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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02089217




Registration number
NCT02089217
Ethics application status
Date submitted
13/03/2014
Date registered
17/03/2014
Date last updated
16/01/2024

Titles & IDs
Public title
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial
Scientific title
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial
Secondary ID [1] 0 0
U01NS080168
Secondary ID [2] 0 0
13-004051
Universal Trial Number (UTN)
Trial acronym
CREST-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carotid Stenosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Carotid endarterectomy (CEA)
Treatment: Devices - Carotid Stenting (CAS)
Other interventions - Intensive Medical Management - no CEA
Other interventions - Intensive Medical Management - no CAS

Active Comparator: Carotid Endarterectomy (CEA) - Carotid Endarterectomy

Active Comparator: Carotid Stenting (CAS) - Carotid Stenting

Experimental: Intensive Medical Management - no CEA - Intensive Medical Management alone - no CEA

Experimental: Intensive Medical Management - no CAS - Intensive Medical Management alone - no CAS


Treatment: Surgery: Carotid endarterectomy (CEA)
Carotid endarterectomy

Treatment: Devices: Carotid Stenting (CAS)
Carotid stenting

Other interventions: Intensive Medical Management - no CEA
Intensive Medical Management alone - no CEA

Other interventions: Intensive Medical Management - no CAS
Intensive Medical Management alone - no CAS
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Devices
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stroke and death
Timepoint [1] 0 0
4 years
Secondary outcome [1] 0 0
Cognitive Function
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Major Stroke
Timepoint [2] 0 0
4 years
Secondary outcome [3] 0 0
Effect modification
Timepoint [3] 0 0
4 years

Eligibility
Key inclusion criteria
General Inclusion Criteria

1. Patients =35 years old.

2. Carotid stenosis defined as:

- Stenosis =70% by catheter angiography (NASCET Criteria); OR

- by 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. CTA with = 70% stenosis, or

4. MRA with = 70% stenosis.

3. No medical history of stroke or 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).18

4. Patients must have a modified Rankin Scale 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 CEA, CAS, or either procedure.

General
Minimum age
35 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

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 PFO with prior
paradoxical embolism.

14. Unstable angina defined as rest angina with 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 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 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 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 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, CT, 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2026
Actual
Sample size
Target
2480
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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District of Columbia
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New Hampshire
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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Wisconsin
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Canada
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British Columbia
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Canada
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Nova Scotia
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Ontario
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Quebec
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Israel
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Be'er Sheva
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petach Tikva
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Spain
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Barcelona

Funding & Sponsors
Primary sponsor type
Other
Name
Thomas G. Brott, M.D.
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02089217
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas G. Brott, MD
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
CREST-2 Administrative Center
Address 0 0
Country 0 0
Phone 0 0
844-956-1826
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02089217