Clinical trial NCT05693545: GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial
Official title: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A Non-inferiority Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rheumatic Heart Disease
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Uganda Heart Institute
First posted: 2023-01-23
Enrollment: 1004
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression
timeFrame: 2 year endpoint
Secondary outcomes:
measure: Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin
timeFrame: baseline, 6, 12, 18, 24 months post randomization
measure: Obtain cost data associated with the receipt of oral or IM penicillin in the community from a healthcare provider perspective.
timeFrame: 2 year endpoint
measure: Treatment Acceptance
timeFrame: baseline, 6, 12, 18, 24 months post randomization
measure: Treatment Satisfaction
timeFrame: baseline, 6, 12, 18, 24 months post randomization
measure: Health-Related Quality of Life
timeFrame: baseline, 6, 12, 18, 24 months post randomization
measure: Patient-reported outcomes
timeFrame: baseline, 6, 12, 18, 24 months post randomization
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Uganda Heart Institute
Study officials:
affiliation: Cincinnati Chidren's hospital
name: Andrea Z Beaton
role: PRINCIPAL_INVESTIGATOR
References: