Remote Ischemic Conditioning for Reducing Stroke Risk of Symptomatic Vertebrobasilar Lesion of Atherosclerosis

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether remote ischemic conditioning(RIC) would reduce the stroke risk of patients with symptomatic vertebrobasilar lesion of atherosclerosis,then we would observe the haemodynamics and plasma biomarkers changes.

Conditions
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Vertebrobasilar Ischemia

Intervention / Treatment
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* Device: ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with age from 18 to 80 years old. Patients having an ischemic stroke or a TIA within 30 days and with mRS score≤4 prior to randomization. The entry event is attributed to symptomatic atherosclerotic lesion（stenosis is greater than or equal to 50% or occlusion）in vertebrobasilar artery that is documented by magnetic resonance angiography (MRA) or computed tomographic angiography (CTA). Informed consent obtained. Exclusion Criteria: Thrombolytic therapy within 24 hours prior to enrollment. Progressive neurological signs within 24 hours prior to enrollment. Cerebral venous thrombosis/stenosis. vertebrobasilar lesions due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other infection; any artery stenosis associated with cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus. Any of the following unequivocal cardiac source of embolism: rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with the participation. Uncontrolled severe hypertension [sitting systolic blood pressure (SBP) >180 mmHg and/or sitting diastolic blood pressure (DBP) >110 mmHg after medication]. Patients with serious complications or abnormal laboratory parameters: aspartate transaminase (AST) and/or alanine transaminase (ALT) >3×upper limit of normal range; creatinine clearance <0.6 ml/s and/or serum creatinine >265 μmol/l (>3.0 mg/dl); platelets <100×109/L. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural) within 90 days prior to enrollment. Intracranial neoplasm, cerebral aneurysm or arteriovenous malformation. Known retinal hemorrhage or visceral bleeding within 30 days prior to enrollment. Severe hemostatic disorder or severe coagulation dysfunction. Subclavian arterial stenosis≥50% or subclavian steal syndrome. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform one of these procedures within 12 months after enrollment. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within previous 30 days or scheduled in the 6 months after enrollment. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs. Pregnant or breast-feeding women. Unwilling to be followed up or poor compliance for treatment. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIC group<br>Experimental: RIC group The upper limb ischemic conditioning is composed of five cycles of bilateral upper limb ischemia intervened by reperfusion, which is induced by two cuff placed around the upper arms respectively and inflated to 200 mm Hg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. This therapy started within 1 month after stroke. In addition, all participants receive a standard clinical therapy. | Device: ischemic conditioning<br>* In this study, the remote ischemic conditioning treatment was composed of five cycles of bilateral upper limb ischemia intervened by reperfusion, which was induced by two cuff placed around the upper arms respectively and inflated to 200 mm Hg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation.<br>* Other names: Doctormate, IPC-906;|
| No Intervention: Control group<br>The participants receive a standard clinical therapy after diagnosed ischemic stroke. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of ischemic cerebrovascular events with vertebrobasilar responsibility | ischemic cerebrovascular events include ischemic stroke and transient ischemic attack | 0-6 months from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of composite outcomes events | composite outcomes events include Number of ischemic stroke ，transient ischemic attack ，cerebral hemorrhage and mortality | 0-6 months from randomization | 
| Number of participants with adverse events that are related to treatment |  | 0-6 months from randomization | 
| number of participants with mRS 0-1 |  | 0-6 months from randomization | 
| changes of hemodynamics | hemodynamics evaluation by transcranial doppler | 0-6 months from randomization | 
| changes of plasma biomarkers | changes of plasma VEGF and index of thromboelastogramat at the baseline，in the first 3 and 6 months | baseline，3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, Vertebrobasilar atherosclerosis, remote ischemic conditioning