Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)
CREST-H
2 other identifiers
interventional
385
2 countries
58
Brief Summary
We aim to determine whether cognitive impairment attributable to cerebral hemodynamic impairment in patients with high-grade asymptomatic carotid artery stenosis is reversible with restoration of flow. To accomplish this aim CREST-H will add on to the NINDS-sponsored CREST-2 trial (parallel, outcome-blinded Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus intensive medical management (IMM) versus IMM alone (n=1,240), and carotid artery stenting plus IMM versus IMM alone (n=1,240) to prevent stroke and death). CREST-H addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 -randomized patients. We will enroll 385 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We anticipate identifying 100 patients with hemodynamic impairment as measured by an inter-hemispheral MRI perfusion "time to peak" (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are randomized to a revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical-only arm compared with this treatment difference for those who have no flow failure. We hypothesize that hemodynamically significant "asymptomatic" carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2018
Longer than P75 for phase_3
58 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 14, 2017
CompletedFirst Posted
Study publicly available on registry
April 20, 2017
CompletedStudy Start
First participant enrolled
January 18, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2027
September 26, 2025
September 1, 2025
9 years
April 14, 2017
September 23, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Cognitive score at 1 year
Change in composite cognitive Z-score at 1 year will be computed from the cognitive battery of the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2; NCT02089217). Range: -2.0 to 2.0. Positive Z-score change indicates improvement; negative Z-score change indicates worsening.
1 year
Secondary Outcomes (2)
MRI-determined silent infarcts present at 1 year that were not present at baseline.
1 year
Change from baseline of White matter hyperintensity (WMH) volume as measured by T2 FLAIR sequence on brain MRI.
1 year
Other Outcomes (3)
Cognitive score beyond 1 year
2, 3, and 4 years
Correlation between change in cognition at 1 year, as measured in Outcome 1, and change in brain blood flow at 1 year as measured by time-to-peak (TTP) perfusion-weighted imaging (PWI) by MRI or computed tomography (CT).
1 year
Correlation of between change in cognition at 1 year and change in brain blood flow using other MRI PWI markers (CBF, CBV, Tmax).
1 year
Study Arms (2)
Revascularization Arm (CEA or CAS)
ACTIVE COMPARATORThese patients will have been randomized (via the parent trial, CREST-2) to receive intensive medical management as well as either Carotid Endarterectomy (CEA--if they are in the parent study Surgical trial) or Carotid Artery Stenting (CAS--if they are in the parent study Stenting trial).
Intensive Medical Management (IMM) Arm
ACTIVE COMPARATORThese patients will have been randomized (via the parent trial, CREST-2) to receive medical management only, which includes aspirin. high dose cholesterol lowering agent to a target LDL\<70, intensive blood pressure management to target \<130/80, smoking cessation, and diabetic control.
Interventions
Patients in this arm are randomized to CEA/CAS plus IMM
Patients in this arm are randomized to intensive medical management (IMM) alone
Eligibility Criteria
You may qualify if:
- Enrolled and randomized into CREST-2 (parent study)
- age 35-86
You may not qualify if:
- unable to undergo MRI (e.g. metal in body, pacemaker)
- known allergy gadolinium contrast dye
- pre-existing diagnosis of dementia
- contralateral ICA stenosis \>70% by MRA, CTA or Doppler ultrasound
- history of severe head trauma
- major depression
- education less than 8 years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Columbia Universitylead
- National Institute of Neurological Disorders and Stroke (NINDS)collaborator
- Mayo Cliniccollaborator
- University of Alabama at Birminghamcollaborator
- University of Marylandcollaborator
- University of California, Los Angelescollaborator
Study Sites (58)
The University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Huntsville Hospital/ Heart Center Research Alabama
Huntsville, Alabama, 35801, United States
St. Joseph's Hospital and Medical Center/ Barrow
Phoenix, Arizona, 85013, United States
University of Arizona
Tucson, Arizona, 85724, United States
Central Arkansas Veteran's Healthcare System
Little Rock, Arkansas, 72143, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027, United States
Keck Medical Center of University of Southern California
