Clinical trial NCT05779176: Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke
Official title: Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy: a Prospective, Randomized, Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Stroke, Ischemic
Keywords: Therapeutic hypothermia, AIS, Neurological function prognosis
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2023-03-22
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-85 years(inclusive);
2. Patients have clinical signs consistent with acute ischemic stroke,
3. Patients with acute large vessel occlusion including internal carotid artery and middle cerebral artery M1 and M2 demonstrated by CTA，MRA or DSA
4. The possibility to receive arterial thrombus removal treatment （within6 or24 hr of large vessel occlusion ）;
5. Provide the informed consent form of the patient or the patient's agent.

Exclusion Criteria:

1. Coma or altered vigilance defined as a score ≥2 on the level of consciousness 1A subscale of the NIHSS.
2. Associated cerebral hemorrhage.
3. There is dysfunction before the onset, mRS score \>= 2 points;
4. Accompanied by severe comorbidities (such as severe cardiopulmonary insufficiency, the expected survival period of advanced malignant tumors is less than 90 days);
5. Multi-mode CT/MRI examination of the corresponding contrast agent use contraindications (such as contrast agent allergy, etc.);
6. Women during pregnancy or lactation;
7. Patients currently participating in other clinical research trials;
8. Other conditions judged by the investigator as not suitable for inclusion in the clinical study.

Primary outcomes:
measure: Neurological function prognosis
timeFrame: 90±14 days post-operation
Secondary outcomes:
measure: Ratio of mRS score 2 or less
timeFrame: 90±14 days post-operation
measure: Incidence of intracranial hemorrhage and symptomatic intracranial hemorrhage
timeFrame: 24-72 hours post-operation
measure: Target vascular recanalization rate
timeFrame: 24-72 hours post-operation
measure: NIHSS score
timeFrame: 7 days post-operation
measure: Final infarct volume
timeFrame: 7 days post-operation
measure: Death in hospital & within 90 days
timeFrame: Within 90 days after admission
measure: The incidence of adverse event
timeFrame: Within 7 days post-operation
measure: Adverse events of hypothermia and rewarming
timeFrame: Within 24 hours post-operation
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University, School of Medicine
Study officials:
affiliation: Renji Hospital, Shanghai Jiao Tong University School of Moedicine
name: Liqun Yang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.