CREST-2 Long-term Observational Extension Study (C2LOE)

Long-Term Observational Extension of Participants in the CREST-2 Randomized Clinical Trial

The purpose of this Long-Term Observational Extension of Participants in the CREST-2 Randomized Clinical Trial (C2LOE - ClinicalTrials.gov Identifier: NCT02089217) study is to study is to assess post-procedural efficacy of carotid endarterectomy and carotid stenting.

Study Overview

• Status: Active, not recruiting
• Conditions: Stenoses, Carotid
• Intervention / Treatment: Other: Intensive Medical Management; Procedure: FDA-approved carotid stents; Procedure: Carotid Endarterectomy

Detailed Description

Atherosclerotic plaque in the carotid arteries is responsible for 10 to 15% of all ischemic strokes. The ongoing NINDS-funded CREST-2 multicenter randomized clinical trial is testing whether in the short term (up to 4 years after study entry) procedural revascularization improves stroke prevention above and beyond what can be achieved with intensive medical management of vascular risk factors, especially hypertension and hyperlipidemia. Our proposal is for an observational extension of the CREST-2 clinical trial to test whether revascularization improves stroke prevention in the clinically relevant long term (up to 8 to 10 years). The current application proposes to use a site-less, centralized telephone approach to extend the follow-up of CREST-2 trial participants for assessing the primary study outcome (stroke) for up to 10 years. The average follow-up will increase from between 2-3 years (clinic-based randomized trial) to 7-8 years (observational extension). Each patient will be contacted by telephone at 6-month intervals, and queried regarding all hospitalizations since the last contact. Suspected stroke events will be adjudicated by an expert clinical events committee based on medical record review.

• Study Type: Observational
• Enrollment (Estimated): 2480

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Nova Scotia Health Authority
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic of Barcelona
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Pheonix
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72143
      • Central Arkansas VA
  • California
    • Fremont, California, United States, 94538
      • Mission Cardiovascular Research Institute
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles
    • Los Angeles, California, United States, 90033
      • USC/Keck Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Divsion of Research
    • Stockton, California, United States, 95204
      • St. Joseph's Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 16520
      • Yale New Haven Hospital
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Mease Healthcare
    • Gainesville, Florida, United States, 32610
      • University of Florida Health at Shands
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Lyerly Neurosurgery/Baptist Health
    • Miami, Florida, United States, 33176
      • Miami Cardiac and Vascular Institute
    • Panama City, Florida, United States, 32405
      • Cardiovascular Institute NW Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Evanston, Illinois, United States, 60201
      • Endeavor Health/NorthShore University
    • Springfield, Illinois, United States, 62701
      • Prairie Heart/St. John's Hospital
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Deaconess Heart Group
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Health System
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21201
      • VA Medical Center
    • Silver Spring, Maryland, United States, 20904
      • White Oak Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Flint, Michigan, United States, 48532
      • Michigan Vascular Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Clinical Research Institute
    • Ypsilanti, Michigan, United States, 48197
      • Michigan Heart
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • SUNY Buffalo
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • Syracuse, New York, United States, 13210
      • Crouse Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Health St. Vincent
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17043
      • Pinnacle Health
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • VA Pittsburgh
    • Wyomissing, Pennsylvania, United States, 19610
      • Berks Cardiologists
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont CVA Heart Institute
    • Knoxville, Tennessee, United States, 37934
      • Tennova Healthcare
  • Texas
    • Austin, Texas, United States, 78705
      • Seton Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospitals & Clinics
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Clinic, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with asymptomatic carotid stenosis previously randomized in the CREST-2 trial.

Description

Inclusion Criteria:

• Currently active or graduated participants in the CREST-2 randomized trial
• Able to provide written informed consent by self
• Fluent in English or Spanish

Exclusion Criteria:

• Unable to provide written informed consent
• Inability to follow study procedures

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intensive Medical Management Group - no CAS; Subjects assigned to the intensive medical management alone with no carotid stenting (CAS) group in the CREST-2 study (NCT02089217)	Other: Intensive Medical Management; INTERVENT risk factor management program to help manage patient's risk factors. The INTERVENT program will provide individualized risk factor counseling sessions (via telephone or internet) at regular interval by healthcare workers who are specially trained to help patients follow the medical management plan.
Intensive Medical Management Group - no CEA; Subjects assigned to the intensive medical management alone with no carotid endarterectomy (CEA) group in the CREST-2 study (NCT02089217)	Other: Intensive Medical Management; INTERVENT risk factor management program to help manage patient's risk factors. The INTERVENT program will provide individualized risk factor counseling sessions (via telephone or internet) at regular interval by healthcare workers who are specially trained to help patients follow the medical management plan.
Carotid Stenting Group (CAS); Subjects assigned to the intensive medical management with carotid stenting group in the CREST-2 study (NCT02089217)	Other: Intensive Medical Management; INTERVENT risk factor management program to help manage patient's risk factors. The INTERVENT program will provide individualized risk factor counseling sessions (via telephone or internet) at regular interval by healthcare workers who are specially trained to help patients follow the medical management plan.; Procedure: FDA-approved carotid stents; This is the standard proven therapy for carotid stenosis that involves an arteriotomy followed by removal of plaque and reconstruction of the vessel.
Carotid Endarterectomy Group (CEA); Subjects assigned to the intensive medical management with carotid endarterectomy group in the CREST-2 study (NCT02089217)	Other: Intensive Medical Management; INTERVENT risk factor management program to help manage patient's risk factors. The INTERVENT program will provide individualized risk factor counseling sessions (via telephone or internet) at regular interval by healthcare workers who are specially trained to help patients follow the medical management plan.; Procedure: Carotid Endarterectomy; This is the standard proven therapy for carotid stenosis that involves an arteriotomy followed by removal of plaque and reconstruction of the vessel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke	Number of participants to experience a stroke	5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Medical University of South Carolina; University of Maryland; University of Alabama at Birmingham; National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: James Meschia, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Carotid Stenosis; Surgical Procedures, Operative; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Endarterectomy; Endarterectomy, Carotid
• Other Study ID Numbers: 21-007363; 1U01NS119169-01A1 (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