Hypothermia in Acute Stroke With Thrombolysis Imaging Evaluation of Revascularization

Study Overview
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Brief Summary
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The primary objective of this Phase 2 HASTIER study, as an ancillary study to ICTuS 2, is to compare key imaging measurements for serial changes in recanalization and reperfusion between hypothermia and normothermia treatment arms as intermediate outcomes of treatment effect. Secondary exploratory analyses include imaging of the neurovascular impact of reperfusion with hypothermia and tPA, including blood-brain barrier changes or permeability, hemorrhagic transformation, and infarct growth.

Detailed Description
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A prospective imaging ancillary study coincides with recruitment of ICTuS 2 by using currently available imaging tools at a subset of multicenter sites. HASTIER will evaluate therapeutic response with imaging outcome measures for recanalization and reperfusion. Key scientific objectives include the evaluation of hypothermia on benchmark recanalization and reperfusion rates in 120 cases of middle cerebral artery (MCA) stroke. Recanalization will be measured with Thrombolysis in Myocardial Infarction (TIMI) score change from baseline-36 hour CT/MRI angiography. Reperfusion will be measured with Tmax > 6s lesion volume change from baseline-36 hour CT/MRI perfusion imaging. Secondary outcomes will be measured with serial changes in permeability abnormalities derived from CT/MRI perfusion imaging, hemorrhagic transformation, and infarct growth from baseline-36 hours. Correlation of these imaging parameters with clinical outcomes will provide insight to accelerate research during these translational steps in hypothermia treatment for acute ischemic stroke.

Official Title
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An Ancillary Imaging Study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) Trial, an NIH-funded Project on the Safety and Efficacy of Hypothermia Combined With Thrombolysis

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Other: IV t-PA and normothermia
* Device: IV-tPA and hypothermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for inclusion in the ICTuS 2/3 trial. Diagnosis of MCA stroke, confirmed by M1 or M2 proximal MCA occlusion on CT/MRI angiography. Exclusion Criteria: Kidney dysfunction of such severity as to preclude routine administration of contrast media for CT/MRI angiography or perfusion imaging. Severe kidney dysfunction is defined by the American College of Radiology recommendations for use of contrast media. Known adverse reaction or allergy to such contrast media.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 82 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normothermia<br>IV t-PA and normothermia | Other: IV t-PA and normothermia<br> <br> * Other names: t-PA as standard of care and normothermia;|
| Active Comparator: Hypothermia<br>IV t-PA and hypothermia | Device: IV-tPA and hypothermia<br> <br> * Other names: Hypothermia is induced using the Celsius Control™ System and IV-tPA administered;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Recanalization | To determine whether hypothermia alters recanalization with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. The hypothesis is that hypothermia does not impair recanalization (opening of the artery). Recanalization will be measured with Thrombolysis in Myocardial Infarction (TIMI) score change from baseline angiography to 36 hour angiography. TIMI is cored per published definition. Additional data for secondary analyses were not acquired to permit analyses. | 36 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, hypothermia, thrombolysis, imaging, collateral circulation, recanalization, reperfusion