Clinical trial NCT04262206: Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults
Official title: PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr Adults (PREVENTABLE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cognitive Impairment, Mild
Dementia
Cardiovascular Diseases
Keywords: statin
older adults
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Wake Forest University Health Sciences
First posted: 2020-02-10
Enrollment: 20000
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1:1 atorvastatin 40mg vs. placebo
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients without diagnosis of new dementia
timeFrame: 4 years
measure: Number of patients without of persistent disability
timeFrame: 4 years
Secondary outcomes:
measure: Cardiovascular mortality measured as a composite of CV death, hospitalization for myocardial infarction/unstable angina, heart failure, stroke/TIA, or coronary revascularization
timeFrame: 4 years
measure: Cognitive disability as measured as a composite of MCI or probable dementia
timeFrame: 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: Birmingham VA
state: Alabama
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System - Tucson
state: Arizona
city: Little Rock
country: United States
facility: Little Rock VA Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Fresno
country: United States
facility: Fresno VA Medical Center
state: California
city: Long Beach
country: United States
facility: Long Beach VA Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Healthcare System
state: California
city: San Diego
country: United States
facility: VA San Diego Medical Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
city: Bay Pines
country: United States
facility: Bay Pines VA
state: Florida
city: Gainesville
country: United States
facility: Gainesville VA Medical Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Miami VA Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Chicago VA Medical Center/Jesse Brown VA
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Hines
country: United States
facility: Hines VA Medical Center
state: Illinois
city: North Chicago
country: United States
facility: North Chicago VA Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indianapolis VA Medical Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Healthcare
state: Iowa
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: VA Eastern Kansas Healthcare System
state: Kansas
city: Louisville
country: United States
facility: Louisville VA Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Togus
country: United States
facility: Maine VA Health Care System
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: VA Boston Healthcare System
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Duluth
country: United States
facility: Essentia Health
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Jackson
country: United States
facility: VA Medical Center Jackson
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri Health System
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis VA Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Omaha VA Medical Center
state: Nebraska
city: Reno
country: United States
facility: Reno VA/Sierra Nevada Health Care
state: Nevada
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Bronx VA Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Montrose
country: United States
facility: VA Hudson Valley Healthcare System
state: New York
city: New York
country: United States
facility: VA New York Harbor Healthcare System
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Asheville
country: United States
facility: Asheville VA-Charles George VA Medical Center
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Durham
country: United States
facility: PREVENTABLE Tele-Site
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Kannapolis
country: United States
facility: Duke University - Kannapolis
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Hospital-Cardiology
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Hospital - Geriatrics
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Dayton VA Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center-Philadelphia VA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Providence VA Medical Center
state: Rhode Island
city: Charleston
country: United States
facility: Charleston VA Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Columbia VA Health Care/Dorn VA Medical Center
state: South Carolina
city: Memphis
country: United States
facility: VA Medical Center Memphis
state: Tennessee
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Nashville VA Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott and White Medical Center
state: Texas
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Dallas
state: Texas
city: Edinburg
country: United States
facility: Doctors Hospital at Renaissance
state: Texas
city: Houston
country: United States
facility: University of Texas at Houston
state: Texas
city: San Antonio
country: United States
facility: San Antonio VA Medical Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: VA Salt Lake City Healthcare System
state: Utah
city: Richmond
country: United States
facility: Richmond VA
state: Virginia
city: Clarksburg
country: United States
facility: Clarksburg VA Medical Center
state: West Virginia
city: Eau Claire
country: United States
facility: Mayo Clinic Health Systems - NW Wisconsin
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System SW Wisconsin
state: Wisconsin
city: Madison
country: United States
facility: VA Madison Healthcare System
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Milwaukee VA Medical Center
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: VA Carribbean Healthcare
Study officials:
References: