Rheumatic Heart DiseasePhase 2NCT05693545
GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial
A Phase 2 study testing phenoxymethyl penicillin and intramuscular benzathine penicillin G (BPG) prophylaxis in people with Rheumatic Heart Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in Uganda.
Trial summary
The goal of this clinical trial is to determine if twice daily oral penicillin prophylaxis is non-inferior to monthly IM penicillin prophylaxis in preventing latent Rheumatic Heart Disease Progression in children between the ages of 5-17 years. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Rheumatic Heart Disease
- What is being tested?
- phenoxymethyl penicillin and intramuscular benzathine penicillin G (BPG) prophylaxis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,004 participants
- Where
- 1 siteUganda
- Study dates
- 1 Sep 2023to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A Non-inferiority Randomized Trial
The goal of this clinical trial is to determine if twice daily oral penicillin prophylaxis is non-inferior to monthly IM penicillin prophylaxis in preventing latent Rheumatic Heart Disease Progression in children between the ages of 5-17 years. The main objective is to compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.
Read the detailed description
GOALIS is a randomized controlled trial developed to provide high quality contemporary evidence on the efficacy of oral penicillin as RHD prophylaxis.
Aim 1: To compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.
Aim 2: To evaluate the economic equivalence and cost-effectiveness of oral penicillin compared to IM penicillin, after echocardiographic screening for latent RHD detection.
Aim 3: Compare patient-reported outcomes (treatment acceptance, treatment satisfaction, and health-related quality of life) between children receiving oral and IM penicillin prophylaxis.
- Conditions
- Rheumatic Heart Disease
- Being tested
- phenoxymethyl penicillin, intramuscular benzathine penicillin G (BPG) prophylaxis
- Medical subject headings
- Rheumatic Heart Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenoxymethyl penicillinDrug
Also called Pen V
Prophylaxis
intramuscular benzathine penicillin G (BPG) prophylaxisDrug
Also called benzathine penicillin G, BPG, penicillin prophylaxis
Prophylaxis
| Study group | Role | What they receive |
|---|---|---|
| Oral Pencillin | Experimental | Oral phenoxymethyl penicillin (Pen V) prophylaxis 250mg twice daily. Receives: Drug: phenoxymethyl penicillin |
| IM Penicillin | Active comparator | Intramuscular benzathine benzylpenicillin G (BPG) prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days Receives: Drug: intramuscular benzathine penicillin G (BPG) prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression
Progression of echocardiographic features of latent RHD to borderline to definite, or definite to mild or definite to moderate/severe
Measured: 2 year endpoint
Secondary outcomes (6)
Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin
The aim is to understand the costs and effectiveness of the intervention. Costs will include intervention and disease specific costs, capturing both health system and family out of pocket costs. Participants will complete a questionnaire asking about out-of-pocket cost (medications, supplies, consultation fees) and lost productivity (including missed school and workdays) due to the intervention. Costs will be measured in the local currency (Uganda Shillings) and presented in United States dollars (USD)
Measured: baseline, 6, 12, 18, 24 months post randomization
Obtain cost data associated with the receipt of oral or IM penicillin in the community from a healthcare provider perspective.
In order to understand health center and community costs, 10 randomly selected health care facilities (including level II, III, and IV facilities) will be surveyed to obtain direct costs of medications, supplies as well as any administration and professional fees associated with outpatient and inpatient visits.
Measured: 2 year endpoint
Treatment Acceptance
Treatment acceptance will be assessed with the widely-used Chronic Treatment Acceptance (ACCEPT) questionnaire, a generic medication acceptance instrument validated for chronic conditions. This 25-item survey consists of six areas of focus: medication convenience (3 items), length of treatment (2 items), medication constraints (9 items), medication side effects (5 items), medication effectiveness (3 items), medication advantages (3 items). Responses are rated on a 5-point Likert scale and scores of 1 through 4 indicating increasing levels of acceptance.
Measured: 3, 6, 12, and 24 months post randomization
Treatment Satisfaction
Treatment Satisfaction will be assessed with the 14-item Abbreviated Treatment Satisfaction Questionnaire (v 1.4). This widely used survey contains 4 areas of focus including satisfaction of treatment effectiveness (3 items), satisfaction with treatment side effects (5 items), satisfaction with treatment convenience (3 items), and a global treatment satisfaction (3 items). Scores are then transformed to a score of 0-100 to create the overall scale score and the subcategory scores, with higher scores representing higher treatment satisfaction on that domain.
