A Non-Inferiority Trial of Stopping Penicillin in Early Rheumatic Heart Disease: GOAL-Stop

NCT07146048 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-0604
• Study Type: interventional
• Target: 922
• Locations: 0 countries
• Sites: N/A

Brief Summary

GOAL-Stop is a randomized, controlled, non-inferiority trial designed to evaluate whether discontinuing secondary antibiotic prophylaxis (SAP) is non-inferior to continuing SAP in preventing progression of rheumatic heart disease (RHD) among children and adolescents. The trial will enroll participants aged 5-20 years with previously diagnosed mild RHD who have received at least 2 years of SAP and who demonstrate either echocardiographic normalization or stability (persistent mild RHD). Participants will be randomized to either continue SAP or discontinue SAP for 2 years. The primary outcome is echocardiographic progression of RHD at 2 years, assessed by blinded adjudicators using the 2023 World Heart Federation criteria. Subgroup analyses will evaluate outcomes in participants with echocardiographic normalization versus stable mild RHD, and an exploratory analysis will assess whether outcomes differ by prior prophylaxis route (oral vs. intramuscular).

Conditions

Rheumatic Heart Disease

Keywords

Rheumatic heart disease; global health; secondary prophylaxis; children

Outcome Measures

Primary Outcomes (1)

• Presence of echocardiographic progression of RHD at two years

  The Primary Outcome will be the presence of echocardiographic progression of RHD at two years, defined by the 2023 World Heart Federation Criteria (none, mild RHD (stage A/B), or moderate/severe RHD (stage C/D).

  Enrollment to the end of treatment at 2 years

Secondary Outcomes (1)

• Non-inferiority among sub-groups

  Enrollment to the end of 2 years participation

Other Outcomes (1)

• Exploratory sub-analysis

  enrollment to the end of 2 years of participation

Study Arms (2)

Stop prophylaxis

NO INTERVENTION

The intervention arm will not receive prophylaxis.

Continue prophylaxis

ACTIVE COMPARATOR

The control arm will receive intramuscular benzathine benzylpenicillin G (BPG) prophylaxis (600,000 IU for children \<30kg, 1.2 million IU for children ≥30kg), every 28 days for a 2-year period. The standard of care for RHD is BPG injections which is why the control arm is continuation of monthly injections.

Drug: Secondary Prophylaxis

Interventions

Secondary Prophylaxis DRUG

Continue standard of care with continued secondary antibiotic prophylaxis

Continue prophylaxis

Eligibility Criteria

• Age: 5 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participated in GOALIE
• Concluded GOALIE with either echocardiographic normalization or stable mild RHD
• Between ages 5-20 years at time of enrollment

You may not qualify if:

• RHD Stage C/D at GOALIE end of study echocardiogram
• Relocation to extremely distant residence or school
• Clinically documented penicillin allergy

Sponsors & Collaborators

• Open Philanthropy: collaborator
• Thrasher Research Fund: collaborator
• Children's Hospital Medical Center, Cincinnati: lead
• Uganda Heart Institute: collaborator

Related Links

• Related Info

MeSH Terms

Conditions

Rheumatic Heart Disease

Condition Hierarchy (Ancestors)

Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Cardiologists who make up the adjudication panel.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2025
• First Posted: August 28, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 20, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 18, 2025

Record last verified: 2025-12