Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)

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.

Conditions

• Internal Carotid Artery Stenosis
• Cognitive Impairment

Interventions

PROCEDURE

Revascularization

Patients in this arm are randomized to CEA/CAS plus IMM

OTHER

Intensive Medical Management (IMM) alone

Patients in this arm are randomized to intensive medical management (IMM) alone

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• Mayo Clinic

  collaborator OTHER

• University of Alabama at Birmingham

  collaborator OTHER

• University of Maryland

  collaborator OTHER

• University of California, Los Angeles

  collaborator OTHER

• Columbia University

  lead OTHER

Principal Investigators

• Randolph S Marshall, MD · Columbia University

• Ronald M Lazar, PhD · University of Alabama at Birmingham

• E Sander Connolly, MD · Columbia University

• David S Liebeskind, MD · University of California, Los Angeles

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

86 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-18

Primary Completion

2027-01-31

Completion

2027-07-31

Countries

• United States
• Canada

Study Locations