Los Angeles, California, 90033, United States
University of California at Los Angeles
Los Angeles, California, 90095, United States
Kaiser Permanente
San Diego, California, 92123, United States
University of California San Diego
San Diego, California, 92182, United States
San Francisco VA Medical Center
San Francisco, California, 94121, United States
Stanford University Medical Center
Stanford, California, 94305, United States
Yale New Haven Hospital
New Haven, Connecticut, 06520, United States
Morton Plant Hospital
Clearwater, Florida, 33756, United States
University of Florida Health at Shands
Gainesville, Florida, 32610, United States
Mayo Clinic Florida
Jacksonville, Florida, 322224, United States
University of Miami Hospital
Miami, Florida, 33136, United States
University of Chicago
Chicago, Illinois, 60637, United States
Northwestern University
Evanston, Illinois, 60208, United States
Mercy Health Riverside
Rockford, Illinois, 61114, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Ochsner Health System
New Orleans, Louisiana, 70121, United States
Maine Medical Center
Portland, Maine, 04102, United States
University of Maryland VA
Baltimore, Maryland, 21201, United States
Adventist HealthCare/White Oak Medical Center
Gaithersburg, Maryland, 20878, 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
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Mercy Hospital St Louis
St Louis, Missouri, 63141, United States
SUNY Buffalo
Buffalo, New York, 14203, United States
New York Presbyterian Columbia University Medical Center
New York, New York, 10032, United States
Weill Cornell Medical Center
New York, New York, 10065, United States
Novant Health Forsythe
Winston-Salem, North Carolina, 27103, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Louis Stokes Cleveland VA Medical Center
Cleveland, Ohio, 44106, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Ohio State Medical Center
Columbus, Ohio, 43210, United States
Ohio Health Research Institute
Columbus, Ohio, 43214,, United States
UPMC Altoona
Altoona, Pennsylvania, 16601, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
UPMC Presbyterian University Hospital
Pittsburgh, Pennsylvania, 15213, United States
The Miriam Hospital/ Rhode Island Hospital
Providence, Rhode Island, 02906, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
North Central Heart Institute
Sioux Falls, South Dakota, 57108, United States
Tennova Healthcare/ Turkey Creek Medical Center
Knoxville, Tennessee, 37934, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Intermountain Medical Center
Murray, Utah, 84107, 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
Inova Fairfax Health Care
Falls Church, Virginia, 22042, United States
Overlake Hospital Medical Center
Bellevue, Washington, 98004, United States
University of Washington Medicine-Harborview Medical Center
Seattle, Washington, 98104, United States
VA Puget Sound Health Care System
Seattle, Washington, 98108, United States
Gundersen Clinic, Ltd
La Crosse, Wisconsin, 54601, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9, Canada
St. Boniface Hospital
Winnipeg, Manitoba, MB R2H 2A6, Canada
Related Publications (2)
Marshall RS, Lazar RM, Liebeskind DS, Connolly ES, Howard G, Lal BK, Huston J 3rd, Meschia JF, Brott TG. Carotid revascularization and medical management for asymptomatic carotid stenosis - Hemodynamics (CREST-H): Study design and rationale. Int J Stroke. 2018 Dec;13(9):985-991. doi: 10.1177/1747493018790088. Epub 2018 Aug 22.
PMID: 30132751BACKGROUNDMarshall RS, Liebeskind DS, Iii JH, Edwards LJ, Howard G, Meschia JF, Brott TG, Lal BK, Heck D, Lanzino G, Sangha N, Kashyap VS, Morales CD, Cotton-Samuel D, Rivera AM, Brickman AM, Lazar RM. Cortical Thinning in High-Grade Asymptomatic Carotid Stenosis. J Stroke. 2023 Jan;25(1):92-100. doi: 10.5853/jos.2022.02285. Epub 2023 Jan 3.
PMID: 36592969BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Randolph S Marshall, MD
Columbia University
- STUDY DIRECTOR
Ronald M Lazar, PhD
University of Alabama at Birmingham
- STUDY DIRECTOR
E Sander Connolly, MD
Columbia University
- STUDY DIRECTOR
David S Liebeskind, MD
University of California, Los Angeles
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- single blind by outcomes assessor
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Neurology
Study Record Dates
First Submitted
April 14, 2017
First Posted
April 20, 2017
Study Start
January 18, 2018
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
July 31, 2027
Last Updated
September 26, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- As per NIH/NINDS requirements.
- Access Criteria
- All items required by NIH/NINDS will be publicly shared.
To share individual participant data (IPD) of baseline characteristics, follow up, outcomes, etc. based on NIH/NINDS requirements.