Project Details

A Long-Term Follow-up Study for Patients Who Participated in the GOAL Trial (GOAL-Post)

Andrea Beaton, MD

Summary

BACKGROUND: The GOAL trial (GwokO Adunu pa Lutino, “protect the heart of a child”) reached completion in October 2020, finding that secondary antibiotic prophylaxis resulted in a significant and substantial reduction in RHD progression among children with latent rheumatic heart disease (RHD). These data have important clinical and public health implications. However, the GOAL trial also showed that approximately 50% of children with latent RHD regress at two-years, with the majority (85%) returning to a normal echocardiographic study with or without antibiotic prophylaxis. GAP: The recommended duration of prophylaxis, following a diagnosis of latent RHD, is not known. GOAL-Post will help to refine recommendations for those with persistent cardiac involvement and those who show early normalization of echocardiographic findings. AIMS. Building on the infrastructure and successes of the GOAL Trial, we will (1) determine the risk of recurrent RHD following echo normalization and (2) study the longer-term benefit of antibiotic prophylaxis in those with persistent latent RHD . METHODS: GOAL-Post includes two observational cohort studies to investigate outcomes for participants who completed the GOAL Trial, divided by final GOAL diagnosis: 1. normal or 2. persistent latent RHD. GOAL Post will enroll between 953 and 1102 participants in Aim 1 (364 participants with normal echocardiograms after 2-years of participation in the GOAL Trial (Group A) and an appropriate number (up to 811) of age/sex matched controls (Group B) without echocardiographic evidence of RHD. Aim 2 will enroll up to 415 with persistent latent RHD after 2 years of participation in the GOAL Trial. RESULTS: In Aim 1: Three hundred and two of 307 (98.4%) Group A and 675 of 719 (93.9%) Group B participants reached study completion. Only 1 of 302 (0.3%) in Group A and none in Group B progressed to moderate/severe RHD. This means that over 99% of children who had echocardiographic normalization were safe from clinically relevant disease. Sixty-one of 302 (20.0%, 95% CI: 15.5, 24.6) in Group A and 11 of 675 (1.7%, 95% CI: 0.7, 2.7) in Group B showed any RHD - an 18.3% difference (95% CI: 13.6 to 23.0) in incidence between the two groups. Side-by-side comparison of Group A end of GOAL-Post against the beginning of GOAL trial studies showed only 21 of 302 (6.9%, 95% CI: 4.1, 9.8) had echocardiographic evidence of disease progression. In Aim 2: 349 of 359 (97.2%) participants reached study completion. Slightly more participants had been in the SAP arm of GOAL trial (52.4%). The mean age of participants was 15.5 years and there were more females than males (54.9% vs. 45.1%). Only 5 of 349 (1.4%, 95% CI: 0.6, 3.4) progressed to moderate/severe RHD, 111 of 349 (31.8%, 95% CI: 27.1, 36.9) showed disease regression, and 233 of 349 (66.8%, 95% CI: 62.0, 71.4) had stable mild disease. IMPACT: Together, these findings suggest that shorter courses of secondary antibiotic prophylaxis may be possible for children with screen-detected RHD. This may increase the feasibility and scalability of implementing echocardiographic screening reducing the individual and health care system burden imposed by lengthy courses of SAP.