THIS: Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Normothermia arm Patients randomized to normothermia will be maintained at 36-37°C during the entire study period. |
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| Experimental: Therapeutic hypothermia arm Patients assigned to TH will receive intravascular temperature management to achieve the target temperature of 34-35 °C |
Procedure: Therapeutic hypothermia
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.
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Outcome Measures
Primary Outcome Measures
- Neurological function prognosis [90±14 days post-operation]
the score on the modified Rankin Scale, seven grades ranked from 0 to 6, higher scores mean worse outcome
Secondary Outcome Measures
- Ratio of mRS score 2 or less [90±14 days post-operation]
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
- Incidence of intracranial hemorrhage and symptomatic intracranial hemorrhage [24-72 hours post-operation]
Radiological examination（CT or MRI）
- Target vascular recanalization rate [24-72 hours post-operation]
Cerebral angiography
- NIHSS score [7 days post-operation]
The score of National Institute of Health stroke scale, NIHSS score ranked from 0 to 42, higher scores mean a worse neurological outcome
- Final infarct volume [7 days post-operation]
CT scan
- Death in hospital & within 90 days [Within 90 days after admission]
Death in 90 days
- The incidence of adverse event [Within 7 days post-operation]
Surgery-related complications: vascular perforation, arterial dissection, and distal embolization；Incidence of pneumonia within 7 days; Incidence of deep vein thrombosis within 7 days
- Adverse events of hypothermia and rewarming [Within 24 hours post-operation]
arrhythmia (atrial fibrillation, ventricular fibrillation), hypokalemia, Chilblains or pressure ulcers; Rewarming shock and hyperkalemia
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 18-85 years(inclusive);
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Patients have clinical signs consistent with acute ischemic stroke,
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Patients with acute large vessel occlusion including internal carotid artery and middle cerebral artery M1 and M2 demonstrated by CTA，MRA or DSA
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The possibility to receive arterial thrombus removal treatment （within6 or24 hr of large vessel occlusion ）;
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Provide the informed consent form of the patient or the patient's agent.
Exclusion Criteria:
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Coma or altered vigilance defined as a score ≥2 on the level of consciousness 1A subscale of the NIHSS.
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Associated cerebral hemorrhage.
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There is dysfunction before the onset, mRS score >= 2 points;
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Accompanied by severe comorbidities (such as severe cardiopulmonary insufficiency, the expected survival period of advanced malignant tumors is less than 90 days);
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Multi-mode CT/MRI examination of the corresponding contrast agent use contraindications (such as contrast agent allergy, etc.);
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Women during pregnancy or lactation;
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Patients currently participating in other clinical research trials;
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Other conditions judged by the investigator as not suitable for inclusion in the clinical study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Renji Hospital, Shanghai Jiao Tong University, School of Medicine | Shanghai | China | 200127 |
Sponsors and Collaborators
- RenJi Hospital
Investigators
- Principal Investigator: Liqun Yang, Ph.D., Renji Hospital, Shanghai Jiao Tong University School of Moedicine
Study Documents (Full-Text)
None provided.More Information
Publications
- Chio CC, Kuo JR, Hsiao SH, Chang CP, Lin MT. Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats. Shock. 2007 Sep;28(3):284-90. doi: 10.1097/SHK.0b013e3180311e60.
- Feigin VL, Norrving B, Mensah GA. Global Burden of Stroke. Circ Res. 2017 Feb 3;120(3):439-448. doi: 10.1161/CIRCRESAHA.116.308413.
- Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.
- Hynson JM, Sessler DI, Moayeri A, McGuire J. Absence of nonshivering thermogenesis in anesthetized adult humans. Anesthesiology. 1993 Oct;79(4):695-703. doi: 10.1097/00000542-199310000-00010.
- Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. doi: 10.1056/NEJMoa012689. Erratum In: N Engl J Med 2002 May 30;346(22):1756.
- Mendelson SJ, Prabhakaran S. Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review. JAMA. 2021 Mar 16;325(11):1088-1098. doi: 10.1001/jama.2020.26867.
- RA-2022-180