Determining the Impact of Penicillin in Latent RHD: The GOAL Trial (GOAL)

September 27, 2019 updated by: Andrea Beaton, Children's National Research Institute

The GOAL (GwokO Adunu pa Lutino) Trial: Determining the Impact of Penicillin on Latent Rheumatic Heart Disease: A Randomized Controlled Trial in Uganda

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

807

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Gulu, Uganda, 20010
        • GOAL Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: BPG Arm
Intramuscular BPG prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days
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:
  • benzathine penicillin G
  • BPG
  • penicillin prophylaxis
NO_INTERVENTION: Control Arm
No prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's National Research Institute

Collaborators

University of Cape Town
Thrasher Research Fund
Murdoch Childrens Research Institute
Uganda Heart Institute
Karp Family Foundation
Gift of Life International

Investigators

  • Principal Investigator: Andrea Beaton, MD, Cincinnati Children's

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 26, 2018

Primary Completion (ANTICIPATED)

November 30, 2020

Study Completion (ANTICIPATED)

November 30, 2020

Study Registration Dates

First Submitted

November 15, 2017

First Submitted That Met QC Criteria

November 15, 2017

First Posted (ACTUAL)

November 17, 2017

Study Record Updates

Last Update Posted (ACTUAL)

October 1, 2019

Last Update Submitted That Met QC Criteria

September 27, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOAL: RHD RCT
  • E.W. "Al" Thrasher Award (OTHER: Thrasher Research Fund)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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