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

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

Interventions

DRUG

Benzathine Penicillin

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

DRUG

Azithromycin (Azithro)

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

Sponsors & Collaborators

• Ladoke Akintola University of Technology, Ogbomoso, Nigeria

  lead OTHER

Principal Investigators

• Adeseye A Akintunde · Ladoke Akintola University of Technology, Ogbomoso, Nigeria

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

10 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-05

Primary Completion

2030-12-30

Completion

2031-12-30