Role of Hypothermia in Endovascular Stroke Thrombectomy (COOLING)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Procedure: hypothermia; Procedure: thrombectomy

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guangxiong Yuan, M.S.; Phone Number: 18973223018; Email: yuanguangxiong74@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥ 18 years or more;
2. acute ischemic stroke within 24 hours from onset to randomization;
3. NIHSS ≥6 points before randomization;
4. Internal carotid artery, or the middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA/DSA;
5. Baseline ASPECTS score ≥ 3 and ≤8, or cerebral infarction core volume < 100ml;
6. The patient decides to undergo endovascular therapy;
7. The patient or patient's representative signs a written informed consent form.

Exclusion Criteria:

1. CT or MR evidence of hemorrhage;
2. Currently pregnant or lactating (women patients);
3. Allergy to radiographic contrast agents, or nitinol devices;
4. Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel;
5. Multiple vessel occlusion (e.g., bilateral anterior circulation, or occlusion of both anterior and posterior circulation);
6. Preexisting neurological or psychiatric disease that would confound the neurological functional evaluations;
7. Previous bleeding disorders, severe heart, liver or kidney disease, or sepsis;
8. Brain tumors with mass effect (except meningiomas) that are radiographically pleasant;
9. Intracranial aneurysm, arteriovenous malformation;
10. Any terminal illness with life expectancy less than 6 months;
11. Participating in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: Xiangtan Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: October 22, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: randomized controlled trial; hypothermia; large vessel occlusion; endovascular thrombectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Body Temperature Changes; Stroke; Ischemic Stroke; Hypothermia
• Other Study ID Numbers: COOLING

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report, and Analytic Code will be shared after approval of a proposal from principal investigator 3 years after the trial results are revealed.
• IPD Sharing Time Frame: 3 years after the trial results are revealed.
• IPD Sharing Access Criteria: after approval of a proposal from principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No