Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ji Xunming, Capital Medical University
ClinicalTrials.gov Identifier:
NCT01654666
First received: July 23, 2012
Last updated: October 13, 2015
Last verified: October 2015
  Purpose
Remote limb ischemic preconditioning (RIPC) has neuro-protective and anti-inflammatory effects on ischemia- reperfusion injury. As the extent of its effect is unknown, the investigators will use clinical outcome, serum biochemical markers and brain magnetic resonance imaging (MRI) to determine whether RIPC has neuro-protective and anti-inflammatory effects on patients undergoing carotid artery stenting.

Condition Intervention Phase
Carotid Artery Stenosis
Procedure: Remote ischemic preconditioning
Procedure: Sham remote ischemic preconditioning
Procedure: Carotid Artery Stenting
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting

Further study details as provided by Capital Medical University:

Primary Outcome Measures:
  • Number of Patients With Cerebrovascular Events, Cardiovascular Events or Death. [ Time Frame: Within six months after carotid artery stenting ] [ Designated as safety issue: Yes ]
    Cerebrovascular events included ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage and hyperperfusion syndrome. Cardiovascular events included angina and myocardial infarction.Death included any reason caused death.

  • Participants Who Got New Diffusion-weighted Imaging (DWI) Lesions on Post-treatment Magnetic Resonance Imaging (MRI) Scans. [ Time Frame: Within 48 hours after carotid artery stenting. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum High-sensitive C-reactive Protein (Hs-CRP). [ Time Frame: Baseline, on admission, and 1 and 24 hours after carotid artery stenting. ] [ Designated as safety issue: Yes ]
  • Number of Patients With Any Side Effects of Remote Ischemic Preconditioning (RIPC) Treatment. [ Time Frame: From baseline to 6 months after treatment. ] [ Designated as safety issue: Yes ]
    The side effects referred to any side effects of RIPC or sham RIPC treatment, not including the sides effect of medications and CAS.

  • Serum Neuron Specific Enolase (NSE) Levels. [ Time Frame: Baseline, on admission, and 1 and 24 hours after carotid artery stenting. ] [ Designated as safety issue: Yes ]
  • Serum S-100B Levels. [ Time Frame: Baseline, on admission, and 1 and 24 hours after carotid artery stenting. ] [ Designated as safety issue: Yes ]

Enrollment: 189
Study Start Date: July 2012
Study Completion Date: July 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RIPC group

Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment.

Device:RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by an automated cuff-inflator placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min,each patient in the RIPC group do it twice a day for at least two weeks before carotid artery stenting.

Procedure: Carotid Artery Stenting

Procedure: Remote ischemic preconditioning
Remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by an automated cuff-inflator placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min.
Other Name: RIPC
Procedure: Carotid Artery Stenting
Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.
Other Name: CAS
Active Comparator: Control group
Treatment:Patients in this group received standard medical therapy alone. Procedure: Carotid Artery Stenting
Procedure: Carotid Artery Stenting
Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.
Other Name: CAS
Sham Comparator: Sham RIPC group

Treatment:Patients in this group received standard medical therapy and sham remote ischemic preconditioning treatment.

Device:Sham RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by an automated cuff-inflator placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, each patient in RIPC group do it twice a day for at least two weeks before carotid artery stenting.

Procedure: Carotid Artery Stenting

Procedure: Sham remote ischemic preconditioning
Sham remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by an automated cuff-inflator placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min.
Other Name: Sham RIPC
Procedure: Carotid Artery Stenting
Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.
Other Name: CAS

Detailed Description:

BACKGROUND: Brain ischemia and injury contributed to perioperative morbidity and mortality in Carotid Artery Stenting. Remote ischemic preconditioning (RIPC), brief periods of ischemia followed by reperfusion, can provide systemic protection for prolonged ischemia. Our previous study found no significant protection to the patients who received once RIPC before Carotid Artery Stenting. In order to investigate whether long-term RIPC before Carotid Artery Stenting can protect these patients from the perioperative and long-term complications, a prospective randomized controlled trial will be performed in the current study.

DESIGNING: About 189 patients who are eligible for carotid artery stenting will be randomly assigned in 1:1:1 ratio to RIPC group, sham RIPC group and conventional Carotid Artery Stenting group (control). Remote limb ischemic preconditioning (RIPC) is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, it is induced by an automated cuff-inflator placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min, patients in the RIPC group will do it twice a day for at least two weeks before carotid artery stenting. Patients in the sham RIPC group receive sham RIPC treatment, which is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, induced by an automated cuff-inflator placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, they will do it twice a day for at least two weeks before carotid artery stenting. Patients in the control group receive conventional carotid artery stenting without RIPC or sham RIPC treatment. Cerebral injury is assessed by serum S-100B and Neuron specific enolase (NSE), systematic inflammation is assessed by serum high-sensitivity C-reactive protein (hs-CRP). Post-treatment infarctions, both symptomatic and asymptomatic, are detected by diffusion-weighted imaging (DWI) and clinical outcomes are determined by cerebrovascular events, cardiac events or death.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Symptomatic or asymptomatic carotid artery stenosis. In symptomatic patients the degree of stenosis should more than 60% (Based on NASCET Criteria), in asymptomatic patients the degree of stenosis should more than 70% (Based on NASCET Criteria);
  2. Tolerance to any of the study medications, including clopidogrel, aspirin and statins;
  3. Can cooperate with and complete brain MRI examination;
  4. Has a negative pregnancy test within 7 days before randomization and no childbearing potential;
  5. Vascular ultrasound excluded intravascular thrombosis and unstable plaques in blood vessels of the bilateral upper limbs;
  6. No hemorrhagic tendency;
  7. Stable vital sign, normal renal and hepatic functions;
  8. Informed consent.

Exclusion Criteria:

  1. Evolving stroke;
  2. Prior major ipsilateral stroke, if likely to confound study endpoints;
  3. Severe dementia;
  4. Hemorrhagic conversion of an ischemic stroke within the past 60 days;
  5. Chronic atrial fibrillation;
  6. Myocardial infarction within previous 30 days;
  7. Inability to understand and cooperate with study procedures or provide informed consent;
  8. Participating in other device or drug trial that has not completed the required protocol follow-up period;
  9. Any conditions that hampers proper angiographic assessment or makes percutaneous arterial access unsafe;
  10. High risk candidates defined as the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST);
  11. Any vascular, extremity soft tissue or orthopedic injury that may contraindicate bilateral arm ischemic preconditioning (e.g. superficial wounds and fractures of the arm);
  12. Blood pressure cannot be controlled lower than 200 mmHg by medications;
  13. Peripheral blood vessel disease (especially subclavian arterial and upper limb artery stenosis or occlusion).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01654666

Locations
China, Beijing
Baojun Hou
Beijing, Beijing, China, 100053
Sponsors and Collaborators
Ji Xunming
Investigators
Principal Investigator: Xunming Ji M.D., Ph.D. Capital Medical University
  More Information

Responsible Party: Ji Xunming, XuanWu Hospital, Capital Medical University
ClinicalTrials.gov Identifier: NCT01654666     History of Changes
Other Study ID Numbers: RIPC2012 
Study First Received: July 23, 2012
Results First Received: July 23, 2015
Last Updated: October 13, 2015
Health Authority: China: Food and Drug Administration

Keywords provided by Capital Medical University:
Remote ischemic preconditioning
Stroke secondary prevention
Carotid artery stenting
Carotid stenosis
Inflammation

Additional relevant MeSH terms:
Constriction, Pathologic
Carotid Stenosis
Pathological Conditions, Anatomical
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 23, 2016