Comparing oral and intramuscular penicillin to prevent worsening of latent Rheumatic Heart Disease in children

Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A Non-inferiority Randomized Trial

This study is testing whether taking penicillin by mouth twice a day is just as good as getting it through an injection once a month to help prevent worsening heart problems in children with latent Rheumatic Heart Disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1004 (estimated)
• Ages: 5 Years to 17 Years
• Sex: All
• Sponsor: Children's Hospital Medical Center, Cincinnati (Academic / other)
• Locations: 1 site (Kampala)
• Trial ID: NCT05693545 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of twice-daily oral penicillin compared to monthly intramuscular penicillin in preventing the progression of latent Rheumatic Heart Disease (RHD) in children aged 5-17 years. It is a randomized controlled trial that will assess the proportion of participants who experience worsening valvular disease over a two-year period. Additionally, the study will analyze the cost-effectiveness of both prophylactic methods and gather patient-reported outcomes regarding treatment acceptance and quality of life. The trial is designed to provide contemporary evidence on the efficacy of oral penicillin as a viable alternative to intramuscular injections.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 5-17 years who have been newly diagnosed with latent Rheumatic Heart Disease.

Not a fit: Patients with a known history of Acute Rheumatic Fever or Rheumatic Heart Disease, or those with significant valvular abnormalities, will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a less invasive and more acceptable method of prophylaxis for children at risk of progressing to severe RHD.

How similar studies have performed: Other studies have shown promising results with similar approaches, but this trial aims to provide high-quality contemporary evidence specifically for oral 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)

Where this trial is running

Kampala

• Uganda Heart Institute — Kampala, Uganda (Recruiting)

Study contacts

• Principal investigator: Andrea Z Beaton — Cincinnati Chidren's hospital
• Study coordinator: Ndate Fall, MS RN

Conditions Rheumatic Heart Disease