable. We require objective and reliable methods for identifying, correcting, and rejecting low quality data. To achieve this goal, we developed and tested an automated quality control algorithm that rejects data points below the instrument noise floor, improves tissue optical property recovery, and outputs a detailed data quality report. Using a new protocol for obtaining dark-noise data, we applied the algorithm to ACRIN patient data and successfully improved the quality of recovered physiological data in some cases.

THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

PubMed Central

McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

2013-01-01

Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

PubMed

Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

2010-12-01

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group.

PubMed

Bonadonna, G; Zambetti, M; Bumma, C; Donadio, M; Bolognesi, A; Robustelli Della Cuna, G; Ambrosini, G; Lelli, G; Mansutti, M; Verderio, P; Valagussa, P

2002-07-01

To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to

Balloon expandable transcatheter aortic valve implantation with or without pre-dilation of the aortic valve - rationale and design of a multicenter registry (EASE-IT).

PubMed

Bramlage, Peter; Strauch, Justus; Schröfel, Holger

2014-11-18

In patients with severe calcific aortic stenosis, balloon aortic valvuloplasty (BAV) is routinely performed in order to pre-dilate the stenosed aortic valve prior to transcatheter aortic valve implantation (TAVI). Although pre-dilation is considered to be essential for the preparation of the valve landing zone, there is no clear evidence to support its clinical value. In contrast, BAV has been suggested to be linked to several complications. Notably, while preliminary evidence has supported the feasibility and safety of TAVI without pre-dilation, larger studies directly comparing the benefit/risk profile of TAVI in the presence and absence of pre-dilation are required. Therefore, a prospective, two-armed, multicenter registry (EASE-IT) was designed to obtain essential data concerning procedural success rates, adverse events, and mortality in a large cohort of patients undergoing transapical (TA)-TAVI using the Edwards SAPIEN 3 balloon expandable heart valves with and without pre-ballooning. Data provided by EASE-IT will be used to assess the relevance of BAV during the TAVI procedure and to investigate associations between patient characteristics and outcomes. Therefore, results obtained from the EASE-IT registry could contribute to reduced rates of TAVI-associated morbidity and mortality in patients with severe, calcific aortic stenosis. ClinicalTrials.gov Identifier: NCT02127580.

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

PubMed

Mahaffey, K W; Puma, J A; Barbagelata, N A; DiCarli, M F; Leesar, M A; Browne, K F; Eisenberg, P R; Bolli, R; Casas, A C; Molina-Viamonte, V; Orlandi, C; Blevins, R; Gibbons, R J; Califf, R M; Granger, C B

1999-11-15

The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

[Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study)

PubMed Central

2011-01-01

Background Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration The trial is registered in the Netherlands Trial Register (NTR1593) PMID:21854643

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

PubMed Central

Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-01-01

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. Purpose We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. Methods This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Results Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. Potential limitations Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. Conclusions The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products. PMID:22058086

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C.

PubMed

Reddy, K Rajender; Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-02-01

Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products.

'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial.

PubMed

Tu, Xiang; Liu, Fang; Jordan, James B; Ye, Xue Feng; Fu, Ping; Wang, Fei; Zhong, Sen

2013-07-18

Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals 'securing essence and tonifying the kidney' may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules. A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups: 1. A granule group, at 10 grams, three times daily (G10 group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group (Aprovel group, n = 12).The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial. It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes. The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

Management of Acute Hypertensive Response in Intracerebral Hemorrhage Patients After ATACH-2 Trial.

PubMed

Majidi, Shahram; Suarez, Jose I; Qureshi, Adnan I

2017-10-01

Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis.

PubMed

Chen, Peili; Wu, Xiaoqiang; Wang, Zhiwei; Li, Zhenya; Tian, Xiangyong; Wang, Junpeng; Yan, Tianzhong

2018-06-01

We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. © 2018 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals Inc.

Insight: demographic differences and associations with one-year outcome in schizophrenia and schizoaffective disorder.

PubMed

Wiffen, Benjamin D R; Rabinowitz, Jonathan; Fleischhacker, W Wolfgang; David, Anthony S

2010-10-01

Insight is increasingly seen as an important variable for study in psychotic illness, particularly in relation to treatment adherence. This study aims to quantify the association of insight with outcome, sociodemographic variables and diagnosis in a large stable patient sample. Data are from a one-year, open-label, international, multicenter trial (n=670) of long-acting risperidone in adult symptomatically stable patients with schizophrenia or schizoaffective disorder. Psychopathology and insight were quantified using the Positive and Negative Syndrome Scale (PANSS). Patients were assessed at four time points over the year of the study. 31.2% of the sample showed clinically significant deficits in insight at baseline. There were no differences based on sex, but significant differences in age and diagnosis, with oldest patients and schizophrenia patients (cf., schizoaffective disorder) showing more deficits. Baseline insight impairment was correlated with change in PANSS score at one year (r=-0.243, p<0.001). Recursive partitioning showed that, of those whose symptoms improved, those whose insight also improved were more likely to complete the trial. Insight is important above and beyond the effects of symptoms for predicting continuation in drug trials. This may have implications for the design and analysis of such trials, as well as suggesting the importance of targeting insight in treatment to increase likelihood of adherence to treatment. There also appear to be small but significant differences in insight based on age and diagnosis within the schizophrenia spectrum.

Regional differences in baseline disease activity and remission rates following golimumab treatment for RA: results from the GO-MORE trial.

PubMed

Durez, Patrick; Pavelka, Karel; Lazaro, Maria Alicia; Garcia-Kutzbach, Abraham; Moots, Robert J; Amital, Howard; Govoni, Marinella; Vastesaeger, Nathan

2018-05-01

GO-MORE (NCT00975130) was a large open-label, multinational, multicenter, prospective phase 3 trial evaluating add-on therapy with golimumab in biologic-naïve patients with active rheumatoid arthritis (RA). The objective of this post hoc analysis was to examine regional differences in baseline disease activity and remission rates following golimumab treatment for RA. This was a planned, descriptive post hoc analysis of data from the GO-MORE trial. Baseline disease activity and remission were defined as moderate or severe based on EULAR criteria. This analysis included 3280 participants from the GO-MORE trial. All participants included in this analysis had high or moderate disease activity at baseline. At baseline, high disease activity was least common in Europe (71.0%), Canada (77.0%), and the Middle East (78.2%) and most common in Latin America (90.7%), South Africa (91.5%), and Asia (92.5%). Month 6 remission rates were highest in South Africa (29.1%), Europe (27.9%), and the Middle East (27.3%) and lowest in Canada (19.7%), Latin America (17.2%), and Asia (15.0%). Higher rates of remission in each geographical region generally corresponded with lower baseline disease activity. We suspect that access to care and implementation of the treat-to-target strategy were the most important determinants, but this apparent relationship needs to be confirmed in further studies that include a statistical analysis of prognostic indicators.

Premature trial discontinuation often not accurately reflected in registries: comparison of registry records with publications.

PubMed

Alturki, Reem; Schandelmaier, Stefan; Olu, Kelechi Kalu; von Niederhäusern, Belinda; Agarwal, Arnav; Frei, Roy; Bhatnagar, Neera; Hooft, Lotty; von Elm, Erik; Briel, Matthias

2017-01-01

One quarter of randomized clinical trials (RCTs) are prematurely discontinued and frequently remain unpublished. Trial registries can document whether a trial is ongoing, suspended, discontinued, or completed and therefore represent an important source for trial status information. The accuracy of this information is unclear. To examine the accuracy of completion status and reasons for discontinuation documented in trial registries as compared to corresponding publications of discontinued RCTs and to investigate potential predictors for accurate trial status information in registries. We conducted a cross-sectional study comparing information provided in publications (reference standard) to corresponding registry entries. First, we reviewed publications of RCTs providing information on both discontinuation and registration. We identified eligible publications through systematic searches of MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs initiated between 2000 and 2003. Second, pairs of investigators independently and in duplicate extracted data from publications and corresponding registry records. Third, for each discontinued RCT, we compared publication information to registry information. We used multivariable regression to examine whether accurate labeling of trials as discontinued (vs. other status) in the registry was associated with recent initiation of RCT, industry sponsorship, multicenter design, or larger sample size. We identified 173 publications of RCTs that were discontinued due to slow recruitment (55%), harm (16%), futility (11%), benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries (8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as discontinued and 57 (33%) provided a reason for discontinuation (of which 53, 93%, provided the same reason as in the publication). Labeling of discontinued trials as discontinued (vs. other label) in corresponding trial registry records improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04-1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89-1.29). Less than half of published discontinued RCTs were accurately labelled as discontinued in corresponding registry records. One-third of registry records provided a reason for discontinuation. Current trial status information in registries should be viewed with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

Low intensity vs. self-guided Internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study

PubMed Central

2013-01-01

Background Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. Methods The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. Discussion The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. Trial registration Clinical Trials NCT01611818 PMID:23312003

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

PubMed Central

Baumgartner, Richard; Peterfy, Charles; Balanescu, Andra; Mirea, Gavrila; Harabagiu, Alexandru; Popa, Serghei; Cheng, Amy; Feng, Dai; Ashton, Edward; DiCarlo, Julie; Vallee, Marie-Helene; Dardzinski, Bernard J.

2017-01-01

The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63–1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55–1.45)), RAMRIS synovitis (0.85 (0.38–1.28)) and RAMRIS osteitis (0.99 (0.52–1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. (ClinicalTrials.gov registration: NCT01313520) PMID:29236711

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring.

PubMed

Beals, Chan; Baumgartner, Richard; Peterfy, Charles; Balanescu, Andra; Mirea, Gavrila; Harabagiu, Alexandru; Popa, Serghei; Cheng, Amy; Feng, Dai; Ashton, Edward; DiCarlo, Julie; Vallee, Marie-Helene; Dardzinski, Bernard J

2017-01-01

The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63-1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55-1.45)), RAMRIS synovitis (0.85 (0.38-1.28)) and RAMRIS osteitis (0.99 (0.52-1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. (ClinicalTrials.gov registration: NCT01313520).

Adoptive Immunotherapy for Cancer or Viruses

PubMed Central

Maus, Marcela V.; Fraietta, Joseph A.; Levine, Bruce L.; Kalos, Michael; Zhao, Yangbing; June, Carl H.

2015-01-01

Adoptive immunotherapy, or the infusion of lymphocytes, is a promising approach for the treatment of cancer and certain chronic viral infections. The application of the principles of synthetic biology to enhance T cell function has resulted in substantial increases in clinical efficacy. The primary challenge to the field is to identify tumor-specific targets to avoid off-tissue, on-target toxicity. Given recent advances in efficacy in numerous pilot trials, the next steps in clinical development will require multicenter trials in order to establish adoptive immunotherapy as a mainstream technology. PMID:24423116

Emergency medicine leadership in industry-sponsored clinical trials.

PubMed

Newgard, Craig D; Kim, Sunghye; Camargo, Carlos A

2003-02-01

To identify and characterize emergency medicine (EM) researchers who, since 1990, have served on a steering committee (SC) or as overall principal investigator (PI) of an industry-sponsored, multicenter clinical trial involving a pharmaceutical or device. North American EM research directors (RDs) and other prominent EM investigators (for those hospitals without a RD) were identified from eight sources, including the Society for Academic Emergency Medicine RD Interest Group and the Multicenter Airway Research Collaboration (MARC) database. The identified investigators were sent a screening survey requesting information regarding industry-sponsored clinical research at their site. The individual EM investigators identified by this screening survey were then interviewed by telephone (validation survey) to further explore their leadership experience in industry-sponsored clinical trials. Of 153 identified RDs and prominent EM researchers, 138 responded to the screening survey (90% response rate). Eighty-five EM investigators reportedly had served on a SC or as overall PI for an industry-sponsored clinical trial. Of these 85 North American EM investigators, 77 were available for a structured telephone interview (91% response rate). Although 41 (53%) of the investigators confirmed their leadership role, 36 (47%) had not served in either role. Among the 41 confirmed investigators, 19 (25%) had served as a SC member, 10 (13%) had served as overall PI, and 12 (16%) had experience in both roles. Individual responses provided suggestions for pursuing such leadership positions. These data suggest the opportunity to expand EM leadership in industry-sponsored clinical trials and demonstrate the need for validation of reports obtained by a departmental research contact. The suggestions from EM researchers who have attained these leadership roles may provide strategies for investigators interested in pursuing these positions.

PERFORMANCE OF A COMPUTER-BASED ASSESSMENT OF COGNITIVE FUNCTION MEASURES IN TWO COHORTS OF SENIORS

PubMed Central

Espeland, Mark A.; Katula, Jeffrey A.; Rushing, Julia; Kramer, Arthur F.; Jennings, Janine M.; Sink, Kaycee M.; Nadkarni, Neelesh K.; Reid, Kieran F.; Castro, Cynthia M.; Church, Timothy; Kerwin, Diana R.; Williamson, Jeff D.; Marottoli, Richard A.; Rushing, Scott; Marsiske, Michael; Rapp, Stephen R.

2013-01-01

Background Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials, however its performance in these settings has not been systematically evaluated. Design The Seniors Health and Activity Research Program (SHARP) pilot trial (N=73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Seniors (LIFE) investigators incorporated this battery in a full scale multicenter clinical trial (N=1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intra-class correlations). Results Computer-based assessments of cognitive function had consistent relationships across the pilot and full scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the LIFE cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures, however rates of missing data were higher among older participants (odds ratio=1.06 for each additional year; p<0.001) and those who reported no current computer use (odds ratio=2.71; p<0.001). Intra-class correlations among clinics were at least as low (ICC≤0.013) as for interviewer measures (ICC≤0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. Conclusion Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals. PMID:23589390

Rationale, Design, and Methodology of the APOLLON trial: A comPrehensive, ObservationaL registry of heart faiLure with midrange and preserved ejectiON fraction.

PubMed

Özlek, Bülent; Özlek, Eda; Çelik, Oğuzhan; Çil, Cem; Doğan, Volkan; Tekinalp, Mehmet; Zencirkıran Ağuş, Hicaz; Kahraman, Serkan; Ösken, Altuğ; Rencüzoğulları, İbrahim; Tanık, Veysel Ozan; Bekar, Lütfü; Çakır, Mustafa Ozan; Kaya, Bedri Caner; Tibilli, Hakan; Çelik, Yunus; Başaran, Özcan; Mert, Kadir Uğur; Sevinç, Samet; Demirci, Erkan; Dondurmacı, Engin; Biteker, Murat

2018-05-01

Although almost half of chronic heart failure (HF) patients have mid-range (HFmrEF) and preserved left-ventricular ejection fraction (HFpEF), no studies have been carried out with these patients in our country. This study aims to determine the demographic characteristics and current status of the clinical background of HFmrEF and HFpEF patients in a multicenter trial. A comPrehensive, ObservationaL registry of heart faiLure with mid range and preserved ejectiON fraction (APOLLON) trial will be an observational, multicenter, and noninterventional study conducted in Turkey. The study population will include 1065 patients from 12 sites in Turkey. All data will be collected at one point in time and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT03026114). We will enroll all consecutive patients admitted to the cardiology clinics who were at least 18 years of age and had New York Heart Association class II, III, or IV HF, elevated brain natriuretic peptide levels within the last 30 days, and an left ventricular ejection fraction (LVEF) of at least 40%. Patients fulfilling the exclusion criteria will not be included in the study. Patients will be stratified into two categories according to LVEF: mid-range EF (HFmrEF, LVEF 40%-49%) and preserved EF (HFpEF, LVEF ≥50%). Regional quota sampling will be performed to ensure that the sample was representative of the Turkish population. Demographic, lifestyle, medical, and therapeutic data will be collected by this specific survey. The APOLLON trial will be the largest and most comprehensive study in Turkey evaluating HF patients with a LVEF ≥40% and will also be the first study to specifically analyze the recently designated HFmrEF category.

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PubMed

Sánchez, Mikel; Fiz, Nicolás; Azofra, Juan; Usabiaga, Jaime; Aduriz Recalde, Enmanuel; Garcia Gutierrez, Antonio; Albillos, Javier; Gárate, Ramón; Aguirre, Jose Javier; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2012-08-01

This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (≤40 %) undergoing CABG with cardiopulmonary bypass (LICORN study).

PubMed

Caruba, Thibaut; Hourton, Delphine; Sabatier, Brigitte; Rousseau, Dominique; Tibi, Annick; Hoffart-Jourdain, Cécile; Souag, Akim; Freitas, Nelly; Yjjou, Mounia; Almeida, Carla; Gomes, Nathalie; Aucouturier, Pascaline; Djadi-Prat, Juliette; Menasché, Philippe; Chatellier, Gilles; Cholley, Bernard

2016-08-05

Patients with a left ventricular ejection fraction (LVEF) of less than 40 % are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical assist devices), the mortality rate of such patients remains very high (13 to 24 %). The LICORN trial aims at assessing the efficacy of a preoperative infusion of levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing coronary artery bypass grafting (CABG). LICORN study is a multicenter, randomized double-blind, placebo-controlled trial in parallel groups. 340 patients with LVEF ≤40 %, undergoing CABG will be recruited from 13 French hospitals. The study drug will be started after anaesthesia induction and infused over 24 h (0.1 μg/kg/min). The primary outcome (postoperative LCOS) is evaluated using a composite criterion composed of: 1) need for inotropic agents beyond 24 h following discontinuation of the study drug; 2) need for post-operative mechanical assist devices or failure to wean from these techniques when inserted pre-operatively; 3) need for renal replacement therapy. Secondary outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the composite criterion of the primary outcome; 3) the number of "ventilator-free" days and "out of intensive care unit" days at Day 28. The usefulness of levosimendan in the perioperative period has not yet been documented with a high level of evidence. The LICORN study is the first randomized controlled trial evaluating the clinical value of preoperative levosimendan in high risk cardiac surgical patients undergoing CABG. NCT02184819 (ClinicalTrials.gov).

Efficacy of paracetamol, diclofenac and advice for acute low back pain in general practice: design of a randomized controlled trial (PACE Plus).

PubMed

Schreijenberg, M; Luijsterburg, P A J; Van Trier, Y D M; Rizopoulos, D; Koopmanschap, M A; Voogt, L; Maher, C G; Koes, B W

2017-02-01

Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks. The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal. This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that will assess the effectiveness of advice only, paracetamol, diclofenac and placebo for acute low back pain. Dutch Trial Registration NTR6089 , registered September 14th, 2016. Version 4, June 2016.

Financial management of large, multi-center trials in a challenging funding milieu.

PubMed

Lovegreen, Olivia; Riggs, Danielle; Staten, Myrlene A; Sheehan, Patricia; Pittas, Anastassios G

2018-05-03

Randomized clinical trials that have public health implications but no or low potential for commercial gain are predominantly funded by governmental (e.g., National Institutes of Health (NIH)) and not-for-profit organizations. Our objective was to develop an alternative clinical trial site funding model for judicious allocation of declining public research funds. In the Vitamin D and Type 2 Diabetes (D2d) study, an NIH-supported, large clinical trial testing the effect of vitamin D supplementation on incident diabetes in 2423 participants at high risk for diabetes, a hybrid financial management model for supporting collaborating clinical sites was developed and applied. The funding model employed two reimbursement components: Core (for study start-up and partial efforts throughout the study, ~40% of the total site budget), invoiced by sites, and Performance-Based Payments (for successful enrollment of participants and completion of follow-up visits, ~60% of the total site budget), automatically issued to the sites by the Coordinating Center based on actual recruitment and visits conducted. Underperforming sites transitioned to Performance-Based Payments only. Recruitment occurred from October 2013 through December 2016, requiring one additional year than the 2-year projection. Median enrollment at each site was 88 participants (range 29-318; 20 to 205% of the site target). At the end of year 1, study-wide recruitment was at 12% of the target (vs. 50% projected) and 12% of the total grant award was invested. The model constantly evaluated sites' needs and re-allocated resources to meet the study enrollment goal. If D2d had issued cost reimbursement subaward agreements and sites invoiced for their entire budget, 83% of the award would have been spent for all study activities over the first 4 years of the trial compared to 65% of the award spent (US$26M) under the hybrid model used by D2d. It is feasible to foster a hybrid financial management approach to steward limited available public funds for research in a dynamic and consistent way that does not compromise the trial's scientific integrity and ensures conservation of funds to complete recruitment and continue to follow up participants.

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial

PubMed Central

2011-01-01

Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. Trial Registration ClinicalTrials.gov: NCT01201642 PMID:21693007

Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

PubMed

Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

2013-06-01

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Aquablation Procedural Outcomes for BPH in Large Prostates (80-150cc): Initial Experience.

PubMed

Desai, Mihir; Bidair, Mo; Bhojani, Naeem; Trainer, Andrew; Arther, Andrew; Kramolowsky, Eugene; Doumanian, Leo; Elterman, Dean; Kaufman, Ronald P; Lingeman, James; Krambeck, Amy; Eure, Gregg; Badlani, Gopal; Plante, Mark; Uchio, Edward; Gin, Greg; Goldenberg, Larry; Paterson, Ryan; So, Alan; Humphreys, Mitch; Roehrborn, Claus; Kaplan, Steven; Motola, Jay; Zorn, Kevin C

2018-04-25

To present early safety and feasibility data from a multicenter prospective study of Aquablation in treatment of symptomatic men with large volume BPH. Between September and December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volume of 80-150cc underwent Aquablation in a prospective multicenter international clinical trial. Baseline demographics and standardized postoperative management parameters were carefully recorded in a central independently monitored database. Surgeons answered analog scale questionnaires on intraoperative technical factors and postoperative management. Adverse events through 1 month were adjudicated by an independent clinical events committee. Mean prostate volume was 107cc (range 80 to 150). Mean operative time was 37 minutes (range 15-97) and mean Aquablation resection time was 8 minutes (range 3-15). Adequate adenoma resection was achieved with a single pass in 34 patients and additional passes in 67 patients (mean 1.8 treatment passes), all in a single operative session. Hemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction (N=98, mean duration 18 hours) or direct tamponade using a balloon inflated in the prostate fossa (N=3, mean duration 15 hours). No subject required electrocautery for hemostasis at the time of primary procedure. The average length of stay following the procedure was 1.6 days (range same day-6 days). The observed Clavien-Dindo (CD) grade 2 or higher event rate at 1 month was 29.7%. Bleeding complications were recorded in 10 (9.9%) patients during the index procedure hospitalization prior to discharge and included six (5.9%) peri-operative transfusions. Aquablation is feasible and safe in treating men with men with large prostates (80-150cc). The six month efficacy data are being accrued and will be presented in future publications (number, NCT03123250). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prevalence and Impact on Weaning of Pleural Effusion at the Time of Liberation from Mechanical Ventilation: A Multicenter Prospective Observational Study.

PubMed

Dres, Martin; Roux, Damien; Pham, Tài; Beurton, Alexandra; Ricard, Jean-Damien; Fartoukh, Muriel; Demoule, Alexandre

2017-06-01

Pleural effusion is frequent in intensive care unit patients, but its impact on the outcome of weaning remains unknown. In a prospective study performed in three intensive care units, pleural ultrasound was performed at the first spontaneous breathing trial to detect and quantify pleural effusion (small, moderate, and large). Weaning failure was defined by a failed spontaneous breathing trial and/or extubation requiring any form of ventilatory support within 48 h. The primary endpoint was the prevalence of pleural effusion according to weaning outcome. Pleural effusion was detected in 51 of 136 (37%) patients and was quantified as moderate to large in 18 (13%) patients. As compared to patients with no or small pleural effusion, their counterparts were more likely to have chronic renal failure (39 vs. 7%; P = 0.01), shock as the primary reason for admission (44 vs. 19%; P = 0.02), and a greater weight gain (+4 [0 to 7] kg vs. 0 [-1 to 5] kg; P = 0.02). The prevalence of pleural effusion was similar in weaning success and weaning failure patients (odds ratio, 1.23; 95% CI, 0.61 to 2.49; P = 0.56), as was the prevalence of moderate to large pleural effusion (odds ratio, 0.89; 95% CI, 0.33 to 2.41; P = 1.00). Duration of mechanical ventilation and intensive care unit length of stay were similar between patients with no or small pleural effusion and those with moderate to large pleural effusion. Significant pleural effusion was observed in 13% of patients at the time of liberation from mechanical ventilation and was not associated with an alteration of weaning outcome. (ANESTHESIOLOGY 2017; 126:1107-15).

Stroke subtyping for genetic association studies? A comparison of the CCS and TOAST classifications.

PubMed

Lanfranconi, Silvia; Markus, Hugh S

2013-12-01

A reliable and reproducible classification system of stroke subtype is essential for epidemiological and genetic studies. The Causative Classification of Stroke system is an evidence-based computerized algorithm with excellent inter-rater reliability. It has been suggested that, compared to the Trial of ORG 10172 in Acute Stroke Treatment classification, it increases the proportion of cases with defined subtype that may increase power in genetic association studies. We compared Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications in a large cohort of well-phenotyped stroke patients. Six hundred ninety consecutively recruited patients with first-ever ischemic stroke were classified, using review of clinical data and original imaging, according to the Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications. There was excellent agreement subtype assigned by between Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system (kappa = 0·85). The agreement was excellent for the major individual subtypes: large artery atherosclerosis kappa = 0·888, small-artery occlusion kappa = 0·869, cardiac embolism kappa = 0·89, and undetermined category kappa = 0·884. There was only moderate agreement (kappa = 0·41) for the subjects with at least two competing underlying mechanism. Thirty-five (5·8%) patients classified as undetermined by Trial of ORG 10172 in Acute Stroke Treatment were assigned to a definite subtype by Causative Classification of Stroke system. Thirty-two subjects assigned to a definite subtype by Trial of ORG 10172 in Acute Stroke Treatment were classified as undetermined by Causative Classification of Stroke system. There is excellent agreement between classification using Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke systems but no evidence that Causative Classification of Stroke system reduced the proportion of patients classified to undetermined subtypes. The excellent inter-rater reproducibility and web-based semiautomated nature make Causative Classification of Stroke system suitable for multicenter studies, but the benefit of reclassifying cases already classified using the Trial of ORG 10172 in Acute Stroke Treatment system on existing databases is likely to be small. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Parenteral nutrition in the critically ill.

PubMed

Gunst, Jan; Van den Berghe, Greet

2017-04-01

Feeding guidelines have recommended early, full nutritional support in critically ill patients to prevent hypercatabolism and muscle weakness. Early enteral nutrition was suggested to be superior to early parenteral nutrition. When enteral nutrition fails to meet nutritional target, it was recommended to administer supplemental parenteral nutrition, albeit with a varying starting point. Sufficient amounts of amino acids were recommended, with addition of glutamine in subgroups. Recently, several large randomized controlled trials (RCTs) have yielded important new insights. This review summarizes recent evidence with regard to the indication, timing, and dosing of parenteral nutrition in critically ill patients. One large RCT revealed no difference between early enteral nutrition and early parenteral nutrition. Two large multicenter RCTs showed harm by early supplementation of insufficient enteral nutrition with parenteral nutrition, which could be explained by feeding-induced suppression of autophagy. Several RCTs found either no benefit or harm with a higher amino acid or caloric intake, as well as harm by administration of glutamine. Although unanswered questions remain, current evidence supports accepting low macronutrient intake during the acute phase of critical illness and does not support use of early parenteral nutrition. The timing when parenteral nutrition can be initiated safely and effectively is unclear.

A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

PubMed

Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

2017-09-01

Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

Cost Analysis of Endoscopic Mucosal Resection vs Surgery for Large Laterally Spreading Colorectal Lesions.

PubMed

Jayanna, Mahesh; Burgess, Nicholas G; Singh, Rajvinder; Hourigan, Luke F; Brown, Gregor J; Zanati, Simon A; Moss, Alan; Lim, James; Sonson, Rebecca; Williams, Stephen J; Bourke, Michael J

2016-02-01

Large laterally spreading lesions (LSL) in the colon and rectum can be safely and effectively removed by endoscopic mucosal resection (EMR). However, many patients still undergo surgery. Endoscopic treatment may be more cost effective. We compared the costs of endoscopic versus surgical management of large LSL. We performed a prospective, observational, multicenter study of consecutive patients referred to 1 of 7 academic hospitals in Australia for the management of large LSL (≥ 20 mm) from January 2010 to December 2013. We collected data on numbers of patients undergoing EMR, actual endoscopic management costs (index colonoscopy, hospital stay, adverse events, and first surveillance colonoscopy), characteristics of patients and lesions, outcomes, and adverse events, and findings from follow-up examinations 14 days, 4-6 months, and 16-18 months after treatment. We compared data from patients who underwent EMR with those from a model in which all patients underwent surgery without any complications. Event-specific costs, based on Australian refined diagnosis-related group codes, were used to estimate average cost per patient. EMR was performed on 1489 lesions (mean size, 36 mm) in 1353 patients (mean age, 67 years; 52.1% male). Total costs involved in the endoscopic management of large LSL were US $6,316,593 and total inpatient hospitalization length of stay was 1180 days. The total cost predicted for the surgical management group was US $16,601,502, with a total inpatient hospitalization length of stay of 4986 days. Endoscopic management produced a potential total cost saving of US $10,284,909; the mean cost difference per patient was US $7602 (95% confidence interval, $8458-$9220; P < .001). Inpatient hospitalization length of stay was reduced by 2.81 nights per patient (95% confidence interval, 2.69-2.94; P < .001). In a large multicenter study, endoscopic management of large LSL by EMR was significantly more cost-effective than surgery. Endoscopic management by EMR at an appropriately experienced and resourced tertiary center should be considered the first line of therapy for most patients with this disorder. This approach is likely to deliver substantial overall health expenditure savings. ClinicalTrials.gov, Number: NCT01368289. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Comparison of the long-term clinical performance of a biodegradable and a titanium fixation system in maxillofacial surgery: A multicenter randomized controlled trial.

PubMed

Gareb, B; van Bakelen, N B; Buijs, G J; Jansma, J; de Visscher, J G A M; Hoppenreijs, Th J M; Bergsma, J E; van Minnen, B; Stegenga, B; Bos, R R M

2017-01-01

Biodegradable fixation systems could reduce or eliminate problems associated with titanium removal of implants in a second operation. The aim of this study was to compare the long-term (i.e. >5 years postoperatively) clinical performance of a titanium and a biodegradable system in oral and maxillofacial surgery. The present multicenter Randomized Controlled Trial (RCT) was performed in four hospitals in the Netherlands. Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or zygoma were included from December 2006 to July 2009. The patients were randomly assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS). After >5 years postoperatively, plate removal was performed in 22 of the 134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable (95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ showed good and (almost) pain free mandibular function in both groups. In conclusion, the performance of the Inion CPS biodegradable system was inferior compared to the KLS Martin titanium system regarding plate/screws removal in the abovementioned surgical procedures. http://controlled-trials.com ISRCTN44212338.

Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4-12 Years.

PubMed

Katsunuma, Toshio; Fujisawa, Takao; Mizuho, Nagao; Akira, Akasawa; Nomura, Ichiro; Yamaoka, Akiko; Kondo, Hisashi; Masuda, Kei; Yamaguchi, Koichi; Terada, Akihiko; Ikeda, Masanori; Nishioka, Kenji; Adachi, Yuichi; Kurihara, Kazuyuki

2013-01-01

Few studies have examined the efficacy or safety of a transdermal β2 agonist as add-on medicationto long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients. In this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2 mg daily) or oral sustained-release theophylline (usual dose, 4-5 mg_kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events. Thirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group. These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy. © 2013 Japanese Society of Allergology.

Early Predictors of Hypertension in Prematurely Born Adolescents

PubMed Central

Vohr, Betty R.; Allan, Walter; Katz, Karol H.; Schneider, Karen C.; Ment, Laura R.

2010-01-01

Objective To assess the blood pressure of former preterm and term matched adolescent controls, and identify risk factors associated with blood pressure at 16 years. Design Observational cohort study. Secondary analysis of a randomized clinical trial. Setting Three academic centers participating in the Multicenter Indomethacin IVH Prevention Trial. Participants 296 children born in 1989–1992 with birth weights 600- <1250g who participated in the Multicenter Indomethacin IVH Prevention Trial and 95 term controls were evaluated at 16 years. Main Outcome Measures Blood pressure and predictors of blood pressure. Results The adjusted mean difference in blood pressure for preterm adolescents was 5.1 mm Hg; p=0.002 for systolic and 2.1 mm Hg; p=0.027 for diastolic blood pressure. Among preterms, the primary predictors of increased systolic blood pressure were weight gain velocity between birth and 36 months (b=8.54, p<.001), preeclampsia (b=5.67, p=0.020), non-white race (b=3.77, p=0.04) and male gender (b=5.09). Predictors of diastolic blood pressure were weight gain velocity between birth and 36 months, (b=4.69, p=0.001, brain injury (b=6.51, p=0.002 and male gender (b=−2.4, p=0.02). Conclusions Early programming secondary to increased early weight gain velocity, intrauterine stress and neonatal brain injury may all contribute to risk of increased blood pressure among former preterm adolescents. PMID:20586997

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

PubMed Central

Janz, David R.; Bernard, Gordon R.; May, Addison K.; Kangelaris, Kirsten N.; Matthay, Michael A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. METHODS: We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. RESULTS: In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. CONCLUSIONS: Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively. PMID:26033126

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

PubMed

Starling, R C; Stehlik, J; Baran, D A; Armstrong, B; Stone, J R; Ikle, D; Morrison, Y; Bridges, N D; Putheti, P; Strom, T B; Bhasin, M; Guleria, I; Chandraker, A; Sayegh, M; Daly, K P; Briscoe, D M; Heeger, P S

2016-01-01

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Use of Standardized, Quantitative Digital Photography in a Multicenter Web-based Study

PubMed Central

Molnar, Joseph A.; Lew, Wesley K.; Rapp, Derek A.; Gordon, E. Stanley; Voignier, Denise; Rushing, Scott; Willner, William

2009-01-01

Objective: We developed a Web-based, blinded, prospective, randomized, multicenter trial, using standardized digital photography to clinically evaluate hand burn depth and accurately determine wound area with digital planimetry. Methods: Photos in each center were taken with identical digital cameras with standardized settings on a custom backdrop developed at Wake Forest University containing a gray, white, black, and centimeter scale. The images were downloaded, transferred via the Web, and stored on servers at the principal investigator's home institution. Color adjustments to each photo were made using Adobe Photoshop 6.0 (Adobe, San Jose, Calif). In an initial pilot study, model hands marked with circles of known areas were used to determine the accuracy of the planimetry technique. Two-dimensional digital planimetry using SigmaScan Pro 5.0 (SPSS Science, Chicago, Ill) was used to calculate wound area from the digital images. Results: Digital photography is a simple and cost-effective method for quantifying wound size when used in conjunction with digital planimetry (SigmaScan) and photo enhancement (Adobe Photoshop) programs. The accuracy of the SigmaScan program in calculating predetermined areas was within 4.7% (95% CI, 3.4%–5.9%). Dorsal hand burns of the initial 20 patients in a national study involving several centers were evaluated with this technique. Images obtained by individuals denying experience in photography proved reliable and useful for clinical evaluation and quantification of wound area. Conclusion: Standardized digital photography may be used quantitatively in a Web-based, multicenter trial of burn care. This technique could be modified for other medical studies with visual endpoints. PMID:19212431

Use of standardized, quantitative digital photography in a multicenter Web-based study.

PubMed

Molnar, Joseph A; Lew, Wesley K; Rapp, Derek A; Gordon, E Stanley; Voignier, Denise; Rushing, Scott; Willner, William

2009-01-01

We developed a Web-based, blinded, prospective, randomized, multicenter trial, using standardized digital photography to clinically evaluate hand burn depth and accurately determine wound area with digital planimetry. Photos in each center were taken with identical digital cameras with standardized settings on a custom backdrop developed at Wake Forest University containing a gray, white, black, and centimeter scale. The images were downloaded, transferred via the Web, and stored on servers at the principal investigator's home institution. Color adjustments to each photo were made using Adobe Photoshop 6.0 (Adobe, San Jose, Calif). In an initial pilot study, model hands marked with circles of known areas were used to determine the accuracy of the planimetry technique. Two-dimensional digital planimetry using SigmaScan Pro 5.0 (SPSS Science, Chicago, Ill) was used to calculate wound area from the digital images. Digital photography is a simple and cost-effective method for quantifying wound size when used in conjunction with digital planimetry (SigmaScan) and photo enhancement (Adobe Photoshop) programs. The accuracy of the SigmaScan program in calculating predetermined areas was within 4.7% (95% CI, 3.4%-5.9%). Dorsal hand burns of the initial 20 patients in a national study involving several centers were evaluated with this technique. Images obtained by individuals denying experience in photography proved reliable and useful for clinical evaluation and quantification of wound area. Standardized digital photography may be used quantitatively in a Web-based, multicenter trial of burn care. This technique could be modified for other medical studies with visual endpoints.

Outcomes for patients with congenital hepatoblastoma.

PubMed

Trobaugh-Lotrario, Angela D; Chaiyachati, Barbara H; Meyers, Rebecka L; Häberle, Beate; Tomlinson, Gail E; Katzenstein, Howard M; Malogolowkin, Marcio H; von Schweinitz, Dietrich; Krailo, Mark; Feusner, James H

2013-11-01

Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies.

PubMed

Calfee, Carolyn S; Janz, David R; Bernard, Gordon R; May, Addison K; Kangelaris, Kirsten N; Matthay, Michael A; Ware, Lorraine B

2015-06-01

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

ERIC Educational Resources Information Center

Loebel, Antony; Brams, Matthew; Goldman, Robert S.; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L.

2016-01-01

The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to…

Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: A randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. Multicenter (26 pediatric en...

Listening to Girls and Boys Talk about Girls' Physical Activity Behaviors

ERIC Educational Resources Information Center

Vu, Maihan B.; Murrie, Dale; Gonzalez, Vivian; Jobe, Jared B.

2006-01-01

As part of the formative assessment for the Trial of Activity for Adolescent Girls (TAAG), a multicenter study to reduce the decline of physical activity in adolescent girls, girls and boys with diverse ethnicity from six states participated in focus groups and semistructured interviews. Data from 13 girls' focus groups (N = 100), 11 boys' focus…

The Effect of the Infant Behavioral Assessment and Intervention Program on Mother-Infant Interaction after Very Preterm Birth

ERIC Educational Resources Information Center

Meijssen, Dominique; Wolf, Marie-Jeanne; Koldewijn, Karen; Houtzager, Bregje A.; Van Wassenaer, Aleid; Tronick, Ed; Kok, Joke; Van Baar, Anneloes

2010-01-01

Background: Prematurity and perinatal insults lead to increased developmental vulnerability. The home-based Infant Behavioral Assessment and Intervention Program (IBAIP) was designed to improve development of preterm infants. In a multicenter randomized controlled trial the effect of IBAIP on mother-infant interaction was studied as a secondary…

Umbilical Cord Blood Use for Admission Blood Tests of VLBW (Very Low Birth Weight) Preterm Neonates: A Multi-center Randomized Clinical Trial

DTIC Science & Technology

2016-09-12

agents (erythropoietin and darbepoetin alfa ), and limiting phlebotomy via use of point-of-care testing devices, benchtop laboratory analyzers, and...Manual, 2014. 18: p. 571-592. 6. Ohls, R.K., et al., A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants. Pediatrics

Personalized ovarian stimulation for assisted reproductive technology: study design considerations to move from hype to added value for patients.

PubMed

Mol, Ben W; Bossuyt, Patrick M; Sunkara, Sesh K; Garcia Velasco, Juan A; Venetis, Christos; Sakkas, Denny; Lundin, Kersti; Simón, Carlos; Taylor, Hugh S; Wan, Robert; Longobardi, Salvatore; Cottell, Evelyn; D'Hooghe, Thomas

2018-06-01

Although most medical treatments are designed for the average patient with a one-size-fits-all-approach, they may not benefit all. Better understanding of the function of genes, proteins, and metabolite, and of personal and environmental factors has led to a call for personalized medicine. Personalized reproductive medicine is still in its infancy, without clear guidance on treatment aspects that could be personalized and on trial design to evaluate personalized treatment effect and benefit-harm balance. While the rationale for a personalized approach often relies on retrospective analyses of large observational studies or real-world data, solid evidence of superiority of a personalized approach will come from randomized trials comparing outcomes and safety between a personalized and one-size-fits-all strategy. A more efficient, targeted randomized trial design may recruit only patients or couples for which the personalized approach would differ from the previous, standard approach. Multiple monocenter studies using the same study protocol (allowing future meta-analysis) might reduce the major center effect associated with multicenter studies. In certain cases, single-arm observational studies can generate the necessary evidence for a personalized approach. This review describes each of the main segments of patient care in assisted reproductive technologies treatment, addressing which aspects could be personalized, emphasizing current evidence and relevant study design. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bayesian hierarchical models for cost-effectiveness analyses that use data from cluster randomized trials.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G

2010-01-01

Cost-effectiveness analyses (CEA) may be undertaken alongside cluster randomized trials (CRTs) where randomization is at the level of the cluster (for example, the hospital or primary care provider) rather than the individual. Costs (and outcomes) within clusters may be correlated so that the assumption made by standard bivariate regression models, that observations are independent, is incorrect. This study develops a flexible modeling framework to acknowledge the clustering in CEA that use CRTs. The authors extend previous Bayesian bivariate models for CEA of multicenter trials to recognize the specific form of clustering in CRTs. They develop new Bayesian hierarchical models (BHMs) that allow mean costs and outcomes, and also variances, to differ across clusters. They illustrate how each model can be applied using data from a large (1732 cases, 70 primary care providers) CRT evaluating alternative interventions for reducing postnatal depression. The analyses compare cost-effectiveness estimates from BHMs with standard bivariate regression models that ignore the data hierarchy. The BHMs show high levels of cost heterogeneity across clusters (intracluster correlation coefficient, 0.17). Compared with standard regression models, the BHMs yield substantially increased uncertainty surrounding the cost-effectiveness estimates, and altered point estimates. The authors conclude that ignoring clustering can lead to incorrect inferences. The BHMs that they present offer a flexible modeling framework that can be applied more generally to CEA that use CRTs.

Psoriasis and Cardiovascular Risk: Strength in Numbers Part II

PubMed Central

Gelfand, Joel M.; Mehta, Nehal N.; Langan, Sinéad M.

2012-01-01

Summary The Psoralen plus Ultraviolet-A (PUVA) cohort study has been a tremendous success in determining how a novel treatment (i.e. PUVA) impacts the long-term risk of keratinocyte carcinoma. The ability to follow patients from the initial multi-center clinical trial for over three decades has been a remarkable achievement in dermatoepidemiology. In this issue, Stern and Huibregste report results from the PUVA follow-up study and conclude that only patients with exceptionally severe psoriasis have an increased overall mortality risk and that there is no significant risk of cardiovascular mortality associated with psoriasis. The results are in contrast to a large and growing body of literature that suggests patients with more severe psoriasis have a clinically significant increased risk of mortality in general, and cardiovascular disease in particular. In addition, the authors found no association between severe psoriasis and obesity or between obesity and cardiovascular mortality, despite extensive literature establishing these associations. Basic principles of epidemiological study design may explain these discrepancies. Ultimately, however, , randomized clinical trials will be necessary to determine whether severe psoriasis is in fact a “visible killer”, as four decades ago (after many years of controversy), hypertension was recognized to be a “silent killer”. PMID:21494241

Are mammographic changes in the tumor bed more pronounced after intraoperative radiotherapy for breast cancer? Subgroup analysis from a randomized trial (TARGIT-A).

PubMed

Engel, Dorothee; Schnitzer, Andreas; Brade, Joachim; Blank, Elena; Wenz, Frederik; Suetterlin, Marc; Schoenberg, Stefan; Wasser, Klaus

2013-01-01

Intraoperative radiotherapy (IORT) with low-energy x-rays is increasingly used in breast-conserving therapy (BCT). Previous non-randomized studies have observed mammographic changes in the tumor bed to be more pronounced after IORT. The purpose of this study was to reassess the postoperative changes in a randomized single-center subgroup of patients from a multicenter trial (TARGIT-A). In this subgroup (n = 48) 27 patients received BCT with IORT, 21 patients had BCT with standard whole-breast radiotherapy serving as controls. Overall 258 postoperative mammograms (median follow-up 4.3 years, range 3-8) were retrospectively evaluated by two radiologists in consensus focusing on changes in the tumor bed. Fat necroses showed to be significantly more frequent (56% versus 24%) and larger (8.7 versus 1.6 sq cm, median) after IORT than those in controls. Scar calcifications were also significantly more frequent after IORT (63% versus 19%). The high incidence of large fat necroses in our study confirms previous study findings. However, the overall higher incidence of calcifications in the tumor bed after IORT represents a new finding, requiring further attention. © 2012 Wiley Periodicals, Inc.

Chinese herbal medicine for the treatment of Henoch-Schönlein purpura nephritis in children: A prospective cohort study protocol.

PubMed

Zhang, Jun; Lv, Jing; Pang, Shuang; Bai, Xiaohong; Yuan, Fang; Wu, Yubin; Jiang, Hong; Yang, Guanqi; Zhang, Shaoqing

2018-06-01

Henoch-Schönlein purpura nephritis (HSPN) involves the renal impairment of Henoch-Schönlein purpura and can easily relapse into life-threatening late nephropathy in severe cases. Although there is a lack of validated evidence for its effectiveness, Chinese herbal medicine (CHM) is one of the most commonly used methods in China to treat HSPN. It is thus need to report the protocol of a prospective cohort trial using CHM to investigate the effectiveness, safety and advantages for children with HSPN. This large, prospective, multicenter cohort study started in May 2015 in Shenyang. Six hundred children diagnosed with HSPN were recruited from 3 institutions and are followed-up every 2 to 4 weeks till May 2020. Detailed information of participants includes general information, history of treatment, physical examination, and symptoms of TCM is taken face-to-face at baseline. This study has received ethical approval from the ethics committee of institutional review board of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (No.2016CS(KT)-002-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Clinical Trials Registration: NCT02878018.

A Review of Esophageal Chest Pain

PubMed Central

Coss-Adame, Enrique

2015-01-01

Noncardiac chest pain is a term that encompasses all causes of chest pain after a cardiac source has been excluded. This article focuses on esophageal sources for chest pain. Esophageal chest pain (ECP) is common, affects quality of life, and carries a substantial health care burden. The lack of a systematic approach toward the diagnosis and treatment of ECP has led to significant disability and increased health care costs for this condition. Identifying the underlying cause(s) or mechanism(s) for chest pain is key for its successful management. Common etiologies include gastroesophageal reflux disease, esophageal hypersensitivity, dysmotility, and psychological conditions, including panic disorder and anxiety. However, the pathophysiology of this condition is not yet fully understood. Randomized controlled trials have shown that proton pump inhibitor therapy (either omeprazole, lansoprazole, or rabeprazole) can be effective. Evidence for the use of antidepressants and the adenosine receptor antagonist theophylline is fair. Psychological treatments, notably cognitive behavioral therapy, may be useful in select patients. Surgery is not recommended. There remains a large unmet need for identifying the phenotype and prevalence of pathophysiologic mechanisms of ECP as well as for well-designed multicenter clinical trials of current and novel therapies. PMID:27134590

Advances in clinical studies of cardiopulmonary resuscitation

PubMed Central

Chen, Shou-quan

2015-01-01

BACKGROUND: The survival rate of patients after cardiac arrest (CA) remains lower since 2010 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) was published. In clinical trials, the methods and techniques for CPR have been overly described. This article gives an overview of the progress in methods and techniques for CPR in the past years. DATA SOURCES: Original articles about cardiac arrest and CPR from MEDLINE (PubMed) and relevant journals were searched, and most of them were clinical randomized controlled trials (RCTs). RESULTS: Forty-two articles on methods and techniques of CPR were reviewed, including chest compression and conventional CPR, chest compression depth and speed, defibrillation strategies and priority, mechanical and manual chest compression, advanced airway management, impedance threshold device (ITD) and active compression-decompression (ACD) CPR, epinephrine use, and therapeutic hypothermia. The results of studies and related issues described in the international guidelines had been testified. CONCLUSIONS: Although large multicenter studies on CPR are still difficult to carry out, progress has been made in the past 4 years in the methods and techniques of CPR. The results of this review provide evidences for updating the 2015 international guidelines. PMID:26056537

Rationale and Design of Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) Trial.

PubMed

Miyauchi, Katsumi; Kimura, Takeshi; Shimokawa, Hiroaki; Daida, Hiroyuki; Iimuro, Satoshi; Iwata, Hiroshi; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Ohashi, Yasuo; Ohtsu, Hiroshi; Saito, Yasushi; Matsuzaki, Masunori; Nagai, Ryozo

2018-03-30

Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD.REAL-CAD is a prospective, multicenter, randomized, open-label, blinded-endpoint, physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group and 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event, including CV death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients and the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit.After the study is completed, we will have categorical evidence on the optimal statin dose and target LDL-C level for secondary prevention in Japanese patients.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in all-comers population. Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

PubMed

Godino, Cosmo; Beneduce, Alessandro; Ferrante, Giuseppe; Ielasi, Alfonso; Pivato, Andrea Carlo; Chiarito, Mauro; Cappelletti, Alberto; Perfetti, Giulia; Magni, Valeria; Prati, Eugenio; Falcone, Stefania; Pierri, Adele; De Martini, Stefano; Montorfano, Matteo; Parisi, Rosario; Rutigliano, David; Locuratolo, Nicola; Anzuini, Angelo; Tespilli, Maurizio; Margonato, Alberto; Benassi, Alberto; Briguori, Carlo; Fabbiocchi, Franco; Reimers, Bernhard; Bartorelli, Antonio; Colombo, Antonio

2018-06-01

This study was designed to confirm in a large population of unselected patients the promising results of Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) already shown in previous trial. ULISSE is an observational, multicenter, national registry evaluating all patients undergoing PCI with the Ultimaster® BP-SES. Incidence of 1-year TLF (cardiac death or target vessel MI or clinically indicated TLR) was the primary endpoint. Pre-specified subgroup analysis was performed for diabetic patients and for those with lesion longer than 25 mm, bifurcation and CTO lesions. 1660 patients were enrolled in 9 Italian cardiology centers, 82% were males, mean age of 68 ± 10 years, and 29% were diabetics. Overall 2422 lesions were treated, 65% type B2/C lesions, 7% CTOs, 17% bifurcations and 38% long lesions. The incidence of 1-year TLF was 5%, with 3.2% of clinically indicated TLR. TLF occurred in 8% of the patients with diabetes mellitus, and 7% in bifurcation, 6.7% in CTO and 6.2% in long lesions. Definite overall ST was 0.9%, and 1.2% in patients treated for type B2/C lesions. Multivariate logistic regression analysis identified stenting on unprotected LMT (OR = 4.80), stenting on ISR lesion (OR = 3.19) and need for rotational atherectomy (OR = 6.24) as the strongest independent predictors of TLF. The results of this national all-comers registry show that the Ultimaster® BP-SES real-world performance was comparable with that observed in the clinical trial, with low rate of primary endpoint and TLR. Long term follow-up will be necessary to prove the theoretical advantage of the BP-SES over time. Copyright © 2017. Published by Elsevier B.V.

Long-term Outcomes of Laparoscopic Versus Open Surgery for Clinical Stage II/III Gastric Cancer: A Multicenter Cohort Study in Japan (LOC-A Study).

PubMed

Kinoshita, Takahiro; Uyama, Ichiro; Terashima, Masanori; Noshiro, Hirokazu; Nagai, Eishi; Obama, Kazutaka; Tamamori, Yutaka; Nabae, Toshinaga; Honda, Michitaka; Abe, Takayuki

2018-04-24

A large-scale multicenter historical cohort study was conducted to investigate the efficacy of laparoscopic gastrectomy (LG) in comparison to open gastrectomy (OG) for locally advanced gastric cancer. LG is now practiced widely, but its applicability for advanced gastric cancer is still controversial. As oncologic outcomes of randomized trials are still pending, there is an urgent need for information that would be relevant to current practice. Through a consensus meeting involving surgeons and biostatisticians, 30 preoperative variables possibly influencing the choice of surgical approach and associated with outcome were identified to enable rigorous estimation of propensity scores. A total of 1948 consecutive patients who underwent gastrectomy for clinical stage II/III gastric adenocarcinoma between 2008 and 2014 were identified, and their clinical data were collected from 8 participating hospitals. After propensity score matching, 610 cases (OG = 305, LG = 305) were finally selected for comparison of long-term outcomes. In the propensity-matched OG and LG populations, the mean observation period was 3.5 and 3.4 years, and the 5-year overall survival was 53.0% and 54.2%, respectively. The hazard ratio (LG/OG) for overall survival was 1.01 (95% confidence interval, 0.80-1.29), and noninferiority of LG was demonstrated statistically as the upper 95% confidence limit was less than the prespecified margin (1.33). The recurrence rate was 30.8% and 29.8% for OG and LG, respectively, and the hazard ratio for recurrence was 0.98 (95% confidence interval, 0.74-1.31). The patterns of recurrence in the 2 groups were similar. This observational study strictly adjusted for confounding factors has provided evidence to suggest that LG is oncologically comparable to OG for locally advanced gastric cancer. The validity of this result will be examined in ongoing randomized trials.

Outcome of Burns Treated With Autologous Cultured Proliferating Epidermal Cells: A Prospective Randomized Multicenter Intrapatient Comparative Trial.

PubMed

Gardien, Kim L M; Marck, Roos E; Bloemen, Monica C T; Waaijman, Taco; Gibbs, Sue; Ulrich, Magda M W; Middelkoop, Esther

2016-01-01

Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5-7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound epithelialization after 5-7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only. The relevance of cultured autologous cells in treatment of extensive burns is supported by our current findings.

A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury

PubMed Central

Synnot, Anneliese; Maas, Andrew I.; Menon, David K.; Cooper, D. James; Rosenfeld, Jeffrey V.; Gruen, Russell L.

2016-01-01

Abstract Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n > 100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients. PMID:26711675

Protocolized fluid therapy in brain-dead donors: The multi-center randomized MOnIToR trial

PubMed Central

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S.; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-01-01

BACKGROUND Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multi-center randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases organs transplanted. METHODS We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor and our primary analysis was intention-to-treat. Secondary analyses included: 1) modified intention-to-treat where only subjects able to receive the intervention were included, and 2) twelve-month survival in transplant recipients. The study was stopped early. RESULTS We enrolled 556 donors; 279 protocolized care, 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76% of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor, (95%CI: 3.14-3.63) with protocolized care, compared to usual care 3.29 (95%CI: 3.04-3.54) (mean difference, 0.1, 95%CI: -0.25 to 0.45; p=0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95%CI: 3.23-3.8) but was not statistically significant (mean difference, 0.23, 95%CI: -0.15-0.61; p=0.23). Among the 1430 recipients of organs from study subjects, with data available, 56 deaths (7.8%) occurred in the protocolized care arm and 56 (7.9%) in the usual care arm in the first year (Hazard Ratio: 0.97, p=0.86). CONCLUSIONS In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor. PMID:25583616

Comparison of eye movement desensitization and reprocessing therapy, cognitive behavioral writing therapy, and wait-list in pediatric posttraumatic stress disorder following single-incident trauma: a multicenter randomized clinical trial.

PubMed

de Roos, Carlijn; van der Oord, Saskia; Zijlstra, Bonne; Lucassen, Sacha; Perrin, Sean; Emmelkamp, Paul; de Jongh, Ad

2017-11-01

Practice guidelines for childhood posttraumatic stress disorder (PTSD) recommend trauma-focused psychotherapies, mainly cognitive behavioral therapy (CBT). Eye movement desensitization and reprocessing (EMDR) therapy is a brief trauma-focused, evidence-based treatment for PTSD in adults, but with few well-designed trials involving children and adolescents. We conducted a single-blind, randomized trial with three arms (n = 103): EMDR (n = 43), Cognitive Behavior Writing Therapy (CBWT; n = 42), and wait-list (WL; n = 18). WL participants were randomly reallocated to CBWT or EMDR after 6 weeks; follow-ups were conducted at 3 and 12 months posttreatment. Participants were treatment-seeking youth (aged 8-18 years) with a DSM-IV diagnosis of PTSD (or subthreshold PTSD) tied to a single trauma, who received up to six sessions of EMDR or CBWT lasting maximally 45 min each. Both treatments were well-tolerated and relative to WL yielded large, intent-to-treat effect sizes for the primary outcomes at posttreatment: PTSD symptoms (EMDR: d = 1.27; CBWT: d = 1.24). At posttreatment 92.5% of EMDR, and 90.2% of CBWT no longer met the diagnostic criteria for PTSD. All gains were maintained at follow-up. Compared to WL, small to large (range d = 0.39-1.03) intent-to-treat effect sizes were obtained at posttreatment for negative trauma-related appraisals, anxiety, depression, and behavior problems with these gains being maintained at follow-up. Gains were attained with significantly less therapist contact time for EMDR than CBWT (mean = 4.1 sessions/140 min vs. 5.4 sessions/227 min). EMDR and CBWT are brief, trauma-focused treatments that yielded equally large remission rates for PTSD and reductions in the severity of PTSD and comorbid difficulties in children and adolescents seeking treatment for PTSD tied to a single event. Further trials of both treatments with PTSD tied to multiple traumas are warranted. © 2017 Association for Child and Adolescent Mental Health.

Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Maguire, Maureen G; Ying, Gui-shuang; McCannel, Colin A; Liu, Chengcheng; Dai, Yang

2009-12-01

To evaluate the impact of statin use on the incidence of advanced age-related macular degeneration (AMD) and its components, choroidal neovascularization (CNV) and geographic atrophy (GA), among patients with bilateral large drusen. Cohort study within a multicenter, randomized, clinical trial. Patients enrolled in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for the clinical trial required that participants have >or=10 large (>125 microm) drusen and visual acuity >or=20/40 in each eye. Patients scheduled for their final CAPT visit after May 2005 were interviewed on their history of use of cholesterol-lowering medications, including statins. Trained readers identified CNV and end point GA (>1 Macular Photocoagulation Study disc area of GA) based on review of fluorescein angiograms and fundus photographs taken at annual follow-up visits and when patients reported symptoms. The risk ratio for participants developing CNV or developing GA associated with statin use was estimated with time-dependent Cox proportional hazards models. Development of advanced AMD, CNV, and end point GA. Among 764 patients eligible for the interview, 744 (97.4%) patients completed the interview on medication use. Statin use was reported by 296 (39.8%) of those interviewed, with the majority, 187 (63.2%) of the 296, beginning use after enrollment in CAPT. Among 744 patients, advanced AMD developed in 332 (22.5%) eyes of 242 (32.5%) patients, CNV in 222 (15%) eyes of 176 (23.7%) patients, and GA in 114 (7.7%) eyes of 80 (10.8%) patients. With adjustment for other risk factors, the estimated risk ratio for eyes (95% confidence interval) associated with statin use was 1.15 (0.87-1.52) for advanced AMD, 1.35 (0.99-1.83) for CNV, and 0.80 (0.46-1.39) for GA. The CAPT data are not consistent with a strong protective effect (risk ratio,

Interrelationships between glutamine and citrulline metabolism

PubMed Central

2015-01-01

Purpose of review To analyze the evidence that glutamine supplementation increases citrulline production. To determine the contribution of glutamine to the synthesis of citrulline. Recent findings Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter randomized controlled trial resulted in increased mortality in the glutamine supplemented group. Within this context, defining the contribution of glutamine to the production of citrulline, and thus to de novo arginine synthesis, has become a pressing issue. Summary The beneficial effects of glutamine supplementation may be partially mediated by the effects of glutamine on citrulline synthesis by the gut and the de novo synthesis of arginine by the kidney and other tissues. Although there is no strong evidence to support that glutamine is a major precursor for citrulline synthesis in humans, glutamine has the potential to increase overall gut function and in this way increase citrulline production. PMID:26560519

The ADNI PET Core: 2015

PubMed Central

Jagust, William J.; Landau, Susan M.; Koeppe, Robert A.; Reiman, Eric M.; Chen, Kewei; Mathis, Chester A.; Price, Julie C.; Foster, Norman L.; Wang, Angela Y.

2015-01-01

INTRODUCTION This paper reviews the work done in the ADNI PET core over the past 5 years, largely concerning techniques, methods, and results related to amyloid imaging in ADNI. METHODS The PET Core has utilized [18F]florbetapir routinely on ADNI participants, with over 1600 scans available for download. Four different laboratories are involved in data analysis, and have examined factors such as longitudinal florbetapir analysis, use of FDG-PET in clinical trials, and relationships between different biomarkers and cognition. RESULTS Converging evidence from the PET Core has indicated that cross-sectional and longitudinal florbetapir analyses require different reference regions. Studies have also examined the relationship between florbetapir data obtained immediately after injection, which reflects perfusion, and FDG-PET results. Finally, standardization has included the translation of florbetapir PET data to a centiloid scale. CONCLUSION The PET Core has demonstrated a variety of methods for standardization of biomarkers such as florbetapir PET in a multicenter setting. PMID:26194311

Zoster vaccine live for the prevention of shingles in the elderly patient

PubMed Central

Zussman, Jamie; Young, Lorraine

2008-01-01

Shingles, also known as herpes zoster, is a common disease in the elderly population that is caused by reactivation of latent varicella zoster virus. Its manifestations and complications can lead to significant short- and long-term morbidity. In 2006, the United States Food and Drug Administration approved Zoster Vaccine Live (Zostavax®) for the prevention of herpes zoster in immunocompetent adults age 60 and over. The approval was based on the results of a large, multi-center clinical trial, the Shingles Prevention Study. This study showed that vaccination significantly decreased shingles incidence, burden of illness due to disease, and the development of, and severity of postherpetic neuralgia. This review offers an overview of varicella zoster virus infection and complications, a summary of the Shingles Prevention Study, and a critical analysis designed to aid the practicing physician who has questions about vaccine administration. PMID:18686747

Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach

PubMed Central

McCorquodale, Donald; Pucillo, Evan M; Johnson, Nicholas E

2016-01-01

Charcot–Marie–Tooth (CMT) disease is the most common inherited neuropathy and one of the most common inherited diseases in humans. The diagnosis of CMT is traditionally made by the neurologic specialist, yet the optimal management of CMT patients includes genetic counselors, physical and occupational therapists, physiatrists, orthotists, mental health providers, and community resources. Rapidly developing genetic discoveries and novel gene discovery techniques continue to add a growing number of genetic subtypes of CMT. The first large clinical natural history and therapeutic trials have added to our knowledge of each CMT subtype and revealed how CMT impacts patient quality of life. In this review, we discuss several important trends in CMT research factors that will require a collaborative multidisciplinary approach. These include the development of large multicenter patient registries, standardized clinical instruments to assess disease progression and disability, and increasing recognition and use of patient-reported outcome measures. These developments will continue to guide strategies in long-term multidisciplinary efforts to maintain quality of life and preserve functionality in CMT patients. PMID:26855581

TERMTrial--terminology-based documentation systems for cooperative clinical trials.

PubMed

Merzweiler, A; Weber, R; Garde, S; Haux, R; Knaup-Gregori, P

2005-04-01

Within cooperative groups of multi-center clinical trials a standardized documentation is a prerequisite for communication and sharing of data. Standardizing documentation systems means standardizing the underlying terminology. The management and consistent application of terminology systems is a difficult and fault-prone task, which should be supported by appropriate software tools. Today, documentation systems for clinical trials are often implemented as so-called Remote-Data-Entry-Systems (RDE-systems). Although there are many commercial systems, which support the development of RDE-systems there is none offering a comprehensive terminological support. Therefore, we developed the software system TERMTrial which consists of a component for the definition and management of terminology systems for cooperative groups of clinical trials and two components for the terminology-based automatic generation of trial databases and terminology-based interactive design of electronic case report forms (eCRFs). TERMTrial combines the advantages of remote data entry with a comprehensive terminological control.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

PubMed

Meretoja, Atte; Churilov, Leonid; Campbell, Bruce C V; Aviv, Richard I; Yassi, Nawaf; Barras, Christen; Mitchell, Peter; Yan, Bernard; Nandurkar, Harshal; Bladin, Christopher; Wijeratne, Tissa; Spratt, Neil J; Jannes, Jim; Sturm, Jonathan; Rupasinghe, Jayantha; Zavala, Jorge; Lee, Andrew; Kleinig, Timothy; Markus, Romesh; Delcourt, Candice; Mahant, Neil; Parsons, Mark W; Levi, Christopher; Anderson, Craig S; Donnan, Geoffrey A; Davis, Stephen M

2014-06-01

No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

PubMed

Paajanen, Hannu; Grönroos, Juha M; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Hurme, Saija; Dean, Kirsti; Jartti, Airi; Mecklin, Jukka-Pekka; Sand, Juhani; Salminen, Paulina

2013-02-08

Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors

PubMed Central

Hobday, Timothy J.; Qin, Rui; Reidy-Lagunes, Diane; Moore, Malcolm J.; Strosberg, Jonathan; Kaubisch, Andreas; Shah, Manisha; Kindler, Hedy Lee; Lenz, Heinz-Josef; Chen, Helen; Erlichman, Charles

2015-01-01

Purpose There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway–targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted. PMID:25488966

Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial.

PubMed

Mejía, Omar Asdrúbal Vilca; Sá, Michel Pompeu Barros Oliveira; Deininger, Maurilio Onofre; Dallan, Luís Roberto Palma; Segalote, Rodrigo Coelho; Oliveira, Marco Antonio Praça de; Atik, Fernando Antibas; Santos, Magaly Arrais Dos; Silva, Pedro Gabriel Melo de Barros E; Milani, Rodrigo Mussi; Hueb, Alexandre Ciappina; Monteiro, Rosangela; Lima, Ricardo Carvalho; Lisboa, Luiz Augusto Ferreira; Dallan, Luís Alberto Oliveira; Puskas, John; Jatene, Fabio Biscegli

2017-01-01

Advances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients. FRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs. FRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients. ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.

Continuous wound infiltration or epidural analgesia for pain prevention after hepato-pancreato-biliary surgery within an enhanced recovery program (POP-UP trial): study protocol for a randomized controlled trial.

PubMed

Mungroop, Timothy H; Veelo, Denise P; Busch, Olivier R; van Dieren, Susan; van Gulik, Thomas M; Karsten, Tom M; de Castro, Steve M; Godfried, Marc B; Thiel, Bram; Hollmann, Markus W; Lirk, Philipp; Besselink, Marc G

2015-12-09

Postoperative pain prevention is essential for the recovery of surgical patients. Continuous (thoracic) epidural analgesia (CEA) is routinely practiced for major abdominal surgery, but evidence is conflicting on its benefits in this setting. Potential disadvantages of epidural analgesia are a) perioperative hypotension, frequently requiring additional intravenous fluid boluses or prolonged use of vasopressors; b) relatively high failure rates, with periods of inadequate analgesia; and c) the risk of rare but serious, at times persistent, neurologic complications (hematoma and abscess). In recent years, continuous (subfascial) wound infiltration (CWI) plus patient-controlled analgesia (PCA) has been suggested as a safe and reliable alternative, which does not have the previously mentioned disadvantages, but evidence from multicenter trials targeting a specific surgical population is lacking. We hypothesize that CWI+PCA is equally as effective as CEA, without the mentioned disadvantages. POP-UP is a randomized controlled noninferiority multicenter trial, recruiting adult patients scheduled for elective hepato-pancreato-biliary surgery via laparotomy in an enhanced recovery setting. A total of 102 patients are being randomly allocated to CWI+PCA or (P)CEA. Our primary endpoint is the Overall Benefit of Analgesic Score (OBAS), a composite endpoint of pain intensity, opioid-related adverse effects and patient satisfaction, during postoperative days 1 to 5. Secondary endpoints include length of the hospital stay, number of patients with severe pain, and the use of rescue medication. POP-UP is a pragmatic trial that will provide evidence of whether CWI+PCA is noninferior as compared to (P)CEA after elective hepato-pancreato-biliary surgery via laparotomy in an enhanced recovery setting. If this hypothesis is confirmed, this finding could contribute to more widespread implementation of this technique, especially when the described disadvantages of epidural analgesia are less often observed with CWI+PCA. Netherlands Trial Register NTR4948 (registry date 2 January 2015).

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

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

Estimating relative risks in multicenter studies with a small number of centers - which methods to use? A simulation study.

PubMed

Pedroza, Claudia; Truong, Van Thi Thanh

2017-11-02

Analyses of multicenter studies often need to account for center clustering to ensure valid inference. For binary outcomes, it is particularly challenging to properly adjust for center when the number of centers or total sample size is small, or when there are few events per center. Our objective was to evaluate the performance of generalized estimating equation (GEE) log-binomial and Poisson models, generalized linear mixed models (GLMMs) assuming binomial and Poisson distributions, and a Bayesian binomial GLMM to account for center effect in these scenarios. We conducted a simulation study with few centers (≤30) and 50 or fewer subjects per center, using both a randomized controlled trial and an observational study design to estimate relative risk. We compared the GEE and GLMM models with a log-binomial model without adjustment for clustering in terms of bias, root mean square error (RMSE), and coverage. For the Bayesian GLMM, we used informative neutral priors that are skeptical of large treatment effects that are almost never observed in studies of medical interventions. All frequentist methods exhibited little bias, and the RMSE was very similar across the models. The binomial GLMM had poor convergence rates, ranging from 27% to 85%, but performed well otherwise. The results show that both GEE models need to use small sample corrections for robust SEs to achieve proper coverage of 95% CIs. The Bayesian GLMM had similar convergence rates but resulted in slightly more biased estimates for the smallest sample sizes. However, it had the smallest RMSE and good coverage across all scenarios. These results were very similar for both study designs. For the analyses of multicenter studies with a binary outcome and few centers, we recommend adjustment for center with either a GEE log-binomial or Poisson model with appropriate small sample corrections or a Bayesian binomial GLMM with informative priors.

Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure.

PubMed

Trullàs, Joan Carles; Morales-Rull, José Luís; Casado, Jesús; Freitas Ramírez, Adriana; Manzano, Luís; Formiga, Francesc

2016-07-01

Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance. CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed. CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: An assessment of trial quality.

PubMed

Kistler, Kristin D; Xu, Yingxin; Zou, Kelly H; Ntanios, Fady; Chapman, Douglass S; Luo, Xuemei

2018-01-01

Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. MEDLINE ® , Embase ® , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly"). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting-of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly. © 2017 Wiley Periodicals, Inc.

Rationale and design of the SAIL trial for intramuscular injection of allogeneic mesenchymal stromal cells in no-option critical limb ischemia.

PubMed

Wijnand, Joep G J; Teraa, Martin; Gremmels, Hendrik; van Rhijn-Brouwer, Femke C C; de Borst, Gert J; Verhaar, Marianne C

2018-02-01

Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and has an immense impact on quality of life, morbidity, and mortality. A considerable proportion of CLI patients are ineligible for revascularization, leaving amputation as the only option. Mesenchymal stromal cells (MSCs), because of their vasculoregenerative and immunomodulatory characteristics, have emerged as a potential new treatment. The primary objective of this trial is to investigate whether intramuscular administration of allogeneic bone marrow (BM)-derived MSCs is safe and potentially effective. The SAIL (allogeneic mesenchymal Stromal cells for Angiogenesis and neovascularization in no-option Ischemic Limbs) trial is a double-blind, placebo-controlled randomized clinical trial to investigate the effect of allogeneic BM-MSCs in patients with CLI who are not eligible for conventional revascularization. A total of 66 patients will be included and randomized (1:1) to undergo 30 intramuscular injections with either BM-MSCs (5 × 10 6 MSCs per injection) or placebo in the ischemic lower extremity. Primary outcome, that is, therapy success, a composite outcome consisting of mortality, limb status, clinical status, and changes in pain score, will be assessed at 6 months. All study-related procedures will take place in the University Medical Center Utrecht in The Netherlands. If our results indicate that intramuscular allogeneic BM-MSC therapy for CLI is safe and potentially effective, this will have important consequences for treatment of patients with CLI. A large multicenter clinical trial with longer follow-up focusing on hard end points should then be initiated to confirm these findings. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s < 0.001 except for week 3, which was 0.006), with clinically significant differences as follows: week 6 – RR 0.28 [95% CI, 0.10, 0.79]; week 11- RR 0.17 [95% CI, 0.03, 1.07]. Similar findings were seen for MDASI-HN scores and MDASI-Intrusion scores. Group differences for UWSFR and SSFR were not found. Conclusions In this small pilot study, true acupuncture given concurrently with radiotherapy significantly reduced xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

Clinical trials for drug registrations in Asian-Pacific countries: proposal for a new paradigm from a statistical perspective.

PubMed

Shih, W J

2001-08-01

The world has become more interdependent in the movement of free trade and global markets. The regulations for approval of new drugs in the Asian markets have always been an important issue in the free trade negotiation between the U.S.- and E.U.-based international manufacturers and the Asian-Pacific countries, since pharmaceuticals are of large trade value for them. In 1998 the University of Hong Kong and the Singapore National Medical Research Council jointly hosted the first Asian Clinical Trials Conference. The Society for Clinical Trials was invited as a collaborator for the event, which signified a milestone for interaction between the East and West in the discussion of clinical trials. Many have participated in the discussion of drug approval and registration issues for the Asian region based on the drug development experience in the United States. However, there are many interesting differences between the two regions, which lead to different approval processes for new drugs developed by the U.S.- and E.U.-based international manufacturers. This article highlights some regulatory dilemmas and some key statistical concepts pertinent to these differences. The purpose of this paper is to resolve the regional regulatory and scientific dilemma. A new paradigm of sample size design and data analysis for drug approval for countries in the Asian-Pacific region is proposed. The central premise is that substantial information from multicenter studies has already shown efficacy in the United States or the European Union when a drug manufacturer seeks marketing approval in an Asian country. This leads to the idea of a "consistency trial" using the method of Bayesian most plausible prediction. The method is illustrated with an example.

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

PubMed

Feig, Denice S; Asztalos, Elizabeth; Corcoy, Rosa; De Leiva, Alberto; Donovan, Lois; Hod, Moshe; Jovanovic, Lois; Keely, Erin; Kollman, Craig; McManus, Ruth; Murphy, Kellie; Ruedy, Katrina; Sanchez, J Johanna; Tomlinson, George; Murphy, Helen R

2016-07-18

Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial.

PubMed

Bartl, Christoph; Stengel, Dirk; Bruckner, Thomas; Rossion, Inga; Luntz, Steffen; Seiler, Christoph; Gebhard, Florian

2011-03-22

Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation.Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool.The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central statistical unit, an independent monitoring institute, and a data safety monitoring board. Following approval by the institutional review boards of all participating centers, conduct and reporting will strictly adhere to national and international rules, regulations, and recommendations (e.g., Good Clinical Practice, data safety laws, and EQUATOR/CONSORT proposals). To our knowledge, ORCHID is the first multicenter RCT designed to assess quality of life and functional outcomes following operative treatment compared to conservative treatment of complex, intra-articular fractures of the distal radius in elderly patients. The results are expected to influence future treatment recommendations and policies on an international level. ISRCTN: ISRCTN76120052 Registration date: 31.07.2008; Randomization of first patient: 15.09.2008.

Methodological aspects of multicenter studies with quantitative PET.

