Ischemic Post-conditioning in Acute Ischemic Stroke Thrombectomy (PROTECT-2)

Study Overview
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Brief Summary
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Ischemic post-conditioning is a neuroprotective strategy that has been proven to attenuate reperfusion injury in animal models of stroke. The investigators have conducted a 3 + 3 dose-escalation trial to demonstrate the safety and tolerability of ischemic post-conditioning incrementally for a longer duration of up to 5 min × 4 cycles in stroke patients undergoing mechanical thrombectomy. The purpose of this study is to further determine the efficacy and safety of ischemic post-conditioning in patients with acute ischemic stroke who are treated with mechanical thrombectomy.

Official Title
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Efficacy and Safety of Ischemic Post-conditioning in Patients With Acute Ischemic Stroke After Mechanical Thrombectomy

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Procedure: Mechanical thrombectomy combined with ischemic post-conditioning
* Procedure: Mechanical thrombectomy alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Acute ischemic stroke within 24 hours from stroke onset (or from time last known well) to groin puncture; Previous mRS ≤ 2; Baseline NIHSS ≥ 6; Baseline ASPECTS ≥ 6; With an occlusion of unilateral middle cerebral artery M1 segment/distal intracranial carotid artery; Successful recanalization (mTICI ≥ 2b) after thrombectomy confirmed by DSA; Written informed consent provided by the patients or their legal relatives. Exclusion Criteria: Confirmed or clinically suspected cerebral vasculitis/fibromuscular dysplasia; Difficulty in reaching the designated position of the balloon used for ischemic post-conditioning; Stenting in the middle cerebral artery M1 segment/distal intracranial carotid artery during thrombectomy; > 2 times of balloon dilations as rescue therapy due to angioplasty during thrombectomy; Moderate/severe residual stenosis (≥ 50%) in the offending artery after thrombectomy; Patients with contraindications to MRI; Other conditions that the investigator considered inappropriate for inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ischemic post-conditioning group<br>Mechanical thrombectomy combined with ischemic post-conditioning | Procedure: Mechanical thrombectomy combined with ischemic post-conditioning<br>* Ischemic post-conditioning will be applied after successful recanalization of the culprit artery achieve by thrombectomy. Ischemic post-conditioning consists of briefly repeated 4 cycles × 5 minutes of occlusion and reperfusion (equal duration) of the initially occluded artery using a balloon.<br>|
| Sham Comparator: Control group<br>Mechanical thrombectomy alone | Procedure: Mechanical thrombectomy alone<br>* Successful recanalization was achieved by mechanical thrombectomy without subsequent ischemic post-conditioning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct volume | Infarct volume at 72 hours after procedure | 72 hours after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The progression of infarct volume | Difference of infarct volume between baseline and 72 hours after procedure | Baseline and 72 hours after procedure | 
| The proportion of functional independence | The modified Rankin Scale (mRS) score of 0-2 at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death) | 90 days after procedure | 
| The proportion of favorable outcome | The mRS score of 0-3 at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death) | 90 days after procedure | 
| The distribution of the mRS score | The distribution of the mRS score at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death) | 90 days after procedure | 
| National Institute of Health Stroke Scale (NIHSS) score | NIHSS score at 24 hours after procedure; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits | 24 hours after procedure | 
| The proportion of early neurological improvement | NIHSS 0-2 or ≥8 lower than baseline NIHSS score at 24 hours after procedure; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits | 24 hours after procedure | 
| NIHSS score at 7 days after procedure/discharge | NIHSS score at 7 days after procedure/discharge; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits | 7 days after procedure/discharge | 
| Recanalization rate | Recanalization rate at 24 hours after procedure (mTICI ≥2b) | 24 hours after procedure |