Therapeutic Window for Acute Therapy (P50)

描述(申请人提供)：血管内降温治疗中风2/3试验(ICTUS 2/3)建立在ICTUS-L正在进行的低温研究路线的基础上，从证明血管内降温与溶栓相结合的可行性和安全性发展到与休斯顿SPOTRIAS合作评估在3小时窗口内出现的急性缺血性中风患者血管内诱导低温的有效性。我们招募了一个咨询委员会，随着研究的进展，他们都将担任顾问委员会，并修改了研究，将低温和常温武器纳入疗效设计。Ictus 2/3是一项最终的3期试验，涉及1600名接受溶栓治疗的患者，他们随机分为低温组和常温组。这项试验将分两个阶段进行，这是SPOTRIAS资助的针对450名患者的第二阶段研究，随后是R01资助的试验，以完成研究。我们计划将450名2期患者纳入3期的1,600名样本。SPOTRIAS下2期的目的是确认修订后的方案确实消除了L发作时肺炎的风险增加；静脉注射4C盐水提高了降温效果；以及可以在0.4名患者/站点/月维持招募。此外，在400名患者之后将进行一项关于无效性的正式中期分析。根据SPOTRIAS为450名患者提供的资金将允许我们在对无效性的中期分析期间继续现场活动(登记)。将根据里程碑的实现情况和对无效性的中期分析，作出进行/不进行第三阶段的决定。我们希望从SPOTRIAS资助无缝过渡到R01资助，并最终完成一项关键的1600名患者的血管内低温3期研究。 公共卫生相关性：中风是美国成年人残疾的主要原因。亚低温是中风临床前研究中确定的最有前途的神经保护疗法之一。2/3，将研究低温对临床结果的影响，并进一步描述与溶栓联合应用的安全性。重要的是，我们将确定低温是否可以在广泛的临床试验地点部署。

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.