Warfarin vs Aspirin in Reduced Ejection Fraction - STAT

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DESCRIPTION (provided by applicant): WARCEF-STAT and WARCEF-CLIN are two highly coordinated units which together constitute WARCEF, a two-arm (1:1) double-blind randomized multicenter clinical trial. Its primary aim is to test the primary null hypothesis of no difference between warfarin (INR 2.5-3, target 2.75) and aspirin (325 mg/day) therapies in time to the first to occur of death from any cause, ischemic stroke, or symptomatic non-fatal intracerebral hemorrhage (ICH) among patients with low (< 35%) cardiac Left Ventricular Ejection Fraction (LVEF). The main secondary aim is to test the hypothesis of no difference in these therapies in time to the first to occur of death, ischemic stroke, ICH, myocardial infarction (Ml) or heart failure (HF) hospitalization. The operational goals of WARCEF-STAT remain as stated for the first cycle: 1) to conduct, efficiently integrate, and be responsible for all WARCEF data management, double-blinding, medication management, quality control, and reporting operations. 2) to specify, conduct and be responsible for all interim, safety, and final statistical analyses for WARCEF and for the reporting of these results. 3) to transmit to the Clinical Coordinating Center (CCC) in a timely fashion all of the data which the WARCEF-CLIN principal investigator needs to meet his responsibilities in terms of ensuring patient safety and directing all clinical operations. Extensive changes required by expansion to Europe in 2002 have provided the Statistical Analysis Center (SAC) with a much simpler and more efficient organizational structure than at trial start; equipped the trial with a powerful and highly cost-effective, secure, web-based data management system that is uniform across all countries and continents; and greatly improved its data quality and reporting capabilities. The statistical design is retained, with a straightforward extension to address possible continent-by-treatment interactions. The design is powerful. It compares two active medications with a symmetrical two-tailed test. Any of the three possible efficacy outcomes would be clinically important: If warfarin is better, use warfarin. If aspirin is better, use aspirin. If evidence is insufficient to declare either better, use aspirin given its lower cost and easier administration. The trial is thus expected to be clinically decisive if it is completed with satisfactory power. 3201 patients with 2-6 years of follow-up are required for 80% power for the primary aim. As of 8/01/06, 1,242 have been recruited in North America and Europe. Although major efforts to increase recruitment there are under way, given past performance these two continents alone are not likely to reach the goal. Expansion to India is therefore proposed in detail, and shown to be attainable and cost-effective.