Major trial tests best way to prevent stroke in patients with clogged neck arteries

NCT ID NCT02089217

Disease control Sponsor: Mayo Clinic Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This completed trial enrolled 2,486 people with asymptomatic high-grade carotid stenosis (narrowing of the neck arteries) to see if adding surgery or stenting to intensive medical management reduces stroke risk more than medical management alone. Participants were randomly assigned to one of two trials: one comparing endarterectomy (surgery) plus medical management versus medical management alone, and another comparing carotid stenting plus medical management versus medical management alone. The primary outcome was stroke or death within 44 days after randomization and stroke on the treated side up to 4 years.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Carotid endarterectomy (surgery), carotid stenting (device), and intensive medical management
What this could lead to: If successful, this could show that adding surgery or stenting to medical management reduces stroke risk more than medical management alone for people with asymptomatic carotid stenosis.
What could go wrong: This is a completed trial, but results may not apply to all patients. Surgery and stenting carry risks like stroke, heart attack, or death, and the benefit over medical management alone may be small.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Not a phased trial

Phase numbers describe drug development. The registry uses this when they do not apply, as it does for trials of devices, procedures or behaviour changes, and for observational studies.

Participants

2,486 people

The number who actually took part.

Started

Dec 2014

Finished

Sep 2025

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

35 to 100 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

General Inclusion Criteria 1. Patients ≥35 years old. 2. Carotid stenosis defined as: * Stenosis ≥70% by catheter angiography (NASCET Criteria); OR * by Doppler ultrasonography (DUS) with ≥70% stenosis defined by a peak systolic velocity of at least 230 cm/s plus at least one of the following: 1. an end diastolic velocity ≥100 cm/s, or 2. internal carotid/common carotid artery peak systolic velocity ratio ≥4.0, or 3. computed tomography angiography (CTA) with ≥ 70% stenosis, or 4. magnetic resonance angiography (MRA) with ≥ 70% stenosis. 3. No medical history of stroke or transient ischemic attack (TIA) ipsilateral to the stenosis within 180 days of randomization. Life-long asymptomatic patients will be defined as having no medical history of stroke or transient ischemic attack and negative responses to all of the symptom items on the Questionnaire for Verifying Stroke-free Status (QVSS). 4. Patients must have a modified Rankin Scale (mRS) score of 0 or 1 at the time of informed consent. 5. Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization. 6. Patients must agree to comply with all protocol-specified follow-up appointments. 7. Patients must sign a consent form that has been approved by the local governing Institutional Review Board (IRB)/Medical Ethics Committee (MEC) of the respective clinical site. 8. Randomization to treatment group will apply to only one carotid artery for patients with bilateral carotid stenosis. Management of the non-randomized stenosis may be done in accordance with local PI recommendation. Treatment of the non-study internal carotid artery must take place at least 30 days prior to randomization, or greater than 44 days after randomization and 30 days after the study procedure is completed (whichever is longer). 9. Carotid stenosis must be treatable with carotid endarterectomy (CEA), carotid artery stenting (CAS), or either procedure. General Exclusion Criteria 1. Intolerance or allergic reaction to a study medication without a suitable management alternative. 2. GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy. 3. Prior major ipsilateral stroke in the past with substantial residual disability (mRS ≥ 2) that is likely to confound study outcomes. 4. Severe dementia. 5. History of major symptomatic intracranial hemorrhage within 12 months that was not related to anticoagulation. 6. Prior Intracranial hemorrhage that the investigator believes represents a contraindication to the perioperative or periprocedural antithrombotic and antiplatelet treatments necessary to complete endarterectomy or stenting per protocol. 7. Current neurologic illness characterized by fleeting or fixed neurologic deficits that cannot be distinguished from TIA or stroke. 8. Patient objects to future blood transfusions. 9. Platelet count \<100,000/microliter or history of heparin-induced thrombocytopenia. 10. Anticoagulation with Phenprocoumon (Marcumar®), warfarin, or a direct thrombin inhibitor, or anti-Xa agents. 11. Chronic atrial fibrillation, unless the patient has had successful atrial appendage closure (e.g., Watchman Device) and no longer requires chronic therapeutic anticoagulation. 12. Any episode of atrial fibrillation within the past 6 months or history of paroxysmal atrial fibrillation that is deemed to require chronic anticoagulation. 13. Other high-risk cardiac sources of emboli, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcific aortic stenosis (valve area \< 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus, or any intracardiac mass, or known unrepaired patent foramen ovale (PFO) with prior paradoxical embolism. 14. Unstable angina defined as rest angina with electrocardiogram (ECG) changes that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization). 15. Left Ventricular Ejection fraction \<30% or admission for heart failure in prior 6 months. 16. Respiratory insufficiency with life expectancy \< 4 years or forced expiratory volume (FEV1) \<30% of predicted value. 17. Known malignancy other than basal cell non-melanoma skin cancer. There are two exceptions to this rule: patients with prior cancer treatment and no recurrence for \>5 years are eligible for enrollment and cancer patients with life expectancy of greater than 5 years are eligible for enrollment. 18. Any major surgery, major trauma, revascularization procedure, or acute coronary syndrome within the past 1 month. 19. Either the serum creatinine is ≥ 2.5 mg/dl or the estimated glomerular filtration rate (GFR) is \< 30 cc/min. 20. Major (non-carotid) surgery/procedures planned within 3 months after enrollment. 21. Currently listed or being evaluated for major organ transplantation (i.e. heart, lung, liver, kidney). 22. Actively participating in another drug or aortic arch or cerebrovascular device trial for which participation in CREST-2 would be compromised with regard to follow-up assessment of outcomes or continuation in CREST-2. 23. Inability to understand and cooperate with study procedures or provide informed consent. 24. Non-atherosclerotic carotid stenosis (dissection, fibromuscular dysplasia, or stenosis following radiation therapy). 25. Previous ipsilateral CEA or CAS. 26. Ipsilateral internal or common carotid artery occlusion. 27. Intra-carotid floating thrombus. 28. Ipsilateral intracranial aneurysm \> 5 mm. 29. Extreme morbid obesity that would compromise patient safety during the procedure or would compromise patient safety during the periprocedural period. 30. Coronary artery disease with two or more proximal or major diseased coronary arteries with 70% stenosis that have not, or cannot, be revascularized. Specific Carotid Endarterectomy Exclusion Criteria Patients who are being considered for revascularization by CEA must not have any of the following criteria: 1. Serious adverse reaction to anesthesia not able to be overcome by pre-medication. 2. Distal/intracranial stenosis greater than index lesion. 3. Any of the following anatomical: radical neck dissection; surgically inaccessible lesions (e.g. above cervical spine level 2 (C2)); adverse neck anatomy that limits surgical exposure (e.g. spinal immobility - inability to flex neck beyond neutral or kyphotic deformity, or short obese neck); presence of tracheostomy stoma; laryngeal nerve palsy contralateral to target vessel; or previous extracranial-intracranial or subclavian bypass procedure ipsilateral to the target vessel. Specific Carotid Artery Stenting Exclusion Criteria Patients who are being considered for revascularization by CAS must not have any of the following criteria: 1. Allergy to intravascular contrast dye not amenable to pre-medication. 2. Type III, aortic arch anatomy. 3. Angulation or tortuosity (≥ 90 degree) of the innominate and common carotid artery that precludes safe, expeditious sheath placement or that will transmit a severe loop to the internal carotid after sheath placement. 4. Severe angulation or tortuosity of the internal carotid artery (including calyceal origin from the carotid bifurcation) that precludes safe deployment of embolic protection device or stent. Severe tortuosity is defined as 2 or more ≥ 90 degree angles within 4 cm of the target stenosis. 5. Proximal/ostial common carotid artery (CCA), innominate stenosis or distal/intracranial stenosis greater than index lesion. Excessive circumferential calcification of the stenotic lesion defined as \>3mm thickness of calcification seen in orthogonal views on fluoroscopy.(Note: Anatomic considerations such as tortuosity, arch anatomy, and calcification must be evaluated even more carefully in elderly subjects (≥ 70 years).) 6. Target ICA vessel reference diameter \<4.0 mm or \>9.0 mm. Target internal carotid artery (ICA) measurements may be made from angiography of the contralateral artery. The reference diameter must be appropriate for the devices to be used. 7. Inability to deploy or utilize an FDA-approved Embolic Protection Device (EPD). 8. Non-contiguous lesions and long lesions (\>3 cm). 9. Qualitative characteristics of stenosis and stenosis-length of the carotid bifurcation (common carotid) and/or ipsilateral external carotid artery, that preclude safe sheath placement. 10. Occlusive or critical ilio-femoral disease including severe tortuosity or stenosis that necessitates additional endovascular procedures to facilitate access to the aortic arch or that prevents safe and expeditious femoral access to the aortic arch. "String sign" of the ipsilateral common or internal carotid artery. 11. Angiographic, computed tomography (CT), magnetic resonance (MR) or ultrasound evidence of severe atherosclerosis of the aortic arch or origin of the innominate or common carotid arteries that would preclude safe passage of the sheath and other endovascular devices to the target artery as needed for carotid stenting.

