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

肌肉注射与肠内青霉素预防预防潜在风湿性心脏病进展：一项非劣效性随机试验。

• 批准号: 10571212
• 负责人: Andrea Zawacki Beaton
• 金额: $ 191.31万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10571212
• 关键词: Absenteeism at work; Acute; Adherence; Affect; Antibiotic Prophylaxis; Antibiotics; Bacteria; Biological Availability; Cessation of life; Child; Child Care; Clinical; Collaborations; Communities; Confidence Intervals; Cost Measures; Data; Detection; Diagnosis; Disease; Disease Progression; Echocardiography; Economics; Effectiveness; Eligibility Determination; Endemic Diseases; Enrollment; Ensure; Enteral; Guidelines; Health; Health Personnel; Health system; Heart Valve Diseases; High Prevalence; Infrastructure; Injectable; International; Intramuscular; Intramuscular Injections; Methods; Oral; Outcome; Pain; Parents; Patient Outcomes Assessments; Patients; Penicillins; Persons; Policies; Positioning Attribute; Prophylactic treatment; Protocols documentation; Public Health; Quality of life; Quality-Adjusted Life Years; Randomized; Randomized, Controlled Trials; Recording of previous events; Reporting; Resource-limited setting; Resources; Rheumatic Fever; Rheumatic Heart Disease; Schools; Structure; Time; Training; Travel; Uganda; aged; clinical practice; comparative efficacy; cost; cost effectiveness; cost-effectiveness ratio; economic evaluation; effectiveness evaluation; experience; health related quality of life; improved outcome; incremental cost-effectiveness; low and middle-income countries; patient-level barriers; premature; prevent; randomized trial; recruit; satisfaction; scale up; screening; standard of care; system-level barriers; trial comparing

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.

项目摘要 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疾病， 目前至少有4 000万人受到影响，其中许多人过早死亡。大多数RHD患者 出现较晚，错过了从二级抗生素预防中获益的机会。筛选 超声心动图在风湿性心脏病流行环境中发现许多儿童患有早期、潜伏性风湿性心脏病，但直到最近， 预防性治疗对保护潜伏性风湿性心脏病儿童的有效性尚不清楚。GOAL审判 （由该调查小组在乌干达进行）发现， 预防性肌肉注射青霉素在2年时不太可能进展（0.8%青霉素vs 8.3%未注射青霉素）。 青霉素，p<0.001）。然而，尽管有这些结果，超声心动图筛查的规模扩大和早期 用肌肉注射青霉素预防风湿性心脏病有许多挑战。中 最关键的是患者（包括疼痛和错过工作/学校）和卫生系统层面的障碍 （包括成本、时间和培训），以在低资源环境中提供延长的IM注射疗程。 肌肉注射与肠内注射青霉素预防潜在风湿性心脏病进展的比较 疾病（GOALIE）将决定一种负担较轻的预防形式，口服青霉素，是否是非- 在预防RHD潜在进展方面不如IM青霉素。GOALIE是一种随机非劣效性 一项比较肌肉注射与肠内（口服）青霉素预防性治疗对预防疾病进展的有效性的试验 两年时潜伏性RHD。基于我们强大的招聘和保留的历史，我们将进行学校- 基于超声心动图筛查约10万名儿童，并将1004名儿童纳入GOALIE， 提供90%的把握度来确定口服青霉素预防是否非劣效于IM青霉素预防。 GOALIE还将研究这两种预防策略的经济等效性和成本效益 (Aim 2）和患者报告的这两种策略之间的结果（目标3），提供关键数据， 告知将潜在RHD的预防纳入临床实践。GOALIE建立了我们长达十年的 合作，包括卫生部和社区的大力支持。GOALIE将利用 GOAL试验开发了超声心动图筛查的简化方案（> 102，000 筛选）和非常成功的招募（>99%符合条件的儿童），保留（97%完成）， 坚持支持（99%坚持）策略。我们的研究结果将具有很高的临床和公众 对健康的影响，立即告知关于被诊断患有 潜伏性风湿性心脏病