Remote Ischemic Conditioning in Acute Ischemic Cerebral Vascular Disease Patients With Coexistence of Cerebral and Coronary Atherosclerosis（RIC-CCCA）

Remote ischemic conditioning(RIC) is a protective systemic strategy by organs brief and sublethal ischemia to confer protection from subsequent severe ischemia in distant organs, especially for heart and brain. This study will discuss whether RIC can play a part in preventing the patients with coexistence of cerebral and coronary atherosclerosis from the recurrence of cerebral vascular disease(CVD) or coronary artery disease(CAD). This study selects patients who suffered an ischemic stroke within 14 days prior to enrollment. All patients complete cerebral and coronary artery assessment. And then the the investigators select the patients who both have at least one cerebral vascular and at least one coronary artery stenosis over 50%, or the patients who both have at least one cerebral vascular stenosis over 50% and myocardial ischemic events history. These patients will randomly divide into two groups, RIC group and non-RIC group. Non-RIC group will only accept cardio-cerebrovascular disease secondary prevention treatment. RIC group will use not only cardio-cerebrovascular disease secondary prevention treatment, but also RIC everyday for three months, 5 cycles 5min ischemic-5min reperfusion each day. For the first month, the the investigators will call RIC group patients every week for insuring compliance and adverse effect. All patients will follow up endpoint events, cardio-cerebrovascular disease secondary prevention treatment, and the adverse effect every three months, up to one year.

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Ischemic Cerebral Vascular Disease
• Intervention / Treatment: Device: RIC

• Study Type: Interventional
• Enrollment (Anticipated): 392
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who suffered an ischemic stroke within 14 days prior to enrollment
2. With a baseline NIHSS score 0-15, mRS score 2-4
3. With at least one cerebral and carotid artery stenosis over 50%
4. With at least one coronary artery stenosis over 50% or previous myocardial ischemic events history(tertiary hospital doctors judge angina, myocardial infarction, and coronary revascularization treatment)
5. Age from 18 to 80
6. Informed consent obtained

Exclusion Criteria:

1. Thrombolytic therapy within 24 h prior to enrollment
2. Progressive neurological signs within 24 h prior to enrollment
3. Arterial stenosis due to unequivocal cardiac source of embolism, arterial dissection, vasculitic disease, cerebral venous thrombosis, Moyamoya disease
4. Arterial stenosis due to benign angiopathy of central nervous system, post-partum angiopathy, suspected vasospastic process, suspected recanalized embolus, neurosyphilis, any other intracranial infection
5. Rheumatic mitral disease with or without 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
6. Uncontrolled severe hypertension, defined by sitting systolic blood pressure(SBP) > 180 mm Hg and/or sitting diastolic blood pressure(DBP) > 110 mm Hg after medication
7. Contraindication for remote ischemic conditioning, including severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs
8. Subclavian arterial stenosis 50% or subclavian steal syndrome
9. Severe hemostatic disorder or severe coagulation dysfunction, platelets < 100 ×10^9/L
10. Aspartate aminotransferase(AST) and/or Alanine aminotransferanse(ALT) > 3× the upper limit of the reference range; creatinine clearance < 0.6 mL/s and/or serum creatinine > 265 mmol/L (>3.0 mg/dL)
11. Unwilling to comply with the treatment or follow-up assessments
12. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, or epidural) within 90 days prior to enrollment
13. Intracranial neoplasm, cerebral aneurysm, or arteriovenous malformation
14. Retinal hemorrhage or visceral bleeding within 30 days prior to enrollment
15. Major surgery, including cardiac and open femoral, aortic, or carotid surgery, within 30 days prior to enrollment or intent to undergo within 12 months after enrollment
16. Life expectancy < 3 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RIC group; The patients will accept cardio-cerebrovascular disease secondary prevention treatment and use RIC everyday for three months, 5 cycles 5min ischemic-5min reperfusion each day.	Device: RIC; The patients will use RIC everyday for three months, 5 cycles 5min ischemic-5min reperfusion each day.
NO_INTERVENTION: non-RIC group; The patients will only accept cardio-cerebrovascular disease secondary prevention treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complex ischemic cardio-cerebrovascular events cumulative incidence	include non-fatal acute ischemic cerebral vascular disease, non-fatal acute coronary syndrome, cardio-cerebrovascular events lead to death, elective cardio-cerebralvascular revascularization, myocardial and cerebral ischemia lead to hospitalize	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Events Occur	The first time of the primary outcome events occur	1 year
Rate of all-cause death	One year all-cause death rate	1 year
Score of Modified Rankin Scale(mRS)	The Modified Rankin Scale Score (mRS) is the most comprehensive and most widely used primary outcome measurement to assess the neurological functional disability in contemporary acute stroke trials. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranges from 0 (no symptom) to 5 (severe disability) and 6 (death). We will use mRS to evaluate the degree of disability or dependence during daily activities. The mRS will be assessed by certified study investigator at 3 months. The distribution of mRS will be compared between groups	3 months

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 17, 2018
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (ACTUAL): October 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Vascular Diseases; Ischemia; Atherosclerosis
• Other Study ID Numbers: RIC-CCCA

Drug and device information, study documents

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