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Conditions

The condition(s) this trial relates to.

carotid stenosis hyperlipidemia hypertensive disorder stroke disorder prevention target

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Carotid stenosis

Contacts and locations

Locations

Abrazo Arizona Heart Hospital

Phoenix, Arizona, 85016, United States
Atlanta VA Medical Center

Atlanta, Georgia, 30033, United States
Banner University Medical Center

Phoenix, Arizona, 85006, United States
Banner University Medical Center

Tucson, Arizona, 85724, United States
Baptist Health Lexington

Lexington, Kentucky, 40503, United States
Baptist Memorial Hospital

Memphis, Tennessee, 38017, United States
Berks Cardiologists / St. Joseph's Medical Center

Wyomissing, Pennsylvania, 19610, United States
Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States
CHU de Québec/ Hôpital de l'Enfant-Jésus

Québec, Quebec, G1J1Z4, Canada
CVA Heart Institute

Kingsport, Tennessee, 37660, United States
Cardiac and Vascular Research Center of Northern Michigan/McLaren Northern Michigan

Petoskey, Michigan, 49770, United States
Cardiothoracic and Vascular Surgeons

Austin, Texas, 78756, United States
Cardiovascular Institute of Northwest Florida

Panama City, Florida, 32401, United States
Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States
Central Arkansas Veteran's Healthcare System

Little Rock, Arkansas, 72143, United States
Coastal Carolina Surgical Associates PA

Wilmington, North Carolina, 28401, United States
Columbia University Medical Center

New York, New York, 10032, United States
Cooper University

Camden, New Jersey, 08103, United States
Cox Medical Center

Springfield, Missouri, 65807, United States
Crouse Hospital

Syracuse, New York, 13210, United States
Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States
Deaconess Heart Group

Newburgh, Indiana, 47630, United States
Doylestown Hospital

Doylestown, Pennsylvania, 18901, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
Emory University

Atlanta, Georgia, 30322, United States
Fiona Stanley Hospital

Perth, Australia
First Coast Cardiovascular Institute

Jacksonville, Florida, 32216, United States
Franciscan St. Francis Health

Indianapolis, Indiana, 46237, United States
George E. Wahlen Department of Veterans Affairs Medical Center

Salt Lake City, Utah, 84148, United States
Good Samaritan Hospital

Cincinnati, Ohio, 45220, United States
Gundersen Clinic, Ltd

La Crosse, Wisconsin, 54601, United States
Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States
Hadassah Medical Center

Jerusalem, 91120, Israel
Hartford Hospital

Hartford, Connecticut, 06102, United States
Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States
Henry Ford Health System

Detroit, Michigan, 48202, United States
HonorHealth Scottsdale Osborn Medical Center

Scottsdale, Arizona, 85251, United States
Hospital Clinic Barcelona

Barcelona, Spain
Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States
Houston Methodist Hospital

