Safety and Efficacy of Therapeutic Hypothermia in Acute Ischemic Stroke

Stroke, Ischemic Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05779176
• Other study ID #: RA-2022-180
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: March 2023
• Source: RenJi Hospital
• Contact: Liqun Yang, Ph.D.
• Phone: +8615921969001
• Email: lqyang72721[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 252
• Est. completion date: October 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypothermia
• Ischemia
• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Intervention

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.

Locations

Country	Name	City	State
China	Renji Hospital, Shanghai Jiao Tong University, School of Medicine	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. Erratum In: N Engl J Med 2002 May 30;346(22):1756. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Incidence of intracranial hemorrhage and symptomatic intracranial hemorrhage	Radiological examination(CT or MRI)	24-72 hours post-operation
Secondary	Target vascular recanalization rate	Cerebral angiography	24-72 hours post-operation
Secondary	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
Secondary	Final infarct volume	CT scan	7 days post-operation
Secondary	Death in hospital & within 90 days	Death in 90 days	Within 90 days after admission
Secondary	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
Secondary	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