This is a competitive renewal for the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) that is designed to establish the relative efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS). During the initial funding period we have successfully completed enrollment of our pre-specified cohort of 2522 participants. Peri-procedural and mid-term outcomes, over a projected mean follow-up of 2.8 years, will be reported in February of 2010 or earlier. The primary results from CREST, publication of the primary results from ICSS, and the results of other revascularization trials including SAPPHIRE, EVA-3S, and SPACE will provide solid """"""""Level 1A"""""""" evidence to guide carotid treatment over a 2 to 4 year time horizon. This is in contrast to patients living decades after CEA and CAS have been performed. The discordance between the time horizons of studies and the duration that patients may benefit creates a knowledge gap where there is a true dearth of evidence. In this competitive renewal we seek funding to continue to monitor these participants for an additional 5 years, with the potential for follow-up of up to 10 years. Our Primary Aim is to extend follow-up of the CREST cohort beyond 4 years and to assess the relative efficacy of CEA versus CAS over the 6 to 10 year post-procedural period in the prevention of ipsilateral stroke. Secondary aims will 1) assess if there are effect modifiers of the long-term durability of the two procedures, such as age, sex, pre-operative degree of stenosis and symptomatic status, 2) assess if there is a temporal change or pattern in the relative efficacy of the two procedures, 3) assess differences between groups in the rates of restenosis or revascularization, 4) link Medicare-eligible CREST participants with inpatient and outpatient CMS data files to assess patient outcomes and utilization of healthcare services, 5) collect DNA on available randomized subjects for future studies of genetic determinants of response to revascularization. We plan to extend follow-up of the existing 2522 enrolled with annual clinic visits interspersed with midpoint telephone contacts, from an average 2.8 years at the time of primary outcome reporting to an average 7.5 years, with a maximum follow-up of 10 years. With extended follow-up, statistical analysis of the primary aim will assess post-procedural treatment differences from Day 31 for up to 10 years of follow-up and is designed to provide 90% power to detect a hazard ratio of 1.67. With the focus of long-term follow-up on clinical outcomes, simplification of the follow-up protocol will result in reduced patient/clinic burden, reduced cost, and improved data quality. It is anticipated that CREST long-term results will have practice-changing implications regarding the standard of care for managing symptomatic and asymptomatic carotid arterial stenosis.

Public Health Relevance

CREST will provide data regarding the long-term durability of CEA versus CAS for the medical community, CMS and other healthcare agencies to empower decision-making for the optimum management of carotid disease with a corresponding reduction in the number and cost of strokes annually. Linkage to CMS in- and out-patient data files will provide a model for resource utilization and cost of care for the elderly and future studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01NS038384-12
Application #
7887490
Study Section
Special Emphasis Panel (ZNS1-SRB-G (44))
Program Officer
Cordell, Janice
Project Start
1999-01-15
Project End
2016-12-31
Budget Start
2012-01-15
Budget End
2012-12-31
Support Year
12
Fiscal Year
2012
Total Cost
$3,674,594
Indirect Cost
$831,718
Name
University of Medicine & Dentistry of NJ
Department
Surgery
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
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Sheffet, Alice J; Howard, George; Sam, Albert et al. (2018) Challenge and Yield of Enrolling Racially and Ethnically Diverse Patient Populations in Low Event Rate Clinical Trials. Stroke 49:84-89
Müller, Mandy D; von Felten, Stefanie; Algra, Ale et al. (2018) Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis. Stroke 49:2715-2722
Brott, Thomas G; Meschia, James F; Lal, Brajesh K (2017) Duplex velocity criteria for carotid endarterectomy. J Vasc Surg 65:938-939
Lichtman, Judith H; Jones, Michael R; Leifheit, Erica C et al. (2017) Carotid Endarterectomy and Carotid Artery Stenting in the US Medicare Population, 1999-2014. JAMA 318:1035-1046
Brott, Thomas G; Howard, George; Roubin, Gary S et al. (2016) Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis. N Engl J Med 374:1021-31
Moore, Wesley S; Popma, Jeffrey J; Roubin, Gary S et al. (2016) Carotid angiographic characteristics in the CREST trial were major contributors to periprocedural stroke and death differences between carotid artery stenting and carotid endarterectomy. J Vasc Surg 63:851-7, 858.e1
Hye, Robert J; Voeks, Jenifer H; Malas, Mahmoud B et al. (2016) Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). J Vasc Surg 64:3-8.e1
Howard, George; Hopkins, L Nelson; Moore, Wesley S et al. (2015) Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial. Stroke 46:2183-9
Sheffet, Alice J; Voeks, Jenifer H; Mackey, Ariane et al. (2015) Characteristics of participants consenting versus declining follow-up for up to 10?years in a randomized clinical trial. Clin Trials 12:657-63

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