Clinical trial NCT04695236: A Trial of Intravascular Hypothermia Therapy in Acute Ischemic Stroke Patients
Official title: A Prospective, Multicenter, Randomized Clinical Trial to Evaluate the Safety and Efficacy of Intravascular Hypothermia Therapy of Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypothermia
Reperfusion Injury
Ischemic Stroke
Thrombectomy
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2021-01-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intracranial hemorrhage conversion rate
timeFrame: 7 days after thrombectomy operation or discharge
Secondary outcomes:
measure: Modified Rankin scale (mRS)
timeFrame: 90 days
measure: The rate of functional independency (mRS 0-2)
timeFrame: 90 days
measure: The rate of mortality (mRS 6)
timeFrame: 90 days
measure: NIHSS
timeFrame: 24 hours, 7 days or discharge
measure: Rate of symptomatic intracranial hemorrhage (sICH)
timeFrame: 7 days after thrombectomy operation or discharge
measure: Rate of malignant cerebral edema
timeFrame: 7 days after thrombectomy operation or discharge
measure: Infarct volume
timeFrame: 5-7 days after thrombectomy operation or discharge
Other outcomes:
measure: Rate of any major adverse events
timeFrame: 7 days
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital
Study officials:
affiliation: Department of Neurosurgery & Interventional Neuroradiology Xuanwu Hospital
name: Liqun Jiao,MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: