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

• ClinicalTrials.gov Identifier: NCT04262206
• Recruitment Status: Recruiting
• First Posted: February 10, 2020
• Last Update Posted: April 13, 2023
• Sponsor: Duke University
• Collaborators: National Institute on Aging (NIA); National Heart, Lung, and Blood Institute (NHLBI); Wake Forest University Health Sciences
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: February 7, 2020
• First Posted Date: February 10, 2020
• Last Update Posted Date: April 13, 2023
• Actual Study Start Date: September 1, 2020
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2020)

• Number of patients without diagnosis of new dementia [ Time Frame: 4 years ]
  Number of patients without diagnosis of new dementia in each group (placebo vs. atorvastatin)
• Number of patients without of persistent disability [ Time Frame: 4 years ]
  Number of patients without chronic disability in each group

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 7, 2020)

• Cardiovascular mortality measured as a composite of CV death, hospitalization for myocardial infarction/unstable angina, heart failure, stroke/TIA, or coronary revascularization [ Time Frame: 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 [ Time Frame: 4 years ]
  Cognitive disability is measured by a composite of having mild cognitive impairment or probable dementia.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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 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 Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized 1:1 atorvastatin 40mg vs. placebo

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention

Condition

• Cognitive Impairment, Mild
• Dementia
• Cardiovascular Diseases

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

Study Arms

• Experimental: atorvastatin 40mg
  40mg atorvastatin po qd from consent to study end
  Intervention: Drug: Atorvastatin 40 Mg Oral Tablet
• Placebo Comparator: Placebo
  matching placebo po qd from consent to study end
  Intervention: Drug: Placebo oral tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2020): 20000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 75 Years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jennifer Hervey; 919-668-1965; jennifer.hervey@duke.edu

Contact: Pamela Monds; 9196688695; pamela.monds@duke.edu

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04262206
• Other Study ID Numbers: Pro00103844; 1U19AG065188-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Duke University
• Original Responsible Party: Same as current
• Current Study Sponsor: Duke University
• Original Study Sponsor: Same as current

Collaborators

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

• Investigators: Not Provided
• PRS Account: Duke University
• Verification Date: March 2023