Warfarin vs Aspirin in Reduced Ejection Fraction - STAT

说明(申请人提供)：WARCEF-STAT和WARCEF-CLIN是两个高度协调的单元，共同构成WARCEF，一项双臂(1：1)双盲随机多中心临床试验。它的主要目的是检验华法林(INR 2.5-3，目标2.75)和阿司匹林(325毫克/天)治疗之间没有差异的主要零假设，在心脏左心室射血分数(LVEF)较低(&lt；35%)的患者中，在任何原因导致的死亡、缺血性中风或症状性非致命性脑出血(ICH)首次发生之前的时间。主要的次要目的是检验在死亡、缺血性中风、脑出血、心肌梗死(ML)或心力衰竭(HF)住院的第一次发生之前，这些治疗方法在时间上没有差异的假设。WARCEF-STAT的运营目标保持第一个周期的规定：1)进行、有效地整合并负责WARCEF的所有数据管理、双盲、药物管理、质量控制和报告操作。2)明确、执行和负责WARCEF的所有临时、安全和最终统计分析以及这些结果的报告。3)及时将WARCEF-CLIN首席研究员履行其在确保患者安全和指导所有临床手术方面的职责所需的所有数据传输到临床协调中心(CCC)。2002年扩展到欧洲所需的广泛变化为统计分析中心(统计分析中心)提供了一个比试验开始时简单和高效得多的组织结构；为试验配备了一个强大的、高成本效益的、安全的、基于网络的数据管理系统，该系统在所有国家和各大洲都是统一的；并极大地提高了其数据质量和报告能力。保留了统计设计，并进行了简单的扩展，以解决可能的逐个治疗的相互作用。这个设计很有力量。它用对称的双尾试验比较了两种活性药物。三种可能的疗效结果中的任何一种都具有重要的临床意义：如果华法林效果更好，则使用华法林。如果阿司匹林更好，那就用阿司匹林。如果证据不足以证明这两种药物中的任何一种更好，那么就使用阿司匹林，因为它的成本更低，管理也更容易。因此，如果试验以令人满意的功率完成，则有望在临床上起决定性作用。3201例随访2~6年的患者，以80%的功率为主要目的。截至2006年8月1日，已在北美和欧洲招聘了1242人。尽管在那里增加招聘的重大努力正在进行中，但考虑到过去的表现，仅靠这两个大陆不太可能达到目标。因此，详细地提出了向印度扩张的建议，并证明是可以实现的和具有成本效益的。

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.