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

Carotid Artery Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01654666
• Other study ID #: RIPC2012
• Status: Completed
• Phase: Phase 2
• First received: July 23, 2012
• Last updated: October 13, 2015
• Start date: July 2012
• Est. completion date: July 2015

Study information

• Verified date: October 2015
• Source: Capital Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: July 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carotid Artery Stenosis
• Carotid Stenosis

Intervention

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

Locations

Country	Name	City	State
China	Baojun Hou	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Ji Xunming

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Cerebrovascular Events, Cardiovascular Events or Death.	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.	Within six months after carotid artery stenting	Yes
Primary	Participants Who Got New Diffusion-weighted Imaging (DWI) Lesions on Post-treatment Magnetic Resonance Imaging (MRI) Scans.		Within 48 hours after carotid artery stenting.	Yes
Secondary	Serum High-sensitive C-reactive Protein (Hs-CRP).		Baseline, on admission, and 1 and 24 hours after carotid artery stenting.	Yes
Secondary	Number of Patients With Any Side Effects of Remote Ischemic Preconditioning (RIPC) Treatment.	The side effects referred to any side effects of RIPC or sham RIPC treatment, not including the sides effect of medications and CAS.	From baseline to 6 months after treatment.	Yes
Secondary	Serum Neuron Specific Enolase (NSE) Levels.		Baseline, on admission, and 1 and 24 hours after carotid artery stenting.	Yes
Secondary	Serum S-100B Levels.		Baseline, on admission, and 1 and 24 hours after carotid artery stenting.	Yes