Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults
- Conditions
- Cognitive Impairment, MildDementiaCardiovascular Diseases
- Interventions
- Drug: Placebo oral tablet
- Registration Number
- NCT04262206
- Lead Sponsor
- Duke University
- Brief Summary
PREVENTABLE is a multi-center, randomized, parallel group, placebo-controlled superiority study. Participants will be randomized 1:1 to atorvastatin 40 mg or placebo. This large study conducted in community-dwelling older adults without cardiovascular disease (CVD) or dementia will demonstrate the benefit of statins for reducing the primary composite of death, dementia, and persistent disability and secondary composites including mild cognitive impairment (MCI) and cardiovascular events.
- Detailed Description
PREVENTABLE will randomly assign atorvastatin 40 mg daily or matching placebo daily to approximately 20,000 community-dwelling adults 75 years of age or older without clinically evident cardiovascular disease, significant disability, or dementia, and follow them for up to 5 years (estimated median of 3.8 years). The study will enroll participants from approximately 100 US sites. Community engagement efforts will leverage community groups and practices as collaborators for recruitment. We plan to partner with participants, caregivers, and clinicians in all aspects of the study. The enrolling sites are non-VA and VA sites. To assist in recruitment, sites will apply a study-specific cohort identification algorithm to their electronic health record to create a list of eligible participants based on study inclusion and exclusion criteria. The cohort identification will exclude individuals with clinically evident cardiovascular disease, significant disability, or dementia and other exclusions obtainable from data queries to define a potential cohort. Additionally, the PREVENTABLE CCC will provide a centralized support team to assist with recruitment and retention efforts. This includes mass mailings and/or phone calls to potential participants and a toll-free number for potential participants to call for information and pre-screening. Interested and potentially eligible participants will be referred to an enrolling site near them, if applicable, otherwise, they will be referred to the PREVENTABLE Telesite which is capable of enrolling English and Spanish-speaking participants across the U.S. remotely. Sites will screen potential participants to confirm eligibility and consent and randomize those interested in joining the study. Specifically related to dementia, the qualifying exclusion is a clinical diagnosis in the chart or clinician's assessment that dementia may be present.
Sites will enter contact information, mailing address for study drug, demographic information, height, weight, statin history (if any), Social Security Number, and aspects of the medical history not obtainable from EHR. In addition, a Short Physical Performance Battery (SPPB) and Activities of Daily Living (ADL) screen will be site-performed at baseline. SPPB will provide an objective assessment of function for understanding frailty and physical function of the enrolled population. Baseline lipid panel (core lab) and biospecimen samples will be obtained using the same blood draw for 20cc of blood. Blinded lipid testing will be performed at baseline on all participants (n=20,000) and repeated at 3 months in a random subset (n=2,000). Lipid panels will be sent to the PREVENTABLE Core Lab to maintain study blind. Future testing of lipid panels during routine clinical care will be actively discouraged, but other laboratory testing as indicated by clinical care is permitted. Sites will have the option for telehealth enrollment. Baseline SPPB and Biorepository Labs are not required, but encouraged.
As part of the study operations, with the rationale of providing patient centricity, ease of participation, and access for vulnerable and at risk participants, follow up will be performed by a central call center. The baseline and annual assessments performed centrally will include a phone screen for cognitive function (TICS-M) and physical function (Patient-reported Outcome Measurement Information System-Physical Function \[PROMIS-PF\]). After year 1, if baseline calls indicated by crossing pre-specified cutpoints, in-person assessments will be completed by trained and certified research staff at a mutually agreed upon time and a standardized interview of a knowledgeable informant. Cardiovascular event ascertainment will be via a systematic approach to data curation from the EHR, Medicare, and National Death Index. For convenience and compliance, the study pharmacy will mail a supply of study drug, sufficient for 90 days, directly to participants. This will start immediately after randomization and continue as long as the participant is on study drug.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20000
- Community-dwelling adults
- Age ≥75 years
- English or Spanish as primary language
- Able to provide a trusted contact
- Clinically evident cardiovascular disease defined as prior myocardial Infarction (MI), prior stroke, prior revascularization procedure, or a secondary prevention indication for a statin (clinician determined)
- Hospitalization for a primary diagnosis of heart failure in the prior 12 months (Note: History of heart failure in the absence of recent hospitalization or clinically evident cardiovascular disease is not an exclusion)
- Dementia (clinically evident or previously diagnosed)
- Dependence in any Katz Basic Activities of Daily Living [ADL] (with the exception of urinary or bowel continence)
- Severe hearing impairment (preventing phone follow up)
- Unable to talk (preventing phone follow up)
- Statin use in the past year or for longer than 5 years previously (participant reported)
- Ineligible to take atorvastatin 40 mg (clinician determined)
- Documented intolerance to statins
- Active Liver Disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo oral tablet matching placebo po qd from consent to study end atorvastatin 40mg Atorvastatin 40 Mg Oral Tablet 40mg atorvastatin po qd from consent to study end
- Primary Outcome Measures
Name Time Method Number of patients without of persistent disability 4 years Number of patients without chronic disability in each group
Number of patients without diagnosis of new dementia 4 years Number of patients without diagnosis of new dementia in each group (placebo vs. atorvastatin)
- Secondary Outcome Measures
Name Time Method Cardiovascular mortality measured as a composite of CV death, hospitalization for myocardial infarction/unstable angina, heart failure, stroke/TIA, or coronary revascularization 4 years Cardiovascular mortality is measured by a composite measure of multiple CV conditions.
Cognitive disability as measured as a composite of MCI or probable dementia 4 years Cognitive disability is measured by a composite of having mild cognitive impairment or probable dementia.
Trial Locations
- Locations (102)
Fresno VA Medical Center
🇺🇸Fresno, California, United States
Baylor Scott and White Medical Center
🇺🇸Dallas, Texas, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
VA Boston Healthcare System
🇺🇸Boston, Massachusetts, United States
University of Texas at Houston
🇺🇸Houston, Texas, United States
VA San Diego Medical Center
🇺🇸San Diego, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Indianapolis VA Medical Center
🇺🇸Indianapolis, Indiana, United States
Duke University - Kannapolis
🇺🇸Kannapolis, North Carolina, United States
Corporal Michael J. Crescenz VA Medical Center-Philadelphia VA
🇺🇸Philadelphia, Pennsylvania, United States
VA Hudson Valley Healthcare System
🇺🇸Montrose, New York, United States
Asheville VA-Charles George VA Medical Center
🇺🇸Asheville, North Carolina, United States
Cincinnati VA Medical Center
🇺🇸Cincinnati, Ohio, United States
Northwell Health
🇺🇸Manhasset, New York, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Clarksburg VA Medical Center
🇺🇸Clarksburg, West Virginia, United States
VA Carribbean Healthcare
🇵🇷San Juan, Puerto Rico
Columbia VA Health Care/Dorn VA Medical Center
🇺🇸Columbia, South Carolina, United States
Allina Health
🇺🇸Minneapolis, Minnesota, United States
PREVENTABLE Tele-Site
🇺🇸Durham, North Carolina, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Duke University
🇺🇸Durham, North Carolina, United States
San Antonio VA Medical Center
🇺🇸San Antonio, Texas, United States
Kansas City VA Medical Center
🇺🇸Kansas City, Kansas, United States
VA Eastern Kansas Healthcare System
🇺🇸Topeka, Kansas, United States
Meharry Medical College
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
VA Salt Lake City Healthcare System
🇺🇸Salt Lake City, Utah, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Omaha VA Medical Center
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Milwaukee VA Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
VA New York Harbor Healthcare System
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Birmingham VA
🇺🇸Birmingham, Alabama, United States
Little Rock VA Medical Center
🇺🇸Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
VA Greater Los Angeles
🇺🇸Los Angeles, California, United States
Long Beach VA Medical Center
🇺🇸Long Beach, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
VA Palo Alto Healthcare System
🇺🇸Palo Alto, California, United States
Bay Pines VA
🇺🇸Bay Pines, Florida, United States
Miami VA Medical Center
🇺🇸Miami, Florida, United States
Atlanta VA Medical Center
🇺🇸Atlanta, Georgia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Chicago VA Medical Center/Jesse Brown VA
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
North Chicago VA Medical Center
🇺🇸North Chicago, Illinois, United States
Hines VA Medical Center
🇺🇸Hines, Illinois, United States
University of Iowa Healthcare
🇺🇸Iowa City, Iowa, United States
Maine VA Health Care System
🇺🇸Togus, Maine, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Essentia Health
🇺🇸Duluth, Minnesota, United States
VA Medical Center Jackson
🇺🇸Jackson, Mississippi, United States
University of Missouri Health System
🇺🇸Columbia, Missouri, United States
St. Louis VA Medical Center
🇺🇸Saint Louis, Missouri, United States
Reno VA/Sierra Nevada Health Care
🇺🇸Reno, Nevada, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
VA Medical Center Memphis
🇺🇸Memphis, Tennessee, United States
Nashville VA Medical Center
🇺🇸Nashville, Tennessee, United States
Intermountain
🇺🇸Murray, Utah, United States
Mayo Clinic Health System SW Wisconsin
🇺🇸La Crosse, Wisconsin, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Southern Arizona VA Health Care System - Tucson
🇺🇸Tucson, Arizona, United States
VA Connecticut Healthcare System
🇺🇸West Haven, Connecticut, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Minneapolis VA Health Care System
🇺🇸Minneapolis, Minnesota, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Dayton VA Medical Center
🇺🇸Dayton, Ohio, United States
University of Texas Southwestern Medical Center Dallas
🇺🇸Dallas, Texas, United States
Dallas VA Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Doctors Hospital at Renaissance
🇺🇸Edinburg, Texas, United States
Mayo Clinic Health Systems - NW Wisconsin
🇺🇸Eau Claire, Wisconsin, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Louisville VA Medical Center
🇺🇸Louisville, Kentucky, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Baptist Hospital-Cardiology
🇺🇸Winston-Salem, North Carolina, United States
Charleston VA Medical Center
🇺🇸Charleston, South Carolina, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest Hospital - Geriatrics
🇺🇸Winston-Salem, North Carolina, United States
Gainesville VA Medical Center
🇺🇸Gainesville, Florida, United States
University Medical Center
🇺🇸New Orleans, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Bronx VA Medical Center
🇺🇸Bronx, New York, United States
Richmond VA
🇺🇸Richmond, Virginia, United States
VA Madison Healthcare System
🇺🇸Madison, Wisconsin, United States
Providence VA Medical Center
🇺🇸Providence, Rhode Island, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States