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

DEFUSE 3：缺血性中风影像评估后的血管内治疗 3

• 批准号: 9146680
• 负责人: GREGORY W ALBERS
• 金额: $ 238.31万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9146680
• 关键词: Acute; Blinded; Characteristics; Clinical; Devices; Diffusion; Enrollment; Ensure; Equilibrium; Evolution; Favorable Clinical Outcome; Generations; Goals; Growth; Health; Hour; Image; Image Analysis; Infarction; Internal carotid artery structure; Intravenous; Ischemic Stroke; Lead; Lesion; MRI Scans; Magnetic Resonance Imaging; Mechanics; Medical; Morbidity - disease rate; Multicenter Trials; Odds Ratio; Outcome; Patients; Perfusion; Phase; Population; Randomized; Randomized Controlled Trials; Reperfusion Therapy; Research Personnel; Scanning; Selection Criteria; Site; Specific qualifier value; Stents; Stratification; Stroke; Subgroup; Symptoms; System; Thrombectomy; Time; Tissues; Weight; arm; artery occlusion; base; design; disability; effective therapy; functional outcomes; improved; inclusion criteria; meetings; middle cerebral artery; novel; programs; prospective; response; standard of care; success

 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.

 描述（由适用提供）：在症状发作后6小时内对中风患者施用的血管内再灌注疗法的四项随机对照试验表现出决定性的临床益处。下一个临床命令是确定在延长的时间窗口中血管内治疗是否安全有效。此外，如果有效，必须确定如何在延长时间窗口中最佳选择患者进行血管内治疗。用于理解中风进化研究（DENDUSE）的扩散和灌注加权成像评估表明，预先指定的基线磁共振成像（MRI）曲线可以鉴定出在延长的时间窗口早期再灌注后具有较高临床反应的中风患者。 Duduse 2通过证明有良好的MRI谱的患者在血管内治疗后获得早期再灌注的有利的MRI谱的患者，在发作后长达12小时，其临床结局明显更好。与再灌注有关的有利临床反应的调整后比值比为8*8（95％CI 2*7-29*0）。最近的研究表明，CT灌注的精度与MRI的精度可比，以鉴定可挽救的组织患者。 Duduse 3是一项前瞻性，随机，多中心试验的急性缺血性中风患者，可以在6至16小时的中风发作之间进行治疗。符合纳入标准的患者将在随机物体之前进行MRI或CT灌注扫描。如果患者有主要血管阻塞和成像的证据表明在MRI或CT灌注时可挽救的组织的证据，则与单独使用FDA清除的血栓切除术（血管内治疗）相对于单独的标准医疗疗法，它们将以1：1的比例与1：1的比例随机分配。计划最多476例患者（238臂）随机化。一种新型的自适应设计将基于基线DWI病变体积和中风发作以来的时代确定最大的亚组，从而显示出血管内治疗的积极作用。 Duduse 3的结果将确定血管内治疗是否改善具有良好临床和成像特征的中风患者的功能结果。这些结果有可能增加有资格接受有效疗法的中风患者的数量，这可能会导致中风发病率大大降低。

项目成果

Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study.

使用流行病学数据为临床试验可行性评估提供信息：案例研究。

• DOI: 10.1161/strokeaha.122.041650
• 发表时间: 2023
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Stanton,RobertJ;Robinson,DavidJ;Aziz,YasminN;Sucharew,Heidi;Khatri,Pooja;Broderick,JosephP;Janis,LScott;Kemp,Stephanie;Mlynash,Michael;Lansberg,MaartenG;Albers,GregoryW;Saver,JeffreyL;Flaherty,MatthewL;Adeoye,Opeolu;Wo
• 通讯作者: Wo