Carotid Revascularization Endarterectomy Versus Stenting Trial

Stroke Clinical Trial

— CREST  

Official title:

Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00004732
• Other study ID #: 0119970017
• Secondary ID: R01NS038384
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 25, 2000
• Last updated: January 4, 2016
• Start date: December 2000
• Est. completion date: December 2016

Study information

• Verified date: October 2015
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Data and Safety Monitoring BoardUnited States: Institutional Review BoardCanada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is to compare the relatively new procedure of stent-assisted carotid angioplasty (CAS) to the traditional and accepted surgical approach of carotid endarterectomy (CEA) for the treatment of carotid artery stenosis to prevent recurrent strokes in those patients who have had a TIA (transient ischemic attack) or a mild stroke within the past 6 months (symptomatic) and in those patients who have not had any symptoms within the past 6 months (asymptomatic).

Description:

The primary aim of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is to contrast the relative effectiveness of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in preventing stroke, myocardial infarction, and death. Stents are medical devices approved and commonly used for treatment of heart disease. The stent that will be used in this trial is the Rapid Exchange(RX) ACCULINK(TM) Carotid Stent System, an elastic-like metal scaffold that is expanded inside a carotid artery to hold the vessel open.

The RX ACCUNET(TM) Embolic Protection System (an umbrella-like device that expands above the narrowed portion of the carotid artery) will be used in conjunction with the RX ACCULINK stent. The RX ACCUNET system is designed to capture embolic material that could break off from the narrowed area in the carotid artery while still allowing blood to flow through the vessel during the procedure. Embolic material could block blood flow to the arteries beyond the narrowing and be harmful to the brain. The RX ACCUNET System is closed and removed after the stent is placed.

CEA involves a neck incision and physical removal of the plaque from the inside of the artery. CAS involves insertion of a catheter or tube into an artery in the groin and then threading the catheter through the arteries of the body to the location of the plaque within the carotid artery in the neck. The stent is then placed to cover the plaque and hold the artery open. Participants will be randomly assigned to undergo either CAS or CEA, and all patients will receive best medical management, which includes treatment with aspirin, treatment of high blood pressure, and treatment of other stroke risk factors. Participants will be followed for up to ten years.

With the simplification of the protocol for long-term follow-up, the focus for secondary outcomes is to assess restenosis and viability of the procedure. Restenosis rates on an annual basis in both the endarterectomy and stenting arms of the study will be assessed using carotid duplex ultrasound exams performed annually (standard of care).

In addition to restenosis, the "viability" of the procedures will be assessed by the need (or lack of need) for repeat revascularization (either open surgical or endovascular) after the index procedure. The question "has a new carotid intervention been performed since last follow-up" will be asked at every contact with the patient. If answered positively, additional data will be collected on the appropriate case report forms(CRFs).

LINKAGE OF CREST COHORT WITH CENTERS FOR MEDICAID AND MEDICARE SERVICES(CMS) ADMINISTRATIVE DATA

The purpose of linking Medicare-eligible CREST participants with CMS data files is to assess patient outcomes and utilization of health care services. This plan to link in- and out-patient episodes of care using national Medicare data establishes a new resource that will enhance current follow-up strategies, as well as explore alternative strategies to ascertain patient outcomes for future clinical studies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2502
• Est. completion date: December 2016
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Symptomatic patients with recent neurological events (TIA or non-disabling stroke) with an associated carotid stenosis greater than or equal to 50% by angiography or greater than or equal to 70% by ultrasound or greater than or equal to 70% by Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) are eligible for randomization.

• Asymptomatic patients with no recent (in the last 6 months) neurological events referable to the study with artery and carotid stenosis (patients with symptoms beyond 180 days are considered asymptomatic) greater than or equal to 60% by angiography or greater than or equal to 70% by ultrasound or greater than or equal to 80% by CTA or MRA are eligible for randomization.

Exclusion Criteria:

• Conditions that: (1) interfere with the evaluation of endpoints, (2) are known to interfere with the completion of CEA or CAS, or (3) affect the likelihood of survival for the study period (4 years). Chronic atrial fibrillation and/or anti-coagulation or episodic atrial fibrillation within the last 6 months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atherosclerosis
• Carotid Stenosis
• Cerebral Infarction
• Infarction
• Myocardial Infarction
• Stroke

Intervention

Procedure:
• Carotid Endarterectomy (CEA)
CEA involves a neck incision and physical removal of the plaque from the inside of the carotid artery.

Device:
• Carotid Artery Stenting (CAS)
CAS involves insertion of a catheter or tube into an artery in the groin and then threading the catheter through the arteries of the body to the location of the plaque within the carotid artery in the neck. A stent is then placed to cover the plaque and hold the artery open. Participants randomized to this arm of the trial were treated using the RX Acculink Carotid Stent with or without the RX Accunet Embolic Protection Device.

Locations

Country	Name	City	State
Canada	Governors of the University of Calgary and the Calgary Health Region	Calgary	Alberta
Canada	The Credit Valley Hospital and Trillium Health Centre	Mississauga	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHU de Québec	Quebec City	Quebec
Canada	Lawson Health Research Institute	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	The University of British Columbia and The Vancouver Coastal Health Authority	Vancouver	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
United States	Center for Vascular Awareness, Inc.	Albany	New York
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	University of Michigan	Ann Arbor	Michigan
United States	Anne Arundel Health System Research Institute	Annapolis	Maryland
United States	Emory University	Atlanta	Georgia
United States	Piedmont Hospital/Fuqua Heart Center	Atlanta	Georgia
United States	St. Joseph's of Atlanta	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Vascular Surgery Associates	Baton Rouge	Louisiana
United States	Heritage Valley Medical Group	Beaver	Pennsylvania
United States	The Board of Trustees of the University of Alabama for the University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Womens Hospital, Inc.	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Steward St. Elizabeth's Medical Center of Boston, Inc.	Boston	Massachusetts
United States	Millard Fillmore SUNY Buffalo	Buffalo	New York
United States	UNC at Chapel Hill	Chapel Hill	North Carolina
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	The Charlotte-Mecklenburg Hospital Authority	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Norwestern Memorial Hospital	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	The Cleveland Clinic Lerner College Of Medicine of CWRU	Cleveland	Ohio
United States	South Carolina Heart Center	Columbia	South Carolina
United States	Midwest Ohio Health Research Institute	Columbus	Ohio
United States	The University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Catholic Health Initiatives /Mercy Hospital Center	Des Moines	Iowa
United States	Henry Ford Health System	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Alexian Brothers Specialty Group	Elk Grove Village	Illinois
United States	Michigan Vascular Research Center	Flint	Michigan
United States	Lutheran Medical Group, LLC,	Fort Wayne	Indiana
United States	Parkview Hospital, Inc.	Fort Wayne	Indiana
United States	Spectrum Health Hospital	Grand Rapids	Michigan
United States	Houston Methodist Hospital	Houston	Texas
United States	UT Houston Memorial	Houston	Texas
United States	Cape Cod Health Care, Inc.,	Hyannis	Massachusetts
United States	St. Vincent's Hospital	Indianapolis	Indiana
United States	Mississippi Baptist Medical Center, Inc.	Jackson	Mississippi
United States	Mayo Clinic	Jacksonville	Florida
United States	Heartland Physician Services, LLC	Kansas City	Missouri
United States	Metro Knoxville HMA	Knoxville	Tennessee
United States	Dartmouth College and the constituent members of DARTMOUTH HITCHCOCK MEDICAL CENTER	Lebanon	New Hampshire
United States	Leesburg Medical Center	Leesburg	Florida
United States	Baptist Healthcare System, Inc.	Lexington	Kentucky
United States	Board of Trustees of the University of Arkansas	Little Rock	Arkansas
United States	The Regents of the University of California	Los Angeles	California
United States	USC University Hospital & LA County Hospital	Los Angeles	California
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University of Chicago	Maywood	Illinois
United States	Rogue Valley Medical Center	Medford	Oregon
United States	Baptist Memorial Hospital	Memphis	Tennessee
United States	Miami Cardiac & Vascular Institute of Baptist Hospital of Miami, Inc.	Miami	Florida
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	St. Patrick's Hospital International Heart Institute of MT	Missoula	Montana
United States	Ochsner Foundation Hospital	New Orleans	Louisiana
United States	Columbia Presbyterian	New York	New York
United States	NYU School of Medicine	New York	New York
United States	The Feinstein Institute for Medical Research	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health Services, Inc.	Newark	Delaware
United States	St. Michael's Medical Center	Newark	New Jersey
United States	Oklahoma Foundation for Cardiovascular Research	Oklahoma City	Oklahoma
United States	Florida Hospital Neuroscience Institute, a division of Adventist Health System/Sunbelt, Inc.	Orlando	Florida
United States	Orlando Regional Medical Center	Orlando	Florida
United States	Peoria Radiology Research and Education	Peoria	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Dignity Health dba St. Joseph's Hospital & Medical Center	Phoenix	Arizona
United States	Allegheny Singer Research Institute	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Shadyside	Pittsburgh	Pennsylvania
United States	St. Francis Hospital	Port Washington	New York
United States	Oregon Health Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	North Memorial Health Care	Robbinsdale	Minnesota
United States	Mayo Clinic Rochester/St. Mary's	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Intermountain Health Services	Salt Lake City	Utah
United States	Kaiser Permanente Medical Center	San Diego	California
United States	Northern California Institute for Research and Education	San Francisco	California
United States	St. Joseph's Candler Health System	Savannah	Georgia
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Swedish Health Services	Seattle	Washington
United States	Providence St. John Hopital	Southfield	Michigan
United States	Providence Health & Services - Washington	Spokane	Washington
United States	Prarie Cardiology-St. John's Hospital	Springfield	Illinois
United States	Southern Illinois School of Medicine	Springfield	Illinois
United States	Mercy Hospitals East Communities	St. Louis	Missouri
United States	Richmond University Medical Center	Staten Island	New York
United States	Catholic Healthcare West	Stockton	California
United States	Adventist Healthcare, Inc.	Takoma Park	Maryland
United States	University of South Florida Board of Trustees	Tampa	Florida
United States	Scott & White Memorial Hospital	Temple	Texas
United States	The Toledo Hospital	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	The Arizona Board of Regents for the University of Arizona	Tucson	Arizona
United States	Westchester Medical Center	Valhalla	New York
United States	Central Dupage Hospital	Winfield	Illinois
United States	Forsyth Radiological Associates	Winston-Salem	North Carolina
United States	Wake Forest University	Winston-Salem	North Carolina
United States	Michigan Heart & Vascular Institute/St. Joseph's Mercy Hospital	Ypsilanti	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	National Institute of Neurological Disorders and Stroke (NINDS), University of Alabama at Birmingham

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (17)

Blackshear JL, Cutlip DE, Roubin GS, Hill MD, Leimgruber PP, Begg RJ, Cohen DJ, Eidt JF, Narins CR, Prineas RJ, Glasser SP, Voeks JH, Brott TG; CREST Investigators. Myocardial infarction after carotid stenting and endarterectomy: results from the carotid — View Citation

Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W, Mackey A, Hill MD, Leimgruber PP, Sheffet AJ, Howard VJ, Moore WS, Voeks JH, Hopkins LN, Cutlip DE, Cohen DJ, Popma JJ, Ferguson RD, Cohen SN, Blackshear JL, Silver FL, Mohr JP, Lal BK, Mes — View Citation

Hill MD, Brooks W, Mackey A, Clark WM, Meschia JF, Morrish WF, Mohr JP, Rhodes JD, Popma JJ, Lal BK, Longbottom ME, Voeks JH, Howard G, Brott TG; CREST Investigators. Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endart — View Citation

Hobson RW 2nd, Brott T, Ferguson R, Roubin G, Moore W, Kuntz R, Howard G, Ferguson J. CREST: carotid revascularization endarterectomy versus stent trial. Cardiovasc Surg. 1997 Oct;5(5):457-8. — View Citation

Hobson RW 2nd, Brott TG, Roubin GS, Silver FL, Barnett HJ. Carotid artery stenting: meeting the recruitment challenge of a clinical trial. Stroke. 2005 Jun;36(6):1314-5. Epub 2005 Apr 28. — View Citation

Hobson RW 2nd, Howard VJ, Brott TG, Howard G, Roubin GS, Ferguson RD; For the CREST Executive Committee. Organizing the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): National Institutes of Health, Health Care Financing Administration, and industry funding. Curr Control Trials Cardiovasc Med. 2001 Jul 13;2(4):160-164. — View Citation

Hobson RW 2nd, Howard VJ, Roubin GS, Brott TG, Ferguson RD, Popma JJ, Graham DL, Howard G; CREST Investigators. Carotid artery stenting is associated with increased complications in octogenarians: 30-day stroke and death rates in the CREST lead-in phase. J Vasc Surg. 2004 Dec;40(6):1106-11. — View Citation

Hobson RW 2nd, Howard VJ, Roubin GS, Ferguson RD, Brott TG, Howard G, Sheffet AJ, Roberts J, Hopkins LN, Moore WS; CREST. Credentialing of surgeons as interventionalists for carotid artery stenting: experience from the lead-in phase of CREST. J Vasc Surg. 2004 Nov;40(5):952-7. — View Citation

Hopkins LN, Roubin GS, Chakhtoura EY, Gray WA, Ferguson RD, Katzen BT, Rosenfield K, Goldstein J, Cutlip DE, Morrish W, Lal BK, Sheffet AJ, Tom M, Hughes S, Voeks J, Kathir K, Meschia JF, Hobson RW 2nd, Brott TG. The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase. J Stroke Cerebrovasc Dis. 2010 Mar;19(2):153-62. doi: 10.1016/j.jstrokecerebrovasdis.2010.01.001. — View Citation

Howard VJ, Voeks JH, Lutsep HL, Mackey A, Milot G, Sam AD 2nd, Tom M, Hughes SE, Sheffet AJ, Longbottom M, Avery JB, Hobson RW 2nd, Brott TG. Does sex matter? Thirty-day stroke and death rates after carotid artery stenting in women versus men: results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) lead-in phase. Stroke. 2009 Apr;40(4):1140-7. doi: 10.1161/STROKEAHA.108.541847. Epub 2009 Feb 10. — View Citation

Lal BK, Beach KW, Roubin GS, Lutsep HL, Moore WS, Malas MB, Chiu D, Gonzales NR, Burke JL, Rinaldi M, Elmore JR, Weaver FA, Narins CR, Foster M, Hodgson KJ, Shepard AD, Meschia JF, Bergelin RO, Voeks JH, Howard G, Brott TG; CREST Investigators. Restenosis — View Citation

Lal BK, Brott TG. The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results. J Vasc Surg. 2009 Nov;50(5):1224-31. doi: 10.1016/j.jvs.2009.09.003. — View Citation

Mantese VA, Timaran CH, Chiu D, Begg RJ, Brott TG; CREST Investigators. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): stenting versus carotid endarterectomy for carotid disease. Stroke. 2010 Oct;41(10 Suppl):S31-4. doi: 10.11 — View Citation

Sheffet AJ, Roubin G, Howard G, Howard V, Moore W, Meschia JF, Hobson RW 2nd, Brott TG. Design of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST). Int J Stroke. 2010 Feb;5(1):40-6. doi: 10.1111/j.1747-4949.2009.00405.x. — View Citation

Silver FL, Mackey A, Clark WM, Brooks W, Timaran CH, Chiu D, Goldstein LB, Meschia JF, Ferguson RD, Moore WS, Howard G, Brott TG; CREST Investigators. Safety of stenting and endarterectomy by symptomatic status in the Carotid Revascularization Endarterect — View Citation

Timaran CH, Mantese VA, Malas M, Brown OW, Lal BK, Moore WS, Voeks JH, Brott TG; CREST Investigators. Differential outcomes of carotid stenting and endarterectomy performed exclusively by vascular surgeons in the Carotid Revascularization Endarterectomy v — View Citation

Vilain KR, Magnuson EA, Li H, Clark WM, Begg RJ, Sam AD 2nd, Sternbergh WC 3rd, Weaver FA, Gray WA, Voeks JH, Brott TG, Cohen DJ; CREST Investigators. Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Any Periprocedural Stroke, Myocardial Infarction, or Death or Postprocedural Ipsilateral Stroke	4-year follow-up, proportions reflecting the absolute efficacy of carotid-artery stenting (CAS) over that of carotid endarterectomy (CEA) were based on Kaplan-Meier survival estimates at the end of the 4 years.	4 years	Yes
Secondary	Differential Efficacy of CAS and CEA in Male and Female Participants in the Primary Endpoint (Any Periprocedural Stroke, Myocardial Infarction, or Death or Postprocedural Ipsilateral Stroke).	4-year follow-up, proportions reflecting the absolute efficacy of carotid-artery stenting (CAS) over that of carotid endarterectomy (CEA) were based on Kaplan-Meier survival estimates at the end of the 4 years.	4 years	Yes

External Links

•   CREST Website