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

Cincinnati Children's Hospital Medical Center

Status and phase: Not yet enrolling; Phase 3

Conditions: Rheumatic Heart Disease

Treatments: Drug: Secondary Prophylaxis

Study type: Interventional

Funder types: Other

Identifiers

NCT07146048

2025-0604

Details and patient eligibility

About

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).

Enrollment: 922 estimated patients

Sex: All

Ages: 5 to 20 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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922 participants in 2 patient groups

Stop prophylaxis

No Intervention group

Description:

The intervention arm will not receive prophylaxis.

Continue prophylaxis

Active Comparator group

Description:

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.

Treatment:

Drug: Secondary Prophylaxis