Project Details

A Non-Inferiority Trial of Stopping Penicillin in Early Rheumatic Heart Disease: GOAL-Stop

Andrea Beaton, MD

Summary

BACKGROUND: Rheumatic heart disease (RHD) is a preventable condition that affects more than 54 million people worldwide, with the highest burden in children from low- and middle- income countries. It is the leading cause of acquired heart disease in young people, often resulting in lifelong disability or premature death if not identified and treated early. Secondary antibiotic prophylaxis (SAP) is widely used to prevent progression, but the appropriate duration of prophylaxis is not known. GAP: It is unclear when it is safe to discontinue SAP in children with mild RHD who show echocardiographic normalization. HYPOTHESIS: Stopping SAP in children with mild RHD who achieve echocardiographic normalization after 2 years of SAP is non-inferior to continuing SAP. METHODS: We will conduct a prospective, randomized non-inferiority trial (GOAL-Stop) comparing stopping SAP and continuation of SAP in children with normalized echocardiograms two years after an early RHD diagnosis. Eligible participants (ages 5–20) must complete the GOALIE trial with a normal echocardiogram. Participants will be randomized 1:1 to either stopping or continuing SAP and followed for two additional years. The primary endpoint will be RHD progression as determined by World Heart Federation category determined by a blinded double adjudication. RESULTS: Pending. IMPACT: Global implementation of WHO’s recommendation to screen for RHD and initiate SAP could protect hundreds of thousands of children from severe disease, but without clear guidance on when to stop prophylaxis, it risks imposing long-term burdens on patients, families, and health systems, making GOAL-Stop a timely opportunity to generate the evidence needed for an individualized, risk-based approach to SAP duration, ensuring emerging RHD strategies are effective, sustainable, and globally scalable. Website Link: www.rrcuganda.org