Improving Management and Secondary Prevention Through Azithromycin Comparative Trial in Rheumatic Heart Disease in Nigeria)- IMPACT-RHD Nigeria

NCT07625228 | Not Yet Recruiting DMC

• 1 other identifier: LAUTECH
• Study Type: interventional
• Target: 474
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Nigeria, among other Low and Middle-income countries, bears one of the highest burdens of RHD in Africa, affecting young to middle-aged adults within their productive years. This leads to loss of productivity, high out-of-pocket costs, and increased mortality risk. Challenges such as such as poverty, overcrowding, limited antibiotic access, and inconsistent prophylaxis contribute to the persistence of the disease. Secondary prophylaxis using intramuscular Benzathine Penicillin G (BPG) serves as the current standard for prevention, but has demonstrated poor adherence due to injection pain, fear, physical, and socioeconomic constraints. Oral Azithromycin offers a potential alternative by overcoming these barriers, providing an effective, acceptable, affordable and sustainable preventive strategy in Nigeria. Methods and design: A randomised, non-inferiority, open-label, controlled clinical trial conducted across cardiology clinics of four tertiary hospitals in major Nigerian cities, for a duration of 24 months. This study will recruit participants aged 15 to 45 years with mild to moderate RHD cases (stage A or B as defined by World Heart Federation criteria) confirmed by a blinded adjudication panel, comprising 5 expert cardiologists, who will determine the echocardiographic stage of RHD on enrollment and at completion of the study period. Randomisation of participants will be done in a 1:1 ratio to receive either the standard regimen of intramuscular BPG (1.2 million units) every 28 days or a 3-day course of oral Azithromycin (500mg daily) repeated monthly. A total sample size of 474 participants will provide 90% power to demonstrate non-inferiority, using a margin of 4% with allowance for 15% on follow-up losses. Objectives: The proportion of participants in the oral Azithromycin arm versus the IM BPG arm who demonstrate echocardiographic progression to worsen RHD stages or experience a recurrence of Acute Rheumatic Fever (ARF) within the period of two years will be compared. Additionally, accessing the adherence rates, causes of RHD-related hospitalisations, safety profiles, cost-effectiveness, and patient-reported outcomes, including treatment satisfaction and Health-Related Quality of Life (HRQoL). Significance: This trial is designed to highlight the most effective and readily adoptable secondary prevention strategy for Nigeria's young-to-middle-aged population by evaluating patients' adherence, ease of administration, safety profile, drug availability, cost effectiveness, and other practical considerations in resource-limited settings. Establishing a prevention strategy that addresses the socioeconomic, physical barriers of injection-based prophylaxis and improving long-term adherence and clinical outcomes in Nigeria.

Conditions

Rheumatic Fever; Valvular Heart Diseases; Valvular Cardiomyopathy

Keywords

secondary prevention; Rheumatic Valvular Heart Disease; Benzathine Penicillin; Azithromycin

Outcome Measures

Primary Outcomes (2)

• Recurrence of acute rheumatic fever and progression of valvular cardiomyopathy

  Recurrence of acute rheumatic fever and echocardiographic progression of valvular cardiomyopathy that occurs after 24 months of enrolment

  24 months

• Progression to more advanced RHD in the oral antibiotics arm compared to those in the BPG arm.

  The primary outcome of the study will be the proportion of participants in the oral antibiotics arm who progress to more advanced RHD compared to those in the BPG arm.

  24 months

Secondary Outcomes (2)

• Treatment acceptance and satisfaction.

  24 months

• Health-related Quality of Life

  24 months

Other Outcomes (1)

• Cost and cost-effectiveness comparison of Azithromycin and Benzathine Penicillin

  24 months

Study Arms (2)

Intramuscular Benzathine Penicillin Arm

ACTIVE COMPARATOR

2.4 Million Unit Benzathine Penicillin to be given monthly for 24 months

Drug: Benzathine Penicillin

Oral Azithromycin Group

EXPERIMENTAL

Oral Azithromycin to be given daily for 3 days every month

Drug: Azithromycin (Azithro)

Interventions

Benzathine Penicillin DRUG

Benzathine Penicillin 2.4 Million Units to be given intramuscularly every month for 24 months

Intramuscular Benzathine Penicillin Arm

Azithromycin (Azithro) DRUG

Oral Azithromycin 500 mg once daily for three days to be repeated every month will be given

Oral Azithromycin Group

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• They must be between 10 and 18 years old and have a confirmed diagnosis of mild or moderate RHD.
• They must be under follow-up care at one of the four trial sites and be capable of attending monthly visits or be picked during routine secondary school screening to be performed as part of the study.
• At enrollment, patients must demonstrate cognitive capacity to consent (or assent, if a minor) and a willingness to adhere to the study schedule.
• Females of childbearing potential must agree to avoid pregnancy during the trial.
• Individuals must not have initiated any alternative RHD prophylaxis regimen before enrollment; the trial will provide all prophylaxis during the study

You may not qualify if:

• known allergy to penicillin or any history of anaphylaxis to antibiotics.
• Girls who are pregnant or breastfeeding will be excluded, as well as any patient with severe comorbidities likely to complicate prophylaxis or follow-up. For example, patients with advanced heart failure (NYHA class III-IV), significant chronic kidney or liver disease, uncontrolled diabetes, or other serious chronic illnesses (e.g. active tuberculosis, immunodeficiency).
• Patients with psychiatric conditions or cognitive impairment that preclude informed consent or reliable adherence will also be excluded.
• Any patient currently enrolled in another interventional trial, or who is unwilling or unlikely to comply with monthly visits, will be excluded.

Sponsors & Collaborators

• Ladoke Akintola University of Technology, Ogbomoso, Nigeria: lead

MeSH Terms

Conditions

Rheumatic Fever; Heart Valve Diseases

Interventions

Penicillin G Benzathine; Azithromycin

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Study Officials

• Adeseye A Akintunde

  Ladoke Akintola University of Technology, Ogbomoso, Nigeria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnes Inyam, B.Sc

CONTACT

2348133622392; inyamagnes466@gmail.com

Adeseye Akintunde

CONTACT

2348033932076; aaakintunde@lautech.edu.ng

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The Data monitoring team will be masked to the patient clinical outcomes
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine & Consultant Cardiologist

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: June 4, 2026
• Study Start (Estimated): January 5, 2027
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR, ANALYTIC CODE
• Time Frame: January 2030 for 4 years
• Access Criteria: On reasonable request to the principal Investigator