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

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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.