A Trial of Intravascular Hypothermia Therapy in Acute Ischemic Stroke Patients

A Prospective, Multicenter, Randomized Clinical Trial to Evaluate the Safety and Efficacy of Intravascular Hypothermia Therapy of Patients With Acute Ischemic Stroke

Acute ischemic stroke (AIS) has been one of the major causes of global mortality and morbidity. The superiority of endovascular therapy (EVT) over standard medical therapy in treating AIS due to large vessel occlusion (LVO) in the anterior circulation has been widely accepted. However, a critical concern is that even with an extremely high rate of successful recanalization (the modified thrombolysis in cerebral infarction [mTICI] score 2b-3) around 90%, nearly half of the patients failed to benefit from EVT. So, adjunctive therapy of EVT for neuroprotection is required.

From the previous domestic and foreign literatures, hypothermia can prevent and treat secondary injury caused by ischemia-reperfusion injury and cerebral edema of acute cerebral ischemia, so as to achieve the role of neuroprotection. In this study, intravascular cooling was performed as soon as possible with careful temperature control in patients receiving thrombectomy. The temperature was controlled at 33° C for 48-72 hours. This parallel controlled study is to systematically evaluate the feasibility and safety of adjunctive therapy using early intravascular hypothermia in AIS patients receiving mechanical thrombectomy. The results will clarify a potential modality for neuroprotection and hopefully provide new evidence in improving patient prognosis.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Reperfusion Injury; Hypothermia; Thrombectomy
• Intervention / Treatment: Device: ZOLL Intravascular Temperature Management system, Quattro catheter; Other: Standard Treatment

Detailed Description

In this study, the target subjects were AIS patients with successful recanalization (mTICI 2b-3). Early intravascular hypothermia neuroprotection therapy was given to patients after thrombectomy to evaluate its safety and effectiveness. The neuroprotection effect of endovascular hypothermia therapy is explored regarding several aspects, such as hemorrhagic conversion rate, cerebral edema, and neurological function recovery, with specific evaluation criteria described in detail in the following experimental design.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liqun Jiao,MD, PhD; Phone Number: 13911224991; Email: liqunjiao@sina.cn
• Study Contact Backup: Name: Xin Qu,MD

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Xuanwu Hospital
    • Contact: Liqun Jiao,MD, Phd; Phone Number: 86-10-83199060; Email: liqunjiao@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 and 80 years old
2. Clinical signs consistent with acute ischemic stroke with large vessel occlusion in the anterior circulation (internal carotid artery, middle cerebral artery M1 or M2 segment)
3. ASPECTS score 0-10
4. Arterial puncture could be performed within 24 hours from symptom onset or LKN
5. Baseline NIHSS (NIHSS) score prior to randomization ≥ 10 and NIHSS 1a ≥ 1
6. Candidate for endovascular thrombectomy therapy in accordance with best practices per AHA standard stroke guidelines meeting all labeling requirements for EVT in the trial
7. Successful recanalization of occluded vessel (mTICI 2b-3) after EVT
8. No intracranial hemorrhage postoperative CT examinations immediately after recanalization. If the subject' recanalization of vessel could not achieve mTICI 2b-3, the subject could not enter the per-protocol analysis and will separate another group
9. Informed consent form signed by subjects or their legal guardian

Exclusion Criteria:

1. Subject who suffer serious infection (e.g. sepsis) or multiple organ failure
2. Known presence of an IVC filter
3. End stage renal disease on hemodialysis
4. Known hypersensitivity to antiplatelet agents, anticoagulation drugs, iodinated contrast and/or anesthetics
5. Known hypersensitivity to the components of the medical device
6. Any known history of the following conditions: bleeding diathesis, coagulopathy, cryoglobulinemia, sickle cell anemia, will refuse blood transfusions or contraindication to heparin; history of genetically confirmed hypercoagulable syndrome
7. Use of warfarin with INR > 3
8. Hemodynamically significant cardiac dysrhythmias (eg. QTc interval >450 msec, bradycardia (heart rate less than 50), Mobitz Type II second degree AV block (or higher AV block), and severe ventricular dysrhythmias (sustained VT or VF)) which cause significant hypotension (SBP ≤ 120 mmHg requiring more than two pressor medications)
9. Platelet count<40×10^9/L
10. Blood glucose concentration <2.7 or > 22.2 mmol/L
11. Hypertension uncontrollable by drug treatment (systolic blood pressure≥185 mmHg or diastolic blood pressure≥110mmhg)
12. Expected life expectancy<6 months
13. Temperature < 35°C on admission to Emergency Department
14. With a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations (e.g., dementia or mental illness)
15. Subject participating in a study involving an investigational drug or device that would impact the current study
16. Baseline CT/MR evidence of multiple vascular territory acute stroke
17. Baseline CT/MR showing evidence of arterial vasculitis or dissection
18. Evidence of intracranial hemorrhage or hemorrhagic transformation before thrombectomy
19. Evidence of intracranial hemorrhage or hemorrhagic transformation immediately after thrombectomy
20. Presence of pulmonary embolism, ilio-femoral or deep vein thrombosis
21. Brain vascular lesion (e.g. aneurysm or arteriovenous malformation)
22. Brain tumor or CNS infection
23. Concurrent participation in a study involving an investigational drug or device that would impact the current study
24. Female patient of childbearing potential who is known to be pregnant or lactating
25. For other reasons, the researchers believe that the patient is not suitable for continued treatment
26. Patients without a legally authorized representative to sign the consent form will be excluded

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Study Group: Intravascular hypothermia therapy group ZOLL Intravascular Temperature Management system, Quattro catheter will be used in study group	Device: ZOLL Intravascular Temperature Management system, Quattro catheter; ZOLL Intravascular Temperature Management system, Quattro catheter
Placebo Comparator: Control group; Control group: Without intravascular hypothermia therapy group ZOLL Intravascular Temperature Management system, Quattro catheter will not be used in control group	Other: Standard Treatment; Standard Treatment for Ischemic Strokre

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial hemorrhage conversion rate	ICH	7 days after thrombectomy operation or discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin scale (mRS)	The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death)	90 days
The rate of functional independency (mRS 0-2)	The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death)	90 days
The rate of mortality (mRS 6)	The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death)	90 days
NIHSS	Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits.	24 hours, 7 days or discharge
Rate of symptomatic intracranial hemorrhage (sICH)	The diagnosis of sICH was based on the association of ICH with any of the following. conditions: (1) Increase in NIHSS score > 4 points compared to the score before ICH; (2) Increase in NIHSS score by >2 points in one category; (3) deterioration leading to intubation, hemicraniectomy, external ventricular drain placement, or any other major interventions.	7 days after thrombectomy operation or discharge
Rate of malignant cerebral edema	Development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift >= 5 mm on follow-up imaging.	7 days after thrombectomy operation or discharge
Infarct volume	measured on 5-7 days CT (or MRI if available)	5-7 days after thrombectomy operation or discharge

Other Outcome Measures

Outcome Measure	Time Frame
Rate of any major adverse events	7 days

Collaborators and Investigators

• Sponsor: jiaoliqun
• Investigators: Principal Investigator: Liqun Jiao,MD, PhD, Department of Neurosurgery & Interventional Neuroradiology Xuanwu Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: January 1, 2021
• First Submitted That Met QC Criteria: January 1, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Postoperative Complications; Brain Ischemia; Infarction; Brain Infarction; Body Temperature Changes; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Reperfusion Injury; Hypothermia
• Other Study ID Numbers: ASPIRE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No