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AzTrials

Carotid StenosisCREST-2NCT02089217

Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial

A study testing Carotid endarterectomy (CEA), Carotid Stenting (CAS) and Intensive Medical Management - no CEA in people with Carotid Stenosis, run by Mayo Clinic at 167 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Carotid revascularization for primary prevention of stroke (CREST-2) is two independent multicenter, randomized controlled trials of carotid revascularization and intensive medical management versus medical management alone in patients with asymptomatic high-grade carotid stenosis. Read more about this study

Who is it for?
Ages 35 to 100 years
Conditions the study is for
Carotid Stenosis
What is being tested?
Carotid endarterectomy (CEA), Carotid Stenting (CAS) and Intensive Medical Management - no CEA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,486 participants
Where
167 sitesin 5 countries
Study dates
9 Dec 2014to 12 Sep 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.
  5. 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).
  6. Patients must have a modified Rankin Scale (mRS) score of 0 or 1 at the time of informed consent.
  7. Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization.
  8. Patients must agree to comply with all protocol-specified follow-up appointments.
  9. 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.
  10. 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).
  11. 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.

Trial locations and contacts

167 sites in 5 countries.

167 sites in 5 countries

United States154 sites

  • Lehigh Valley Hospital - Network Office of Research

    Allentown, Pennsylvania, 18103

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • VA Ann Arbor Healthcare System

    Ann Arbor, Michigan, 48105

  • University of Michigan Hospital and Health Systems

    Ann Arbor, Michigan, 48109

  • Atlanta VA Medical Center

    Atlanta, Georgia, 30033

  • Emory University

    Atlanta, Georgia, 30322

  • Seton Medical Center Austin

    Austin, Texas, 78705

  • Cardiothoracic and Vascular Surgeons

    Austin, Texas, 78756

  • University of Maryland VA

    Baltimore, Maryland, 21201

  • Johns Hopkins Medical Institution

    Baltimore, Maryland, 21224

  • Overlake Hospital

    Bellevue, Washington, 98004

  • The University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • St. Elizabeth's Medical Center

    Boston, Massachusetts, 02135

  • Massachusetts General Hospital

    Boston, Massachusetts, 02144

  • Beth Israel Deaconess Medical Center (BIDMC)

    Boston, Massachusetts, 02215

  • SUNY Buffalo

    Buffalo, New York, 14203

  • Cooper University

    Camden, New Jersey, 08103

  • Southern Illinois Healthcare

    Carbondale, Illinois, 62901

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital

    Cincinnati, Ohio, 45220

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Louis Stokes Cleveland VA Medical Center

    Cleveland, Ohio, 44106

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Ohio State Medical Center

    Columbia, Ohio, 43210

  • OhioHealth Research Institute

    Columbus, Ohio, 43214

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • UPMC Hamot

    Erie, Pennsylvania, 16550

  • Northshore University

    Evanston, Illinois, 60201

  • Northwestern University

    Evanston, Illinois, 60208

  • Inova Fairfax Health Care

    Falls Church, Virginia, 22042

  • Sanford Health

    Fargo, North Dakota, 58104

  • Michigan Vascular Center/McLaren- Flint

    Flint, Michigan, 48532

  • Mission Cardiovascular Research Institute

    Fremont, California, 94538

  • Mission Cardiovascular Research

    Fremont, California, 94538

  • University of Florida Health at Shands

    Gainesville, Florida, 32610

  • Minneapolis Clinic of Neurology, Ltd./North Memorial Medical Center

    Golden Valley, Minnesota, 55422

  • St. Mary's Hospital Regional Medical Center

    Grand Junction, Colorado, 81501

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Valley Baptist Medical Center

    Harlingen, Texas, 78551

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • Memorial Hermann Texas Medical Center

