Warfarin vs Aspirin in Reduced Ejection Fraction - STAT

描述（申请人提供）：WARCEF-STAT和WARCEF-CLIN是两个高度协调的单位，共同组成了WARCEF，一项双组（1：1）双盲随机多中心临床试验。其主要目的是检验华法林（INR 2.5-3，目标2.75）和阿司匹林（325 mg/天）治疗在低（< 35%）心源性左心室射血分数（LVEF）患者中首次发生任何原因死亡、缺血性卒中或症状性非致死性脑出血（ICH）的时间方面无差异的主要零假设。主要次要目的是检验这些治疗在至首次发生死亡、缺血性卒中、ICH、心肌梗死（MI）或心力衰竭（HF）住院治疗的时间方面无差异的假设。WARCEF-STAT的运营目标与第一个周期相同：1）进行、有效整合并负责所有WARCEF数据管理、双盲、药物管理、质量控制和报告操作。2)指定、实施并负责所有针对WARCEF的中期、安全性和最终统计分析以及这些结果的报告。3)及时向临床协调中心（CCC）传输WARCEF-CLIN主要研究者在确保患者安全和指导所有临床操作方面履行职责所需的所有数据。2002年扩展到欧洲所需的广泛变化为统计分析中心（SAC）提供了比试验开始时更简单、更有效的组织结构;为试验配备了强大、高成本效益、安全、基于网络的数据管理系统，该系统在所有国家和大陆都是统一的;并大大提高了其数据质量和报告能力。保留了统计设计，并进行了直接扩展，以解决可能的大陆-治疗相互作用。设计是强大的。它用对称双尾检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临床重要性：如果华法林更好，使用华法林。如果阿司匹林效果更好，请使用阿司匹林。如果没有足够的证据证明这两种药物都更好，可以使用阿司匹林，因为它的成本更低，更容易服用。因此，如果完成试验的把握度令人满意，则预计试验将具有临床决定性意义。需要对3201例患者进行2-6年随访，以达到80%的把握度来实现主要目的。截至2006年1月8日，在北美和欧洲招募了1 242人。虽然正在作出重大努力增加征聘，但鉴于过去的业绩，仅这两个大陆不可能实现这一目标。因此，详细提出了向印度推广的建议，并证明是可以实现的，具有成本效益。

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.