Therapeutic Window for Acute Therapy (P50)

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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.