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

Completed

Phase 2 Results

Trial Description

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

Interventions

  • Carotid Artery Stenting Device
    Intervention Desc: Carotid Artery Stenting is an invasive therapy of carotid artery stenosis.
    ARM 1: Kind: Experimental
    Label: RIPC
    Description: Device: RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
    ARM 2: Kind: Experimental
    Label: control
    Description: Procedure: asymptomatic patients undergoing Carotid Artery Stenting
    ARM 3: Kind: Experimental
    Label: sham RIPC
    Description: RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 20 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
    ARM 4: Kind: Experimental
    Label: RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment. Device:RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for at least two weeks. Procedure: Carotid Artery Stenting
    ARM 5: Kind: Experimental
    Label: Control group
    Description: Treatment:Patients in this group received standard medical therapy alone. Procedure: Carotid Artery Stenting
    ARM 6: Kind: Experimental
    Label: Sham RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and sham RIPC treatment. Device:Sham RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 60 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
  • Remote limb ischemic preconditioning Procedure
    Other Names: RIPC
    Intervention Desc: Remote limb ischemic preconditioning consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins.
    ARM 1: Kind: Experimental
    Label: RIPC
    Description: Device: RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
    ARM 2: Kind: Experimental
    Label: RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment. Device:RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for at least two weeks. Procedure: Carotid Artery Stenting
  • Remote ischemic preconditioning Procedure
    Other Names: RIPC
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: RIPC group
    Description: 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
  • Sham Remote Ischemic Preconditioning Procedure
    Other Names: Sham RIPC
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Sham RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and sham RIPC treatment. Device:Sham RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 60 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
  • Sham RIPC Procedure
    Intervention Desc: Remote limb ischemic preconditioning consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 20 mmHg for 5mins followed by deflating the cuff for 5mins.
    ARM 1: Kind: Experimental
    Label: sham RIPC
    Description: RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 20 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting
  • Control of risk factors and standard medical therapy Behavioral
    Intervention Desc: Recognition and control of the modifiable risk factors for stroke. Besides behavior change, antiplatelet agents, antihypertensive agents, antidiabetic agents and statins were admitted if necessary.
    ARM 1: Kind: Experimental
    Label: RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment. Device:RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for at least two weeks. Procedure: Carotid Artery Stenting
    ARM 2: Kind: Experimental
    Label: Control group
    Description: Treatment:Patients in this group received standard medical therapy alone. Procedure: Carotid Artery Stenting
    ARM 3: Kind: Experimental
    Label: Sham RIPC group
    Description: Treatment:Patients in this group received standard medical therapy and sham RIPC treatment. Device:Sham RIPC consisted of five 5-min cycles of right upper arm ischemia/reperfusion, which was induced by an automated cuff-inflator placed on the right upper arm which was inflated to 60 mmHg for 5mins followed by deflating the cuff for 5mins,each patient in RIPC group did it twice a day for two weeks. Procedure: Carotid Artery Stenting

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Composite measure of serum NSE, S-100b and Hs-CRP at baseline. Within 1 week before remote ischemic preconditiong and carotid artery stenting surgery. Yes
Primary Composite measure of serum NSE, S100-b and hs-CRP at 1hour after carotid artery stenting. Right 1hour after carotid artery stenting. Yes
Primary Composite measure of serum NSE, S100-b and hs-CRP at 24 hours after carotid artery stenting. 24 hours after carotid artery stenting. Yes
Secondary The Incidence of Brain or Cardiac Ischemic Events and Death six months after CAS Yes
Secondary the Percentage of Participants Who Got New Brain Lesions After Carotid Artery Stenting (CAS) preoperation and 48 hours after operation Yes
Primary Number of patients with cerebrovascular events, cardiovascular events or death. Within six months after carotid artery stenting Yes
Primary The percentages of participants who get new diffusion-weighted imaging lesions on post-treatment MRI scans. Within 48 hours after carotid artery stenting. Yes
Secondary Serum biomarkers of inflammation and brain injury. Baselin, on admission, and 1 and 24 hours after carotid artery stenting. Yes
Secondary Number of patients with any side effects of RIPC treatment. From baseline to 6 month after treatment. 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. 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

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