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/文摘