PubMed

Boellaard, Ronald

2011-01-01

Quantification of whole-body FDG PET studies is affected by many physiological and physical factors. Much of the variability in reported standardized uptake value (SUV) data seen in the literature results from the variability in methodology applied among these studies, i.e., due to the use of different scanners, acquisition and reconstruction settings, region of interest strategies, SUV normalization, and/or corrections methods. To date, the variability in applied methodology prohibits a proper comparison and exchange of quantitative FDG PET data. Consequently, the promising role of quantitative PET has been demonstrated in several monocentric studies, but these published results cannot be used directly as a guideline for clinical (multicenter) trials performed elsewhere. In this chapter, the main causes affecting whole-body FDG PET quantification and strategies to minimize its inter-institute variability are addressed.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

PubMed

Ivanov, Alexander; Kaczkowska, Beata A; Khan, Saadat A; Ho, Jean; Tavakol, Morteza; Prasad, Ashok; Bhumireddy, Geetha; Beall, Allan F; Klem, Igor; Mehta, Parag; Briggs, William M; Sacchi, Terrence J; Heitner, John F

2017-01-01

Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

Does Patient Time Spent Viewing Computer-Tailored Colorectal Cancer Screening Materials Predict Patient-Reported Discussion of Screening with Providers?

ERIC Educational Resources Information Center

Sanders, Mechelle; Fiscella, Kevin; Veazie, Peter; Dolan, James G.; Jerant, Anthony

2016-01-01

The main aim is to examine whether patients' viewing time on information about colorectal cancer (CRC) screening before a primary care physician (PCP) visit is associated with discussion of screening options during the visit. We analyzed data from a multi-center randomized controlled trial of a tailored interactive multimedia computer program…

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…

Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

2006-01-01

Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

PubMed

Jamieson, Catriona H M; Millan, Maria T; Creasey, Abla A; Lomax, Geoff; Donohoe, Mary E; Walters, Mark C; Abedi, Mehrdad; Bota, Daniela A; Zaia, John A; Adams, John S

2018-06-01

The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges. Copyright © 2018 Elsevier Inc. All rights reserved.

Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the diabetes prevention program

USDA-ARS?s Scientific Manuscript database

We investigated the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. The research design and methods were a prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multi-center trial co...

Serious adverse events in randomized psychosocial treatment studies: Safety or Arbitrary Edicts?

PubMed Central

Petry, Nancy M.; Roll, John M.; Rounsaville, Bruce J.; Ball, Samuel A.; Stitzer, Maxine; Peirce, Jessica M.; Blaine, Jack; Kirby, Kimberly C.; McCarty, Dennis; Carroll, Kathleen M.

2009-01-01

Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network. Substance abusing participants (N=1,687) were randomized to standard care or standard care plus either contingency management or motivational enhancement. Twelve percent of participants experienced one or more SAEs during the 27,198 person-weeks of follow-up. Of the 260 SAEs recorded, none were judged by the Data Safety Monitoring Board to be study related, and there were no significant differences between experimental and control conditions in SAE incidence rates. These data underscore the need to reconsider the rationale behind, and appropriate methods for, monitoring safety during psychosocial therapy trials. PMID:19045975

Transobturator TVT-O versus retropubic TVT: results of a multicenter randomized controlled trial at 24 months follow-up.

PubMed

Deffieux, Xavier; Daher, Nagib; Mansoor, Aslam; Debodinance, Philippe; Muhlstein, Joël; Fernandez, Hervé

2010-11-01

The purpose of this study is to compare the retropubic tension-free vaginal tape (TVT) procedure with the inside-out transobturator approach (TVT-O). Multicenter randomized controlled trial. One hundred forty-nine patients were randomly allocated to either TVT (n = 75) or TVT-O (n = 74). Interview, medical examination, pain scores, success rates, and quality of life assessment were recorded pre-operatively, and 2, 6, 12, and 24 months post-operatively. One hundred forty-nine patients underwent surgery, and 132 completed a 24-month follow-up. Bladder injury rate was 5% (4/75) in the TVT group and 2% (2/74) in the TVT-O group (p = 0.68). There was no significant difference between the two groups, concerning overall cure rate and the patients' satisfaction rate at 24 months follow-up. The range of mean pain scores was significantly higher after the TVT-O procedure post-operatively but not at 24 months follow-up. TVT and TVT-O procedures both have an outcome associated with an increase in quality of life with no significant differences in satisfaction rates at 2 years follow-up.

Treatment in carbon monoxide poisoning patients with headache: a prospective, multicenter, double-blind, controlled clinical trial.

PubMed

Ocak, Tarik; Tekin, Erdal; Basturk, Mustafa; Duran, Arif; Serinken, Mustafa; Emet, Mucahit

2016-11-01

There is a lack of specificity of the analgesic agents used to treat headache and underlying acute carbon monoxide poisoning. To compare effectiveness of "oxygen alone" vs "metoclopramide plus oxygen" vs "metamizole plus oxygen" therapy in treating carbon monoxide-induced headache. A prospective, multicenter, double-blind, controlled trial. Three emergency departments in Turkey. Adult carbon monoxide poisoning patients with headache. A total of 117 carbon monoxide-intoxicated patients with headache were randomized into 3 groups and assessed at baseline, 30 minutes, 90 minutes, and 4 hours. The primary outcome was patient-reported improvement rates for headache. Secondary end points included nausea, need for rescue medication during treatment, and reduction in carboxyhemoglobin levels. During observation, there was no statistical difference between drug type and visual analog scale score change at 30 minutes, 90 minutes, or 4 hours, for either headache or nausea. No rescue medication was needed during the study period. The reduction in carboxyhemoglobin levels did not differ among the 3 groups. The use of "oxygen alone" is as efficacious as "oxygen plus metoclopramide" or "oxygen plus metamizole sodium" in the treatment of carbon monoxide-induced headache. Copyright © 2016 Elsevier Inc. All rights reserved.

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology.

PubMed

Cerrato, Enrico; Quirós, Alicia; Echavarría-Pinto, Mauro; Mejia-Renteria, Hernan; Aldazabal, Andres; Ryan, Nicola; Gonzalo, Nieves; Jimenez-Quevedo, Pilar; Nombela-Franco, Luis; Salinas, Pablo; Núñez-Gil, Iván J; Rumoroso, José Ramón; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

2017-05-19

In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).

The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients.

PubMed

1998-07-01

The purpose of this report is to examine the differences at baseline in demographic, medical, and ophthalmic characteristics between blacks and whites enrolled in the Advanced Glaucoma Intervention Study (AGIS), a multicenter, randomized, clinical trial. Multicenter, randomized, controlled trial. A total of 332 black patients (451 eyes), 249 white patients (325 eyes), and 10 patients of other races (13 eyes) with open-angle glaucoma that could not be controlled by medical therapy alone participated. There was no intervention performed. The investigators compare the baseline demographic, medical, and ophthalmic characteristics of black and white patients, adjusting the comparisons for age and gender. Blacks in the study were younger than whites and had more systemic hypertension and diabetes than whites. The visual field defects of blacks on average were substantially more severe than those of whites. Intraocular pressures and visual acuity scores were similar in the two groups. Blacks were more hyperopic and had relatively fewer disk rim hemorrhages than whites. The findings of the current study concur with those of previous clinical studies of open-angle glaucoma that visual field defects are more severe in blacks than whites.

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

PubMed

Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated. At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2 h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Chinese Clinical Trial Register ChiCTR-TRC-13003159.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

PubMed Central

van Hooft, Jeanin E; Bemelman, Willem A; Breumelhof, Ronald; Siersema, Peter D; Kruyt, Philip M; van der Linde, Klaas; Veenendaal, Roeland A; Verhulst, Marie-Louise; Marinelli, Andreas W; Gerritsen, Josephus JGM; van Berkel, Anne-Marie; Timmer, Robin; Grubben, Marina JAL; Scholten, Pieter; Geraedts, Alfons AM; Oldenburg, Bas; Sprangers, Mirjam AG; Bossuyt, Patrick MM; Fockens, Paul

2007-01-01

Background Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration Current Controlled Trials ISRCTN46462267. PMID:17608947

IMpact of Platelet Rich plasma OVer alternative therapies in patients with lateral Epicondylitis (IMPROVE): protocol for a multicenter randomized controlled study: a multicenter, randomized trial comparing autologous platelet-rich plasma, autologous whole blood, dry needle tendon fenestration, and physical therapy exercises alone on pain and quality of life in patients with lateral epicondylitis.

PubMed

Chiavaras, Mary M; Jacobson, Jon A; Carlos, Ruth; Maida, Eugene; Bentley, Todd; Simunovic, Nicole; Swinton, Marilyn; Bhandari, Mohit

2014-09-01

Lateral epicondylitis, commonly known as tennis elbow, is the most common cause of lateral elbow pain and the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting. Many therapeutic options, including conservative, surgical, and minimally invasive procedures, have been advocated for the treatment of lateral epicondylitis. Although numerous small studies have been performed to assess the efficacy of various treatments, there are conflicting results with no clear consensus on the optimal treatment. In an economic environment with limited health care resources, it is paramount that optimal cost-effective therapies with favorable patient-important outcomes be identified. This is a protocol paper which outlines a multicenter, multidisciplinary, single-blinded, four-arm randomized controlled trial, comparing platelet-rich plasma (PRP), whole blood injection, dry needle tendon fenestration, and sham injection with physical therapy alone for the treatment of lateral epicondylitis. Patients are screened based on pre-established eligibility criteria and randomized to one of the four study groups using an Internet-based system. The patients are followed at 6-week, 12-week, 24-week, and 52-week time points to assess the primary and secondary outcomes of the study. The primary outcome is pain. Secondary outcomes include health-related quality of life and ultrasound appearance of the common extensor tendon. Two university centers (McMaster University and the University of Michigan) are currently recruiting patients. We have planned a sample size of 100 patients (25 patients per arm) to ensure over 80% power to detect a three-point difference in pain scores at 52 weeks of follow-up. This study has ethics approval from the McMaster University Research Ethics Board (REB# 12-146) and the University of Michigan Institutional Review Board (IRB# HUM00067750). Successful completion of this proposed study will significantly impact clinical practice and enhance patients' lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in ultrasound-guided interventions will follow. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Hypothermia for Traumatic Brain Injury in Children-A Phase II Randomized Controlled Trial.

PubMed

Beca, John; McSharry, Brent; Erickson, Simon; Yung, Michael; Schibler, Andreas; Slater, Anthony; Wilkins, Barry; Singhal, Ash; Williams, Gary; Sherring, Claire; Butt, Warwick

2015-07-01

To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. Multicenter prospective randomized controlled phase II trial. All eight of the PICUs in Australia and New Zealand and one in Canada. Children 1-15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. The control group had strict normothermia to a temperature of 36-37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32-33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16-35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4-6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.

Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis.

PubMed

Kemmler, W; Häberle, L; von Stengel, S

2013-07-01

In this meta-analysis, we evaluated the effect of exercise on fracture reduction in the elderly. Our results determined a significantly positive effect on overall fractures, whereas the possibility of a publication bias indicates the need for well-designed (multi-center) trials that generate enough power to focus on osteoporotic fractures. The preventive effect of exercise on fracture incidence has not been clearly determined yet. Thus, the purpose of this study is to evaluate the effectiveness of exercise in preventing overall and vertebral fractures in older adults by meta-analyses technique. This study followed the PRISMA recommendations for systematic reviews and meta-analyses. A systematic review of English articles between 1980 and March 2012 was performed. Terms used were: "exercise", "fractures", "bone", "falls", "osteoporosis", "BMD", "BMC", "bone turnover", while the search was limited to "clinical trial" and "humans". Controlled exercise trials that reported fracture number as endpoint or observation in subjects 45 years and older were included. Ten controlled exercise trials that reported overall fractures and three exercise trials that reported vertebral fractures met our inclusion criteria. Overall fracture number in the exercise group was 36 (n = 754) compared with 73 fractures in the CG (n = 670) (relative risk [RR] = 0.49; 95 % confidence interval [CI], 0.31-0.76). No significant heterogeneity of trial results (p = 0.28; I (2) = 17) was determined; however, there was some evidence to suggest a publication bias. The overall RR for vertebral fracture number (0.56; 95 % CI, 0.30-1.04) (EG: 19 fractures/103 subjects vs. CG: 31 fractures/102 subjects) was borderline non-significant while the heterogeneity of trial results also cannot be ruled out. Although there is evidence that exercise reduces overall and, to a lesser degree, vertebral fractures in the elderly, the possibility of publication bias weakens our result and demonstrates the imperative for large exercise studies with dedicated exercise protocols that focus on fractures as a primary endpoint.

Totem and taboo: fluids in sepsis.

PubMed

Hilton, Andrew K; Bellomo, Rinaldo

2011-01-01

The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care.

Totem and Taboo: Fluids in sepsis

PubMed Central

2011-01-01

The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care. PMID:21672278

CARs in Chronic Lymphocytic Leukemia – Ready to Drive

PubMed Central

Wierda, William; Jena, Bipulendu; Cooper, Laurence J. N.; Shpall, Elizabeth

2013-01-01

Adoptive transfer of antigen-specific T cells has been adapted by investigators for treatment of chronic lymphocytic leukemia (CLL). To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens (TAAs), robust systems for the genetic modification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve potency. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, these early-phase trials are demonstrating impressive anti-tumor effects, particularly for CLL patients, paving the way for multi-center trials to establish the efficacy of CAR+ T cell therapy. PMID:23225251

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resistant hypertension optimal treatment trial: a randomized controlled trial.

PubMed

Krieger, Eduardo M; Drager, Luciano F; Giorgi, Dante Marcelo Artigas; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Barreto-Filho, José Augusto Soares; da Rocha Nogueira, Armando; Mill, José Geraldo

2014-01-01

The prevalence of resistant hypertension (ReHy) is not well established. Furthermore, diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and calcium channel blockers are largely used as the first 3-drug combinations for treating ReHy. However, the fourth drug to be added to the triple regimen is still controversial and guided by empirical choices. We sought (1) to determine the prevalence of ReHy in patients with stage II hypertension; (2) to compare the effects of spironolactone vs clonidine, when added to the triple regimen; and (3) to evaluate the role of measuring sympathetic and renin-angiotensin-aldosterone activities in predicting blood pressure response to spironolactone or clonidine. The Resistant Hypertension Optimal Treatment (ReHOT) study (ClinicalTrials.gov NCT01643434) is a prospective, multicenter, randomized trial comprising 26 sites in Brazil. In step 1, 2000 patients will be treated according to hypertension guidelines for 12 weeks, to detect the prevalence of ReHy. Medical therapy adherence will be checked by pill count monitoring. In step 2, patients with confirmed ReHy will be randomized to an open label 3-month treatment with spironolactone (titrating dose, 12.5-50 mg once daily) or clonidine (titrating dose, 0.1-0.3 mg twice daily). The primary endpoint is the effective control of blood pressure after a 12-week randomized period of treatment. The ReHOT study will disseminate results about the prevalence of ReHy in stage II hypertension and the comparison of spironolactone vs clonidine for blood pressure control in patients with ReHy under 3-drug standard regimen. © 2013 Wiley Periodicals, Inc.

Effect of Sling Exercise Training on Balance in Patients with Stroke: A Meta-Analysis

PubMed Central

Peng, Qiyuan; Chen, Jingjie; Zou, Yucong; Liu, Gang

2016-01-01

Objective This study aims to evaluate the effect of sling exercise training (SET) on balance in patients with stroke. Methods PubMed, Cochrane Library, Ovid LWW, CBM, CNKI, WanFang, and VIP databases were searched for randomized controlled trials of the effect of SET on balance in patients with stroke. The study design and participants were subjected to metrological analysis. Berg balance Scale (BBS), Barthel index score (BI), and Fugl-Meyer Assessment (FMA) were used as independent parameters for evaluating balance function, activities of daily living(ADL) and motor function after stroke respectively, and were subjected to meta-analysis by RevMan5.3 software. Results Nine studies with 460 participants were analyzed. Results of meta-analysis showed that the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS (WMD = 3.81, 95% CI [0.15, 7.48], P = 0.04), BI (WMD = 12.98, 95% CI [8.39, 17.56], P < 0.00001), and FMA (SMD = 0.76, 95% CI [0.41, 1.11], P < 0.0001). Conclusion Based on limited evidence from 9 trials, the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS, BI and FMA, So the SET treatment can improvement of balance function after stroke, but the interpretation of our findings is required to be made with caution due to limitations in included trials such as small sample sizes and the risk of bias. Therefore, more multi-center and large-sampled randomized controlled trials are needed to confirm its clinical applications. PMID:27727288

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: review and update on the use of defibrotide.

PubMed

Ho, Vincent T; Linden, Erica; Revta, Carolyn; Richardson, Paul G

2007-06-01

Veno-occlusive disease (VOD) of the liver remains one of the most feared complications associated with high-dose chemotherapy and hematopoietic stem cell transplantation (SCT). As a clinical syndrome characterized by fluid retention, hyperbilirubinemia, and painful hepatomegaly, VOD incidence varies widely, but it is universally recognized that severe cases of VOD have an extremely poor prognosis, with mortality at day 100 after SCT in excess of 80%. Systemic anticoagulant and thrombolytic therapies have been tested extensively in this disease, but are largely ineffective and are associated with significant bleeding complications. In recent years, defibrotide (DF; a polydisperse oligonucleotide derived from porcine intestinal mucosa with antithrombotic and protective properties on the microvasculature but minimal hemorrhagic risk) has emerged as a promising therapy for VOD. In large, multicenter, international phase I/II trials targeting patients with severe VOD, DF has been associated with complete response rates between 36 and 60%, survival past transplant day 100 in the range of 32 to 50%, and few significant attributable side effects. On the basis of these encouraging results, a pivotal, prospective, multinational, phase III trial of DF is underway in patients with severe VOD, and should provide validation of this agent as a therapy for established disease with a high risk of mortality. This article reviews our current understanding of hepatic VOD after SCT and provides a summary of the data to date on the use of DF as both therapy and prophylaxis for this disease.

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

PubMed

Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

2009-11-01

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2-yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.

Latent Subgroup Analysis of a Randomized Clinical Trial Through a Semiparametric Accelerated Failure Time Mixture Model

PubMed Central

Altstein, L.; Li, G.

2012-01-01

Summary This paper studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time-to-event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all-or-none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley-James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma. PMID:23383608

Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG).

PubMed

Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish; An, Sookee; Arya, Ravindra; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, David B; Goldstein, Joshua L; Goodkin, Howard P; Hahn, Cecil D; Heinzen, Erin L; Mikati, Mohamad A; Peariso, Katrina; Pestian, John P; Ream, Margie; Riviello, James J; Tasker, Robert C; Williams, Korwyn; Loddenkemper, Tobias

2014-02-01

Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

PubMed

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Godet, Thomas; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Blanchon, Loic; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

2018-01-01

Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial.

PubMed

Xia, Feng; Han, Junliang; Liu, Xuedong; Wang, Jingcun; Jiang, Zhao; Wang, Kangjun; Wu, Songdi; Zhao, Gang

2011-06-21

There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. ClinicalTrials.gov: NCT01201642.

Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial.

