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

Phase 2

Completed

• Conditions: Carotid Artery Stenosis
• Interventions: Procedure: Carotid Artery Stenting; Procedure: Sham remote ischemic preconditioning; Procedure: Remote ischemic preconditioning

• Registration Number: NCT01654666
• Lead Sponsor: Ji Xunming

Brief Summary

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.

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.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-23
• Study First Submitted QC: 2012-07-28
• Study First Posted: 2012-08-01
• Primary Completion: 2015-01
• Study Completion: 2015-07
• Results First Submitted: 2015-07-23
• Status Verified: 2015-10
• Results First Submitted QC: 2015-10-13
• Last Update Submitted: 2015-10-13
• Results First Posted: 2015-11-11
• Last Update Posted: 2015-11-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 189

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Carotid Artery Stenting	Treatment:Patients in this group received standard medical therapy alone. Procedure: Carotid Artery Stenting
Sham RIPC group	Carotid Artery Stenting	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
Sham RIPC group	Sham remote ischemic preconditioning	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
RIPC group	Remote ischemic preconditioning	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
RIPC group	Carotid Artery Stenting	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

Primary Outcome Measures

Name	Time	Method
Number of Patients With Cerebrovascular Events, Cardiovascular Events or Death.	Within six months after carotid artery stenting	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.	Within 48 hours after carotid artery stenting.

Secondary Outcome Measures

Name	Time	Method
Serum High-sensitive C-reactive Protein (Hs-CRP).	Baseline, on admission, and 1 and 24 hours after carotid artery stenting.
Number of Patients With Any Side Effects of Remote Ischemic Preconditioning (RIPC) Treatment.	From baseline to 6 months after treatment.	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.	Baseline, on admission, and 1 and 24 hours after carotid artery stenting.
Serum S-100B Levels.	Baseline, on admission, and 1 and 24 hours after carotid artery stenting.

Trial Locations

Locations (1)

Baojun Hou; 🇨🇳 Beijing, Beijing, China