Safety and Efficacy of Remote Ischemic Conditioning in Patients With Carotid Artery Stenosis Receiving Carotid EndArterectomy

Study Overview
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Brief Summary
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The purpose of this study is to explore the safety and efficacy of remote ischemic conditioning in patients with carotid artery stenosis receiving carotid endarterectomy.

Detailed Description
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In this study, 100 patients with carotid artery stenosis receiving carotid endarterectomy are included in our center in China according to the principle of random, and parallel control. The experimental group receive basic treatment and remote ischemic conditioning for 200mmHg, 2 times per day for 6 consecutive days. The control group receive basic treatment and remote ischemic conditioning control for 60mmHg, 2 times per day for 6 consecutive days. Two groups will be followed up for 90 days to evaluate the safety and efficacy of remote ischemic conditioning in patients with carotid artery stenosis receiving carotid endarterectomy.

Official Title
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Safety and Efficacy of Remote Ischemic Conditioning in Patients With Carotid Artery Stenosis Receiving Carotid EndArterectomy: A Pilot, Randomized Controlled Trial

Conditions
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Carotid Artery Stenosis

Intervention / Treatment
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* Procedure: Remote ischemic conditioning
* Procedure: Sham remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years, <80 years, regardless of sex; Symptomatic or asymptomatic carotid artery stenosis. In symptomatic patients the degree of stenosis should more than 50% (Based on North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET) Criteria), in asymptomatic patients the degree of stenosis should more than 70% (Based on NASCET Criteria); Baseline mRS 0-2; Can cooperate with and complete brain magnetic resonance imaging (MRI) examination; Signed and dated informed consent is obtained; Exclusion Criteria: Evolving stroke; Chronic complete occlusion of the carotid artery without obvious symptoms of cerebral ischemia; Severe dementia; The causes of cardiogenic embolism, such as rheumatic mitral or aortic valve stenosis, artificial heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, left ventricular wall thrombosis or valve tumor, congestive heart failure, bacterial endocarditis, etc; Uncontrolled hypertension (defined as systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg, despite medication taken at enrollment); Severe hepatic and renal dysfunction (defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 times higher than the upper limit of the normal range, creatinine >265umol/l (3mg/dl)); The patients who have the contraindication of remote ischemic conditioning treatment, such as severe soft tissue injury, fracture or vascular injury in the upper limb. Acute or subacute venous thrombosis, arterial occlusive disease, subclavian steal syndrome, etc; Pregnant or lactating women; He/She is participating in other clinical research or has participated in other clinical research or has participated in this study within 3 months prior to admission; Other conditions that the researchers think are not suitable for the group.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIC+CEA+Standard medical treatment<br>Remote ischemic conditioning (RIC) is induced by 5 cycles of 5 min of bilateral upper limbs ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 200 mmHg. RIC will be conducted twice daily for 6 consecutive days after enrollment. Additionally, the patients will be treated with carotid endarterectomy (CEA) and standard medical treatment according to the Chinese guideline for the secondary prevention of ischemic stroke and transient ischemic attack 2022. | Procedure: Remote ischemic conditioning<br>* Remote ischemic conditioning (RIC) is induced by 5 cycles of 5 min of bilateral upper limbs ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg.<br>|
| Placebo Comparator: Sham RIC+CEA+Standard medical treatment<br>Remote ischemic conditioning (RIC) is induced by 5 cycles of 5 min of bilateral upper limbs ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 60 mmHg. RIC will be conducted twice daily for 6 consecutive days after enrollment. Additionally, the patients will be treated with carotid endarterectomy (CEA) and standard medical treatment according to the Chinese guideline for the secondary prevention of ischemic stroke and transient ischemic attack 2022. | Procedure: Sham remote ischemic conditioning<br>* Remote ischemic conditioning (RIC) is induced by 5 cycles of 5 min of bilateral upper limbs ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 60 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who got ≥1 new Diffusion Weighted Imaging (DWI)-positive lesions on post-treatment magnetic resonance imaging (MRI) Scans. | Patients underwent magnetic resonance imaging (including DWI)at baseline and 6 days after randomization. | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of new Diffusion Weighted Imaging (DWI)-positive lesions on post-treatment magnetic resonance imaging (MRI) Scans. | Patients underwent magnetic resonance imaging (including DWI)at baseline and 6 days after randomization. | 6 days | 
| The volume of new Diffusion Weighted Imaging (DWI)-positive lesions on post-treatment magnetic resonance imaging (MRI) Scans. | Patients underwent magnetic resonance imaging(including DWI) at baseline and 6 days after randomization. | 6 days | 
| Number of patients with cerebrovascular events, cardiovascular events or death. | Cerebrovascular events included ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage. Cardiovascular events included angina and myocardial infarction. Death included any reason caused death. | 90±7 days | 
| Proportion of patients with any side effects of Remote ischemic conditioning (RIC) treatment. | The side effects referred to any side effects of RIC or sham RIC treatment, not including the sides effect of medications and Carotid Endarterectomy (CEA). | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischemic conditioning, Carotid artery stenosis, Carotid endarterectomy