PubMed

2006-11-01

To evaluate the efficacy and safety of low-intensity laser treatment in the prevention of visual acuity (VA) loss among participants with bilateral large drusen. Multicenter randomized clinical trial. One eye of each participant was assigned to treatment, and the contralateral eye was assigned to observation. A total of 1052 participants who had > or =10 large (>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical centers. The initial laser treatment protocol specified 60 barely visible burns applied in a grid pattern within an annulus between 1500 and 2500 mum from the foveal center. At 12 months, eyes assigned to treatment that had sufficient drusen remaining were retreated with 30 burns by targeting drusen within an annulus between 1000 and 2000 mum from the foveal center. Proportion of eyes at 5 years with loss of > or =3 lines of VA from baseline. Secondary outcome measures included the development of choroidal neovascularization or geographic atrophy (GA), change in contrast threshold, change in critical print size, and incidence of ocular adverse events. At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores > or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an adverse event of a > or =6-line loss in VA in the absence of late age-related macular degeneration or cataract. As applied in the Complications of Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large drusen.

Multicenter Clinical Trial of the Nucleus® Hybrid™ S8 Cochlear Implant: Final Outcomes

PubMed Central

Gantz, Bruce J; Dunn, Camille; Oleson, Jacob; Hansen, Marlan; Parkinson, Aaron; Turner, Christopher

2015-01-01

Objective The concept expanding electrical speech processing to those with more residual acoustic hearing with a less invasive shorter cochlear implant has been ongoing since 1999. A multi-center study of the Nucleus Hybrid S8 CI took place between 2002–11. This report describes the final outcomes of this clinical trial. Study Design Multi-Center longitudinal single subject design Methods Eighty-seven subjects received a Nucleus® Hybrid™ S8 implant in their poorer ear. Speech perception in quiet (CNC words) and in noise (BKB-SIN) was collected pre- and post-operatively at 3, 6, and 12 months. Subjective questionnaire data using the APHAB was also collected. Results Some level of hearing preservation was accomplished in 98% subjects with 90% maintaining a functional low-frequency pure-tone average (LFPTA) at initial activation. By 12 months, 5 subjects had total hearing loss and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the Hybrid and Combined conditions. The majority of had improvements with BKB-SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the 4 subscales of the APHAB. Conclusion The concept of hybrid speech processing has significant advantages for subjects with residual low-frequency hearing. In this study, the Nucleus® Hybrid™ S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device. Level of evidence 2c PMID:26756395

SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.

PubMed

Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

2018-02-12

The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables. The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART. ClinicalTrials.gov ( NCT03088241 ), registered May 05, 2017.

Safety of 6-month duration of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndromes: Rationale and design of the Smart Angioplasty Research Team-safety of 6-month duration of Dual Antiplatelet Therapy after percutaneous coronary intervention in patients with acute coronary syndromes (SMART-DATE) prospective multicenter randomized trial.

PubMed

Lee, Joo Myung; Cho, Deok-Kyu; Hahn, Joo-Yong; Song, Young Bin; Park, Taek Kyu; Oh, Ju-Hyeon; Lee, Jin Bae; Doh, Joon-Hyung; Kim, Sang-Hyun; Yang, Jeong Hoon; Choi, Jin-Ho; Choi, Seung-Hyuck; Lee, Sang Hoon; Gwon, Hyeon-Cheol

2016-12-01

Dual antiplatelet therapy (DAPT) is a fundamental treatment that optimizes clinical outcomes after percutaneous coronary intervention, especially in patients with acute coronary syndrome (ACS). Although current international guidelines recommend DAPT for at least 12 months after implantation of a drug-eluting stent in patients with ACS, these recommendations are not based on randomized controlled trials dedicated to ACS population. The SMART-DATE trial is a prospective, multicenter, randomized, and open-label study to demonstrate the noninferiority of 6-month DAPT compared with 12 months or longer DAPT in patients with ACS undergoing percutaneous coronary intervention. A total of 2,700 patients will undergo prospective, random assignment to either of the DAPT duration groups. To minimize the bias from different stent devices, the type of stents will be randomly assigned (everolimus-eluting stents, zotarolimus-eluting stents, or biolimus A9-eluting stents). The primary end point is a composite of all-cause death, myocardial infarction, and cerebrovascular events at 18 months after the index procedure. The major secondary end points are definite/probable stent thrombosis defined by the Academic Research Consortium and bleeding defined by Bleeding Academic Research Consortium type 2-5. The SMART-DATE randomized trial is the first study exploring the safety of 6-month DAPT compared with conventional 12-month or longer DAPT dedicated to patients with ACS after second-generation drug-eluting stent implantation. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized multicenter trial of Crotalidae polyvalent immune F(ab) antivenom for the treatment of rattlesnake envenomation in dogs.

PubMed

Peterson, Michael E; Matz, Michael; Seibold, Karen; Plunkett, Signe; Johnson, Scott; Fitzgerald, Kevin

2011-08-01

To determine clinical efficacy of the Crotalidae polyvalent immune F(ab) (ovine) antivenom (OPCA) against progressive crotalid envenomation in the dog as reflected in stabilization or improvement of snakebite severity scores (SSS). Additionally, due to the potential decreased half-life of the F(ab) antibodies in dogs we compared SSS between dogs receiving 2 different dosing regimes. Prospective, clinical trial. Five veterinary emergency and critical care facilities. One hundred and fifteen client-owned Crotalid (rattlesnake) snake bitten dogs in whom worsening of the envenomation syndrome was observed before OPCA treatment. In a multicenter randomized clinical trial a single dose (1 vial) of OPCA alone was compared with 2 doses (1/2 vial each) administered 6 hours apart. Standard supportive care was provided in all cases. Data were available for 115 patients, 9 of which were fatalities. All patients' clinical condition was documented with a standardized SSS system accounting for each major body system. Each fatality received maximum severity scores of 20. The mean severity score of the 115 patients decreased from 4.19 to 3.29 points and there was no difference between the 2 treatment groups. The mean severity score of the 107 patients without fatalities decreased from 4.16 to 2.15. Antivenin-related acute reactions occurred in 6 dogs (6%), and no serum sickness occurred within the 95 cases contacted at the 2-week posttreatment follow-up. In the first randomized trial in dogs of antivenin in the United States, OPCA effectively stabilized or terminated venom effects. There were no statistical differences detected between treatment groups within the study time frame. © Veterinary Emergency and Critical Care Society 2011.

The Norwegian Cervical Arthroplasty Trial (NORCAT): 2-year clinical outcome after single-level cervical arthroplasty versus fusion-a prospective, single-blinded, randomized, controlled multicenter study.

PubMed

Sundseth, Jarle; Fredriksli, Oddrun Anita; Kolstad, Frode; Johnsen, Lars Gunnar; Pripp, Are Hugo; Andresen, Hege; Myrseth, Erling; Müller, Kay; Nygaard, Øystein P; Zwart, John-Anker

2017-04-01

Standard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion, but the use of arthroplasty, designed to preserve motion, has increased, and most studies report clinical outcome in its favor. Few of these trials, however, blinded the patients. We, therefore, conducted the Norwegian Cervical Arthroplasty Trial, and present 2-year clinical outcome after arthroplasty or fusion. This multicenter trial included 136 patients with single-level cervical disc disease. The patients were randomized to arthroplasty or fusion, and blinded to the treatment modality. The surgical team was blinded to randomization until nerve root decompression was completed. Primary outcome was the self-rated Neck Disability Index. Secondary outcomes were the numeric rating scale for pain and quality of life questionnaires Short Form-36 and EuroQol-5Dimension-3 Level. There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion (P < 0.001), and no observed significant between-group differences at any follow-up times. However, linear mixed model analyses, correcting for baseline values, dropouts and missing data, revealed a difference in Neck Disability Index (P = 0.049), and arm pain (P = 0.027) in favor of fusion at 2 years. The duration of surgery was longer (P < 0.001), and the frequency of reoperations higher (P = 0.029) with arthroplasty. The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up. However, the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty. http://www.clinicaltrials.gov NCT 00735176.19.

Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

PubMed

Davis, Joshua S; Sud, Archana; O'Sullivan, Matthew V N; Robinson, James O; Ferguson, Patricia E; Foo, Hong; van Hal, Sebastiaan J; Ralph, Anna P; Howden, Benjamin P; Binks, Paula M; Kirby, Adrienne; Tong, Steven Y C; Tong, Steven; Davis, Joshua; Binks, Paula; Majumdar, Suman; Ralph, Anna; Baird, Rob; Gordon, Claire; Jeremiah, Cameron; Leung, Grace; Brischetto, Anna; Crowe, Amy; Dakh, Farshid; Whykes, Kelly; Kirkwood, Maria; Sud, Archana; Menon, Mahesh; Somerville, Lucy; Subedi, Shrada; Owen, Shirley; O'Sullivan, Matthew; Liu, Eunice; Zhou, Fei; Robinson, Owen; Coombs, Geoffrey; Ferguson, Patrician; Ralph, Anna; Liu, Eunice; Pollet, Simon; Van Hal, Sebastian; Foo, Hong; Van Hal, Sebastian; Davis, Rebecca

2016-01-15

In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au). © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The Clavicle Trial: A Multicenter Randomized Controlled Trial Comparing Operative with Nonoperative Treatment of Displaced Midshaft Clavicle Fractures.

PubMed

Ahrens, Philip M; Garlick, Nicholas I; Barber, Julie; Tims, Emily M

2017-08-16

The treatment of displaced midshaft clavicle fractures remains controversial. We undertook a multicenter randomized controlled trial to compare effectiveness and safety between nonoperative management and ORIF (open reduction and internal fixation) for displaced midshaft clavicle fractures in adults. Three hundred and one eligible adult patients were randomized to 1 of the 2 treatment groups and followed at 6 weeks, 3 months, and 9 months after recruitment. The primary outcome was the rate of radiographically evident nonunion at 3 months following treatment. Secondary outcomes were the rate of radiographically evident nonunion at 9 months, limb function measured using the Constant-Murley Score and DASH (Disabilities of the Arm, Shoulder and Hand) score, and patient satisfaction. There was no difference in the proportion of patients with radiographic evidence of nonunion at 3 months between the operative (28%) and nonoperative (27%) groups, whereas at 9 months the proportion with nonunion was significantly lower (p < 0.001) in the operative group (0.8%) than in the nonoperative group (11%). The DASH and Constant-Murley scores and patient satisfaction were all significantly better in the operative group than in the nonoperative group at 6 weeks and 3 months. Although at 3 months there was no evidence that surgery had reduced the rate of nonunion of displaced midshaft clavicle fractures, at 9 months nonoperative treatment had led to a significantly higher nonunion rate (11% compared with <1%). The rate of secondary surgical intervention during the trial period was 12 (11%) of the 147 patients in the nonoperative group. ORIF is a safe and reliable intervention with superior early functional outcomes and should be considered for patients who sustain this common injury. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Drug-Coated Balloon Versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease

PubMed Central

Tepe, Gunnar; Schneider, Peter; Brodmann, Marianne; Krishnan, Prakash; Micari, Antonio; Metzger, Christopher; Scheinert, Dierk; Zeller, Thomas; Cohen, David J.; Snead, David B.; Alexander, Beaux; Landini, Mario; Jaff, Michael R.

2015-01-01

Background— Drug-coated balloons (DCBs) have shown promise in improving the outcomes for patients with peripheral artery disease. We compared a paclitaxel-coated balloon with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic superficial femoral and popliteal artery disease. Methods and Results— The IN.PACT SFA Trial is a prospective, multicenter, single-blinded, randomized trial in which 331 patients with intermittent claudication or ischemic rest pain attributable to superficial femoral and popliteal peripheral artery disease were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The primary efficacy end point was primary patency, defined as freedom from restenosis or clinically driven target lesion revascularization at 12 months. Baseline characteristics were similar between the 2 groups. Mean lesion length and the percentage of total occlusions for the DCB and PTA arms were 8.94±4.89 and 8.81±5.12 cm (P=0.82) and 25.8% and 19.5% (P=0.22), respectively. DCB resulted in higher primary patency versus PTA (82.2% versus 52.4%; P<0.001). The rate of clinically driven target lesion revascularization was 2.4% in the DCB arm in comparison with 20.6% in the PTA arm (P<0.001). There was a low rate of vessel thrombosis in both arms (1.4% after DCB and 3.7% after PTA [P=0.10]). There were no device- or procedure-related deaths and no major amputations. Conclusions— In this prospective, multicenter, randomized trial, DCB was superior to PTA and had a favorable safety profile for the treatment of patients with symptomatic femoropopliteal peripheral artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT01175850 and NCT01566461. PMID:25472980

Neurally adjusted ventilatory assist in patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Villar, Jesús; Belda, Javier; Blanco, Jesús; Suarez-Sipmann, Fernando; Añón, José Manuel; Pérez-Méndez, Lina; Ferrando, Carlos; Parrilla, Dácil; Montiel, Raquel; Corpas, Ruth; González-Higueras, Elena; Pestaña, David; Martínez, Domingo; Fernández, Lorena; Soro, Marina; García-Bello, Miguel Angel; Fernández, Rosa Lidia; Kacmarek, Robert M

2016-10-13

Patient-ventilator asynchrony is a common problem in mechanically ventilated patients with acute respiratory failure. It is assumed that asynchronies worsen lung function and prolong the duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory Assist (NAVA) is a novel approach to MV based on neural respiratory center output that is able to trigger, cycle, and regulate the ventilatory cycle. We hypothesized that the use of NAVA compared to conventional lung-protective MV will result in a reduction of the duration of MV. It is further hypothesized that NAVA compared to conventional lung-protective MV will result in a decrease in the length of ICU and hospital stay, and mortality. This is a prospective, multicenter, randomized controlled trial in 306 mechanically ventilated patients with acute respiratory failure from several etiologies. Only patients ventilated for less than 5 days, and who are expected to require prolonged MV for an additional 72 h or more and are able to breathe spontaneously, will be considered for enrollment. Eligible patients will be randomly allocated to two ventilatory arms: (1) conventional lung-protective MV (n = 153) and conventional lung-protective MV with NAVA (n = 153). Primary outcome is the number of ventilator-free days, defined as days alive and free from MV at day 28 after endotracheal intubation. Secondary outcomes are total length of MV, and ICU and hospital mortality. This is the first randomized clinical trial examining, on a multicenter scale, the beneficial effects of NAVA in reducing the dependency on MV of patients with acute respiratory failure. ClinicalTrials.gov website ( NCT01730794 ). Registered on 15 November 2012.

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis

PubMed Central

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Background and Objectives Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. Methods This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. Results There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. Conclusions This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. Clinical Trial Registration: ClinicalTrials.gov (NCT02343003). PMID:29095245

Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials.

PubMed

Nakane, Takahiko; Nakamae, Hirohisa; Yamaguchi, Takuhiro; Kurosawa, Saiko; Okamura, Atsuo; Hidaka, Michihiro; Fuji, Shigeo; Kohno, Akio; Saito, Takeshi; Aoyama, Yasutaka; Hatanaka, Kazuo; Katayama, Yoshio; Yakushijin, Kimikazu; Matsui, Toshimitsu; Yamamori, Motohiro; Takami, Akiyoshi; Hino, Masayuki; Fukuda, Takahiro

2017-04-01

To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7-8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II-IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8-62.5) and 25.8% (90% CI 13.9-39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.

The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

PubMed

Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

2015-11-01

In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein. Copyright © 2015 Elsevier Inc. All rights reserved.

Electroacupuncture versus sham electroacupuncture for urinary retention in poststroke patients: study protocol for a multicenter, randomized controlled trial.

PubMed

Shin, Seungwon; Lee, Jiwon; Yoo, Junghee; Lim, Sung Min; Lee, Euiju

2016-04-12

This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control. A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles. The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors. This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015.

Quantitative quality assurance in a multicenter HARDI clinical trial at 3T.

PubMed

Zhou, Xiaopeng; Sakaie, Ken E; Debbins, Josef P; Kirsch, John E; Tatsuoka, Curtis; Fox, Robert J; Lowe, Mark J

2017-01-01

A phantom-based quality assurance (QA) protocol was developed for a multicenter clinical trial including high angular resolution diffusion imaging (HARDI). A total of 27 3T MR scanners from 2 major manufacturers, GE (Discovery and Signa scanners) and Siemens (Trio and Skyra scanners), were included in this trial. With this protocol, agar phantoms doped to mimic relaxation properties of brain tissue are scanned on a monthly basis, and quantitative procedures are used to detect spiking and to evaluate eddy current and Nyquist ghosting artifacts. In this study, simulations were used to determine alarm thresholds for minimal acceptable signal-to-noise ratio (SNR). Our results showed that spiking artifact was the most frequently observed type of artifact. Overall, Trio scanners exhibited less eddy current distortion than GE scanners, which in turn showed less distortion than Skyra scanners. This difference was mainly caused by the different sequences used on these scanners. The SNR for phantom scans was closely correlated with the SNR from volunteers. Nearly all of the phantom measurements with artifact-free images were above the alarm threshold, suggesting that the scanners are stable longitudinally. Software upgrades and hardware replacement sometimes affected SNR substantially but sometimes did not. In light of these results, it is important to monitor longitudinal SNR with phantom QA to help interpret potential effects on in vivo measurements. Our phantom QA procedure for HARDI scans was successful in tracking scanner performance and detecting unwanted artifacts. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study.

PubMed

Nozue, Tsuyoshi; Fukui, Kazuki; Koyama, Yutaka; Fujii, Hiroyuki; Kunishima, Tomoyuki; Hikita, Hiroyuki; Hibi, Kiyoshi; Miyazawa, Akiyoshi; Michishita, Ichiro

2016-05-01

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

PubMed

Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

2018-02-15

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Quantitative Quality Assurance in a Multicenter HARDI Clinical Trial at 3T

PubMed Central

Zhou, Xiaopeng; Sakaie, Ken E.; Debbins, Josef P.; Kirsch, John E.; Tatsuoka, Curtis; Fox, Robert J.; Lowe, Mark J.

