DEFUSE 3: EnDovascular ThErapy Following Imaging EvalUation for ISchemic StrokE 3

 描述(由申请人提供)：最近对中风患者在症状出现后6小时内进行血管内再灌注治疗的四项随机对照试验显示了决定性的临床益处。下一个临床当务之急是确定血管内治疗在延长的时间窗口内是否安全有效。此外，如果它是有效的，至关重要的是确定如何在延长的时间窗口内最佳地选择患者进行血管内治疗。扩散和灌流加权成像评估了解卒中演变研究(FUSE)表明，预先指定的基线磁共振成像(MRI)特征可以在延长的时间窗口内识别早期再灌注后有相当大临床反应的中风患者。FUSE 2前瞻性地验证了FUSE的发现，证明MRI特征良好的患者在血管内治疗后早期再通的患者在发病后12小时内的临床结果显著改善；与再灌注相关的良好临床反应的调整后优势比为8*8(95%可信区间2*7-29*0)。最近的研究表明，在识别有可挽救组织的患者方面，CT灌注成像具有与MRI相当的准确性。FUSE 3是一项针对急性缺血性中风患者的前瞻性、随机、多中心试验，患者可在中风发病后6至16小时内接受治疗。符合纳入标准的患者将在随机分组之前接受MRI或CT灌注扫描。如果患者有大血管闭塞的证据，以及MRI或CT灌注显示可挽救组织的成像证据，他们将被随机分成1：1的比例，接受FDA批准的血栓消融器(血管内治疗)治疗，与单纯标准药物治疗相比。计划将最多476名患者(238名/ARM)随机分组。一种新的适应性设计将根据基线DWI病变体积和卒中起病以来的时间确定最大的亚组，这些亚组显示血管内治疗的积极效果。FUSE 3的结果将决定血管内治疗是否能改善中风患者的功能结果，具有良好的临床和影像特征。这些结果有可能增加有资格接受有效治疗的中风患者的数量，这可能会导致中风发病率的大幅降低。

 DESCRIPTION (provided by applicant): Four recent randomized controlled trials of endovascular reperfusion therapy administered to stroke patients within 6 hours after symptom onset have demonstrated decisive clinical benefits. The next clinical imperative is to determine whether endovascular therapy is safe and effective in an extended time window. In addition, if it is effective, it is essential to determine how to optimally select patients for endovascular therap in extended time windows. The Diffusion and Perfusion Weighted Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE) demonstrated that pre-specified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a sizeable clinical response after early reperfusion in an extended time window. DEFUSE 2 prospectively validated the DEFUSE findings by demonstrating that patients with favorable MRI profiles who achieved early reperfusion after endovascular therapy had significantly better clinical outcomes up to 12 hours after onset; the adjusted odds ratio for favorable clinical response associated with reperfusion was 8*8 (95% CI 2*7-29*0). Recent studies have demonstrated that CT Perfusion has comparable accuracy to MRI for identifying patients with salvageable tissue. DEFUSE 3 is a prospective, randomized, multicenter trial of patients with an acute ischemic stroke who can be treated between 6 and 16 hours of stroke onset. Patients who meet the inclusion criteria will undergo an MRI or CT Perfusion scan prior to randomization. If patients have evidence of a major vessel occlusion and imaging evidence of salvageable tissue on MRI or CT perfusion, they will be randomized in a 1:1 ratio to treatment with an FDA cleared thrombectomy device (endovascular therapy) versus standard medical therapy alone. Randomization of a maximum of 476 patients (238/arm) is planned. A novel adaptive design will identify the largest subgroup, based on baseline DWI lesion volumes and the times since stroke onset, which show a positive effect from endovascular treatment. The results of DEFUSE 3 will determine if endovascular therapy improves functional outcome in stroke patients with favorable clinical and imaging characteristics. These results have the potential to increase the number of stroke patients who are eligible to receive an effective therapy, which could lead to a major reduction in stroke morbidity.