Heart Diseases Clinical Trial
— GOALOfficial title:
The GOAL (GwokO Adunu pa Lutino) Trial: Determining the Impact of Penicillin on Latent Rheumatic Heart Disease: A Randomized Controlled Trial in Uganda
Verified date | September 2019 |
Source | Children's Research Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Rheumatic heart disease (RHD) affects at least 32.9 million people, mostly children living in
low-resource settings. Long-term intramuscular benzathine penicillin G (BPG) prophylaxis is
proven to prevent progression of chronic valve changes in patients with established rheumatic
heart disease (RHD) and to allow regression of valve changes in patients with a history of
acute rheumatic fever (ARF) with mild RHD. However, in low-resource settings ARF is an
elusive diagnosis, and most patients (85%) are diagnosed only when RHD is severe and
irreversible, medications ineffective, and surgical intervention is expensive and/or
unavailable.
Identification of latent RHD might be an opportunity to substantially reduce RHD morbidity
and mortality. However, detection of latent RHD is only important if outcomes are improved.
The appropriate management of children with latent RHD is unknown and no formal
recommendations exist. While some clinicians prescribe penicillin prophylaxis for children
with latent RHD, clinical equipoise exists regarding the best practice.
To fill this gap, the investigators propose a randomized controlled trial in children with
latent RHD to evaluate the efficacy of BPG prophylaxis compared to no prophylaxis. Our
primary outcome measure is progression of valvular changes on echocardiogram at 2 years. A
sample size of 916 children is needed to detect a 50% reduction of progression (expected
range 7.5-12.5% progression in BPG-arm vs. 15%-25% progression in control-arm) with 90%
power.
AIM 1: To compare the proportion of children (aged 5-17 years) with latent RHD receiving BPG
prophylaxis who progress to worse valvular disease at 2-years compared to children not
receiving BPG prophylaxis.
Hypothesis 1: Prophylaxis with BPG will result in fewer children with latent RHD showing
progression of echocardiographic valve changes at 2 years compared to children with latent
RHD not receiving BPG prophylaxis. (The investigators expect at least a 50% relative
reduction in progression in the BPG arm: range 15%-25% control arm vs. 7.5-12.5% BPG-arm.)
AIM 2: To compare the proportion of children (aged 5-17 years) with latent RHD receiving BPG
prophylaxis who regress to improved valvular disease at 2-years compared to children not
receiving BPG prophylaxis.
Hypothesis 2: Prophylaxis with BPG will result in more children with latent RHD showing
regression of echocardiographic valve changes by 2 years compared to children with latent RHD
not receiving BPG prophylaxis. (The investigators expect at least a 50% relative increase in
regression in the BPG arm: range 10-20% control arm vs. 20-40% BPG arm.)
This study is highly significant because it will establish if BPG prophylaxis improves
outcomes for children with latent RHD. Feasibility will be ensured through the experience,
resources, community support, and accessible patient population of our investigational team.
The results of our study will have high impact, immediately informing international policy on
the standard of care for children diagnosed with latent RHD and shaping, over 2-3 years,
practical and scalable programs that could substantially decrease the global burden of RHD.
Status | Active, not recruiting |
Enrollment | 807 |
Est. completion date | November 30, 2020 |
Est. primary completion date | November 30, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 5 Years to 17 Years |
Eligibility |
Inclusion Criteria: - Children will be eligible for study participation if they are (1) between the ages of 5-17 years and (2) have a new diagnosis of latent RHD detected through primary school echo screening and confirmed by blinded consensus review. All children will be recruited from schools in Gulu District in Uganda. Exclusion Criteria: - Patients will be excluded from the study for the following reasons: - Known history of ARF or RHD - Newly diagnosed RHD by echo screening consider 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 = 5mmHg) (WHF, definite B), 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). - Prior allergic reaction to penicillin - Any known conditions predisposing to thrombocytopenia or hypercoagulability, or other contraindications to intramuscular injection - Any known co-morbid conditions (HIV, renal deficiencies, severe malnutrition among others) that have resulted in prescription of regular antibiotic prophylaxis |
Country | Name | City | State |
---|---|---|---|
Uganda | GOAL Office | Gulu |
Lead Sponsor | Collaborator |
---|---|
Children's Research Institute | Children's National Hospital, Gift of Life International, Karp Family Foundation, Murdoch Childrens Research Institute, Thrasher Research Fund, Uganda Heart Institute, University of Cape Town |
Uganda,
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* Note: There are 22 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | progression of valvular changes on echocardiogram at 2 years | To compare the proportion of children (aged 5-17 years) with latent RHD receiving BPG prophylaxis who progress to worse valvular disease at 2-years compared to children not receiving BPG prophylaxis | 2 years | |
Secondary | regression of vavular changes on electrocardiogram at 2 years | To compare the proportion of children (aged 5-17 years) with latent RHD receiving BPG prophylaxis who regress to improved valvular disease at 2-years compared to children not receiving BPG prophylaxis | 2 years |
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