2016-01-01

A phantom-based quality assurance (QA) protocol was developed for a multicenter clinical trial including high angular resolution diffusion imaging (HARDI). A total of 27 3T MR scanners from 2 major manufacturers, GE (Discovery and Signa scanners) and Siemens (Trio and Skyra scanners), were included in this trial. With this protocol, agar phantoms doped to mimic relaxation properties of brain tissue are scanned on a monthly basis, and quantitative procedures are used to detect spiking and to evaluate eddy current and Nyquist ghosting artifacts. In this study, simulations were used to determine alarm thresholds for minimal acceptable signal-to-noise ratio (SNR). Our results showed that spiking artifact was the most frequently observed type of artifact. Overall, Trio scanners exhibited less eddy current distortion than GE scanners, which in turn showed less distortion than Skyra scanners. This difference was mainly caused by the different sequences used on these scanners. The SNR for phantom scans was closely correlated with the SNR from volunteers. Nearly all of the phantom measurements with artifact-free images were above the alarm threshold, suggesting that the scanners are stable longitudinally. Software upgrades and hardware replacement sometimes affected SNR substantially but sometimes did not. In light of these results, it is important to monitor longitudinal SNR with phantom QA to help interpret potential effects on in vivo measurements. Our phantom QA procedure for HARDI scans was successful in tracking scanner performance and detecting unwanted artifacts. PMID:27587227

Prevention of Posttraumatic Contractures with Ketotifen (PERK)

DTIC Science & Technology

2017-10-01

opportunity to design a Phase III RCT on the use of ketotifen in post -traumatic joint contractures. The goal is to design and develop the infrastructure to...Research (CIHR) for the Phase III RCT. 2. KEYWORDS Post -traumatic contractures, elbow fractures, randomized clinical trial, multicenter, ketotifen...application to use ketotifen in post -traumatic joint contracture prevention was submitted to the Division of Pulmonary, Allergy, and Rheumatology

Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

DTIC Science & Technology

2014-05-01

syndrome (MDS) [36-41]. Multiple Phase III trials of tipifarnib monotherapy in acute myeloid leukemia (AML) and in refractory advanced colorectal...cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome . Cancer 2011;117(6):1236-44 42. Harousseau JL...multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome . Blood 2007;109(10):4158

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

DTIC Science & Technology

2008-12-01

PDT is currently in worldwide multicenter clinical trials for the localized prostate cancer therapy. The available results indicate that PDT employing...advanced laser fiber technology and sophisticated light dosimetry is able to treat localized prostate cancer in an effective and safe way. The...combination of photosensitization with current chemotherapy or other new drug therapies will further improve its treatment for the localized prostate

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

DTIC Science & Technology

2007-12-01

anticancer drug effectiveness. PDT is currently in worldwide multicenter clinical trials for the localized prostate cancer therapy. The available results...indicate that PDT employing advanced laser fiber technology and sophisticated light dosimetry is able to treat localized prostate cancer in an...treatment for localized prostate cancer patients that accounts for more than 90% of total prostate cancer population. 15. SUBJECT TERMS Photodynamic

Prevention of Posttraumatic Contractures with Ketotifen (PERK)

DTIC Science & Technology

2016-10-01

the Peer Reviewed Orthopaedic Research Program (PRORP) Clinical Trial Award (CTA), W81XWH-16-PRORP-CTA, was submitted. Database development and Pre...and Safety Months Identify database and partner – Clinical Research Unit 1-2 Completed Develop Case Report Forms, consent forms 6-12 Case...report forms completed, consent forms pending – 80% completed Develop database and multicenter submission process 12-18 In progress, 30% completed

COPD online-rehabilitation versus conventional COPD rehabilitation - rationale and design for a multicenter randomized controlled trial study protocol (CORe trial).

PubMed

Hansen, Henrik; Bieler, Theresa; Beyer, Nina; Godtfredsen, Nina; Kallemose, Thomas; Frølich, Anne

2017-11-16

Rehabilitation of patients with chronic obstructive pulmonary disease (COPD) is a key treatment in COPD. However, despite the existing evidence and a strong recommendation from lung associations worldwide, 50% of patients with COPD decline to participate in COPD rehabilitation program and 30-50% drop-out before completion. The main reasons are severe symptoms, inflexible accessibility and necessity for transportation. Currently there are no well-established and evident rehabilitation alternatives. Supervised online screen rehabilitation could be a useful approach to increase accessibility and compliance. The aim of this multicenter RCT study is to compare the potential benefits of a 10-week online COPD rehabilitation program (CORe) with conventional outpatient COPD rehabilitation (CCRe). This study is a randomized assessor- and statistician blinded superiority multicenter trial with two parallel groups, employing 1:1 allocation to the intervention and the comparison group.On the basis of a sample size calculation, 134 patients with severe or very severe COPD and eligible to conventional hospital based outpatient COPD rehabilitation will be included and randomized from eight different hospitals. The CORe intervention group receives group supervised resistance- and endurance training and patient education, 60 min, three times/week for 10 weeks at home via online-screen. The CCRe comparison group receives group based supervised resistance- and endurance training and patient education, 90 min, two times/week for 10 weeks (two hospitals) or 12 weeks (six hospitals) in groups at the local hospital. The primary outcome is change in the 6-min walking distance after 10/12 weeks; the secondary outcomes are changes in 30 s sit-to-stand chair test, physical activity level, symptoms, anxiety and depression symptoms, disease specific and generic quality of life. Primary endpoint is 10/12 weeks from baseline, while secondary endpoints are 22, 36, 62 weeks from baseline assessments. The study will likely contribute to knowledge regarding COPD tele-rehabilitation and to which extent it is more feasible and thereby more efficient than conventional COPD rehabilitation in patients with severe and very severe COPD. Clinicaltrials.gov Identifier: NCT02667171 . Registration data: January 28th 2016.

Universal Screening for Intimate Partner and Sexual Violence in Trauma Patients - What About the Men? An EAST Multicenter Trial.

PubMed

Zakrison, Tanya L; Rattan, Rishi; Milian Valdés, Davel; Ruiz, Xiomara; Gelbard, Rondi; Cline, John; Turay, David; Luo-Owen, Xian; Namias, Nicholas; George, Jessica; Yeh, Dante; Pust, Daniel; Williams, Brian H

2018-02-14

A recent EAST-supported, multicenter trial demonstrated a similar rate of intimate partner and sexual violence (IPSV) between male and female trauma patients, regardless of mechanism. Our objective was to perform a subgroup analysis of our affected male cohort as this remains an understudied group in the trauma literature. We conducted a recent EAST-supported, cross-sectional, multicenter trial over one year (03/15-04/16) involving four Level I trauma centers throughout the United States. We performed universal screening of adult trauma patients using the validated HITS (Hurt, Insult, Threaten, Scream) and SAVE (sexual violence) screening surveys. Risk factors for male patients were identified. Chi-squared test compared categorical variables with significance at p<0.05. Parametric data is presented as mean +/-standard deviation. A total of 2,034 trauma patients were screened, of which 1,281 (63%) were men. Of this cohort, 119 men (9.3%) screened positive for intimate partner violence, 14.1% for IPSV and 6.5% for sexual violence. On categorical analysis of the HITS screen, the proportion of men that were physically hurt was 4.8% compared to 4.3% for women (p = 0.896). A total of 4.8% of men screened positive for both intimate partner and sexual violence. The total proportion of men who presented with any history of intimate partner violence, sexual violence or both (IPSV) was 15.8%. More men affected by penetrating trauma screened positive for IPSV (p < 0.00001). IPSV positivity in men was associated with mental illness, substance abuse, and trauma recidivism. One out of every twenty men that present to trauma centers is a survivor of both intimate partner and sexual violence, with one out of every six men experiencing some form of violence. Men are at similar risk for physical abuse as women when this intimate partner violence occurs. IPSV is associated with penetrating trauma in men. Support programs for this population may potentially impact associated mental illness, substance abuse, trauma recidivism and even societal-level violence. III STUDY TYPE: Diagnostic.

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

PubMed

van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2017-03-01

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. pain reduction. Secondary outcome measure: Global Perceived Effect. No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basch, Ethan, E-mail: ebasch@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Pugh, Stephanie L.

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visitsmore » when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.« less

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PubMed

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O'Mara, Ann M; Denicoff, Andrea M; Minasian, Lori M; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-06-01

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

PubMed Central

Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

2015-01-01

Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

Appropriate and inappropriate use of dronedarone in 2013.

PubMed

Naccarelli, Gerald V

2013-08-01

Dronedarone is a multichannel blocking antiarrhythmic agent that has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In the ANDROMEDA trial, dronedarone treatment increased mortality and cardiovascular hospitalizations patients with decompensated heart failure. In the ATHENA trial, dronedarone was used in elderly high risk patients with paroxysmal or persistent AF/AFl, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. Dronedarone increased mortality and cardiovascular hospitalizations in a different patient group with permanent AF/AFl. Although organic toxicity from the drug is very rare, post-marketing data has reported rare hepatic toxicity associated with dronedarone use. Current guidelines position dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, dronedarone should not be used in patients with advanced heart failure or in permanent AF. Clinical trial results have helped us define appropriate and inappropriate candidates for dronedarone.

Predictors of Outcome in Conservative and Minimally Invasive Surgical Management of Pain Originating From the Sacroiliac Joint

PubMed Central

Dengler, Julius; Duhon, Bradley; Whang, Peter; Frank, Clay; Glaser, John; Sturesson, Bengt; Garfin, Steven; Cher, Daniel; Rendahl, Aaron; Polly, David

2017-01-01

Study Design. A pooled patient-level analysis of two multicenter randomized controlled trials and one multicenter single-arm prospective trial. Objective. The aim of this study was to identify predictors of outcome of conservative and minimally invasive surgical management of pain originating from the sacroiliac joint (SIJ). Summary of Background Data. Three recently published prospective trials have shown that minimally invasive SIJ fusion (SIJF) using triangular titanium implants produces better outcomes than conservative management for patients with pain originating from the SIJ. Due to limitations in individual trial sample size, analyses of predictors of treatment outcome were not conducted. Methods. We pooled individual patient data from the three trials and used random effects models with multivariate regression analysis to identify predictors for treatment outcome separately for conservative and minimally invasive surgical treatment. Outcome was measured using visual analogue scale (VAS), Oswestry Disability Index (ODI), and EuroQOL-5D (EQ-5D). Results. We included 423 patients assigned to either nonsurgical management (NSM, n = 97) or SIJF (n = 326) between 2013 and 2015. The reduction in SIJ pain was 37.9 points larger [95% confidence interval (95% CI) 32.5–43.4, P < 0.0001] in the SIJF group than in the NSM group. Similarly, the improvement in ODI was 18.3 points larger (95% CI 14.3–22.4), P < 0.0001). In NSM, we found no predictors of outcome. In SIJF, a reduced improvement in outcome was predicted by smoking (P = 0.030), opioid use (P = 0.017), lower patient age (P = 0.008), and lower duration of SIJ pain (P = 0.028). Conclusions. Our results support the view that SIJF leads to better treatment outcome than conservative management of SIJ pain and that a higher margin of improvement can be predicted in nonsmokers, nonopioid users, and patients of increased age and with longer pain duration. Level of Evidence: 1 PMID:28350586

Efficacy of the unified protocol for the treatment of emotional disorders in the Spanish public mental health system using a group format: study protocol for a multicenter, randomized, non-inferiority controlled trial.

PubMed

Osma, Jorge; Suso-Ribera, Carlos; García-Palacios, Azucena; Crespo-Delgado, Elena; Robert-Flor, Cristina; Sánchez-Guerrero, Ana; Ferreres-Galan, Vanesa; Pérez-Ayerra, Luisa; Malea-Fernández, Amparo; Torres-Alfosea, Mª Ángeles

2018-03-12

Emotional disorders, which include both anxiety and depressive disorders, are the most prevalent psychological disorders according to recent epidemiological studies. Consequently, public costs associated with their treatment have become a matter of concern for public health systems, which face long waiting lists. Because of their high prevalence in the population, finding an effective treatment for emotional disorders has become a key goal of today's clinical psychology. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders might serve the aforementioned purpose, as it can be applied to a variety of disorders simultaneously and it can be easily performed in a group format. The study is a multicenter, randomized, non-inferiority controlled clinical trial. Participants will be 220 individuals with emotional disorders, who are randomized to either a treatment as usual (individual cognitive behavioral therapy) or to a Unified Protocol condition in group format. Depression, anxiety, and diagnostic criteria are the primary outcome measures. Secondary measures include the assessment of positive and negative affect, anxiety control, personality traits, overall adjustment, and quality of life. An analysis of treatment satisfaction is also conducted. Assessment points include baseline, post-treatment, and three follow-ups at 3, 6, and 12 months. To control for missing data and possible biases, intention-to-treat and per-protocol analyses will be performed. This is the first randomized, controlled clinical trial to test the effectiveness of a transdiagnostic intervention in a group format for the treatment of emotional disorders in public settings in Spain. Results obtained from this study may have important clinical, social, and economic implications for public mental health settings in Spain. Retrospectively registered at https://clinicaltrials.gov/ . Trial NCT03064477 (March 10, 2017). The trial is active and recruitment is ongoing. Recruitment is expected to finish by January 2020.

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.

Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial).

PubMed

Mandrioli, Jessica; D'Amico, Roberto; Zucchi, Elisabetta; Gessani, Annalisa; Fini, Nicola; Fasano, Antonio; Caponnetto, Claudia; Chiò, Adriano; Dalla Bella, Eleonora; Lunetta, Christian; Mazzini, Letizia; Marinou, Kalliopi; Sorarù, Gianni; de Biasi, Sara; Lo Tartaro, Domenico; Pinti, Marcello; Cossarizza, Andrea

2018-06-01

Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.

Validity, Reliability, and Feasibility of Durometer Measurements of Scleroderma Skin Disease in a Multicenter Treatment Trial

PubMed Central

MERKEL, PETER A.; SILLIMAN, NANCY P.; DENTON, CHRISTOPHER P.; FURST, DANIEL E.; KHANNA, DINESH; EMERY, PAUL; HSU, VIVIEN M.; STREISAND, JAMES B.; POLISSON, RICHARD P.; ÅKESSON, ANITA; COPPOCK, JOHN; van den HOOGEN, FRANK; HERRICK, ARIANE; MAYES, MAUREEN D.; VEALE, DOUGLAS; SEIBOLD, JAMES R.; BLACK, CAROL M.; KORN, JOSEPH H.

2013-01-01

Objective To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma. Methods Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry. Results Forty-three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24–76], median disease duration 6.4 months [range 0.3–23], and median baseline MRSS 22 [range 11–38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82–0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54–0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self-assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self-assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self-assessment. Conclusion Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self-assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma. PMID:18438905

Hartmann's Procedure or Primary Anastomosis for Generalized Peritonitis due to Perforated Diverticulitis: A Prospective Multicenter Randomized Trial (DIVERTI).

PubMed

Bridoux, Valerie; Regimbeau, Jean Marc; Ouaissi, Mehdi; Mathonnet, Muriel; Mauvais, Francois; Houivet, Estelle; Schwarz, Lilian; Mege, Diane; Sielezneff, Igor; Sabbagh, Charles; Tuech, Jean-Jacques

2017-12-01

About 25% of patients with acute diverticulitis require emergency intervention. Currently, most patients with diverticular peritonitis undergo a Hartmann's procedure. Our objective was to assess whether primary anastomosis (PA) with a diverting stoma results in lower mortality rates than Hartmann's procedure (HP) in patients with diverticular peritonitis. We conducted a multicenter randomized controlled trial conducted between June 2008 and May 2012: the DIVERTI (Primary vs Secondary Anastomosis for Hinchey Stage III-IV Diverticulitis) trial. Follow-up duration was up to 18 months. A random sample of 102 eligible participants with purulent or fecal diverticular peritonitis from tertiary care referral centers and associated centers in France were equally randomized to either a PA arm or to an HP arm. Data were analyzed on an intention-to-treat basis. The primary end point was mortality rate at 18 months. Secondary outcomes were postoperative complications, operative time, length of hospital stay, rate of definitive stoma, and morbidity. All 102 patients enrolled were comparable for age (p = 0.4453), sex (p = 0.2347), Hinchey stage III vs IV (p = 0.2347), and Mannheim Peritonitis Index (p = 0.0606). Overall mortality did not differ significantly between HP (7.7%) and PA (4%) (p = 0.4233). Morbidity for both resection and stoma reversal operations were comparable (39% in the HP arm vs 44% in the PA arm; p = 0.4233). At 18 months, 96% of PA patients and 65% of HP patients had a stoma reversal (p = 0.0001). Although mortality was similar in both arms, the rate of stoma reversal was significantly higher in the PA arm. This trial provides additional evidence in favor of PA with diverting ileostomy over HP in patients with diverticular peritonitis. ClinicalTrials.gov Identifier: NCT 00692393. Copyright © 2017. Published by Elsevier Inc.

REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure.

PubMed

Patel, Amit N; Mittal, Sanjay; Turan, Goekmen; Winters, Amalia A; Henry, Timothy D; Ince, Hueseyin; Trehan, Naresh

2015-09-01

Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients. This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery. ©AlphaMed Press.

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

PubMed

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and Management.

PubMed

Cheung, Chui Ming Gemmy; Lai, Timothy Y Y; Ruamviboonsuk, Paisan; Chen, Shih-Jen; Chen, Youxin; Freund, K Bailey; Gomi, Fomi; Koh, Adrian H; Lee, Won-Ki; Wong, Tien Yin

2018-05-01

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Homocysteine and venous thrombosis: outline of a vitamin intervention trial.

PubMed

Willems, H P; den Heijer, M; Bos, G M

2000-01-01

In the past years several case-control studies established the association of an elevated plasma homocysteine concentration and the risk of venous thromboembolism. It is still unclear if elevated homocysteine concentrations can cause venous thrombosis. The VITRO (VItamins and ThROmbosis) trial is the first multicenter, randomized, double-blind and placebo-controlled study to evaluate the effect of homocysteine-lowering therapy by means of 5 mg folic acid, 0.4 mg vitamin B12 and 50 mg vitamin B6. The study is a secondary prevention trial in 600 patients who suffered from a first episode of idiopathic deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. There will be 300 hyperhomocysteinemic and 300 normohomocysteinemic patients included, all with an objectivated venous thrombosis. The end point is recurrence of venous thrombosis.

Medical abortion options may advance in 1998.

PubMed

1997-12-01

The US debut of mifepristone (RU-486) was delayed in 1997 by legal and manufacturer problems. However, the Population Council is searching worldwide for companies to produce mifepristone for the US market. In the meantime, women in a number of US cities can obtain mifepristone through clinical trials coordinated by the New York City-based Abortion Rights Mobilization. The trials are evaluating the effectiveness of a 200 mg dosage of the drug and will continue until there is a commercial product. New developments in medical abortion will be announced in 1998. Currently, 29 Planned Parenthood Federation of America (PPFA) affiliates are recruiting women for its study of methotrexate and misoprostol. By midsummer 1998, the organization expects to have data from what is the largest multicenter trial to date of a methotrexate and misoprostol medical abortion regimen.

CARs: Driving T-cell specificity to enhance anti-tumor immunity

PubMed Central

Kebriaei, Partow; Kelly, Susan S.; Manuri, Pallavi; Jena, Bipulendu; Jackson, Rineka; Shpall, Elizabeth; Champlin, Richard; Cooper, Laurence J. N.

2013-01-01

Adoptive transfer of antigen-specific T cells is a compelling tool to treat cancer. To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens, robust systems for the genetic modification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve the potency of genetically modified T cells. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, antitumor activity, paving the way for multi-center trials to establish the efficacy of this novel T-cell therapy. PMID:22202074

Theoretical study of electron impact triple differential cross sections of N2O by a multicenter distorted-wave method

NASA Astrophysics Data System (ADS)

Gong, Maomao; Li, Xingyu; Zhang, Song Bin; Chen, Xiangjun

2018-05-01

A coplanar asymmetric (e, 2e) measurement on N2O has been reported in 1999 by Cavanagh and Lohmann (1999 J. Phys. B: At. Mol. Opt. Phys. 32 L261), however, the relevant ab initio theoretical study is not available even up to now. In this work, we report theoretical studies of (e, 2e) triple differential cross sections of N2O at the same kinematics using a multicenter distorted-wave method. The influence of the multicenter nature of N2O molecule on the continuum wave function of the ejected electron has been largely considered. The computed results show good agreement with the experimental data for both outer valence 2π and inner valence 4σ orbitals.

