Abstract 12503: A Randomized Controlled Trial of Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

Abstract

Introduction: Rheumatic heart disease affects 40.5 million people globally and causes 306,000 annual deaths. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. However, it is unknown if secondary antibiotic prophylaxis is effective at preventing progression of latent rheumatic heart disease. Methods: We conducted a randomized controlled trial of secondary antibiotic prophylaxis among Ugandan children (5-17 years) with latent rheumatic heart disease. We randomized children to receive either 4-weekly injections of benzathine benzylpenicillin G or no prophylaxis. All children underwent echocardiography at baseline and 2 years after randomization. Changes from baseline were adjudicated by a panel blinded to treatment allocation. The primary outcome was rheumatic heart disease progression. The trial was registered at ClinicalTrials.org (NCT03346525) on November 17, 2017. Results: 818 were included in the modified intention to treat analysis and 799 participants (97.7%) reached study completion. Three participants in the prophylaxis group (0.8%) demonstrated echocardiographic progression, compared to 33 (8.3%) in the control group (risk difference -7.5%, 95%CI, -10.2 to -4.7, p<0.001). The number of children with latent rheumatic heart disease needed to receive prophylaxis to prevent one child from developing progression was 13 (95%CI, 10 to 21). There were 2 serious adverse events in the prophylaxis group, including one episode of a mild anaphylactic reaction (0.01% of all treatment doses). Conclusions: Secondary antibiotic prophylaxis reduces the risk of latent rheumatic heart disease progression at 2 years. These data provide new information for our understanding of the role of screening for latent rheumatic heart disease. Further research is needed before the implementation of population-level screening can be recommended.