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

NCT ID: NCT01654666

Last Updated: 2015-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 189 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-07-31

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.

Conditions

Carotid Artery Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Remote ischemic preconditioning

Intervention Type: PROCEDURE

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.

Carotid Artery Stenting

Intervention Type: PROCEDURE

Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.

Control group

Treatment:Patients in this group received standard medical therapy alone. Procedure: Carotid Artery Stenting

Group Type: ACTIVE_COMPARATOR

Carotid Artery Stenting

Intervention Type: PROCEDURE

Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.

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

Group Type: SHAM_COMPARATOR

Sham remote ischemic preconditioning

Intervention Type: PROCEDURE

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.

Carotid Artery Stenting

Intervention Type: PROCEDURE

Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Carotid Artery Stenting

Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.

Intervention Type: PROCEDURE

Other Intervention Names

RIPC; Sham RIPC; CAS

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ji Xunming

OTHER

Sponsor Role: lead

Responsible Party

Ji Xunming

XuanWu Hospital

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Xunming Ji M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Capital Medical University

Locations

Baojun Hou

Beijing, Beijing Municipality, China

Countries

China

References

Liang F, Liu S, Liu G, Liu H, Wang Q, Song B, Yao L. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD008472. doi: 10.1002/14651858.CD008472.pub3.

Reference Type: DERIVED

PMID: 36645250 (View on PubMed)

Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F, Wu W, Shi J, Duan Y, Zhang R, Zhang J, Sun Y, Zhang H, Ling F, Wang Y, Feng W, Ding Y, Ovbiagele B, Ji X. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation. 2017 Apr 4;135(14):1325-1335. doi: 10.1161/CIRCULATIONAHA.116.024807. Epub 2017 Feb 7.

Reference Type: DERIVED

PMID: 28174194 (View on PubMed)

Other Identifiers

RIPC2012

Identifier Type: -

Identifier Source: org_study_id