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

Sponsor
Duke University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04262206
Collaborator
National Institute on Aging (NIA) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Wake Forest University Health Sciences (Other)
20,000
Enrollment
84
Locations
2
Arms
76
Anticipated Duration (Months)
238.1
Patients Per Site
3.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Atorvastatin 40 Mg Oral Tablet
  • Drug: Placebo oral tablet
 Phase 4

Detailed Description

PREVENTABLE will randomly assign atorvastatin 40 mg daily or matching placebo daily to 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. Each site 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. 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 combination of central and distributed research teams. This includes a call center as well as a nationwide system of decentralized research staff trained on the protocol able to meet the patient in their home or other desired location. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20000 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized 1:1 atorvastatin 40mg vs. placeboRandomized 1:1 atorvastatin 40mg vs. placebo
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Prevention
Official Title:
PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr Adults (PREVENTABLE)
Actual Study Start Date :
Sep 1, 2020
Anticipated Primary Completion Date :
Jun 30, 2026
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: atorvastatin 40mg

40mg atorvastatin po qd from consent to study end

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,
Other Names:
  • Lipitor

    		•
    Placebo Comparator: Placebo

    matching placebo po qd from consent to study end

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

    Outcome Measures

    Primary Outcome Measures

    1. Number of patients without diagnosis of new dementia [4 years]

      Number of patients without diagnosis of new dementia in each group (placebo vs. atorvastatin)

    2. Number of patients without of persistent disability [4 years]

      Number of patients without chronic disability in each group

    Secondary Outcome Measures

    1. 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.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    75 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Community-dwelling adults

    • Age ≥75 years

    • English or Spanish as primary language

    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)

    • Severe visual impairment (preventing cognitive testing)

    • 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

    • Long-term use of daily colchicine, verapamil at any dose, or diltiazem at a dose

    240mg/day.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham VA Birmingham Alabama United States 35233
    2 Southern Arizona VA Health Care System - Tucson Tucson Arizona United States 85723
    3 Little Rock VA Medical Center Little Rock Arkansas United States 72114
    4 Fresno VA Medical Center Fresno California United States 93703
    5 Long Beach VA Medical Center Long Beach California United States 90822
    6 VA Greater Los Angeles Los Angeles California United States 90073
    7 VA Palo Alto Healthcare System Palo Alto California United States 94550
    8 VA San Diego Medical Center San Diego California United States 92161
    9 VA Connecticut Healthcare System West Haven Connecticut United States 006111
    10 Bay Pines VA Bay Pines Florida United States 33744
    11 Gainesville VA Medical Center Gainesville Florida United States 32608
    12 University of Florida Gainesville Florida United States 32610
    13 University of Florida Jacksonville Florida United States 32608
    14 Miami VA Medical Center Miami Florida United States 33125
    15 University of Miami Miami Florida United States 33136
    16 Advent Health Orlando Florida United States 32804
    17 Atlanta VA Medical Center Atlanta Georgia United States 30033
    18 University of Illinois at Chicago Chicago Illinois United States 60608
    19 Chicago VA Medical Center/Jesse Brown VA Chicago Illinois United States 60612
    20 Rush University Medical Center Chicago Illinois United States 60612
    21 University of Chicago Chicago Illinois United States 60637
    22 Hines VA Medical Center Hines Illinois United States 60141
    23 North Chicago VA Medical Center North Chicago Illinois United States 60064
    24 Indianapolis VA Medical Center Indianapolis Indiana United States 46202
    25 University of Iowa Healthcare Iowa City Iowa United States 52242
    26 Kansas City VA Medical Center Kansas City Kansas United States 64128
    27 University of Kansas Medical Center Kansas City Kansas United States 66160
    28 VA Eastern Kansas Healthcare System Topeka Kansas United States 66622
    29 Louisville VA Medical Center Louisville Kentucky United States 40206
    30 University Medical Center New Orleans Louisiana United States 70112
    31 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    32 Johns Hopkins University Baltimore Maryland United States 21287
    33 VA Boston Healthcare System Boston Massachusetts United States 002130
    34 VA Ann Arbor Healthcare System Ann Arbor Michigan United States 48105
    35 Essentia Health Duluth Minnesota United States 55805
    36 Allina Health Minneapolis Minnesota United States 55407
    37 Minneapolis VA Health Care System Minneapolis Minnesota United States 55417
    38 Mayo Clinic Rochester Minnesota United States 55905
    39 University of Mississippi Medical Center Jackson Mississippi United States 39216
    40 VA Medical Center Jackson Jackson Mississippi United States 39216
    41 University of Missouri Health System Columbia Missouri United States 65212
    42 St. Louis VA Medical Center Saint Louis Missouri United States 63106
    43 University of Nebraska Medical Center Omaha Nebraska United States 67105
    44 Omaha VA Medical Center Omaha Nebraska United States 68105
    45 Reno VA/Sierra Nevada Health Care Reno Nevada United States 89502
    46 Albert Einstein College of Medicine Bronx New York United States 10461
    47 Bronx VA Medical Center Bronx New York United States 10468
    48 VA Hudson Valley Healthcare System Montrose New York United States 10548
    49 VA New York Harbor Healthcare System New York New York United States 10010
    50 Weill Cornell Medical College New York New York United States 10021
    51 Asheville VA-Charles George VA Medical Center Asheville North Carolina United States 28805
    52 University of North Carolina Chapel Hill North Carolina United States 27599
    53 Durham VA Medical Center Durham North Carolina United States 27705
    54 Duke University Durham North Carolina United States 27710
    55 Salisbury VA Medical Center Salisbury North Carolina United States 28144
    56 Wake Forest Baptist Hospital Winston-Salem North Carolina United States 27157
    57 Cincinnati VA Medical Center Cincinnati Ohio United States 45220
    58 Ohio State University Columbus Ohio United States 43210
    59 Dayton VA Medical Center Dayton Ohio United States 45428
    60 Corporal Michael J. Crescenz VA Medical Center-Philadelphia VA Philadelphia Pennsylvania United States 19104
    61 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213
    62 Providence VA Medical Center Providence Rhode Island United States 002908
    63 Charleston VA Medical Center Charleston South Carolina United States 29401
    64 Columbia VA Health Care/Dorn VA Medical Center Columbia South Carolina United States 29209
    65 Monument Health Rapid City South Dakota United States 57701
    66 VA Medical Center Memphis Memphis Tennessee United States 38104
    67 Meharry Medical College Nashville Tennessee United States 37208
    68 Nashville VA Medical Center Nashville Tennessee United States 37212
    69 Vanderbilt University Medical Center Nashville Tennessee United States 37212
    70 Dallas VA Medical Center Dallas Texas United States 75216
    71 University of Texas Southwestern Medical Center Dallas Dallas Texas United States 75390
    72 Doctors Hospital at Renaissance Edinburg Texas United States 78539
    73 San Antonio VA Medical Center San Antonio Texas United States 78229
    74 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    75 Baylor Scott and White Medical Center Temple Texas United States 76508
    76 Intermountain Murray Utah United States 84107
    77 University of Utah Salt Lake City Utah United States 84132
    78 VA Salt Lake City Healthcare System Salt Lake City Utah United States 84148
    79 Clarksburg VA Medical Center Clarksburg West Virginia United States 26301
    80 VA Madison Healthcare System Madison Wisconsin United States 53705
    81 Marshfield Clinic Marshfield Wisconsin United States 54449
    82 Medical College of Wisconsin Milwaukee Wisconsin United States 53295
    83 Milwaukee VA Medical Center Milwaukee Wisconsin United States 53295
    84 VA Carribbean Healthcare San Juan Puerto Rico 00921

    Sponsors and Collaborators

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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Duke University
    ClinicalTrials.gov Identifier:
    NCT04262206
    Other Study ID Numbers:
    • Pro00103844
    • 1U19AG065188-01
    First Posted:
    Feb 10, 2020
    Last Update Posted:
    Jul 11, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Duke University
    statin
    older adults
    Additional relevant MeSH terms:
    Cardiovascular Diseases
    Cognitive Dysfunction
    Atorvastatin

    Study Results

    No Results Posted as of Jul 11, 2022