Abstract
Objectives: The study investigated whether the number of participants enrolled per site in an acute heart failure trial is associated with participant characteristics and outcomes. Background: Whether and how site enrollment volume affects clinical trials is not known. Methods: A total of 4,133 participants enrolled among 359 sites were grouped on the basis of total enrollment into 1 to 10, 11 to 30, and >30 participants per site and were compared for outcomes (cardiovascular mortality or heart failure hospitalization). Results: Per-site enrollment ranged from 0 to 75 (median 6; 77 sites had no enrollment). Regional differences in enrollment were noted between North and South America, and Western and Eastern Europe (p < 0.001). Participants from sites with fewer enrollments were more likely to be older and male, have lower ejection fraction and blood pressure as well as worse comorbidity and laboratory profile, and were less likely to be on angiotensin-converting enzyme inhibitors or aldosterone antagonists. During a median follow-up of 9.9 months, 1,700 (41%) participants had an outcome event. Compared to event rate at sites with >30 participants (32%), those with 1 to 10 (51%, hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.56 to 2.02) and 11 to 30 (42%, HR: 1.44, 95% CI: 1.28 to 1.62) participants per site groups had worse outcomes. This relationship was comparable across regions (p = 0.43). After adjustment for risk factors, participants enrolled at sites with fewer enrollees were at higher risk for adverse outcomes (HR: 1.26, 95% CI: 1.08 to 1.46 for 1 to 10; HR: 1.22, 95% CI: 1.07 to 1.38 for 11 to 30 vs. >30 participant sites). Higher proportion of participants from site with >30 participants completed the protocol (45.5% for <10, 61.7% for 11 to 30, and 68.4% for sites enrolling >30 participants; p < 0.001). Conclusions: Baseline characteristics, protocol completion, and outcomes differed significantly among higher versus lower enrolling sites. These data imply that the number of participant enrolled per site may influence trials beyond logistics.
Original language | English (US) |
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Pages (from-to) | 571-579 |
Number of pages | 9 |
Journal | Journal of the American College of Cardiology |
Volume | 61 |
Issue number | 5 |
DOIs | |
State | Published - Feb 5 2013 |
Funding
Dr. Butler has a relationship with Takeda, Gambro, Ono Pharma, Trevena, CardioMEMS, Alere, Bayer, AMGEN, Corthera, and Medtronic. Dr. Fonarow receives research support from the Agency for Healthcare Research and Quality and serves as a consultant for Medtronic and Novartis. Dr. Konstam has received research support and/or served as a consultant for Merck, Otsuka, Johnson & Johnson, Amgen, Novartis, and Cardiokine. Dr. Maggioni receives honoraria from Otsuka. Dr. Mentz has received grants from Medtronic and research funding from Gilead Sciences . Dr. Swedberg receives research grants from AstraZeneca , Servier , and Amgen ; honoraria from AstraZeneca, Otsuka, Servier, and Amgen; and is a consultant for Cytokinetics, Servier, and Novartis. Dr. Zannad has received honoraria from and served on advisory boards for Pfizer Inc. Dr. Gheorghiade has a relationship with Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG, Cardiorentis Ltd, Corthera, Cytokinetics, CytoPherx, Inc., DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, Inc., Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Ono Pharmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, PeriCor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals North America, Inc., and Trevena Therapeutics; and has received support from Bayer Schering Pharma AG, DebioPharm S.A., Medtronic, Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, and Takeda Pharmaceuticals North America, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Keywords
- acute heart failure
- clinical trials
- outcomes assessment
- quality of care
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine