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（由申请人提供）：近期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已证明具有决定性的临床益处。下一个临床任务是确定血管内治疗在较长时间内是否安全有效。此外，如果它是有效的，那么有必要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，该研究表明，了解中风演变的扩散和灌注加权成像评估（DEFUSE）。预先指定的基线磁共振成像 (MRI) 概况可以识别在延长的时间窗口内早期再灌注后具有相当大临床反应的中风患者，DEFUSE 2 通过证明具有良好 MRI 概况的患者在延长的时间范围内实现了早期再灌注，从而前瞻性地验证了 DEFUSE 的结果。血管内治疗在发病后 12 小时内具有明显更好的临床结果；与再灌注相关的良好临床反应的调整优势比为 8*8 (95% CI 2*7-29*0)。 CT 灌注在识别具有可挽救组织的患者方面具有与 MRI 相当的准确性 DEFUSE 3 是一项前瞻性、随机、多中心试验，对象是可在中风发作后 6 至 16 小时内接受治疗的患者。在随机分组之前将接受 MRI 或 CT 灌注扫描。 如果患者有主要血管闭塞的证据，并且 MRI 或 CT 灌注上有可挽救组织的影像学证据，则他们将被随机分组​​。 FDA 批准的血栓切除装置（血管内治疗）与单独标准药物治疗的比例为 1:1 计划对最多 476 名患者（238 名/组）进行随机化，根据基线确定最大的亚组。 DWI 病变体积和中风发病后的时间显示出血管内治疗的积极作用，DEFUSE 3 的结果将确定血管内治疗是否可以改善具有良好临床和影像特征的中风患者的功能结果。增加有资格接受有效治疗的中风患者数量，这可能会导致中风发病率大幅降低。

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。

• 发表时间: 2023-04
• 影响因子: 8.3
• 作者: Stanton, Robert J;Robinson, David J;Aziz, Yasmin N;Sucharew, Heidi;Khatri, Pooja;Broderick, Joseph P;Janis, L Scott;Kemp, Stephanie;Mlynash, Michael;Lansberg, Maarten G;Albers, Gregory W;Saver, Jeffrey L;Flaherty, Matthew L;Adeoye, Opeolu;Wo
• 通讯作者: Wo