Study on Prevention and Treatment of Atherosclerotic Cerebral Occlusive Disease With Remote Ischemic Conditioning

The primary objective of the study will be to determine whether remote limb ischemic conditioning (RLIC) together with conventional medication therapy compared with only medication therapy reduces the 3-month risk of composite cardio-cerebral vascular event in patients with a recent TIA or IS caused by occlusion of a cerebral artery.

After screening period, eligible patients will be randomly allocated into 2 groups.In addition, all participants receive an usual clinical therapy.

Study Overview

• Status: Unknown
• Conditions: Cerebral Atherosclerosis
• Intervention / Treatment: Combination product: Doctormate®+Medical Management; Drug: Medical Management

Detailed Description

In this study, Patients in the RLIC group will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) twice daily and conventional medication; patients in the control group will be treated only with conventional medication. In the study, the RLIC treatment will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation.

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female with age from 40 to 80 years old.
2. Patients with cerebral arterial occlusion which have been confirmed by CTA, MRA, or other evidence (including intracranial and extracranial arterial occlusion), and there is no indication of intervention and surgery, and at the same time the patients combined more than two risk factors for atherosclerosis.
3. The entry event is acute ischemic cerebrovascular disease (TIA or cerebral infarction), of which the condition was relatively stable within 30 days of onset, and mRS≤4.
4. Informed consent obtained.

Exclusion Criteria:

1. Thrombolytic therapy within 24 hours prior to enrollment.
2. Progressive neurological signs within 24 hours prior to enrollment.
3. Cerebral venous thrombosis/stenosis.
4. Intracranial arterial occlusion due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial 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.
5. 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.
6. Uncontrolled severe hypertension [sitting systolic blood pressure (SBP) >180 mmHg and/or sitting diastolic blood pressure (DBP) >110 mmHg after medication].
7. Patients with 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.
8. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural) within 90 days prior to enrollment.
9. Intracranial neoplasm, cerebral aneurysm or arteriovenous malformation.
10. Known retinal hemorrhage or visceral bleeding within 30 days prior to enrollment.
11. Severe hemostatic disorder or severe coagulation dysfunction.
12. Subclavian arterial stenosis≥50% or subclavian steal syndrome.
13. Extracranial stenosis ≥50%.
14. 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.
15. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within previous 30 days or scheduled in the 12 months after enrollment.
16. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
17. Life expectancy<3 years.
18. Pregnant or breast-feeding women.
19. Unwilling to be followed up or poor compliance for treatment.
20. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial.
21. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Control	Drug: Medical Management; Patients will be treated with conventional medication for 3 months.
EXPERIMENTAL: Experiment	Combination product: Doctormate®+Medical Management; Patients will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) twice daily and conventional medication for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
3-month composite cardio-cerebral vascular event rate	During the first 3 months from randomization.

Secondary Outcome Measures

Outcome Measure	Time Frame
Recurrence of TIA or infarction rate in the area of responsible vessel domination within 3 months	During the first 3 months from randomization.
Changes in National Institutes of Health Stroke Scale(NIHSS) within 3 months	During the first 3 months from randomization.
Changes in modified Rankin Scale(mRS) within 3 months	During the first 3 months from randomization.
Changes in Barthel Index(BI) within 3 months	During the first 3 months from randomization.
12-month composite cardio-cerebral vascular event rate	During the first 12 months from randomization.

Collaborators and Investigators

• Sponsor: Ji Xunming,MD,PhD

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2020
• Primary Completion (ANTICIPATED): August 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (ACTUAL): July 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; ischemic stroke; cerebral atherosclerotic occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Atherosclerosis; Intracranial Arteriosclerosis
• Other Study ID Numbers: RICO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No