Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial).

Autor: Rwebembera J; Division of Adult Cardiology, Department of Adult Cardiology, Uganda Heart Institute, Kampala, Uganda. Electronic address: joselynr36@gmail.com., Ndagire E; Division of Paediatric Cardiology, Department of Paediatric Cardiology, Uganda Heart Institute, Kampala, Uganda., Carvalho N; Economics of Global Health and Infectious Diseases Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia., Webel AR; Department of Child, Family and Population Health Nursing, University of Washington, Seattle, Washington., Sable C; Division of Cardiology, Children's National Hospital, Washington, DC., Okello E; Division of Adult Cardiology, Department of Adult Cardiology, Uganda Heart Institute, Kampala, Uganda., Sarnacki R; Global Cardiology Research Initiative, Children's National Hospital, Washington, DC., Spaziani AM; Global Cardiology Research Initiative, Children's National Hospital, Washington, DC., Mucunguzi A; Department of Finance and Administration, Rheumatic Heart Disease Research Collaborative in Uganda, Uganda Heart Institute, Kampala, Uganda., Engelman D; Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Melbourne Children's Global Health Initiative, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia., Grobler A; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia., Steer A; Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Melbourne Children's Global Health Initiative, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia., Beaton A; Department of Paediatrics, School of Medicine, University of Cincinnati, Cincinnati, OH; Division of Cardiology, The Heart Institute, Cincinnati Children's Medical Center, Cincinnati, OH.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2024 Sep; Vol. 275, pp. 74-85. Date of Electronic Publication: 2024 May 24.
DOI: 10.1016/j.ahj.2024.05.012
Abstrakt: Background: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years.
Methods/design: The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up.
Discussion: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs.
Trial Registration: ClinicalTrials.gov: NCT05693545.
Competing Interests: Conflict of Interest None.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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