Role of Hypothermia in Endovascular Stroke Thrombectomy

Study Overview
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Brief Summary
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Reducing or suspending the increase of the infarcted core, i.e., freezing the ischemic penumbra, may help improve the efficacy of mechanical thrombectomy. Hypothermia effectively reduces the metabolic level of brain tissue, may prolong the time window for recanalization therapy, and its multi-target therapeutic effect make it one of the most promising neuro-protection approach. In recent years, hypothermia has been increasingly used to treat acute ischemic stroke. However, its role in acute ischemic stroke is unclear. The objective of this trial is to investigate whether hypothermia combined with endovascular thrombectomy could add additional benefit without increasing the risk of adverse events such as pneumonia, intracerebral hemorrhage, and mortality.

Official Title
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Efficacy and Safety of Endovascular Thrombectomy With Versus Without Hypothermia in Acute Large Vessel Occlusion Stroke: a Randomized Controlled Trial

Conditions
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Stroke, Acute Ischemic

Intervention / Treatment
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* Procedure: hypothermia
* Procedure: thrombectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years or more; acute ischemic stroke within 24 hours from onset to randomization; NIHSS ≥6 points before randomization; Internal carotid artery, or the middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA/DSA; Baseline ASPECTS score ≥ 3 and ≤8, or cerebral infarction core volume < 100ml; The patient decides to undergo endovascular therapy; The patient or patient's representative signs a written informed consent form. Exclusion Criteria: CT or MR evidence of hemorrhage; Currently pregnant or lactating (women patients); Allergy to radiographic contrast agents, or nitinol devices; Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel; Multiple vessel occlusion (e.g., bilateral anterior circulation, or occlusion of both anterior and posterior circulation); Preexisting neurological or psychiatric disease that would confound the neurological functional evaluations; Previous bleeding disorders, severe heart, liver or kidney disease, or sepsis; Brain tumors with mass effect (except meningiomas) that are radiographically pleasant; Intracranial aneurysm, arteriovenous malformation; Any terminal illness with life expectancy less than 6 months; Participating in other clinical trials.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypothermia<br>Patients in Hypothermia group received hypothermia combined with endovascular thrombectomy. | Procedure: hypothermia<br>* In this trial, intra-arterial select cooling infusion is used to reduce brain tissue temperature to 33-35°C.<br>Procedure: thrombectomy<br>* Thrombectomy includes treatment with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or the various combinations of these approaches.<br>|
| Active Comparator: Control<br>Patients in Control group received endovascular thrombectomy alone. | Procedure: thrombectomy<br>* Thrombectomy includes treatment with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or the various combinations of these approaches.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin scale score (mRS) | Modified Rankin scale score (mRS): scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death | 90 days post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excellent outcome | Score of 0-1 on the modified Rankin scale | 90 days post-randomization | 
| Functional independence | Score of 0-2 on the modified Rankin scale | 90 days post-randomization | 
| Moderate outcome | Score of 0-3 on the modified Rankin scale | 90 days post-randomization | 
| Early neurological improvement | Compared with baseline NIHSS, the 72h NIHSS score is reduced by 8 points or more, or the 72h NIHSS is 0 1 point | 72 hours post-randomization | 
| EQ-5D-5L scale score | The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. | 90 days post-randomization | 
| Successful reperfusion at final angiogram | Successful reperfusion was defined as grade 2b to 3 on the extended Thrombectomy in the Cerebral Ischemia system. | At the end of angiography or procedure | 
| Difference between baseline and within 48h after procedure of infarction core volume (ml) |  | 48 hours post-randomization | 
| Reperfusion on follow-up CT or MR angiography |  | 48 hours post-randomization | 
| Incidence of symptomatic intracranial hemorrhage (SICH) | using Heidelberg criteria to assess SICH | 48 hours post-randomization | 
| incidence of any intracranial hemorrhage (any ICH) |  | 48 hours post-randomization | 
| 90-day mortality |  | 90 days post-randomization | 
| Difference of hematocrit between baseline and 24-hour post-randomization |  | 24-hour post-randomization | 
| Non-hemorrhagic serious adverse event rate | including pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc. | 90 days post-randomization | 
| Complications related to operation and device | vasospasm, arterial rupture, arterial dissection, vascular puncture point complications, etc. | 90 days post-randomization | 
| Other serious adverse events |  | 90 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endovascular thrombectomy, hypothermia, large vessel occlusion, randomized controlled trial