Determining the Impact of Penicillin in Latent RHD: The GOAL Trial (GOAL)
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| ClinicalTrials.gov Identifier: NCT03346525 |
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Recruitment Status : Unknown
Verified September 2019 by Andrea Beaton, Children's Hospital Medical Center, Cincinnati.
Recruitment status was: Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : October 1, 2019
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatic Heart Disease in Children Latent Rheumatic Heart Disease Rheumatic Heart Disease Heart Diseases | Drug: intramuscular benzathine penicillin G (BPG) prophylaxis | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 807 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | The GOAL (GwokO Adunu pa Lutino) Trial: Determining the Impact of Penicillin on Latent Rheumatic Heart Disease: A Randomized Controlled Trial in Uganda |
| Actual Study Start Date : | June 26, 2018 |
| Estimated Primary Completion Date : | November 30, 2020 |
| Estimated Study Completion Date : | November 30, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: BPG Arm
Intramuscular BPG prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days
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Drug: intramuscular benzathine penicillin G (BPG) prophylaxis
Intramuscular BPG prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days.
Other Names:
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No Intervention: Control Arm
No prophylaxis
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- progression of valvular changes on echocardiogram at 2 years [ Time Frame: 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
- regression of vavular changes on electrocardiogram at 2 years [ Time Frame: 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
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| Ages Eligible for Study: | 5 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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:
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03346525
| Uganda | |
| GOAL Office | |
| Gulu, Uganda, 20010 | |
| Principal Investigator: | Andrea Beaton, MD | Cincinnati Children's |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Andrea Beaton, Pediatric Cardiologist, Associate Professor of Pediatrics, Children's Hospital Medical Center, Cincinnati |
| ClinicalTrials.gov Identifier: | NCT03346525 |
| Other Study ID Numbers: |
GOAL: RHD RCT E.W. "Al" Thrasher Award ( Other Identifier: Thrasher Research Fund ) |
| First Posted: | November 17, 2017 Key Record Dates |
| Last Update Posted: | October 1, 2019 |
| Last Verified: | September 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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echocardiography penicillin prophylaxis intramuscular benzathine penicillin G benzathine penicillin G low-resource setting |
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Rheumatic Heart Disease Rheumatic Diseases Heart Diseases Cardiovascular Diseases Musculoskeletal Diseases Connective Tissue Diseases Rheumatic Fever Streptococcal Infections Gram-Positive Bacterial Infections |
Bacterial Infections Bacterial Infections and Mycoses Infections Penicillins Penicillin G Penicillin G Benzathine Penicillin G Procaine Anti-Bacterial Agents Anti-Infective Agents |