    Houston, Texas, 77030

  • Huntsville Hospital/ Heart Center Research Alabama

    Huntsville, Alabama, 35801

  • Franciscan St. Francis Health

    Indianapolis, Indiana, 46237

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

  • University of California Irvine

    Irvine, California, 92868

  • Lyerly Neurosurgery

    Jacksonville, Florida, 32207

  • UF Jacksonville

    Jacksonville, Florida, 32209

  • First Coast Cardiovascular Institute

    Jacksonville, Florida, 32216

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • CVA Heart Institute

    Kingsport, Tennessee, 37660

  • Tennova Healthcare/ Turkey Creek Medical Center

    Knoxville, Tennessee, 37934

  • Gundersen Clinic, Ltd

    La Crosse, Wisconsin, 54601

  • UC San Diego Health

    La Jolla, California, 92037

  • Sparrow Clinical Research Institute

    Lansing, Michigan, 48912

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Baptist Health Lexington

    Lexington, Kentucky, 40503

  • University of Kentucky Hospital

    Lexington, Kentucky, 40536

  • Central Arkansas Veteran's Healthcare System

    Little Rock, Arkansas, 72143

  • Kaiser Permanente Los Angeles

    Los Angeles, California, 90027

  • Keck Medical Center of University of Southern California

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 90095

  • University of Louisville Hospital

    Louisville, Kentucky, 40202

  • Medical Center of the Rockies

    Loveland, Colorado, 80538

  • University of Wisconsin Hospitals & Clinics

    Madison, Wisconsin, 53792

  • The Feinstein Institute of Medical Research/Northwell Health

    Manhasset, New York, 11030

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Baptist Memorial Hospital

    Memphis, Tennessee, 38017

  • University of Miami Hospital

    Miami, Florida, 33136

  • Miami Cardiac and Vascular Institute at Baptist Hospital of Miami

    Miami, Florida, 33176

  • Mount Sinai Medical Center of Florida

    Miami Beach, Florida, 33140

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • West Virginia University

    Morgantown, West Virginia, 26554

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale New Haven Hospital

    New Haven, Connecticut, 06520

  • Tulane University Heart and Vascular

    New Orleans, Louisiana, 70112

  • Ochsner Health System

    New Orleans, Louisiana, 70121

  • Mount Sinai Hospital New York

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Weill Cornell Medical College

    New York, New York, 10065

  • Deaconess Heart Group

    Newburgh, Indiana, 47630

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

  • Cardiovascular Institute of Northwest Florida

    Panama City, Florida, 32401

  • Cardiac and Vascular Research Center of Northern Michigan/McLaren Northern Michigan

    Petoskey, Michigan, 49770

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Banner University Medical Center

    Phoenix, Arizona, 85006

  • St. Joseph's Hospital and Medical Center/Barrow Neurological Institute

    Phoenix, Arizona, 85013

  • Abrazo Arizona Heart Hospital

    Phoenix, Arizona, 85016

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • UPMC Presbyterian University Hospital

    Pittsburgh, Pennsylvania, 15213

  • VA Pittsburgh Healthcare

    Pittsburgh, Pennsylvania, 15240

  • Maine Medical Center

    Portland, Maine, 04102

  • Providence Brain and Spine Institute

    Portland, Oregon, 97225

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • The Miriam Hospital

    Providence, Rhode Island, 02906

  • North Carolina Heart & Vascular Research

    Raleigh, North Carolina, 27607

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Mercy Health Riverside

    Rockford, Illinois, 61114

  • St. Francis Hospital

    Roslyn, New York, 11576

  • William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • St. Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • University of Utah Hospitals and Clinics