Houston, Texas, 77030, United States
Huntsville Hospital/ Heart Center Research Alabama

Huntsville, Alabama, 35801, United States
Inova Fairfax Health Care

Falls Church, Virginia, 22042, United States
Intermountain Medical Center

Murray, Utah, 84107, United States
Jobst Vascular Institute/University of Toledo

Toledo, Ohio, 43606, United States
John Cochran VA Medical Center

St Louis, Missouri, 63106, United States
Johns Hopkins Medical Institution

Baltimore, Maryland, 21224, United States
Kaiser Permanente

San Diego, California, 92116, United States
Kaiser Permanente Los Angeles

Los Angeles, California, 90027, United States
Kaiser Permanente Northern California

San Francisco, California, 94115, United States
Keck Medical Center of University of Southern California

Los Angeles, California, 90033, United States
Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States
Lehigh Valley Hospital - Network Office of Research

Allentown, Pennsylvania, 18103, United States
Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, 44106, United States
Loyola University Medical Center

Maywood, Illinois, 60153, United States
Lyerly Neurosurgery

Jacksonville, Florida, 32207, United States
Maine Medical Center

Portland, Maine, 04102, United States
Massachusetts General Hospital

Boston, Massachusetts, 02144, United States
Mayo Clinic

Jacksonville, Florida, 32224, United States
Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States
Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States
Medical Center of the Rockies

Loveland, Colorado, 80538, United States
Medical University of South Carolina

Charleston, South Carolina, 29425, United States
Medstar/Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States
Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States
Mercy Health Riverside

Rockford, Illinois, 61114, United States
Mercy Health St. Vincent Medical Center

Toledo, Ohio, 43608, United States
Mercy Hospital

St Louis, Missouri, 63141, United States
Mercy Medical Research Institute

Springfield, Missouri, 65807, United States
Miami Cardiac and Vascular Institute at Baptist Hospital of Miami

Miami, Florida, 33176, United States
Michigan Vascular Center/McLaren- Flint

Flint, Michigan, 48532, United States
Minneapolis Clinic of Neurology, Ltd./North Memorial Medical Center

Golden Valley, Minnesota, 55422, United States
Mission Cardiovascular Research

Fremont, California, 94538, United States
Mission Cardiovascular Research Institute

Fremont, California, 94538, United States
Morton Plant Hospital

Clearwater, Florida, 33756, United States
Mount Sinai Hospital New York

New York, New York, 10029, United States
Mount Sinai Medical Center of Florida

Miami Beach, Florida, 33140, United States
North Carolina Heart & Vascular Research

Raleigh, North Carolina, 27607, United States
North Central Heart Institute

Sioux Falls, South Dakota, 57108, United States
Northshore University

Evanston, Illinois, 60201, United States
Northwestern University

Evanston, Illinois, 60208, United States
Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 3A7, Canada
Novant Health/Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States
Ochsner Health System

New Orleans, Louisiana, 70121, United States
Ohio State Medical Center

Columbia, Ohio, 43210, United States
OhioHealth Research Institute

Columbus, Ohio, 43214, United States
Oregon Health & Science University

Portland, Oregon, 97239, United States
Overlake Hospital

Bellevue, Washington, 98004, United States
Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States
Pinnacle Health Cardiovascular Institute

Wormleysburg, Pennsylvania, 17043, United States
Prairie Heart/St. John's Hospital

Springfield, Illinois, 62701, United States
Providence Brain and Spine Institute

Portland, Oregon, 97225, United States
Providence Little Company of Mary Medical Center

Torrance, California, 90503, United States
Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States
Rabin Medical Center

Petah Tikva, Israel
Rambam Healthcare

Haifa, 3109601, Israel
SUNY Buffalo

Buffalo, New York, 14203, United States
San Francisco VA Medical Center

San Francisco, California, 94121, United States
Sanford Health

Fargo, North Dakota, 58104, United States
Seton Medical Center Austin

Austin, Texas, 78705, United States
Shaare-Zedek Medical Center

Jerusalem, Israel
Soroka University Medical Center

Beersheba, Israel
Soroka University Vascular Surgery

Beersheba, Israel
Southern Illinois Healthcare

Carbondale, Illinois, 62901, United States
Sparrow Clinical Research Institute

Lansing, Michigan, 48912, United States
St. Boniface Hospital

Winnipeg, Ontario, R2H 2A6, Canada
St. Cloud Hospital

Saint Cloud, Minnesota, 56303, United States
St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States
St. Francis Hospital

