Remote Ischemic Preconditioning for Carotid Endarterectomy (RIP-CEA)

February 6, 2019 updated by: Natalie Domenick Sridharan, University of Pittsburgh
This is a randomized controlled trial designed to test an intervention (Remote ischemic preconditioning) in patients undergoing carotid endarterectomy (CEA) for carotid artery stenosis (CAS). The outcomes of interest include neurocognitive function, cardiac complications, and biomarkers of brain ischemia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multiple large, high quality randomized trials have shown carotid endarterectomy (CEA) is effective in decreasing future risk of stroke in patients with carotid artery stenosis. Outcomes after carotid endarterectomy have improved over time. The major risks including stroke and myocardial infarction (MI) are rare (<3% stroke and 4% for MI. However, subtle degrees of cerebral ischemia and myocardial injury are more common. Research is now focused finding ways to reduce these subclinical adverse effects of CEA.

Due to its high metabolic activity, the brain is especially vulnerable to periods of ischemia during carotid cross clamping. Ischemic tolerance has been demonstrated after direct ischemic conditioning in the brain. However, direct conditioning is difficult and potentially dangerous when is comes to carotid interventions making remote ischemic preconditioning an attractive alternative. In animal models, remote ischemic preconditioning (RIPC) has been shown to produce an equivalent response to direct neuronal conditioning at the cellular level.

The precise mechanisms underlying the phenomenon of RIPC have yet to be fully elucidated. However, It is likely that both neural and humoral mechanisms are at play. Multiple studies have shown decreased levels of inflammatory markers in brains of animal models undergoing RIPC and then middle cerebral artery occlusion.

There has only been one study of RIPC in carotid endarterectomy so far. Patients were randomized to 10 min ischemia on each leg prior to clamping the carotid. Primary outcome was significant postoperative deterioration in saccadic latency determined by quantitative oculometry (time taken to respond and fix on a visual stimulus that appears suddenly). Additionally, troponins were drawn up to 48 hours post operatively. There was deterioration in quantitative oculometry in 8/25 RIPC and 16/30 control (p=0.11) and no difference in troponins. However this was a small number of patients.

Major clinical events such as stroke or MI are uncommon following CEA. This hampers the assessment of new, novel interventions as any trial would require several thousand patients to detect a useful clinical effect. The only alternative is to use surrogate end points to obtain "proof of concept" justifying larger trials. Several serum markers of neuronal damage such as S100-beta and neuron-specific enolase have been identified but are not reliable or specific enough to be used clinically. Another surrogate that is directly related to the concept of subtle degrees of neuronal ischemia occurring during CEA is neurocognitive function.

20-25% of patients have been shown to experience significant cognitive decline following CEA. This has been correlated with findings of ischemia on diffusion weighted MRI in patients after CEA indicating that local ischemia and microemboli are responsible for this decline. Thus, neurocognitive testing before and after carotid revascularization may be an ideal surrogate end point to study in remote ischemic preconditioning and it's potential to mediate the subtle degree of neuronal ischemia produced during carotid revascularization. However, neurocognitive function is also an endpoint with clinical relevance to patients.

This study will be a double armed randomized trial. The treatment arm will be Remote ischemic preconditioning and the Control arm will be Usual care. Intervention allocation ratio will be 1:1 RIPC:usual care. Randomization strategy will be a using a 1:1 fixed block of 4 randomization stratified by symptom status and age. Those randomized to RIPC will undergo a standard protocol of 4 cycles of 5 minutes of forearm ischemia with 5 minutes of reperfusion requiring 35 minutes for an application. Forearm ischemia will be induced by a blood pressure cuff inflated to 200 millimeters of mercury (mmHg) or at least 15mmHg higher than the systolic pressure if systolic > 185mmHg or until the radial pulse is obliterated. This can occur during anesthesia induction and incision/dissection prior to manipulation or clamping of the carotid.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
86

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

55 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing carotid endarterectomy
  • Indication for surgery must be symptomatic disease with >50% stenosis by duplex ultrasound or asymptomatic disease with >60% stenosis by duplex ultrasound

Exclusion Criteria:

  • Lack of radial pulse on either arm
  • Known Deep venous thrombosis (DVT) in arm
  • Arteriovenous fistula or graft in both arms
  • Diagnosed hypercoagulable state
  • Pre-existing lymphedema or axillary node dissection both arms
  • Diagnosis of dementia, intellectual disability, or mental illness including depression, anxiety, or schizophrenia
  • Simultaneous coronary artery bypass grafting

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Usual Care
Patients in the usual care arm will undergo CEA without RIPC.
Experimental: Remote Ischemic Preconditioning
Patients in the RIPC arm will undergo CEA with RIPC.
Procedure: Remote Ischemic Preconditioning
Those randomized to RIPC will undergo a standard protocol of 4 cycles of 5 minutes of forearm ischemia with 5 minutes of reperfusion requiring 35 minutes for an application. Forearm ischemia will be induced by a blood pressure cuff inflated to 200mmHg or at least 15mmHg higher than the systolic pressure if systolic > 185mmHg or until the radial pulse is obliterated. This can occur during anesthesia induction and incision/dissection prior to manipulation or clamping of the carotid.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Immediate change in Neurocognitive function
Time Frame: 1 month before surgery and post operative day 1
Montreal cognitive assessment
1 month before surgery and post operative day 1
Longterm change in Neurocognitive function
Time Frame: 1 month before surgery and 1 month post operatively
Montreal cognitive assessment
1 month before surgery and 1 month post operatively

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
S100-beta biomarker
Time Frame: Post operative day one
serum level of S100-beta
Post operative day one
Troponin
Time Frame: post operative day one
serum troponin level
post operative day one
Stroke
Time Frame: within 30 days post operative
Stroke diagnosed by MRI findings of new stroke (obtained if symptomatic)
within 30 days post operative
Neuron specific enolase (NSE) biomarker
Time Frame: Post operative day one
Serum level of NSE
Post operative day one
Adverse cardiac events
Time Frame: 30 days postoperative
Any new myocardial infarction, new arrhythmia, or new onset heart failure
30 days postoperative
Severity of stroke
Time Frame: 30 days postoperative
National Institute of Health Stroke Scale
30 days postoperative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pittsburgh

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Natalie Sridharan, MD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 8, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO16030479
  • UL1TR001857 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carotid Stenosis

Clinical Trials on Remote Ischemic Preconditioning

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings