Role of Statins in Slowing Rheumatic Heart Disease (RHD) Progression: A Feasibility Study for a Randomized Controlled Trial

他汀类药物在减缓风湿性心脏病 (RHD) 进展中的作用：随机对照试验的可行性研究

• 批准号: 9762976
• 负责人: Nona Sotoodehnia
• 金额: $ 23.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762976
• 关键词: 18 year old; Accounting; Acute; Address; Adherence; Adult; Affect; Anti-Inflammatory Agents; Antigen Mimicry; Autoimmune Process; Benign; Benzathine Penicillin; Biological; Blood; Blood Vessels; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Childhood; Clinic; Clinical; Collaborations; Country; Data; Data Collection; Databases; Developed Countries; Developing Countries; Development; Disease; Disease Management; Disease Progression; Dose; Double-Blind Method; Echocardiography; Endemic Diseases; Enrollment; Ensure; Event; Feasibility Studies; Future; Goals; Government; Healthcare; Heart Valve Diseases; Heart Valves; Heart failure; Hospitals; Immigration; Immune response; Incidence; Inflammation; Inflammatory; Inflammatory Response; Institution; Link; Lipids; Longevity; Methods; Mitral Valve; Monitor; Morbidity - disease rate; Nepal; Observational Study; Outcome; Participant; Pathogenesis; Pathology; Patient Recruitments; Patients; Pharmaceutical Preparations; Pilot Projects; Placebos; Population; Positioning Attribute; Poverty; Prevalence; Prophylactic treatment; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Registries; Research; Research Personnel; Rheumatic Fever; Rheumatic Heart Disease; Role; Safety; Sample Size; Streptococcal Infections; Streptococcus pyogenes; Testing; Therapeutic; United States; Universities; University Hospitals; Washington; adherence rate; adverse outcome; aortic valve disorder; arm; atorvastatin; burden of illness; cost; cytokine; design; disease diagnosis; efficacy testing; heart damage; implementation trial; improved; improved outcome; insight; low and middle-income countries; medication compliance; medication safety; mortality; prevent; programs; randomized trial; recruit; retention rate; transplant centers

PROJECT SUMMARY/ABSTRACT Rheumatic Heart Disease (RHD), the most common cardiovascular disease in those under 25, remains a significant public health problem in lower and middle-income countries (LMIC). Currently no proven treatment exists that prevents or delays the development and progression of cardiac sequelae in patients with RHD. Despite compelling biologic and observational data that suggests statin use delays progression of valvular heart disease, to date there has not been a randomized controlled trial to test this hypothesis. If statin therapy indeed delays progression of cardiac sequelae and improves clinical outcomes in patients with RHD, it will fundamentally shift RHD management strategies world-wide and importantly impact millions of lives, mostly in LMIC but also in Western countries. The largely benign safety profile of statins and their wide availability will further guarantee the usage and scalability of such therapy. We aim to leverage our long-existing collaborations between colleagues at the University of Washington, Seattle, and institutions in Nepal (Manmohan Cardiothoracic, Vascular and Transplant Center; Dhulikhel Hospital Kathmandu University Hospital), an RHD endemic country, to conduct a pilot study to assess feasibility and gain implementation insights for conducting a larger RCT that will evaluate safety and efficacy of atorvastatin among RHD patients. The goal of this R34 application is to address specific implementation questions necessary and sufficient to ensure the feasibility of the larger RCT. With this study, we will build a registry of RHD patients in order to facilitate research on RHD subjects. We will then pilot a small feasibility study, administering low dose atorvastatin or placebo in a double blind randomized controlled fashion to 100 adult RHD patients, obtaining echocardiograms at baseline and end of study in 18 months, and following patients for RHD-related cardiovascular events. The feasibility study will address the following aims: (1) understand the recruitment, adherence, and retention rates and (2) evaluate the rate of valvular disease progression, and secondarily, composite cardiovascular endpoints in this population. The answers to the above questions are both necessary and sufficient to effectively design a larger trial to test the efficacy of statins in mitigating valvular damage.

项目总结/摘要 风湿性心脏病（RHD）是25岁以下人群中最常见的心血管疾病， 低收入和中等收入国家（LMIC）的重大公共卫生问题。目前尚无有效的治疗方法 存在预防或延迟RHD患者心脏后遗症的发生和进展的药物。 尽管有令人信服的生物学和观察数据表明他汀类药物可延迟瓣膜病的进展， 心脏病，迄今为止还没有一个随机对照试验来检验这一假设。如果他汀类药物治疗 确实延缓了心脏后遗症的进展，改善了RHD患者的临床结局， 从根本上改变全球RHD管理策略，并对数百万人的生活产生重要影响，主要是在 LMIC以及西方国家也是如此。他汀类药物在很大程度上是良性的安全性特征及其广泛的可用性将 进一步保证这种治疗的使用和可扩展性。我们的目标是利用我们长期存在的 华盛顿大学、西雅图大学和尼泊尔机构的同事之间的合作 （加德满都大学Dhulikhel医院Manmohan心胸、血管和移植中心 医院），一个风湿性心脏病流行的国家，进行试点研究，以评估可行性和获得实施 进行更大规模的随机对照试验的见解，该试验将评估阿托伐他汀在RHD患者中的安全性和疗效。 此R34应用程序的目标是解决必要的特定实现问题， 以确保更大RCT的可行性。通过这项研究，我们将建立一个RHD患者的注册表 以促进风湿性心脏病主题的研究。然后，我们将进行一项小型可行性研究， 以双盲随机对照的方式对100例成人RHD患者给予阿托伐他汀或安慰剂， 在基线和18个月研究结束时获得超声心动图，并随访患者的RHD相关 心血管事件。可行性研究将达到以下目的：（1）了解招聘情况， 依从性和保留率，以及（2）评价瓣膜疾病进展的速率，其次， 该人群的复合心血管终点。上述问题的答案都是必要的 并且足以有效地设计更大的试验来测试他汀类药物在减轻瓣膜损伤中的功效。