PREPARE (A5361s) Ancillary Study of REPRIEVE (A5332)

NCT ID: NCT03070223

Last Updated: 2024-10-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

602 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-14

Study Completion Date

2023-08-21

Brief Summary

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Aging with HIV is associated with earlier development of frailty (weakness) or disability, including loss of physical and muscle strength, and walking speed. Few treatments have been shown to prevent or slow these impairments in people with or without HIV. Some studies have suggested that the class of drugs called statins (for example, pitavastatin) might be helpful in slowing frailty or disability. This might happen by decreasing fat within the muscle or by decreasing inflammation markers (substances in the blood that determine how the body reacts to infection or irritation) in the blood. Other studies have shown that statins increase the risk of muscle aches and pains. This ancillary study was done to determine the impact of the drug pitavastatin on physical and muscle function.

Detailed Description

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The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE (A5332), subsequently referred to as REPRIEVE; NCT02344290) was a prospective, randomized, placebo-controlled, multicenter phase III trial to evaluate pitavastatin as prevention for cardiovascular disease events among people with HIV. PREPARE (A5361s, subsequently referred to as PREPARE) was an ancillary study of REPRIEVE to determine the effects of pitavastatin on physical and muscle function. The study enrolled participants:

1. enrolled in both REPRIEVE and its Mechanistic Substudy (A5333s, subsequently referred to as Mechanistic Substudy) within 24 of their REPRIEVE enrollment
2. enrolled in REPRIEVE alone concurrently with their REPRIEVE enrollment.

The target sample size was 600 participants. The study was conducted at the REPRIEVE U.S. sites participating in the Mechanistic Substudy, and enrollment from the Mechanistic Substudy was prioritized to maximize the number of participants with computed tomography (CT) scan data performed as part of the Mechanistic Substudy.

Treatment groups (pitavastatin vs placebo) were defined according to randomization in REPRIEVE. Participants were enrolled into PREPARE blinded to their REPRIEVE treatment allocation. No intervention was provided in this ancillary study.

Originally the study duration was 48 months after participants' REPRIEVE entry. An additional visit was added at Month 60 due to missed in-person evaluations during the COVID-19 related restrictions in 2020 through early 2021.

Study visits were scheduled at PREPARE entry and at months 12, 24, 36, 48 and 60 after REPRIEVE entry. Each study visit included evaluation of physical function, frailty and self-reported physical activity and sedentary time. In addition, demographic and clinical data, laboratory specimens and CT scans collected as part of the main study REPRIEVE or its Mechanistic Substudy were used.

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants were randomized as part of REPRIEVE.
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Pitavastatin

Participants who were randomized to pitavastatin in the main study REPRIEVE.

Group Type EXPERIMENTAL

Pitavastatin

Intervention Type DRUG

One tablet (4 mg) taken once daily, orally with or without food for the entire time participant was in REPRIEVE follow-up.

Placebo

Participants who were randomized to placebo for pitavastatin in the main study REPRIEVE.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

One tablet taken once daily, orally with or without food for the entire time participant was in REPRIEVE follow-up.

Interventions

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Pitavastatin

One tablet (4 mg) taken once daily, orally with or without food for the entire time participant was in REPRIEVE follow-up.

Intervention Type DRUG

Placebos

One tablet taken once daily, orally with or without food for the entire time participant was in REPRIEVE follow-up.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Ambulatory participants enrolled in both REPRIEVE (A5332) and its Mechanistic Substudy (A5333s) or ambulatory participants who are newly enrolling into REPRIEVE (A5332) at A5333s ACTG sites.

