Therapeutic Window for Acute Therapy (P50)

描述（由申请人提供）：血管内冷却治疗卒中2/3试验（ICTuS 2/3）建立在正在进行的ICTuS- l的低温研究轨道上，从证明血管内冷却联合溶栓的可行性和安全性，发展到与Houston SPOTRIAS合作评估血管内诱导急性缺血性卒中患者在3小时内出现的低温的疗效。我们招募了一个咨询委员会，所有人都将参与研究的进展，并修改了研究，在疗效设计中纳入了低温和常温组。ICTuS 2/3是一项明确的3期试验，有1600名接受溶栓治疗的患者随机分为低温组和常温组。该试验将分两个阶段进行，第一阶段是spotrias资助的450名患者的第二阶段研究，然后是R01资助的试验以完成该研究。我们计划将450例2期患者纳入1600例3期样本量。SPOTRIAS第二阶段的目的是确认修订后的方案确实消除了ICTuS-L中出现的肺炎风险升高；静脉注射4ºC生理盐水可以提高降温效果；这种招募可以维持在0.4个患者/地点/月。此外，在400例患者后，将对无效进行正式的中期分析。对450名SPOTRIAS患者的资助将允许我们在无效的中期分析期间继续进行现场活动（入组）。将根据里程碑的实现情况和对无效性的中期分析，作出是否进入第三阶段的决定。我们希望从SPOTRIAS资金到R01资金的无缝过渡，并最终进行1600例血管内低温的关键3期研究。

DESCRIPTION (provided by applicant): The Intravascular Cooling in the Treatment of Stroke 2/3 trial (ICTuS 2/3) builds on the ongoing hypothermia research track of ICTuS-L, evolving from demonstration of the feasibility and safety of intravascular cooling in combination with thrombolysis to collaborative assessment, with Houston SPOTRIAS, of the efficacy of the endovascular induction of hypothermia in acute ischemic stroke patients presenting within the 3-hour window. We recruited an Advisory Committee, all of whom will serve as the study progresses, and revised the study to include hypothermia and normothermia arms in an efficacy design. ICTuS 2/3 is a definitive Phase 3 trial of 1600 patients who receive thrombolysis randomized to hypothermia vs normothermia. The trial will be run in 2 stages, a SPOTRIAS-funded Phase 2 study of 450 patients, followed by an R01 funded trial to complete the study. We plan that the 450 Phase 2 patients will be included in the 1600 sample size for phase 3. The purpose of Phase 2 under SPOTRIAS is to confirm that the revised protocol indeed eliminates the elevated risk of pneumonia seen in ICTuS-L; that intravenous 4¿C saline improves cooling effectiveness; and that recruitment can be sustained at 0.4 patients/site/month. In addition, a formal interim analysis for futility will occur after 400 patients. Funding for 450 patients under SPOTRIAS will allow us to continue site activity (enrollment) during the time of the interim analysis for futility. A go/no-go decision to proceed to Phase 3 will be made based on the achievement of the milestones and the interim analysis for futility. We hope to have a seamless transition from SPOTRIAS funding to R01 funding and end up with a pivotal 1600 patient Phase 3 study of endovascular hypothermia. PUBLIC HEALTH RELEVANCE: Stroke is the leading cause of adult disability in the US. Hypothermia is one of the most promising neuroprotective therapies identified in preclinical studies for stroke. ICTuS 2/3, will investigate the effect of hypothermia on clinical outcome and further delineate safety in combination with thrombolysis. Importantly, we will determine whether hypothermia can be deployed across a wide range of clinical trial sites.