Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A non-inferiority randomized trial. (GOALIE)

项目总结摘要 风湿性心脏病(RHD)在低收入和中等收入国家仍然是一种高患病率， 目前影响到至少4000万人，其中许多人过早死亡。大多数风湿性心脏病患者 目前为时已晚，错过了从二级抗生素预防中受益的机会。筛选 风湿性心脏病流行环境中的超声心动图发现许多儿童患有早期、潜伏性风湿性心脏病，但直到最近 预防措施对潜伏性风湿性心脏病儿童的保护效果尚不清楚。目标选拔赛 (由这个调查小组在乌干达进行的)发现，患有潜伏性风湿性心脏病的儿童 肌肉注射青霉素的预防在两年内进展较小(0.8%青霉素对8.3%否 青霉素，p&lt；0.001)。然而，尽管有这些结果，扩大超声心动图筛查和早期 肌肉注射青霉素(IM)开始预防风湿性心脏病有许多挑战。在这些人中 最严重的是严重的患者(包括疼痛和旷工/上学)和卫生系统层面的障碍 (包括成本、时间和培训)到在低资源环境下提供长时间的IM注射课程。 肌肉注射与肠内注射青霉素预防潜伏性风湿性心脏病进展的比较 疾病(守门员)将决定一种负担较轻的预防形式，口服青霉素是否非 在预防潜伏性风湿性心脏病进展方面不如肌注青霉素。守门员是一种随机的非劣势 肌肉注射和肠内(口服)青霉素预防食管炎进展的疗效比较 潜伏期为两年的风湿性心脏病。基于我们强大的招聘和留住历史，我们将开展- 基于超声心动图对约100,000名儿童进行筛查，并将1004名儿童招募为守门员，这将 提供90%的力量来确定口服青霉素预防是否不逊于IM青霉素预防。 守门员还将检查这两种预防策略的经济等价性和成本效益。 (目标2)和患者报告了这两种策略之间的结果(目标3)，为 将潜伏性风湿性心脏病的预防措施融入临床实践。守门员在我们十年的基础上建立起来 合作，包括卫生部和社区的大力支持。守门员将利用这一结构 开发了简化的超声心动图筛查方案的Goal试验(&gt；102,000 经过筛选)和非常成功的招募(99%符合条件的儿童)、保留(97%完成)，以及 遵守支持(99%遵守)战略。我们的研究结果将具有很高的临床和公众价值。 对健康的影响，立即通知国际政策，为确诊为儿童的儿童提供护理标准 潜伏性风湿性心脏病。

PROJECT SUMMARY ABSTRACT Rheumatic heart disease (RHD) remains a high prevalence condition in low-and-middle-income countries, currently affecting at least 40 million people, many of whom suffer premature death. Most patients with RHD present late, missing the opportunity to benefit from secondary antibiotic prophylaxis. Screening echocardiography in RHD endemic settings identifies many children with early, latent RHD, but until recently the effectiveness of prophylaxis to protect children with latent RHD was not known. The GOAL Trial (conducted in Uganda by this investigative team) found that children with latent RHD who receive prophylaxis with intramuscular penicillin are less likely to progress at two-years (0.8% penicillin vs. 8.3% no penicillin, p<0.001). However, despite these results, scale-up of echocardiographic screening and early initiation of prophylaxis with intramuscular (IM) penicillin for RHD has a myriad of challenges. Among the most critical are substantial patient (including pain and missed work/school) and health system-level barriers (including cost, time, and training) to delivering prolonged courses of IM injections in low-resource settings. Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease (GOALIE) will determine if a less burdensome form of prophylaxis, oral penicillin, is non- inferior to IM penicillin in preventing latent RHD progression. GOALIE is a randomized non-inferiority trial comparing the efficacy of Intramuscular to Enteral (oral) penicillin prophylaxis to prevent progression of latent RHD at two years. Based on our strong history of recruitment and retention, we will conduct school- based echocardiographic screening of ~100,000 children and enroll 1004 children into GOALIE, which will provide 90% power to determine if oral penicillin prophylaxis is non-inferior to IM penicillin prophylaxis. GOALIE will also examine economic equivalence and cost-effectiveness of these two prophylaxis strategies (Aim 2) and the patient reported outcomes between these two strategies (Aim 3), providing critical data to inform the integration of prophylaxis for latent RHD into clinical practice. GOALIE builds off our decade long collaboration, including strong Ministry of Health and community support. GOALIE will leverage the structure of the GOAL Trial which developed streamlined protocols for echocardiographic screening (>102,000 screened) and highly successful recruitment (>99% eligible children), retention (97% completion), and adherence support (99% adherence) strategies. The results of our study will have high clinical and public health impact, immediately informing international policy on the standard of care for children diagnosed with latent RHD.