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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
3P50NS044148-08S1
Application #
7762017
Study Section
Special Emphasis Panel (ZNS1-SRB-G (37))
Program Officer
Janis, Scott
Project Start
2002-07-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
8
Fiscal Year
2010
Total Cost
$921,728
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Lyden, Patrick; Hemmen, Thomas; Grotta, James et al. (2016) Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2). Stroke 47:2888-2895
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Neil, William P; Raman, Rema; Hemmen, Thomas M et al. (2015) Association of Hispanic ethnicity with acute ischemic stroke care processes and outcomes. Ethn Dis 25:19-23
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Spokoyny, Ilana; Raman, Rema; Ernstrom, Karin et al. (2014) Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen activator-treated patients. J Stroke Cerebrovasc Dis 23:1046-50

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