Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 602
- 试验地点
- 31
- 主要终点
- Physical Function: Rate of Change in Chair Rise Rate
研究概览
简要总结
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.
详细描述
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:
- enrolled in both REPRIEVE and its Mechanistic Substudy (A5333s, subsequently referred to as Mechanistic Substudy) within 24 of their REPRIEVE enrollment
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Inability to ambulate independently (use of a cane or a walker is permitted) or rise from a chair without assistance.
研究组 & 干预措施
Pitavastatin
Participants who were randomized to pitavastatin in the main study REPRIEVE.
干预措施: Pitavastatin (Drug)
Placebo
Participants who were randomized to placebo for pitavastatin in the main study REPRIEVE.
干预措施: Placebos (Drug)
结局指标
主要结局
Physical Function: Rate of Change in Chair Rise Rate
时间窗: Entry and months 12, 24, 36, 48, 60
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.
Mechanistic: Rate of Change in Inflammatory Index Score (IIS)
时间窗: Baseline and 12 months
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.
Muscle Quality: Paraspinal Muscle Density
时间窗: Baseline and 24 months
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).
次要结局
- 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)
- Physical Function: Impairment According to DASI(Baseline, month 24 and end of REPRIEVE (average at 5.6 years))
- Frailty Phenotype(Entry and months 12, 24, 36, 48, 60)
- Physical Activity: Frequency of <30 Minutes of Physical Activity 3 or More Days a Week(Baseline and months 12, 24, 36, 48, 60)
- Physical Activity: Frequency of Watching >2 Hours of TV or Videos a Day(Baseline and months 12, 24, 36, 48, 60)
- Muscle Quality: Pectoral Muscle Density(Baseline and month 24)
- Muscle Quality: Infraspinatus Muscle Density(Baseline and month 24)
- Muscle Area: Paraspinal Muscle Area(Baseline and month 24)
- Muscle Area: Pectoral Muscle Area(Baseline and month 24)
- Muscle Area: Infraspinatus Muscle Area(Baseline and month 24)
- Mechanistic: Serum Concentrations of Biomarkers(Baseline and month 12)