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Principal Investigator: Thomas G Brott
Organization: MAYO CLINIC JACKSONVILLE
Fiscal Year: 2024
Award: $1,284,994
Funding agency: National Institute of Neurological Disorders and Stroke
The broad, long-term objective of this application is to advance primary prevention of stroke in patients at risk for stroke due to atherosclerosis of the carotid artery. One to two percent of adults in the U.S. have asymptomatic atherosclerotic stenosis of the carotid artery exceeding 50% luminal narrowing. Carotid stenosis is often managed either by endarterectomy or stenting. About 100,000 carotid endarterectomies and 40,000 carotid stenting procedures are done each year in the US. Up to 90% of these procedures are done on asymptomatic patients. The findings of trials assessing the efficacy of revascularization begun in the 1980’s and 1990’s that showed efficacy of revascularization are now in question because of improvements in medical therapy to prevent atherosclerosis and atherothrombosis and concurrent improvements in revascularization by endarterectomy and by carotid stenting. To address the question of how best to treat patients with ≥70% carotid bifurcation stenosis to prevent stroke, we are currently completing the first funding cycle for the CREST-2 trials. CREST-2 is a pair of parallel randomized, multicenter trials with the primary aims: 1) to compare the effectiveness of intensive medical management (IMM) vs. carotid endarterectomy plus IMM (n=1240), and 2) to compare the effectiveness of IMM vs. carotid stenting plus IMM (n=1240). The primary endpoint is a composite of any stroke or death within 44 days of randomization (periprocedural risk) plus ipsilateral stroke up to 4 years of follow-up. An important secondary endpoint is cognitive function, assessed periodically and by a centralized, standardized computer- aided telephone interview. Endpoints are assessed in a manner blinded to treatment assignment. IMM involves central management of vascular risk factors, including hypertension, diabetes mellitus, cigarette smoking and hyperlipidemia. Primary risk factor therapeutic targets are systolic blood pressure <130 mmHg and a low- density lipoprotein (LDL) cholesterol level of <70 mg/dL. IMM also includes telephone-delivered periodic lifestyle coaching. Preliminary data show that the IMM has significantly favorably improved vascular risk factors across treatment arms. As of October 26, 2020, a total of 70% (1734/2480) of the required patients have been randomized across the US, Canada, and Spain. All procedures are performed only by rigorously credentialed surgeons and interventionists. IMM and revascularization procedures are being successfully delivered. Cross- overs and withdrawal from the study are within design assumptions, and the quality of the data is high. CREST-2 supports a companion ancillary study known as CREST-H (NCT03121209) that tests the cognitive implications of revascularization in patients with hemispheric hypoperfusion. We are requesting support to complete recruitment, complete follow-up of the cohort (2-years after recruitment of last patient), and report study results.
Terms: <21+ years old><Abbreviations><Acceleration><Active Follow-up><Address><Adult><Adult Human><Affect><Age><Alabama><Ancillary Study><Apoplexy><Applications Grants><Atherosclerosis><Atherosclerotic Cardiovascular Disease><Blinded><Blood Pressure><Brain Vascular Accident><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CV-19><Canada><Carotid Arteries><Carotid Artery Narrowing><Carotid Artery Stenosis><Carotid Atheroscleroses><Carotid Atherosclerotic Disease><Carotid Endarterectomy><Carotid Stenosis><Carotid stent><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Cessation of life><Clinical><Clinical Trials><Clinical Trials Data Monitoring Committees><Companions><Computer Assisted><Coronavirus Infectious Disease 2019><Credentialing><Data><Data Coordinating Center><Data Coordination Center><Data Monitoring Committees><Data and Safety Monitoring Boards><Death><Detection><Devices><Diabetes Mellitus><Doppler Ultrasound><Endarterectomy><Enrollment><Ensure><Event><Funding><Goals><Grant Proposals><Hyperlipemia><Hyperlipidemia><Hypertension><Informed Consent><Investigators><Ipsilateral><Knowledge><LDL Cholesterol><LDL Cholesterol Lipoproteins><Life Style><Lifestyle><Lipoproteins><Low Density Lipoprotein Cholesterol><Medical><Medical Records><Modernization><Monitor><Multi-center trial><Multicenter Trials><Operative Procedures><Operative Surgical Procedures><Outcome><Outcome Assessment><Outcome Study><Pathologic Constriction><Pathological Constriction><Patient Recruitments><Patients><Periodicals><Primary Prevention><Procedures><Proprotein Convertases><Protocol><Protocols documentation><Radial><Radius><Randomization trial><Randomized><Recommendation><Reporting><Research Design><Research Personnel><Researchers><Risk><Risk Factors><Risk Reduction><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Safety Monitoring Boards><Serine Endopeptidases><Serine Protease><Serine Protein Hydrolases><Serine Proteinases><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severities><Site><Spain><Standardization><Stenosis><Stents><Stroke><Stroke prevention><Study Subject><Study Type><Subtilisins><Surgeon><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><Telephone Interviews><United States><Universities><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Withdrawal><active followup><adjudication><adjudicative process and procedure><adulthood><ages><artery stenosis><atheromatosis><atherosclerotic disease><atherosclerotic vascular disease><atherothrombosis><beta-Lipoprotein Cholesterol><brain attack><cardiovascular risk><cardiovascular risk factor><carotid artery stent><carotid stenting><cerebral vascular accident><cerebrovascular accident><cigarette smoking><cigarette use><cognitive assessment><cognitive change><cognitive function><cognitive testing><cohort><compare effectiveness><computer aided><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><data management><data management and coordinating center><data management center><delivered via telephone><design><designing><determine efficacy><diabetes><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><enroll><evaluate efficacy><examine efficacy><experience><follow up><follow up assessment><follow-up><followed up><followup><followup assessment><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><hypoperfusion><improved><inhibitor><intervention arm><meeting><meetings><operation><operations><participant recruitment><periodic><periodical><prevent><prevent stroke><preventing><primary end point><primary endpoint><primary outcome><randomisation><randomization><randomized trial><randomized, clinical trials><randomly assigned><recruit><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><restenosis><revascularization><risk for stroke><risk of stroke><risk-reducing><safe patient><safety study><secondary end point><secondary endpoint><secondary outcome><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><stroke event><stroke risk><stroked><strokes><study design><success><surgery><telephone based delivery><telephone delivered><telephone delivery><therapeutic target><treatment arm><treatment group><trial comparing><vascular risk factor>