2/2 REPRIEVE Extension for Trial Completion

项目摘要/摘要 该提案将支持数据协调中心(DCC)进行预防血管疾病的随机试验 艾滋病毒试验中的事件(暂缓)延长最多两年，再延长一年的研究 绝杀。这段额外的时间是收集主要不良心血管事件(MACE)所必需的 需要确保有足够的权力来实现缓刑的主要目标，以确定 他汀类药物作为HIV的主要心血管预防策略。审判的完成将保护 NIH的初始投资和利用现有的暂缓基础设施，以及其数据分析和监督 结构。该DCC提案是缓刑临床协调中心(CCC)提案的补充。 REPREVE是一项多中心、随机、安慰剂对照的务实试验，研究他汀类药物的疗效 用于7,770名艾滋病毒携带者心血管疾病(CVD)事件的一级预防(主要终点) (PWH)根据2013年ACC/AHA合并队列，无已知心血管疾病且有低至中等心血管疾病风险 方程式，(称为ASCVD风险)。为了了解他汀类药物的生物学效应，805名参与者被联合 参加一项嵌入式机制子研究，以确定他汀类药物对非钙化斑块的影响 使用冠状动脉CT血管成像(CTA)的体积和高危斑块形态，以及 4个月和2年后血管炎症和免疫激活的血液生物标志物。此外，在 应对全球SARS-CoV-2大流行，缓刑将解决有关 威尔斯亲王医院SARS-CoV-2感染及COVID相关心血管并发症的流行病学调查 他汀类药物对全球COVID疾病的保护作用。 在拟议的延期期间，暂缓执行委员会将继续提供方法和后勤支助 用于数据收集、质量控制和分析，包括严格、及时和独立的裁决 潜在的重大赛事。此外，统计协调委员会仍负责统计设计和分析， 协助制定方案、数据管理、CTA数据采集和解释、生物检疫 分析和电子通信。

Project Summary/Abstract This proposal will support the Data Coordinating Center (DCC) for the Randomized Trial to Prevent Vascular Events in HIV Trial (REPRIEVE) Extension for up to two additional years, with an additional year for study close-out. This additional time is necessary to collect the major adverse cardiovascular events (MACE) required to ensure adequate power to address the primary aim of REPRIEVE, to determine the efficacy of statins as a primary cardiovascular prevention strategy in HIV. Completion of the trial will protect the value of the initial NIH investment and leverage existing REPRIEVE infrastructure, with its data analytical and oversight structures. This DCC proposal is a companion to the REPRIEVE Clinical Coordinating Center (CCC) proposal. REPRIEVE is a multicenter, randomized, placebo controlled, pragmatic trial investigating the efficacy of statins for primary prevention of cardiovascular disease (CVD) events (primary endpoint) in 7,770 persons with HIV (PWH) without known CVD and with low to moderate CVD risk as per the 2013 ACC/AHA Pooled Cohort Equations, (referred to as ASCVD risk). To understand the biology of statin effects, 805 participants were co- enrolled in an embedded mechanistic substudy that will determine the effects of statins on non-calcified plaque volume and high risk plaque morphology using coronary computed tomographic angiography (CTA), as well as on blood biomarkers of vascular inflammation and immune activation after 4 months and two years. Further, in response to the global SARS-CoV-2 pandemic, REPRIEVE will address critical knowledge gaps regarding the epidemiology of SARS-CoV-2 infection and COVID-related CVD complications among PWH, and determine the protective statin effects for COVID disease across the globe. In the proposed extension, the REPRIEVE DCC will continue to provide methodological and logistical support for the collection, quality control, and analysis of data including rigorous, timely, and independent adjudication of potential MACE events. Furthermore, the DCC remains responsible for statistical design and analysis, assistance in protocol development, data management, CTA data acquisition and interpretation, biospecimen analysis, and electronic communications.