Measured: 3, 6, 12, and 24 months post randomization
Health-Related Quality of Life
Health Related Quality of Life will be measured using the Pediatric Quality of Life Inventory Version 4.0 Generic Core (PedsQL 4.0) questionnaire. The PedsQLTM4.0 is a 23-item survey for children aged 5-18 which assesses HRQOL. It has four areas of focus: Physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), school functioning (5 items). Each item has five possible responses measuring the extent to which the item was a problem during the past month. The possible responses are measured using a 5-point Likert scale from 0=never a problem to 4 = almost always a problem. These reverse scaled scores are then transformed to a score of 0-100 to create the overall scaled score and the subcategory scores, with higher scores representing better quality of life.
Measured: baseline, 3, 6, 12, and 24 months post randomization
Patient-reported outcomes
Interviews will be used to collect qualitative data around participants perceptions of the impact of RHD and its treatment on their activities of daily living and quality of life including experiences with IM or oral penicillin prophylaxis.
Measured: baseline, 6, 12, 18, 24 months post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2023
- Study start1 Sep 2023
- Primary completion31 Mar 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatic Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,004 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Uganda Heart Institute
- Responsible party
- Sponsor
- Investigators
- Andrea Z Beaton, Principal investigator, Cincinnati Chidren's hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05693545
- Sponsor's protocol ID
- 2022-0892
- Status last verified
- Oct 2026
- First submitted
- 4 Jan 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rwebembera J, Ndagire E, Carvalho N, Webel AR, Sable C, Okello E, Sarnacki R, Spaziani AM, Mucunguzi A, Engelman D, Grobler A, Steer A, Beaton A. Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial). Am Heart J. 2024 Sep;275:74-85. doi: 10.1016/j.ahj.2024.05.012. Epub 2024 May 24.
PubMed 38797460
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A Non-inferiority Randomized Trial
- ClinicalTrials.gov ID
- NCT05693545
- Acronym / sponsor ID
- 2022-0892
- Conditions
- Rheumatic Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,004 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Uganda Heart Institute
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 23 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to determine if twice daily oral penicillin prophylaxis is non-inferior to monthly IM penicillin prophylaxis in preventing latent Rheumatic Heart Disease Progression in children between the ages of 5-17 years. The main objective is to compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.
Detailed description
GOALIS is a randomized controlled trial developed to provide high quality contemporary evidence on the efficacy of oral penicillin as RHD prophylaxis.
Aim 1: To compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.
Aim 2: To evaluate the economic equivalence and cost-effectiveness of oral penicillin compared to IM penicillin, after echocardiographic screening for latent RHD detection.
Aim 3: Compare patient-reported outcomes (treatment acceptance, treatment satisfaction, and health-related quality of life) between children receiving oral and IM penicillin prophylaxis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Pencillin | Experimental | Drug: phenoxymethyl penicillinOral phenoxymethyl penicillin (Pen V) prophylaxis 250mg twice daily. |
| IM Penicillin | Active comparator | Drug: intramuscular benzathine penicillin G (BPG) prophylaxisIntramuscular benzathine benzylpenicillin G (BPG) prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| phenoxymethyl penicillinAlso: Pen VProphylaxis | Drug | Oral Pencillin |
| intramuscular benzathine penicillin G (BPG) prophylaxisAlso: benzathine penicillin G, BPG, penicillin prophylaxisProphylaxis | Drug | IM Penicillin |
Primary outcome
Progression
Time frame: 2 year endpoint
Progression of echocardiographic features of latent RHD to borderline to definite, or definite to mild or definite to moderate/severe
6 secondary outcomes
Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin
Time frame: baseline, 6, 12, 18, 24 months post randomization
Obtain cost data associated with the receipt of oral or IM penicillin in the community from a healthcare provider perspective.
Time frame: 2 year endpoint
Treatment Acceptance
Time frame: 3, 6, 12, and 24 months post randomization
Treatment Satisfaction
Time frame: 3, 6, 12, and 24 months post randomization
Health-Related Quality of Life
Time frame: baseline, 3, 6, 12, and 24 months post randomization
Patient-reported outcomes
Time frame: baseline, 6, 12, 18, 24 months post randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Derived from this study: PubMed 38797460Rwebembera J, Ndagire E, Carvalho N, Webel AR, Sable C, Okello E, Sarnacki R, Spaziani AM, Mucunguzi A, Engelman D, Grobler A, Steer A, Beaton A. Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial). Am Heart J. 2024 Sep;275:74-85. doi: 10.1016/j.ahj.2024.05.012. Epub 2024 May 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Z Beaton principal investigator
Cincinnati Chidren's hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing phenoxymethyl penicillin and intramuscular benzathine penicillin G (BPG) prophylaxis in people with Rheumatic Heart Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression (time frame: 2 year endpoint). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05693545, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.