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Background: Prior hospitalized heart failure (HF) trials have specified enrollment early after admission. This requirement is intended to capture a particular patient profile, but may be a barrier to efficient trial enrollment and retention. ASTRONAUT was the only phase III hospitalized HF trial with no such requirement, and allows comparison of patients randomized at various points during hospitalization. Methods: The ASTRONAUT trial randomized 1,615 patients hospitalized for HF with ejection fraction ≤40% to long-term use of aliskiren or placebo in addition to standard care. The present analysis compared patient profile, rates of protocol non-completion, and clinical outcomes by quartile of time from hospital admission to randomization. Per protocol, patients could be randomized at any time prior to hospital discharge after ≥6 hours of hemodynamic stability. Results: Median time to enrollment was 5 days (interquartile range [IQR] 3-8 days) and ranged from <1 day to 47 days. Time to enrollment varied by geographic region, with shortest times in North America (median 2 [IQR 2-4] days) and longest times in Eastern Europe (median 6 [IQR 3-9] days) (P <0.01). With few exceptions, baseline patient characteristics were similar by time to randomization quartile (Table). Rates of protocol non-completion were low and comparable across quartiles. There were no significant differences in rates of all-cause mortality or composite of cardiovascular mortality or HF hospitalization at 12 months by time to randomization quartile. Conclusion: In this clinical trial of patients hospitalized for HF, timing of randomization varied by geographic region. Patients randomized early and late during hospitalization had similar baseline characteristics and similar rates of protocol completion and trial endpoints. [ABSTRACT FROM AUTHOR]

Background: Sharing of patient-level clinical trial data has been widely endorsed. Little is known about how extensively these data have been used for cardiometabolic diseases. We sought to evaluate the availability and use of shared data from cardiometabolic clinical trials.Methods: We extracted data from ClinicalStudyDataRequest.com, a large, multisponsor data-sharing platform hosting individual patient-level data from completed studies sponsored by 13 pharmaceutical companies.Results: From January 2013 to May 2017, the platform had data from 3374 clinical trials, of which 537 (16%) evaluated cardiometabolic therapeutics (phase 1, 36%; phase 2, 17%; phase 2/3, 1%; phase 3, 42%; phase 4, 4%). They covered 74 therapies and 398 925 patients. Diabetes mellitus (60%) and hypertension (15%) were the most common study topics. Median time from study completion to data availability was 79 months. As of May 2017, ClinicalStudyDataRequest.com had received 318 submitted proposals, of which 163 had signed data-sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 79 unique studies (15% of all trials, 29% of phase 3/4 trials). Most (96%) data requesters of cardiometabolic clinical trial data were from academic centers in North America and Western Europe, and half the proposals were unfunded. Most proposals were for secondary hypothesis-generating questions, with only 1 proposed reanalysis of the original study primary hypothesis. To date, 3 peer-reviewed articles have been published after a median of 19 months (9-32 months) from the data-sharing agreement.Conclusions: Despite availability of data from >500 cardiometabolic trials in a multisponsor data-sharing platform, only 15% of these trials and 29% of phase 3/4 trials have been accessed by investigators thus far, and a negligible minority of analyses have reached publication. [ABSTRACT FROM AUTHOR]

Background: Efficient conduct of clinical trials is essential for the timely generation of critical medical knowledge., Methods: We systematically assessed size, duration, enrollment rates, and geographic distribution of randomized cardiovascular trials published between 2001 and 2012 in the 8 highest-impact journals in general medicine and cardiology., Results: Of the 1,224 trials, 27.0% were conducted in North America, 36.5% in Western Europe, and 7.7% in other countries, and 28.8% were multiregional. Trials enrolled a median of 452 patients (interquartile range 167-1,530) in 20 sites (2-76). Median duration was 2.1 (1.3-3.3) years, with an estimated enrollment rate of 1.1 (0.5-3.5) patients/site per month. Between 2001-2003 and 2009-2012, the proportion of North American trials decreased from 34.5% to 25.7% (P = .006), whereas that of multiregional trials (from 26.0% to 30.3%; P = .046) and trials conducted in other countries (from 4.6% to 10.3%; P = .012) increased. Over time, trials involved more patients (from 400 to 500 [median]; P = .032) and sites (from 20 to 22; P = .049), multiregional trials involved more countries (from 12 to 18; P = .031), and enrollment rate declined from 1.2 to 0.9 patients/site per month (P = .017). The proportion of trials meeting their primary end point ("positive") decreased from 69% to 57% (P < .001). Trials with higher enrollment rates were more likely to be positive (odds ratio 1.20 per doubling, 95% CI 1.12-1.29), as were industry-sponsored compared with government-sponsored trials (odds ratio 2.62, 95% CI 1.67-4.12)., Conclusions: From 2001 to 2012, cardiovascular clinical trials have become larger, more global, and less likely to meet their primary end point. Enrollment rates have declined, requiring more sites and regions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Translation of evidence-based heart failure (HF) therapies to clinical practice is incomplete and may vary internationally. We examined common measures of quality of care in patients enrolled in the international Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial., Methods and Results: Patients were admitted to 398 hospitals for acute HF in 5 regions (North America, n=3149; Latin America, n=658; Asia Pacific, n=1744; Central Europe, n=966; and Western Europe, n=490). Predefined quality indicators assessed at hospital discharge included the following: medications (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-blockers, aldosterone antagonists, hydralazine/nitrates, statin therapy, and warfarin), use (or planned use) of implantable intracardiac devices, and blood pressure control (<140/90 mm Hg). We determined regional variations in quality indicators as well as the temporal variation of these indicators during the course of the trial. There was significant variation in conformity among different quality indicators, ranging from 0% to 89%. Of all potential performance opportunities, 19 076 of 32 268 (59%) were met, with Central Europe highest at 64%, followed by North America (63%), Western Europe (61%), Latin America (56%), and Asia Pacific (51%; P<0.0001). North America, Central Europe, and Asia Pacific regions demonstrated a modest increase in quality indicator conformity over time, although there was no significant change in other regions., Conclusions: Quality of care for patients hospitalized with acute HF varies and remains suboptimal even within a randomized clinical trial, which included quality improvement interventions. Specific measures designed to improve performance measures should be implemented even within multicenter clinical trials.