Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults

Cardiovascular Diseases Clinical Trial

— PREVENTABLE  

Official title:

PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr Adults (PREVENTABLE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04262206
• Other study ID #: Pro00103844
• Secondary ID: 1U19AG065188-01
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Duke University
• Contact: Jennifer Hervey
• Phone: 919-668-1965
• Email: jennifer.hervey[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 75 Years and older

Eligibility

Inclusion Criteria:

• Community-dwelling adults

• Age =75 years

• English or Spanish as primary language

• Able to provide a trusted contact

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cognitive Dysfunction
• Cognitive Impairment, Mild
• Dementia

Intervention

Drug:
• Atorvastatin 40 Mg Oral Tablet
To generate knowledge about the role of statins in older adults in whom risk/benefit for primary prevention is understudied,
• Placebo oral tablet
To generate knowledge about the role of statins in older adults in whom risk/benefit for primary prevention is understudied,

Locations

Country	Name	City	State
Puerto Rico	VA Carribbean Healthcare	San Juan
United States	University of Michigan	Ann Arbor	Michigan
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Asheville VA-Charles George VA Medical Center	Asheville	North Carolina
United States	Atlanta VA Medical Center	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Bay Pines VA	Bay Pines	Florida
United States	Birmingham VA	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	VA Boston Healthcare System	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Bronx VA Medical Center	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Charleston VA Medical Center	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health	Charlotte	North Carolina
United States	Chicago VA Medical Center/Jesse Brown VA	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Cincinnati VA Medical Center	Cincinnati	Ohio
United States	Clarksburg VA Medical Center	Clarksburg	West Virginia
United States	Case Western Reserve University	Cleveland	Ohio
United States	Columbia VA Health Care/Dorn VA Medical Center	Columbia	South Carolina
United States	University of Missouri Health System	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	Baylor Scott and White Medical Center	Dallas	Texas
United States	Dallas VA Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center Dallas	Dallas	Texas
United States	Dayton VA Medical Center	Dayton	Ohio
United States	Essentia Health	Duluth	Minnesota
United States	Duke University	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina
United States	PREVENTABLE Tele-Site	Durham	North Carolina
United States	Mayo Clinic Health Systems - NW Wisconsin	Eau Claire	Wisconsin
United States	Doctors Hospital at Renaissance	Edinburg	Texas
United States	Fresno VA Medical Center	Fresno	California
United States	Gainesville VA Medical Center	Gainesville	Florida
United States	University of Florida	Gainesville	Florida
United States	Hines VA Medical Center	Hines	Illinois
United States	University of Texas at Houston	Houston	Texas
United States	Indianapolis VA Medical Center	Indianapolis	Indiana
United States	University of Iowa Healthcare	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	VA Medical Center Jackson	Jackson	Mississippi
United States	University of Florida	Jacksonville	Florida
United States	Duke University - Kannapolis	Kannapolis	North Carolina
United States	Kansas City VA Medical Center	Kansas City	Kansas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Mayo Clinic Health System SW Wisconsin	La Crosse	Wisconsin
United States	Little Rock VA Medical Center	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Long Beach VA Medical Center	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	VA Greater Los Angeles	Los Angeles	California
United States	Louisville VA Medical Center	Louisville	Kentucky
United States	VA Madison Healthcare System	Madison	Wisconsin
United States	Northwell Health	Manhasset	New York
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	VA Medical Center Memphis	Memphis	Tennessee
United States	Miami VA Medical Center	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Milwaukee VA Medical Center	Milwaukee	Wisconsin
United States	Allina Health	Minneapolis	Minnesota
United States	Minneapolis VA Health Care System	Minneapolis	Minnesota
United States	VA Hudson Valley Healthcare System	Montrose	New York
United States	Intermountain	Murray	Utah
United States	Meharry Medical College	Nashville	Tennessee
United States	Nashville VA Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	University Medical Center	New Orleans	Louisiana
United States	VA New York Harbor Healthcare System	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	North Chicago VA Medical Center	North Chicago	Illinois
United States	Omaha VA Medical Center	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	VA Palo Alto Healthcare System	Palo Alto	California
United States	Corporal Michael J. Crescenz VA Medical Center-Philadelphia VA	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence VA Medical Center	Providence	Rhode Island
United States	Reno VA/Sierra Nevada Health Care	Reno	Nevada
United States	Richmond VA	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	St. Louis VA Medical Center	Saint Louis	Missouri
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	VA Salt Lake City Healthcare System	Salt Lake City	Utah
United States	San Antonio VA Medical Center	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	VA San Diego Medical Center	San Diego	California
United States	Maine VA Health Care System	Togus	Maine
United States	VA Eastern Kansas Healthcare System	Topeka	Kansas
United States	Southern Arizona VA Health Care System - Tucson	Tucson	Arizona
United States	VA Connecticut Healthcare System	West Haven	Connecticut
United States	Wake Forest Baptist Hospital-Cardiology	Winston-Salem	North Carolina
United States	Wake Forest Hospital - Geriatrics	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Duke University	National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA), Wake Forest University Health Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients without diagnosis of new dementia	Number of patients without diagnosis of new dementia in each group (placebo vs. atorvastatin)	4 years
Primary	Number of patients without of persistent disability	Number of patients without chronic disability in each group	4 years
Secondary	Cardiovascular mortality measured as a composite of CV death, hospitalization for myocardial infarction/unstable angina, heart failure, stroke/TIA, or coronary revascularization	Cardiovascular mortality is measured by a composite measure of multiple CV conditions.	4 years
Secondary	Cognitive disability as measured as a composite of MCI or probable dementia	Cognitive disability is measured by a composite of having mild cognitive impairment or probable dementia.	4 years