PREPARE (A5361s) Ancillary Study of REPRIEVE (A5332)

NCT03070223 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: ACTG A5361sUM1AI068636R01AG054366
• Study Type: interventional
• Target: 602
• Locations: 2 countries
• Sites: 31

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Physical Function: Rate of Change in Chair Rise Rate

  Chair rise rate was calculated as the number of chair stands performed divided by the time to complete 10 chair stands. Participants unable to attempt the test were assigned the worst time (9 seconds/stand for every stand not done). Linear mixed effects models for repeated measures were used to estimate annualized rate of change (slope), and the difference between treatment groups (interaction between slope and treatment group). Negative annualized rate of change reflects decline over time, positive improvement over time.

  Entry and months 12, 24, 36, 48, 60

• Mechanistic: Rate of Change in Inflammatory Index Score (IIS)

  Conditional on the positive findings on the primary physical function, the IIS score will be calculated as 1/3 log \[interleukin-6 (IL-6)\] + 2/3 log \[soluble tumor necrosis factor receptor 1 (sTNFR-1)\] using specimens collected as part of the main study REPRIEVE, and used to evaluate mechanistic pathways through which pitavastatin affects physical function.

  Baseline and 12 months

• Muscle Quality: Paraspinal Muscle Density

  Paraspinal muscle (a back muscle) density was measured in Hounsfield units (HU, lower values indicate fattier muscle) from central reading of CT scans performed as part of A5333s, the Mechanistic Substudy of REPRIEVE. HU are used to measure the radiation attenuation of muscle in CT scans. Muscle tissue was identified as voxels with attenuation of -190 HU (very low density muscle, the fattiest) to 100 HU (high density muscle, the leanest).

  Baseline and 24 months

Secondary Outcomes (15)

• Physical Function: Rate of Change in Gait Speed

  Entry and months 12, 24, 36, 48 and 60.

• Physical Function: Rate of Change in Grip Strength

  Entry and months 12, 24, 36, 48 and 60

• Physical Function: Rate of Change in Risk of Impairment According to Balance

  Entry and months 12, 24, 36, 48, 60

• Physical Function: Rate of Change in Modified SPPB Score

  Entry and months 12, 24, 36, 48 and 60

• Physical Function: Rate of Change in Risk of Impairment According to SPPB

  Entry and months 12, 24, 36, 48, 60

Study Arms (2)

Pitavastatin

EXPERIMENTAL

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

Drug: Pitavastatin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Pitavastatin DRUG

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

Pitavastatin

Placebos DRUG

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

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (31)

Alabama CRS (31788)

Birmingham, Alabama, 35294, United States

Location

University of Southern California (1201)

Los Angeles, California, 90033-1079, United States

Location

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

Los Angeles, California, 90035, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

2701 Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University CRS (201)

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital (MGH) CRS (101)

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS (7804)

New York, New York, 10010, United States

Location

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

New York, New York, 10011, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital (TMH) ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS (31443)

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team (HART) CRS (31473)

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, PR, 00935, Puerto Rico

Location

Related Publications (4)

• 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.

  PMID: 37368931 RESULT

• 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.

  PMID: 38180893 RESULT

• 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.

  PMID: 32645163 RESULT

• 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.

  PMID: 39159048 DERIVED

MeSH Terms

Interventions

pitavastatin

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Todd Brown, MD, PhD

  Johns Hopkins University

  STUDY CHAIR

• Kristine Erlandson, MD

  University of Colorado, Denver

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Participants were randomized as part of REPRIEVE.

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 3, 2017
• Study Start: March 14, 2017
• Primary Completion: August 21, 2023
• Study Completion: August 21, 2023
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-09

Locations

PR (1); US (30)