Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke

Study Overview
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Brief Summary
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Therapeutic hypothermia (TH) in stroke has demonstrated robust neuroprotection in animals especially after ischemia-reperfusion injury, but its safety and efficacy remain controversial. The investigators propose this trial to study the clinical and radiological effects of therapeutic hypothermia in acute ischemic stroke patients treated with intravascular thrombectomy (IVT).

Detailed Description
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The study intervention is therapeutic hypothermia. After intubation, patients assigned to therapeutic hypothermia will receive central venous catheterization through right jugular vein or femoral vein depending on the cooling application and the unique needs, a flexible catheter will be inserted and iced saline will be circulated through the multiple balloons of the catheter in a closed-loop design to induce therapeutic hypothermia. This system also has a hydrophilic coating with heparin and a triple-lumen central venous catheter to satisfy the need of fluid or drug infusion, blood draw and central venous pressure monitoring. After central venous catheterization, patients assigned to TH will receive intravascular temperature management to achieve the target temperature of 34-35 °C, which is superior to surface methods in cooling performance in terms of faster rate of cooling, shorter induced cooling time, precise control during maintenance. Thereafter, hypothermia will be maintained for 24 hrs from the start of hypothermia. The patients will be rewarmed slowly at a rate of no greater than 0.5 °C every 4 h. What's more, patients in TH group will execute anti-shivering protocol during awaking and extubation.

Official Title
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Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy: a Prospective, Randomized, Controlled Clinical Study

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Procedure: Therapeutic hypothermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-85 years(inclusive); Patients have clinical signs consistent with acute ischemic stroke, Patients with acute large vessel occlusion including internal carotid artery and middle cerebral artery M1 and M2 demonstrated by CTA，MRA or DSA The possibility to receive arterial thrombus removal treatment （within6 or24 hr of large vessel occlusion ）; Provide the informed consent form of the patient or the patient's agent. Exclusion Criteria: Coma or altered vigilance defined as a score ≥2 on the level of consciousness 1A subscale of the NIHSS. Associated cerebral hemorrhage. There is dysfunction before the onset, mRS score >= 2 points; Accompanied by severe comorbidities (such as severe cardiopulmonary insufficiency, the expected survival period of advanced malignant tumors is less than 90 days); Multi-mode CT/MRI examination of the corresponding contrast agent use contraindications (such as contrast agent allergy, etc.); Women during pregnancy or lactation; Patients currently participating in other clinical research trials; Other conditions judged by the investigator as not suitable for inclusion in the clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: Safety and efficacy of therapeutic hypothermia in acute ischemic stroke (AIS) patients treated with Intravascular thrombectomy is a prospective, multi-center, randomized, parallel-group interventional study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Normothermia arm<br>Patients randomized to normothermia will be maintained at 36-37°C during the entire study period. | |
| Experimental: Therapeutic hypothermia arm<br>Patients assigned to TH will receive intravascular temperature management to achieve the target temperature of 34-35 °C | Procedure: Therapeutic hypothermia<br>* The study intervention is therapeutic hypothermia. After intubation, patients assigned to therapeutic hypothermia will receive central venous catheterization through right jugular vein or femoral vein depending on the cooling application and the unique needs, a flexible catheter will be inserted and iced saline was circulated through the multiple balloons of the catheter in a closed-loop design to induce therapeutic hypothermia. This system also has a hydrophilic coating with heparin and a triple-lumen central venous catheter to satisfy the need of fluid or drug infusion, blood draw and central venous pressure monitoring. After central venous catheterization, patients assigned to TH will receive intravascular temperature management to achieve the target temperature of 34-35 °C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological function prognosis | the score on the modified Rankin Scale, seven grades ranked from 0 to 6, higher scores mean worse outcome | 90±14 days post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of mRS score 2 or less | the ratio of modified Rankin Scale score 2 or less, modified Rankin Scale has seven grades ranked from 0 to 6, higher scores mean worse outcome | 90±14 days post-operation | 
| Incidence of intracranial hemorrhage and symptomatic intracranial hemorrhage | Radiological examination（CT or MRI） | 24-72 hours post-operation | 
| Target vascular recanalization rate | Cerebral angiography | 24-72 hours post-operation | 
| NIHSS score | The score of National Institute of Health stroke scale, NIHSS score ranked from 0 to 42, higher scores mean a worse neurological outcome | 7 days post-operation | 
| Final infarct volume | CT scan | 7 days post-operation | 
| Death in hospital & within 90 days | Death in 90 days | Within 90 days after admission | 
| The incidence of adverse event | Surgery-related complications: vascular perforation, arterial dissection, and distal embolization；Incidence of pneumonia within 7 days; Incidence of deep vein thrombosis within 7 days | Within 7 days post-operation | 
| Adverse events of hypothermia and rewarming | arrhythmia (atrial fibrillation, ventricular fibrillation), hypokalemia, Chilblains or pressure ulcers; Rewarming shock and hyperkalemia | Within 24 hours post-operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic hypothermia, AIS, Neurological function prognosis