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.

项目摘要/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， 中低收入国家(LMIC)的重大公共卫生问题。目前还没有经过验证的治疗方法 可以预防或延缓风湿性心脏病患者心脏后遗症的发展和进展。 尽管令人信服的生物和观察数据表明他汀类药物的使用延缓了瓣膜的进展 心脏病，到目前为止还没有随机对照试验来检验这一假设。IF他汀类药物治疗 事实上，它将延缓风湿性心脏病患者心脏后遗症的进展并改善临床结果。 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也是在西方国家。他汀类药物的基本无害的安全性及其广泛的可获得性将 进一步保证了这种疗法的实用性和可扩展性。我们的目标是利用我们长期存在的 西雅图华盛顿大学的同事与尼泊尔机构之间的合作 加德满都大学Dhulikhel医院心胸、血管和移植中心 风湿性心脏病流行国家)进行一项试点研究，以评估可行性并实施 开展一项更大规模的随机对照试验，评估阿托伐他汀在风湿性心脏病患者中的安全性和有效性。 此R34应用程序的目标是解决特定的实施问题 足以确保更大规模的区域现金转移的可行性。通过这项研究，我们将建立风湿性心脏病患者的登记 以促进风湿性心脏病课题的研究。然后，我们将试行一项小型可行性研究，管理低 100例成人风湿性心脏病患者随机双盲对照服用阿托伐他汀或安慰剂， 在18个月的基线和研究结束时获得超声心动图，并跟踪风湿性心脏病相关患者 心血管事件。可行性研究将针对以下目标：(1)了解招聘情况； 粘附率和保留率，以及(2)评估瓣膜疾病进展率，其次， 这一人群中的复合心血管终点。以上两个问题的答案都是必要的 并足以有效地设计一项更大的试验，以测试他汀类药物在减轻瓣膜损伤方面的疗效。