Effect of a web-based chronic disease management system on asthma control and health-related quality of life: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Asthma is a prevalent and costly disease resulting in reduced quality of life for a large proportion of individuals. Effective patient self-management is critical for improving health outcomes. However, key aspects of self-management such as self-monitoring of behaviours and symptoms, coupled with regular feedback from the health care team, are rarely addressed or integrated into ongoing care. Health information technology (HIT) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team, and access to their health information, presented in personalized ways that can alert them when there is a need for action. The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system, My Asthma Portal (MAP), linked to a case-management system on asthma control, and asthma health-related quality of life. Methods The trial is a parallel multi-centered 2-arm pilot randomized controlled trial. Participants are randomly assigned to one of two conditions: a) MAP and usual care; or b) usual care alone. Individuals will be included if they are between 18 and 70, have a confirmed asthma diagnosis, and their asthma is classified as not well controlled by their physician. Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug database, and asthma quality of life using the Mini Asthma Related Quality of Life Questionnaire. Power calculations indicated a needed total sample size of 80 subjects. Data are collected at baseline, 3, 6, and 9 months post randomization. Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010. Discussion Self-management support from the care team is critical for improving chronic disease outcomes. Given the high volume of patients and time constraints during clinical visits, primary care physicians have limited time to teach and reinforce use of proven self-management strategies. HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change. Trial Registration Current Controlled Trials ISRCTN34326236. PMID:22168530

Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis: A Systematic Review and Meta-Analysis

PubMed Central

Bdair, Fadi; Akl, Elie A.; Garg, Amit X.; Thiessen-Philbrook, Heather; Salameh, Hassan; Kisra, Sood; Nesrallah, Gihad; Al-Jaishi, Ahmad; Patel, Parth; Patel, Payal; Mustafa, Ahmad A.; Schünemann, Holger J.

2016-01-01

Background and objectives Lowering the dialysate temperature may improve outcomes for patients undergoing chronic hemodialysis. We reviewed the reported benefits and harms of lower temperature dialysis. Design, setting, participants, & measurements We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and Pubmed until April 15, 2015. We reviewed the reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included all randomized, controlled trials that evaluated the effect of reduced temperature dialysis versus standard temperature dialysis in adult patients receiving chronic hemodialysis. We followed the Grading of Recommendations Assessment, Development and Evaluation approach to assess confidence in the estimates of effect (i.e., the quality of evidence). We conducted meta-analyses using random effects models. Results Twenty-six trials were included, consisting of a total of 484 patients. Compared with standard temperature dialysis, reduced temperature dialysis significantly reduced the rate of intradialytic hypotension by 70% (95% confidence interval, 49% to 89%) and significantly increased intradialytic mean arterial pressure by 12 mmHg (95% confidence interval, 8 to 16 mmHg). Symptoms of discomfort occurred 2.95 (95% confidence interval, 0.88 to 9.82) times more often with reduced temperature compared with standard temperature dialysis. The effect on dialysis adequacy was not significantly different, with a Kt/V mean difference of −0.05 (95% confidence interval, −0.09 to 0.01). Small sample sizes, loss to follow-up, and a lack of appropriate blinding in some trials reduced confidence in the estimates of effect. None of the trials reported long-term outcomes. Conclusions In patients receiving chronic hemodialysis, reduced temperature dialysis may reduce the rate of intradialytic hypotension and increase intradialytic mean arterial pressure. High–quality, large, multicenter, randomized trials are needed to determine whether reduced temperature dialysis affects patient mortality and major adverse cardiovascular events. PMID:26712807

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

A Systematic Review of the Use of Bupropion for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.

PubMed

Ng, Qin Xiang

2017-03-01

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders of childhood and adolescence. Stimulants are usually the first choice of drug; however, as many as 20% of patients do not respond to them. Stimulants may also worsen comorbid sleep, mood, and anxiety disorders, and they are associated with problems of misuse and diversion. Bupropion, a dopamine and norepinephrine reuptake inhibitor, is a promising nonstimulant alternative with reports of positive outcomes for ADHD management in both adolescent and adult populations. This study systematically reviews clinical trials on the subject. Using the keywords bupropion or Wellbutrin or Zyban or Elontril and attention deficit hyperactivity disorder or ADHD or ADDH, a preliminary search on the PubMed and Ovid databases yielded 25,455 articles published in English between January 1, 1988 and May 1, 2016. Of these, there were only six articles on clinical trials involving children. Full articles were also reviewed for references of interest. All available open, controlled, and randomized trials demonstrated bupropion's efficacy in improving ADHD symptoms. The three head-to-head trials found that bupropion had efficacy comparable to methylphenidate (p > 0.05). However, a large double-blind, placebo-controlled multicenter study of bupropion found smaller effect sizes for bupropion, as quantified using teacher and parent ratings of ADHD symptoms, than methylphenidate. In terms of tolerability, a head-to-head trial found that headache was observed more frequently in the methylphenidate-treated group than in the bupropion-treated group, whereas the frequency of other side effects did not differ significantly. Current findings should be interpreted with caution because of the very limited database. Bupropion should be considered for pharmacological management of childhood and adolescent ADHD, but more randomized controlled trials with larger sample sizes are warranted. There is also some evidence of its benefits in children with comorbid ADHD and conduct, substance use, or depressive disorders.

Optimizing Radiation Therapy Quality Assurance in Clinical Trials: A TROG 08.03 RAVES Substudy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trada, Yuvnik, E-mail: yuvnik@gmail.com; Kneebone, Andrew; Paneghel, Andrea

2015-12-01

Purpose: To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. Methods and Materials: RAVES (Radiation Therapy–Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol requiredmore » remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. Results: Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P=.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P=.02) and site level (OR 0.72, P=.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P=.05). Conclusion: Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation and clinician experience.« less

An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method

PubMed Central

Asada, Naoya; Fedorov, Dmitri G.; Kitaura, Kazuo; Nakanishi, Isao; Merz, Kenneth M.

2012-01-01

We propose an approach based on the overlapping multicenter ONIOM to evaluate intermolecular interaction energies in large systems and demonstrate its accuracy on several representative systems in the complete basis set limit at the MP2 and CCSD(T) level of theory. In the application to the intermolecular interaction energy between insulin dimer and 4′-hydroxyacetanilide at the MP2/CBS level, we use the fragment molecular orbital method for the calculation of the entire complex assigned to the lowest layer in three-layer ONIOM. The developed method is shown to be efficient and accurate in the evaluation of the protein-ligand interaction energies. PMID:23050059

The Lifestyle Interventions and Independence for Elders Study: design and methods.

PubMed

Fielding, Roger A; Rejeski, W Jack; Blair, Steven; Church, Tim; Espeland, Mark A; Gill, Thomas M; Guralnik, Jack M; Hsu, Fang-Chi; Katula, Jeffrey; King, Abby C; Kritchevsky, Stephen B; McDermott, Mary M; Miller, Michael E; Nayfield, Susan; Newman, Anne B; Williamson, Jeff D; Bonds, Denise; Romashkan, Sergei; Hadley, Evan; Pahor, Marco

2011-11-01

As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years. LIFE's primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness. Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.

Diversity of assessing circulating tumor cells (CTCs) emphasizes need for standardization: a CTC Guide to design and report trials.

PubMed

Bünger, S; Zimmermann, M; Habermann, J K

2015-09-01

Hematogenous spreading of tumor cells from primary tumors is a crucial step in the cascade to metastasis, the latter being the most limiting factor for patients' survival prognosis. Therefore, circulating tumor cells (CTCs) have become a field of intensive research. However, the process of isolation and identification of CTCs lacks standardization. This article presents an overview of 71 CTC studies reported in PUBMED since 2000 and focusing on colorectal cancer. These studies are evaluated regarding standardization of CTC isolation and identification, marker proteins used, study population and blood sample quality management, clinical performance, and quality measures. Overall, standardization of CTC assessment seems insufficient. Thus, comparability of CTC studies is hampered and results should be interpreted carefully. We here propose a standardized CTC guideline (CTC Guide) to prospectively design and report studies/trials in a harmonized form. Despite the current interstudy heterogeneity, the data indicate that CTC detection is of clinical relevance and CTCs should be considered as a surrogate prognostic marker. Many studies indicate the high potential for CTCs as prognostic markers, e.g., in colorectal cancer treatment. However, standardized, large-scale multicenter validation studies are still needed to pave the way for clinical implementation of CTC detection that could ameliorate individualized medicine regimes.

Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

PubMed Central

Tashiro, Jun; Rubio, Gustavo A.; Limper, Andrew H.; Williams, Kurt; Elliot, Sharon J.; Ninou, Ioanna; Aidinis, Vassilis; Tzouvelekis, Argyrios; Glassberg, Marilyn K.

2017-01-01

Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans. PMID:28804709

The Ontario Uterine Fibroid Embolization Trial. Part 1. Baseline patient characteristics, fibroid burden, and impact on life.

PubMed

Pron, Gaylene; Cohen, Marsha; Soucie, Jennifer; Garvin, Greg; Vanderburgh, Leslie; Bell, Stuart

2003-01-01

To determine baseline characteristics of women undergoing uterine artery embolization (UAE) for symptomatic fibroids. Multicenter, prospective, single-arm clinical treatment trial. Eight Ontario university and community hospitals. Five hundred fifty-five women undergoing UAE for fibroids. Baseline questionnaires completed before UAE. Questionnaires were analyzed for demographic, medical, and gynecologic histories. Fibroid symptoms, impact of symptoms, previous consultations, and treatments were also analyzed. The Ontario cohort (66% white, 23% black, 11% other races) had an average age of 43. Thirty-one percent were under age 40. Most women were university educated (68%) and working outside the home (85%). Women reported heavy menstrual bleeding (80%), urinary urgency/frequency (73%), pain during intercourse (41%), and work absences (40%). They experienced fibroid-related symptoms for an average of 5 years and consulted with on average of three gynecologists before UAE. High fibroid life-impact scores were reported by 58%. Black women were significantly younger (40.7 vs. 44.0 years), more likely to experience symptoms longer (7 vs. 5 years), and more likely to undergo myomectomy before UAE (24% vs. 9%) than white women. Our study illustrates that large numbers of women with highly symptomatic fibroid disease are averse to surgery despite their burden of suffering and are actively seeking alternatives to hysterectomy.

Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial.

PubMed

Mannucci, Pier Mannuccio; Kempton, Christine; Millar, Carolyn; Romond, Edward; Shapiro, Amy; Birschmann, Ingvild; Ragni, Margaret V; Gill, Joan Cox; Yee, Thynn Thynn; Klamroth, Robert; Wong, Wing-Yen; Chapman, Miranda; Engl, Werner; Turecek, Peter L; Suiter, Tobias M; Ewenstein, Bruce M

2013-08-01

Safety and pharmacokinetics (PK) of recombinant von Willebrand factor (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII) were investigated in 32 subjects with type 3 or severe type 1 von Willebrand disease (VWD) in a prospective phase 1, multicenter, randomized clinical trial. rVWF was well tolerated and no thrombotic events, inhibitors, or serious adverse events were observed. The PK of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar to those of the comparator plasma-derived (pd) VWF-pdFVIII. In vivo cleavage of ultra-large molecular-weight rVWF multimers by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; the endogenous VWF protease) and generation of characteristic satellite bands were demonstrated. In 2 subjects with specific nonneutralizing anti-VWF-binding antibodies already detectable before rVWF infusion, a reduction in VWF multimers and VWF activity was observed. Stabilization of endogenous FVIII was enhanced following post-rVWF-rFVIII infusion as shown by the difference in area under the plasma concentration curve compared with pdVWF-pdFVIII (AUC0-∞) (P < .01). These data support the concept of administering rVWF alone once a therapeutic level of endogenous FVIII is achieved.

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

PubMed Central

van den Broek, Frank JC; de Graaf, Eelco JR; Dijkgraaf, Marcel GW; Reitsma, Johannes B; Haringsma, Jelle; Timmer, Robin; Weusten, Bas LAM; Gerhards, Michael F; Consten, Esther CJ; Schwartz, Matthijs P; Boom, Maarten J; Derksen, Erik J; Bijnen, A Bart; Davids, Paul HP; Hoff, Christiaan; van Dullemen, Hendrik M; Heine, G Dimitri N; van der Linde, Klaas; Jansen, Jeroen M; Mallant-Hent, Rosalie CH; Breumelhof, Ronald; Geldof, Han; Hardwick, James CH; Doornebosch, Pascal G; Depla, Annekatrien CTM; Ernst, Miranda F; van Munster, Ivo P; de Hingh, Ignace HJT; Schoon, Erik J; Bemelman, Willem A; Fockens, Paul; Dekker, Evelien

2009-01-01

Background Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group. Discussion The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas. Trial registration number (trialregister.nl) NTR1422 PMID:19284647

The Effectiveness of Parent Training as a Treatment for Preschool Attention-Deficit/Hyperactivity Disorder: Study Protocol for a Randomized Controlled, Multicenter Trial of the New Forest Parenting Program in Everyday Clinical Practice

PubMed Central

Daley, David; Frydenberg, Morten; Rask, Charlotte U; Sonuga-Barke, Edmund; Thomsen, Per H

2016-01-01

Background Parent training is recommended as the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD. Objective The objective of this trial is to investigate whether the NFPP can be effectively delivered for children referred through official community pathways in everyday clinical practice. Methods A multicenter randomized controlled parallel arm trial design is employed. There are two treatment arms, NFPP and treatment as usual. NFPP consists of eight individually delivered parenting sessions, where the child attends during three of the sessions. Outcomes are examined at three time points (T1, T2, T3): T1 (baseline), T2 (week 12, post intervention), and T3 (6 month follow/up). 140 children between the ages of 3-7, with a clinical diagnosis of ADHD, informed by the Development and Well Being Assessment, and recruited from three child and adolescent psychiatry departments in Denmark will take part. Randomization is on a 1:1 basis, stratified for age and gender. Results The primary endpoint is change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (ADHD-RS) by T2. Secondary outcome measures include: effects on this measure at T3 and T2 and T3 measures of teacher reported Preschool ADHD-RS scores, parent and teacher rated scores on the Strength & Difficulties Questionnaire, direct observation of ADHD behaviors during Child’s Solo Play, observation of parent-child interaction, parent sense of competence, and family stress. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of nonpharmacological treatments. Conclusions The trial will provide evidence as to whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice. Trial Registration ClinicalTrials.gov NCT01684644; https://clinicaltrials.gov/ct2/show/NCT01684644?term= NCT01684644&rank=1 (Archived by WebCite at http://www.webcitation/6eOOAe8Qe) PMID:27076496

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial.

PubMed

Lacasse, Yves; Bernard, Sarah; Sériès, Frédéric; Nguyen, Van Hung; Bourbeau, Jean; Aaron, Shawn; Maltais, François

2017-01-09

Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT. The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years. The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight. Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).

Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment.

PubMed

Lamunu, D; Chapman, K N; Nsubuga, P; Muzanyi, G; Mulumba, Y; Mugerwa, M A; Goldberg, S; Bozeman, L; Engle, M; Saukkonen, J; Mastranunzio, S; Mayanja-Kizza, H; Johnson, J L

2012-04-01

Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials.

A Multicenter, Randomized Controlled Trial of Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury

DTIC Science & Technology

2017-10-01

PRINCIPAL INVESTIGATOR: Nicholas Theodore, MD CONTRACTING ORGANIZATION: Dignity Health San Francisco, CA 94107-1773 REPORT DATE: October 2017...theodore@jhmi.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dignity Health 8. PERFORMING ORGANIZATION REPORT NUMBER 185...at all three active centers, which include: Barrow Neurological Institute/Dignity Health (the main study site) in Arizona, the University of Arizona

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2014-07-25

Research in Transplantation : Create a platform that facilitates multicenter collaboration and data management. 15. SUBJECT TERMS Research in HLA ...Confirmatory Testing OTTR Organ Transplant Tracking Record CTA Clinical Trial Application P2P Peer-to-Peer PBMC Peripheral Blood Mononuclear Cells...NUMBER Project 1, 2, 3, 4 5f. WORK UNIT NUMBER N/A 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) National Marrow Donor Program 3001

Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis.

PubMed

Crowther, Michael J; Look, Maxime P; Riley, Richard D

2014-09-28

Multilevel mixed effects survival models are used in the analysis of clustered survival data, such as repeated events, multicenter clinical trials, and individual participant data (IPD) meta-analyses, to investigate heterogeneity in baseline risk and covariate effects. In this paper, we extend parametric frailty models including the exponential, Weibull and Gompertz proportional hazards (PH) models and the log logistic, log normal, and generalized gamma accelerated failure time models to allow any number of normally distributed random effects. Furthermore, we extend the flexible parametric survival model of Royston and Parmar, modeled on the log-cumulative hazard scale using restricted cubic splines, to include random effects while also allowing for non-PH (time-dependent effects). Maximum likelihood is used to estimate the models utilizing adaptive or nonadaptive Gauss-Hermite quadrature. The methods are evaluated through simulation studies representing clinically plausible scenarios of a multicenter trial and IPD meta-analysis, showing good performance of the estimation method. The flexible parametric mixed effects model is illustrated using a dataset of patients with kidney disease and repeated times to infection and an IPD meta-analysis of prognostic factor studies in patients with breast cancer. User-friendly Stata software is provided to implement the methods. Copyright © 2014 John Wiley & Sons, Ltd.

A multicenter randomized clinical trial of one-rod etonogestrel and two-rod levonorgestrel contraceptive implants with nonrandomized copper-IUD controls: methodology and insertion data.

PubMed

Meirik, Olav; Brache, Vivian; Orawan, Kiriwat; Habib, Ndema Abu; Schmidt, Johannes; Ortayli, Nuriye; Culwell, Kelly; Jackson, Emily; Ali, Moazzam

2013-01-01

Comparative data on etonogestrel and two-rod levonorgestrel contraceptive implants are lacking. A multicenter, open, parallel-group trial with random allocation of implants was performed. For every second implant user, an age-matched woman choosing an intrauterine device (IUD) (TCu380A) was admitted. Methods and data on implant/IUD insertion and 6-week follow-up are reported. A total of 2008 women were randomized to an implant, and 974 women were enrolled in the IUD group. Results from 997 etonogestrel implant users, 997 levonorgestrel implant users and 971 IUD users were analyzed. In the etonogestrel and levonorgestrel groups, respectively, mean insertion durations were 51 (SD 50.2) s and 88 (SD 60.8) s; complication rates at insertion were 0.8% and 0.2%; and at follow-up, 27.2% and 26.7% of women, respectively, had signs or symptoms at the insertion site. At follow-up within 6 weeks after insertion, all implants were in situ, while 2.1% of IUDs were expelled. Performance of etonogestrel and levonorgestrel implants at insertion and within the first 6 weeks is similar. Short-term (6 weeks) continuation rates appear higher for implants than TCu380A. Copyright © 2013 Elsevier Inc. All rights reserved.