    Salt Lake City, Utah, 84132

  • George E. Wahlen Department of Veterans Affairs Medical Center

    Salt Lake City, Utah, 84148

  • University of California San Diego

    San Diego, California, 92103

  • Kaiser Permanente

    San Diego, California, 92116

  • Kaiser Permanente Northern California

    San Francisco, California, 94115

  • University of California San Francisco

    San Francisco, California, 94115

  • San Francisco VA Medical Center

    San Francisco, California, 94121

  • HonorHealth Scottsdale Osborn Medical Center

    Scottsdale, Arizona, 85251

  • University of Washington Medicine-Harborview Medical Center

    Seattle, Washington, 98104

  • VA Puget Sound Health Care System

    Seattle, Washington, 98108

  • Swedish Medical Center

    Seattle, Washington, 98122

  • North Central Heart Institute

    Sioux Falls, South Dakota, 57108

  • Providence Sacred Heart Medical Center

    Spokane, Washington, 99204

  • Prairie Heart/St. John's Hospital

    Springfield, Illinois, 62701

  • Cox Medical Center

    Springfield, Missouri, 65807

  • Mercy Medical Research Institute

    Springfield, Missouri, 65807

  • John Cochran VA Medical Center

    St Louis, Missouri, 63106

  • Mercy Hospital

    St Louis, Missouri, 63141

  • Stanford University Medical Center

    Stanford, California, 94305

  • St. Joseph's Medical Center

    Stockton, California, 95204

  • Stony Brook University

    Stony Brook, New York, 11794

  • Crouse Hospital

    Syracuse, New York, 13210

  • White Oak Medical Center

    Takoma Park, Maryland, 20912

  • Tallahassee Neurological Clinic

    Tallahassee, Florida, 32308

  • Tampa General/University of South Florida

    Tampa, Florida, 33606

  • Jobst Vascular Institute/University of Toledo

    Toledo, Ohio, 43606

  • Mercy Health St. Vincent Medical Center

    Toledo, Ohio, 43608

  • Providence Little Company of Mary Medical Center

    Torrance, California, 90503

  • Banner University Medical Center

    Tucson, Arizona, 85724

  • St. John Clinical Research Institute

    Tulsa, Oklahoma, 74104

  • Medstar/Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Coastal Carolina Surgical Associates PA

    Wilmington, North Carolina, 28401

  • Winchester Medical Center

    Winchester, Virginia, 22601

  • Novant Health/Forsyth Medical Center

    Winston-Salem, North Carolina, 27103

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Memorial Hospital

    Worcester, Massachusetts, 01605

  • Pinnacle Health Cardiovascular Institute

    Wormleysburg, Pennsylvania, 17043

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • Berks Cardiologists / St. Joseph's Medical Center

    Wyomissing, Pennsylvania, 19610

  • Trinity Health/Michigan Heart

    Ypsilanti, Michigan, 48197

Other trials in United States

Israel6 sites

  • Soroka University Medical Center

    Beersheba

  • Soroka University Vascular Surgery

    Beersheba

  • Rambam Healthcare

    Haifa, 3109601

  • Hadassah Medical Center

    Jerusalem, 91120

  • Shaare-Zedek Medical Center

    Jerusalem

  • Rabin Medical Center

    Petah Tikva

Other trials in Israel

Canada5 sites

  • Nova Scotia Health Authority

    Halifax, Nova Scotia, B3H 3A7

  • CHU de Québec/ Hôpital de l'Enfant-Jésus

    Québec, Quebec, G1J1Z4

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

  • St. Boniface Hospital

    Winnipeg, Ontario, R2H 2A6

Other trials in Canada

Australia1 site

  • Fiona Stanley Hospital

    Perth

Other trials in Australia

Spain1 site

  • Hospital Clinic Barcelona

    Barcelona

Other trials in Spain

About this study

Carotid revascularization for primary prevention of stroke (CREST-2) is two independent multicenter, randomized controlled trials of carotid revascularization and intensive medical management versus medical management alone in patients with asymptomatic high-grade carotid stenosis. One trial will randomize patients in a 1:1 ratio to endarterectomy versus no endarterectomy and another will randomize patients in a 1:1 ratio to carotid stenting with embolic protection versus no stenting. Medical management will be uniform for all randomized treatment groups and will be centrally directed.

Read the detailed description

Prevention of stroke involves managing and treating risk factors. Most strokes are caused when blood flow to a portion of the brain is blocked. One place this often happens is in the carotid artery. This blockage is called atherosclerosis or hardening of the arteries.

The purpose of this trial is to determine the best way to prevent strokes in people who have a high amount of blockage of their carotid artery but no stroke symptoms related to that blockage. Each eligible participant will be evaluated to determine which procedure(s) is best for him/her. All participants will receive intensive medical treatment. In addition, participants will be randomized to receive the selected procedure or not.

The trial will be conducted in the United States and Canada by physicians carefully selected on their ability to perform the procedures at low risk. Another key component of the trial is that important stroke risk factors, including hypertension, diabetes, high cholesterol, cigarette smoking, physical activity, and diet will be managed intensively. Participants will remain in the study for 4 years.

Being tested
Carotid endarterectomy (CEA), Carotid Stenting (CAS), Intensive Medical Management - no CEA, Intensive Medical Management - no CAS
Keywords
asymptomatic, carotid, stent, endarterectomy, embolic protection, medical management, hypertension, hyperlipidemia, cognition, risk factor control
Medical subject headings
Carotid Stenosis, Hypertension, Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carotid endarterectomy (CEA)Procedure or surgery

    Carotid endarterectomy

  • Carotid Stenting (CAS)Device

    Carotid stenting

  • Intensive Medical Management - no CEAOther

    Intensive Medical Management alone - no CEA

  • Intensive Medical Management - no CASOther

    Intensive Medical Management alone - no CAS

Study groups in NCT02089217
Study groupRoleWhat they receive
Carotid Endarterectomy (CEA)Active comparatorCarotid Endarterectomy
Receives: Procedure: Carotid endarterectomy (CEA)
Carotid Stenting (CAS)Active comparatorCarotid Stenting
Receives: Device: Carotid Stenting (CAS)
Intensive Medical Management - no CEAExperimentalIntensive Medical Management alone - no CEA
Receives: Other: Intensive Medical Management - no CEA
Intensive Medical Management - no CASExperimentalIntensive Medical Management alone - no CAS
Receives: Other: Intensive Medical Management - no CAS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Stroke and death

    The primary outcome is the composite of stroke plus death within 44 days after randomization and ipsilateral stroke thereafter up to 4 years.

    Measured: 4 years

Secondary outcomes (3)

  1. Cognitive Function

    The assess if MEDICAL management differs from CAS, and differs from CEA, to maintain the level of cognitive function at the 4-year assessment.

    Measured: 4 years

  2. Major Stroke

    if there are treatment differences in the incidence of major stroke at 4-years among all arms of the study

    Measured: 4 years

  3. Effect modification

    Potential effect modification of the CAS or CEA versus MEDICAL differences, based on patient age, sex, severity of carotid stenosis, restenosis, risk factor level, and duration of asymptomatic period.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2014 (estimated)
  2. Study start9 Dec 2014
  3. Primary completion12 Sep 2025
  4. Study completion12 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
CREST-2 is two parallel multi-center randomized, observer-blinded endpoint clinical trials.
Masking
Single blind
Who is masked
Investigator
Enrolment
2,486 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02089217
Sponsor's protocol ID
13-004051
Other IDs
U01NS080168
Acronym
CREST-2
Status last verified
Sep 2025
First submitted
13 Mar 2014
Last updated
1 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Brott TG, Howard G, Lal BK, Voeks JH, Turan TN, Roubin GS, Lazar RM, Brown RD Jr, Huston J 3rd, Edwards LJ, Jones M, Clark WM, Chamorro A, Llull L, Mena-Hurtado C, Heck D, Marshall RS, Howard VJ, Moore WS, Barrett KM, Demaerschalk BM, Sangha N, Aronow H, Foster M, Sternbergh WC 3rd, Shawl F, Lanzino G, Rapp J, Tran HS, Ecker R, Mackey A, Ali V, Given C 2nd, Teal P, Kashyap VS, Mukherjee D, Harrigan M, Silverman S, Koopmann M, Wadley VG, Zhang Y, Rhodes JD, Chaturvedi S, Meschia JF; CREST-2 Investigators. Medical Management and Revascularization for Asymptomatic Carotid Stenosis. N Engl J Med. 2026 Jan 15;394(3):219-231. doi: 10.1056/NEJMoa2508800. Epub 2025 Nov 21.

    PubMed 41269206

  • Meschia JF, Lal B, Roubin G, Turan TN, Howard VJ, Benson RT, Carman K, Howard G, Brott TG. Adapting to Evolving Technologies and Treatment Guidelines in a Procedural Trial: A Qualitative Review of the CREST-2 Experience. Neurology. 2023 May 30;100(22):1060-1066. doi: 10.1212/WNL.0000000000207075. Epub 2023 Feb 6.

    PubMed 36746636

  • Kamtchum-Tatuene J, Saba L, Heldner MR, Poorthuis MHF, de Borst GJ, Rundek T, Kakkos SK, Chaturvedi S, Topakian R, Polak JF, Jickling GC; Carotid Atherosclerosis and Stroke Collaboration (CASCO). Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression. Circ Res. 2022 Jul 8;131(2):e22-e33. doi: 10.1161/CIRCRESAHA.122.320877. Epub 2022 Jun 17.

