GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial

Phase 2RecruitingNCT05693545

Children's Hospital Medical Center, Cincinnati1,004 enrolled

Overview

The goal of this clinical trial is to determine if twice daily oral penicillin prophylaxis is non-inferior to monthly IM penicillin prophylaxis in preventing latent Rheumatic Heart Disease Progression in children between the ages of 5-17 years. The main objective is to compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.

GOALIS is a randomized controlled trial developed to provide high quality contemporary evidence on the efficacy of oral penicillin as RHD prophylaxis. Aim 1: To compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis. Aim 2: To evaluate the economic equivalence and cost-effectiveness of oral penicillin compared to IM penicillin, after echocardiographic screening for latent RHD detection. Aim 3: Compare patient-reported outcomes (treatment acceptance, treatment satisfaction, and health-related quality of life) between children receiving oral and IM penicillin prophylaxis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,004

Conditions

Rheumatic Heart Disease

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has a new diagnosis of latent RHD detected through primary or secondary school echocardiographic screening. * Has agreed to participate in the study via the study's informed consent/assent process. Operational Definition of Latent RHD Borderline RHD or Mild Definite RHD (to include no more than mild regurgitation at the mitral or aortic valve, normal mean mitral and aortic valve gradients, normal bi-ventricular function) according to the 2012 WHF consensus criteria. Exclusion Criteria: * Known history of ARF or RHD * Newly diagnosed RHD by echo screening considered to be "missed clinical RHD" as compared to true latent RHD including: \> mild pathological valvular regurgitation at the mitral valve or aortic valve, mitral stenosis (mean MV gradient ≥ 4mmHg) (definite B61), aortic stenosis (mean AV gradient ≥ 20mmHg) * Structural or functional cardiac defects, other than those consistent with RHD, that were known prior to or detected through echo screening (except patent foramen ovale, small atrial septal defect, small ventricular septal defect, small patent ductus arteriosus) * Self-report of prior allergic reaction to penicillin * Any known conditions predisposing to thrombocytopenia or hypercoagulability, or other contraindications to intramuscular injection * Any known co-morbid conditions (ex. HIV, renal deficiencies, severe malnutrition) that have resulted in prescription of regular antibiotic prophylaxis)

Outcomes

Primary Outcomes

Progression

Progression of echocardiographic features of latent RHD to borderline to definite, or definite to mild or definite to moderate/severe

Time frame: 2 year endpoint

Secondary Outcomes

Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin

The aim is to understand the costs and effectiveness of the intervention. Costs will include intervention and disease specific costs, capturing both health system and family out of pocket costs. Participants will complete a questionnaire asking about out-of-pocket cost (medications, supplies, consultation fees) and lost productivity (including missed school and workdays) due to the intervention. Costs will be measured in the local currency (Uganda Shillings) and presented in United States dollars (USD)