To Assess the Effectiveness and Safety of Catheter-based Focal Intracranial Hypothermia Combined with Endovascular Reperfusion Therapy for Patients with Acute Anterior Circulation Large Artery Occlusion (CHILL-ART)

Local Hypothermia and Endovascular Recanalization for Acute Large Artery Occlusive Stroke-A Multicenter, Prospective, Open-label, Blinded-Endpoint, Randomized Controlled Trial

A multicenter, prospective, open-label, blinded-endpoint, randomized controlled trial to assess the effectiveness and safety of catheter-based focal intracranial hypothermia combined with endovascular reperfusion therapy for patients with acute anterior circulation large artery occlusion.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke; Acute Cerebrovascular Accident; Middle Cerebral Artery Occlusion; Internal Carotid Artery
• Intervention / Treatment: Procedure: Mechanical thrombectomy; Drug: 4°C saline infusion; Drug: Normothermic saline infusion

Detailed Description

This trial aims to assess the effectiveness and safety of catheter-based focal intracranial hypothermia combined with endovascular reperfusion therapy for patients with acute anterior circulation large artery occlusion. This study used a stratified randomization method, with participants randomly allocated in a 1:1 ratio by a central network randomization system to either the mechanical thrombectomy (MT) combined with arterial selective cooling infusion (intravenous recombinant tissue plasminogen activator) (hypothermia) group or the MT combined with normal saline infusion (normothermia) group (hereinafter referred to as the hypothermia group or normothermia group). Randomization was stratified by ASPECTS score (≥8 or <8) and age (≥75 years or <75 years).

• Study Type: Interventional
• Enrollment (Estimated): 262
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhixin Huang, PhD; Phone Number: 8613607548156; Email: hzxd6@163.com
• Study Contact Backup: Name: Wen Sun, PhD; Phone Number: 8615050589620; Email: sunwen_medneuro@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510317
      • Recruiting
      • Guangdong Second Provincial General Hospital
      • Contact: Zhixin Huang, PhD; Phone Number: 8613607548156; Email: hzxd6@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 and ≤85 years old.
2. Symptoms of sudden focal or general neurological impairment.
3. There may be a causal relationship between vascular occlusion and nerve function defect.
4. Time from symptom onset to randomization ≤24h.
5. The National Institutes of Health Stroke Scale (NIHSS) score was ≥6 points before randomization.
6. According to the judgment of the clinician, the operation path is reasonable, and the operation and operation related instruments can reach the disease smoothly.
7. Patients or their guardians can understand the purpose of the trial, voluntarily participate and sign a written informed consent, and are capable of receiving clinical follow-up.
8. Prior to randomization, CTA, MRA, or DSA confirmed the presence of anterior circulatory large vessel occlusion (internal carotid artery or M1segment).
9. The symptoms are aggravated by recurrent cerebral infarction in the same drainage basin and/or the pathogenesis is caused by decreased blood perfusion.

Exclusion Criteria:

1. Pre stroke mRS>1 score.
2. There are acute infarcts in both cerebral hemispheres and/or anterior and posterior circulation.
3. NIHSS≤6 points.
4. Cerebral hemorrhage/subarachnoid hemorrhage was confirmed by CT or MRI. 5.The presence of active bleeding, severe anemia, coagulation dysfunction, or an uncorrected bleeding tendency (Presence of at least one of the following laboratory tests: hemoglobin < 10g /dl, platelet count < 100,000 /μl, uncorrected INR>1.5, PT> 1 minute above the upper limit of normal, or heparin-related thrombocytopenia).

6.Patients with heart function of grade 1 or above, or with a clear history of acute or chronic heart dysfunction, are at greater risk of acute heart failure or fluid perfusion intolerance as determined by clinicians.

7. Severe heart, liver, kidney disease. 8.With malignant diseases such as malignant tumors, the expected survival time is less than 3 months.

9.Participating in other clinical trials, in the investigational phase or in the follow-up phase.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mechanical thrombectomy combined with intra-arterial selective cooling infusion (hypothermia) group; Patients received a total of 350 ml of 4°C saline infusion in addition to mechanical thrombectomy (MT).	Procedure: Mechanical thrombectomy; Mechanical thrombectomy; Drug: 4°C saline infusion; Patients received a total of 350 ml of 4°C saline infusion in addition to mechanical thrombectomy (MT).
Active Comparator: Mechanical thrombectomy combined with normothermic saline infusion (normothermia) group; Patients received a total of 350 ml of roomtemperature saline infusion in addition to mechanical thrombectomy (MT).	Procedure: Mechanical thrombectomy; Mechanical thrombectomy; Drug: Normothermic saline infusion; Patients received a total of 350 ml of roomtemperature saline infusion in addition to mechanical thrombectomy (MT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with modified Rankin Score 0-2 at 90 days.	The modified Rankin Score is an ordinal hierarchical scale ranging from 0 to 6, with higher scores indicating more severe disability.	90 days after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with modified Rankin Score 0-1 at 90 days	The modified Rankin Score is an ordinal hierarchical scale ranging from 0 to 6, with higher scores indicating more severe disability.	90 days after procedure
Successful reperfusion rate	Successful reperfusion was indicated by modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b or 3.	At the end of the operation
Cerebral infarction volume was measured by CT or magnetic resonance DWI 72 hours to 7 days after operation	Cerebral infarction volume was measured by CT or DWI 72 hours to 7 days after operation.	72 hours to 7 days after procedure
Incidence of early neurological deterioration	Early neurological deterioration was defined as an increase of 4 or more points on the NIHSS within 24 hours that was not attributable to intracerebral hemorrhage.	Within 24 hours after procedure
Rate of recurrent occlusion on MRA or CTA (postoperative 24 Hours to 7 Days)	Recurrent occlusion was measured by MRA or CTA 24 hours to 7 days after operation.	postoperative 24 Hours to 7 Days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of symptomatic intracranial hemorrhage within 72 hours (Heidelberg Bleeding Classification)	Intracranial hemorrhage (ICH) was assessed with the Heidelberg Bleeding Classification within 72 hours of endovascular treatment. Intracranial hemorrhage was classified as hemorrhagic infarction or parenchymal hematoma. The sICH was defined as ICH associated with a worsening of 4 or more points on the NIHSS or resulting in death, and cerebral herniation, which were not present at baseline.	Within 72 hours after procedure
Rate of coagulation disorders	Rate of coagulation disorders within 7 days	7 days

Collaborators and Investigators

• Sponsor: Guangdong Second Provincial General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 27, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemia; Intracranial Arterial Diseases; Body Temperature Changes; Cerebral Arterial Diseases; Cerebral Infarction; Ischemic Stroke; Stroke; Hypothermia; Infarction, Middle Cerebral Artery
• Other Study ID Numbers: CHILL-ART

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No