Roslyn, New York, 11576, United States
St. John Clinical Research Institute

Tulsa, Oklahoma, 74104, United States
St. Joseph's Hospital and Medical Center/Barrow Neurological Institute

Phoenix, Arizona, 85013, United States
St. Joseph's Medical Center

Stockton, California, 95204, United States
St. Mary's Hospital Regional Medical Center

Grand Junction, Colorado, 81501, United States
St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada
Stanford University Medical Center

Stanford, California, 94305, United States
Stony Brook University

Stony Brook, New York, 11794, United States
Swedish Medical Center

Seattle, Washington, 98122, United States
Tallahassee Neurological Clinic

Tallahassee, Florida, 32308, United States
Tampa General/University of South Florida

Tampa, Florida, 33606, United States
Tennova Healthcare/ Turkey Creek Medical Center

Knoxville, Tennessee, 37934, United States
The Feinstein Institute of Medical Research/Northwell Health

Manhasset, New York, 11030, United States
The Miriam Hospital

Providence, Rhode Island, 02906, United States
The University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States
The University of Chicago Medical Center

Chicago, Illinois, 60637, United States
Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States
Trinity Health/Michigan Heart

Ypsilanti, Michigan, 48197, United States
Tulane University Heart and Vascular

New Orleans, Louisiana, 70112, United States
UC San Diego Health

La Jolla, California, 92037, United States
UF Jacksonville

Jacksonville, Florida, 32209, United States
UPMC Altoona

Altoona, Pennsylvania, 16601, United States
UPMC Hamot

Erie, Pennsylvania, 16550, United States
UPMC Presbyterian University Hospital

Pittsburgh, Pennsylvania, 15213, United States
University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States
University of California Irvine

Irvine, California, 92868, United States
University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States
University of California San Diego

San Diego, California, 92103, United States
University of California San Francisco

San Francisco, California, 94115, United States
University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States
University of Florida Health at Shands

Gainesville, Florida, 32610, United States
University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States
University of Kansas Medical Center

Kansas City, Kansas, 66160, United States
University of Kentucky Hospital

Lexington, Kentucky, 40536, United States
University of Louisville Hospital

Louisville, Kentucky, 40202, United States
University of Maryland VA

Baltimore, Maryland, 21201, United States
University of Massachusetts Memorial Hospital

Worcester, Massachusetts, 01605, United States
University of Miami Hospital

Miami, Florida, 33136, United States
University of Michigan Hospital and Health Systems

Ann Arbor, Michigan, 48109, United States
University of Minnesota

Minneapolis, Minnesota, 55455, United States
University of Rochester Medical Center

Rochester, New York, 14642, United States
University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States
University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States
University of Virginia Health System

Charlottesville, Virginia, 22908, United States
University of Washington Medicine-Harborview Medical Center

Seattle, Washington, 98104, United States
University of Wisconsin Hospitals & Clinics

Madison, Wisconsin, 53792, United States
VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105, United States
VA Palo Alto Health Care System

Palo Alto, California, 94304, United States
VA Pittsburgh Healthcare

Pittsburgh, Pennsylvania, 15240, United States
VA Puget Sound Health Care System

Seattle, Washington, 98108, United States
Valley Baptist Medical Center

Harlingen, Texas, 78551, United States
Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada
Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States
Weill Cornell Medical College

New York, New York, 10065, United States
West Virginia University

Morgantown, West Virginia, 26554, United States
White Oak Medical Center

Takoma Park, Maryland, 20912, United States
William Beaumont Hospital

Royal Oak, Michigan, 48073, United States
Winchester Medical Center

Winchester, Virginia, 22601, United States
Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

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