A Trial of Intravascular Hypothermia Therapy in Acute Ischemic Stroke Patients

Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04695236
• Other study ID #: ASPIRE
• Status: Recruiting
• Phase: N/A
• Start date: December 31, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2022
• Source: Xuanwu Hospital, Beijing
• Contact: Liqun Jiao,MD, PhD
• Phone: 13911224991
• Email: liqunjiao[@]sina.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Infarction
• Hypothermia
• Ischemia
• Ischemic Stroke
• Reperfusion Injury
• Stroke
• Thrombectomy

Intervention

Device:
• ZOLL Intravascular Temperature Management system, Quattro catheter
ZOLL Intravascular Temperature Management system, Quattro catheter

Other:
• Standard Treatment
Standard Treatment for Ischemic Strokre

Locations

Country	Name	City	State
China	Xuanwu Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
jiaoliqun

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of any major adverse events		7 days
Primary	Intracranial hemorrhage conversion rate	ICH	7 days after thrombectomy operation or discharge
Secondary	Modified Rankin scale (mRS)	The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death)	90 days
Secondary	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
Secondary	The rate of mortality (mRS 6)	The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death)	90 days
Secondary	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
Secondary	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
Secondary	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
Secondary	Infarct volume	measured on 5-7 days CT (or MRI if available)	5-7 days after thrombectomy operation or discharge