Exclusion Criteria

* Inability to ambulate independently (use of a cane or a walker is permitted) or rise from a chair without assistance.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Todd Brown, MD, PhD

Role: STUDY_CHAIR

Johns Hopkins University

Kristine Erlandson, MD

Role: STUDY_CHAIR

University of Colorado, Denver

Locations

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Alabama CRS (31788)

Birmingham, Alabama, United States

Site Status

University of Southern California (1201)

Los Angeles, California, United States

Site Status

University of California, Los Angeles CARE Center CRS (601)

Los Angeles, California, United States

Site Status

Ucsd, Avrc Crs (701)

San Diego, California, United States

Site Status

Ucsf Aids Crs (801)

San Francisco, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, United States

Site Status

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

Site Status

2701 Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, United States

Site Status

Johns Hopkins University CRS (201)

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital (MGH) CRS (101)

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, United States

Site Status

Washington University CRS (2101)

St Louis, Missouri, United States

Site Status

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, United States

Site Status

Weill Cornell Chelsea CRS (7804)

New York, New York, United States

Site Status

Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)

New York, New York, United States

Site Status

Columbia Physicians and Surgeons CRS (30329)

New York, New York, United States

Site Status

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, United States

Site Status

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Site Status

Greensboro CRS (3203)

Greensboro, North Carolina, United States

Site Status

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

Site Status

Case CRS (2501)

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, United States

Site Status

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, United States

Site Status

The Miriam Hospital (TMH) ACTG CRS (2951)

Providence, Rhode Island, United States

Site Status

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, United States

Site Status

Trinity Health and Wellness Center CRS (31443)

Dallas, Texas, United States

Site Status

Houston AIDS Research Team (HART) CRS (31473)

Houston, Texas, United States

Site Status

University of Washington AIDS CRS (1401)

Seattle, Washington, United States

Site Status

Puerto Rico-AIDS CRS (5401)

San Juan, PR, Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Erlandson KM, Umbleja T, Lu MT, Taron J, Ribaudo HJ, Overton ET, Presti RM, Haas DW, Sax PE, Yin MT, Zhai BK, Louis R, Upadhyay N, Eslami P, Douglas PS, Zanni MV, Fitch KV, Fulda ES, Fichtenbaum CJ, Malvestutto CD, Grinspoon SK, Brown TT. Associations of Muscle Density and Area With Coronary Artery Plaque and Physical Function. J Acquir Immune Defic Syndr. 2023 Oct 1;94(2):174-184. doi: 10.1097/QAI.0000000000003244.

Reference Type RESULT
PMID: 37368931 (View on PubMed)

Abidi MZ, Umbleja T, Overton ET, Burdo T, Flynn JM, Lu MT, Taron J, Schnittman SR, Fitch KV, Zanni MV, Fichtenbaum CJ, Malvestutto C, Aberg JA, Fulda ES, Eckard AR, Manne-Goehler J, Tuan JJ, Ribaudo HJ, Douglas PS, Grinspoon SK, Brown TT, Erlandson KM. Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV. J Acquir Immune Defic Syndr. 2024 Apr 15;95(5):470-478. doi: 10.1097/QAI.0000000000003377.

Reference Type RESULT
PMID: 38180893 (View on PubMed)

Umbleja T, Brown TT, Overton ET, Ribaudo HJ, Schrack JA, Fitch KV, Douglas PS, Grinspoon SK, Henn S, Arduino RC, Rodriguez B, Benson CA, Erlandson KM. Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE. J Infect Dis. 2020 Jul 9;222(Suppl 1):S52-S62. doi: 10.1093/infdis/jiaa249.

Reference Type RESULT
PMID: 32645163 (View on PubMed)

Erlandson KM, Umbleja T, Ribaudo HJ, Schrack JA, Overton ET, Fichtenbaum CJ, Fitch KV, Roa JC, Diggs MR, Wood K, Zanni MV, Bloomfield GS, Malvestutto C, Aberg JA, Rodriguez-Barradas MC, Morones RG, Breaux K, Douglas PS, Grinspoon SK, Brown TT. Pitavastatin Is Well-Tolerated With no Detrimental Effects on Physical Function. Clin Infect Dis. 2025 Feb 24;80(2):425-433. doi: 10.1093/cid/ciae422.

Reference Type DERIVED
PMID: 39159048 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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UM1AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01AG054366

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5361s

Identifier Type: -

Identifier Source: org_study_id

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