PREPARE (A5361s) Ancillary Study of REPRIEVE (A5332)

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Placebos; Drug: Pitavastatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT03070223

UM1AI068636 (U.S. NIH Grant/Contract)

ACTG A5361s

R01AG054366 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 602 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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602 participants in 2 patient groups, including a placebo group

Pitavastatin

Experimental group

Description:

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

Treatment:

Drug: Pitavastatin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos