Rheumatic Heart Disease in Children
Conditions
Keywords
Rheumatic Heart Disease, Pragmatic Randomized Controlled Trial, Oral Penicillin V, Group A Streptococcus
Brief summary
This study will look at whether children ages 5-8 who take Penicillin V by mouth twice a day are less likely to develop rheumatic heart disease (RHD) over a 3-year period compared to children who do not take the medicine.
Interventions
Twice-daily oral Pen V 250 mg
Sponsors
The University of Western Australia
Uganda Heart Institute
Ochsner Health System
Murdoch Childrens Research Institute
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 8 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 5-8 years at enrollment * Residence within the participating study catchment area (Gulu District or Gulu City) * Normal study echocardiogram confirmed by the expert adjudication panel * Parent/guardian able and willing to provide written informed consent * Participant able to provide written assent (age 8 years)
Exclusion criteria
* History of prior ARF or RHD with or without cardiac involvement * Evidence of RHD on baseline echocardiography * Congenital heart disease (excluding small PFO, small ASD) or other cardiac abnormality at baseline echocardiography * Self-reported known allergy to penicillin * Medical conditions that would preclude safe participation, adherence, or follow-up * Anticipated inability to complete 36 months of study follow-up * Any known co-morbid condition requiring regular antibiotic prophylaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Rheumatic Heart Disease | 3 years | Proportion of participants with newly diagnosed RHD based on blinded echocardiographic adjudication among children with a normal baseline echocardiogram. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants who Develop Early RHD | 3 years | Proportion of participants who develop Stage A or Stage B rheumatic heart disease as determined by blinded echocardiographic adjudication. |
| Number of Participants who Develop Advanced RHD | 3 years | Proportion of participants who develop Stage C or Stage D rheumatic heart disease as determined by blinded echocardiographic adjudication. |
| Number of Participants who Develop Acute Rheumatic Fever | 3 years | Percentage of participants who develop acute rheumatic fever (ARF) diagnosed according to the 2015 Revised Jones Criteria among participants in each study arm. |
| Cumulative Incidence of RHD at Two Years | 2 years | Proportion of participants with newly diagnosed rheumatic heart disease based on blinded echocardiographic adjudication. |
| Cumulative Incidence of RHD at One Year | 1 year | Proportion of participants with newly diagnosed rheumatic heart disease based on blinded echocardiographic adjudication. |
| Number of Participants Achieving at least 80% Adherence to Oral Penicillin V Prophylaxis Based on Pill Count | 3 years | Proportion of participants assigned to Arm 2 who achieve ≥80% adherence to prescribed oral Penicillin V prophylaxis, as assessed by pill count. At each bimonthly school-based visit, remaining tablets will be counted and adherence calculated as the proportion of prescribed doses taken during the assessment interval. |
| Number of Participants Achieving at Least 80% Adherence to Oral Penicillin V Prophylaxis Based on DoseSmart® Bottle Opening Records | 3 years | Proportion of participants assigned to Arm 2 who achieve ≥80% adherence to prescribed oral Penicillin V prophylaxis, as assessed using DoseSmart® electronic bottle opening data downloaded at each bi-monthly visit. Adherence will be calculated as the proportion of expected dosing events recorded over the assessment interval. |
| Number of Participants Experiencing Treatment-Emergent Adverse Events | 3 years | Number and proportion of participants experiencing treatment-emergent adverse events, serious adverse events, treatment discontinuations, or other safety-related events attributable to oral Penicillin V. |
| Number of Participants Achieving at Least 80% Adherence to Oral Penicillin V Prophylaxis Based on Caregiver-Reported Dosing Diary | 3 years | Proportion of participants assigned to Arm 2 who achieve ≥80% adherence to prescribed oral Penicillin V prophylaxis, as assessed using a participant/parent paper diary in which caregivers record each administered dose. Adherence will be calculated as the proportion of prescribed doses documented as taken during the assessment interval. |
Countries
Uganda
Contacts
CONTACTAlison Spaziani
CONTACTMary Banks
PRINCIPAL_INVESTIGATORJoselyn Rwebembera
Uganda Heart Institute
Outcome results
None listed