Multi-arm Optimization of Stroke Thrombolysis (MOST) Stroke Trial

卒中溶栓多臂优化(MOST)卒中试验将是一项双盲多中心试验， 随机对照第三阶段试验，最多1200名受试者。试验将确定成年人(18岁≥ 年)美国国立卫生研究院中风评分为≥6的受试者在症状出现后三小时内接受治疗 Rt-PA联合阿加曲班或依替非那肽在3个月后(MRS)更有可能获得良好的结果，因为 与仅接受标准静脉注射rt-PA的受试者进行比较。所有治疗武器的受试者可以继续进行 临床需要的血管内治疗(ET)。试验的三个方面包括：rt-PA加安慰剂，rt-PA 再加上阿加曲班和rt-PA加依替非那肽。受试者最初以1：1：1的比例随机选择最多150名受试者 已注册。反应自适应随机化将有利于治疗臂看起来最 基于应计数据的有利因素。500名受试者入选后，出现最多的治疗臂(S) 将选择有利的固定随机对照标准治疗。固定的随机化手臂必须 从500名受试者中选出。如果没有干预臂，试验可能会因500名受试者无效而提前停止 似乎比单独使用rt-PA更好(预测概率为20%)。中期分析也将在700和900进行 研究对象。在这些时候，如果没有比rt-PA更好的干预臂，试验可能会因无效而停止 单独(&lt；5%的预测概率)；如果手臂看起来更好，试验可能会提前停止以获得疗效 高于rt-PA(&gt；99%预测概率)。主要的3个月疗效终点由Central执行 调查人员对治疗任务视而不见。其他终点将包括：(1)其他成果衡量标准 包括NIHSS，90天时通过EuroQol EQ-5D测量的生活质量效用)；(2)对 治疗由24小时的NIHSSS 0-2来确定；(3)30天的MRS；(4)治疗的差异 ET对非ET受试者的影响；(5)治疗效果的种族/民族和性别差异。这场审判 将得到三笔NINDS合作协议赠款的支持：(1)给辛辛那提大学NINDS 中风试验网络(NSTN)国家临床协调中心(PI：Joseph P.Broderick，MD)提供 项目和现场管理；(2)至NSTN国家数据管理中心(NDMC) 南卡罗来纳大学(PI：Yuko Y.Palesch博士)提供数据管理和统计专业知识； 和(3)临床领导、现场招聘、研究进行和操作的PI项目(多个PI： Opeolu Adeoye医学博士；Andrew Barreto医学博士；Joseph P.Broderick医学博士；James Grotta医学博士)。

The Multi-arm Optimization of Stroke Thrombolysis (MOST) stroke trial will be a double-blinded multi-center, randomized controlled Phase 3 trial with a maximum of 1200 subjects. The trial will determine if adult (age ≥18 years) subjects with an NIH stroke scale score ≥6 at baseline treated within three hours of symptom onset with rt-PA followed by argatroban or eptifibatide are more likely to have a favorable outcome at 3 months (mRS) as compared to subjects treated with standard IV rt-PA alone. Subjects in all treatment arms may proceed to endovascular therapy (ET) as clinically warranted. The three arms of the trial include: rt-PA plus placebo, rt-PA plus argatroban, and rt-PA plus eptifibatide. Subjects are initially randomized in a 1:1:1 ratio up to 150 subjects enrolled. Response adaptive randomization would then favor the treatment arm that appears to be most favorable based on accrued data. After 500 subjects are enrolled, the treatment arm(s) that appears most favorable will be selected for fixed randomization versus standard treatment. Fixed randomization arms must be selected at 500 subjects. The trial may be stopped early for futility at 500 subjects if no intervention arm appears better than rt-PA alone (<20% predictive probability). Interim analyses will also occur at 700 and 900 subjects. At these times, the trial may be stopped for futility if no intervention arm appears better than rt-PA alone (<5% predictive probability); the trial may be stopped early for efficacy if an arm appears to be better than rt-PA (>99% predictive probability). The primary 3-month efficacy endpoint is performed by central investigators blinded to treatment assignment. Additional endpoints will include: (1) other outcome measures including NIHSS, the quality of life utility as measured via EuroQol EQ-5D at 90 days); (2) early response to treatment as determined by an NIHSSS of 0-2 at 24 hours; (3) mRS at 30 days; (4) differences in treatment effect in ET versus non-ET subjects; and, (5) racial/ethnic and gender differences in treatment effect. The trial will be supported by three NINDS cooperative agreement grants: (1) to the University of Cincinnati NINDS Stroke Trial Network (NSTN) National Clinical Coordinating Center (PI: Joseph P. Broderick, MD) to provide project and site management; (2) to the NSTN National Data Management Center (NDMC) at the Medical University of South Carolina (PI: Yuko Y. Palesch, PhD) to provide data management and statistical expertise; and (3) to the Project PI for clinical leadership, site recruitment and study conduct and operations (Multiple PIs: Opeolu Adeoye, MD; Andrew Barreto, MD; Joseph P. Broderick, MD; James Grotta, MD).