    PubMed 35713008

  • Lazar RM, Wadley VG, Myers T, Jones MR, Heck DV, Clark WM, Marshall RS, Howard VJ, Voeks JH, Manly JJ, Moy CS, Chaturvedi S, Meschia JF, Lal BK, Brott TG, Howard G. Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial. Stroke. 2021 Dec;52(12):3855-3863. doi: 10.1161/STROKEAHA.120.032972. Epub 2021 Aug 26.

    PubMed 34433306

  • Haley W, Shawl F, Charles Sternbergh W 3rd, Turan TN, Barrett K, Voeks J, Brott T, Meschia JF. Non-Adherence to Antihypertensive Guidelines in Patients with Asymptomatic Carotid Stenosis. J Stroke Cerebrovasc Dis. 2021 Aug;30(8):105918. doi: 10.1016/j.jstrokecerebrovasdis.2021.105918. Epub 2021 Jun 18.

    PubMed 34148021

  • Turan TN, Meschia JF, Chimowitz MI, Roldan A, LeMatty T, Luke S, Breathitt L, Eiland R, Foley J, Brott TG. Mitigating the effects of COVID-19 pandemic on controlling vascular risk factors among participants in a carotid stenosis trial. J Stroke Cerebrovasc Dis. 2020 Dec;29(12):105362. doi: 10.1016/j.jstrokecerebrovasdis.2020.105362. Epub 2020 Sep 30.

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  • Turan TN, Voeks JH, Chimowitz MI, Roldan A, LeMatty T, Haley W, Lopes-Virella M, Chaturvedi S, Jones M, Heck D, Howard G, Lal BK, Meschia JF, Brott TG. Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial. Stroke. 2020 Oct;51(10):2960-2971. doi: 10.1161/STROKEAHA.120.030730. Epub 2020 Sep 21.

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  • Lal BK, Meschia JF, Roubin GS, Jankowitz B, Heck D, Jovin T, White CJ, Rosenfield K, Katzen B, Dabus G, Gray W, Matsumura J, Hopkins LN, Luke S, Sharma J, Voeks JH, Howard G, Brott TG; CREST-2 Investigators. Factors influencing credentialing of interventionists in the CREST-2 trial. J Vasc Surg. 2020 Mar;71(3):854-861. doi: 10.1016/j.jvs.2019.05.035. Epub 2019 Jul 26.

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  • Musialek P, Roubin GS. Commentary: Double-Layer Carotid Stents: From the Clinical Need, through a Stent-in-Stent Strategy, to Effective Plaque Isolation... the Journey Toward Safe Carotid Revascularization Using the Endovascular Route. J Endovasc Ther. 2019 Aug;26(4):572-577. doi: 10.1177/1526602819861546. No abstract available.

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  • Lal BK, Meschia JF, Brott TG. Clinical need, design, and goals for the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis trial. Semin Vasc Surg. 2017 Mar;30(1):2-7. doi: 10.1053/j.semvascsurg.2017.04.004. Epub 2017 Apr 27.

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  • Demaerschalk BM, Brown RD Jr, Roubin GS, Howard VJ, Cesko E, Barrett KM, Longbottom ME, Voeks JH, Chaturvedi S, Brott TG, Lal BK, Meschia JF, Howard G; CREST-2 Investigators. Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial. Stroke. 2017 Sep;48(9):2511-2518. doi: 10.1161/STROKEAHA.117.016976. Epub 2017 Aug 2.

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  • Howard VJ, Meschia JF, Lal BK, Turan TN, Roubin GS, Brown RD Jr, Voeks JH, Barrett KM, Demaerschalk BM, Huston J 3rd, Lazar RM, Moore WS, Wadley VG, Chaturvedi S, Moy CS, Chimowitz M, Howard G, Brott TG; CREST-2 study investigators. Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials. Int J Stroke. 2017 Oct;12(7):770-778. doi: 10.1177/1747493017706238. Epub 2017 May 2.

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Questions about this trial

What is this clinical trial studying?

A study testing Carotid endarterectomy (CEA), Carotid Stenting (CAS) and Intensive Medical Management - no CEA in people with Carotid Stenosis, run by Mayo Clinic at 167 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 167 sites in United States, Israel, Canada, Australia, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Stroke and death (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02089217, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.

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