Project Details

E.W. "Al" Thrasher

Status: Funded - Open

Determining the Impact of Penicillin on Latent Rheumatic Heart Disease

Andrea Beaton, MD

Summary

BACKGROUND: Rheumatic heart disease (RHD) is a cumulative heart valve disease that results from Group A streptococcal infection, triggering the systemic inflammatory condition acute rheumatic fever (ARF), mainly in children, and leading to chronic cardiac valve disease.

GAP: Echocardiography can “see” latent RHD before symptoms develop, allowing for early disease detection and initiation of benzathine penicillin G (BPG) prophylaxis. While BPG prophylaxis is known to stop disease progression and cause disease regression among patients with ARF, it’s effect on latent RHD is not known.

HYPOTHESIS: Hypothesis 1: Prophylaxis with BPG will result in fewer children with latent RHD showing progression of echocardiographic valve changes at 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative reduction in progression in the BPG arm: range 15%-25% control arm vs. 7.5-12.5% BPG-arm.); Hypothesis 2: Prophylaxis with BPG will result in more children with latent RHD showing regression of echocardiographic valve changes by 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative increase in regression in the BPG arm: range 10-20% control arm vs. 20-40% BPG arm.)

METHODS: We will conduct a randomized controlled trial of penicillin prophylaxis in children (5-15 years) with latent RHD according to the 2012 World Heart Federation (WHF) criteria. We will screen 30,000 children (half in pre-trial period and half over first 6 months) to identify approximately 900 cases of latent RHD, to account for non-participation and attrition.

RESULTS: Pending.

IMPACT: Results of our study will immediately inform the standard of care for children diagnosed with latent RHD, and could help shape, over 2-3 years, practical and scalable screening programs that could substantially decrease the burden of RHD in our lifetime.