Clinical Research Directory

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

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.

Delayed Initiation of ARNI and SGLT2i in Heart Failure With Corrected Aetiology (DELAY-HF), Pilot Study

In patients with heart failure due to a reversible underlying cause-such as valvular heart disease or coronary artery disease-surgical or procedural correction of the underlying lesion (valve repair/replacement, TAVI, PCI, or CABG) frequently leads to spontaneous recovery of cardiac function, even without neurohormonal modulators. In this clinical setting, a substantial proportion of patients may not require the full set of guideline-directed medical therapies routinely prescribed for chronic HFrEF. The purpose of this study is to determine whether ARNI (angiotensin receptor-neprilysin inhibitor) and SGLT2 inhibitors are truly necessary in patients whose left ventricular function recovers spontaneously after treatment of a correctable cause of heart failure. The DELAY-HF trial (DELayed initiation of ARNI and SGLT2i in heart failure with corrected aetiologY) is a multi-center, randomized controlled non-inferiority trial evaluating whether a delayed-initiation strategy of ARNI and SGLT2i is non-inferior to immediate initiation in patients with heart failure whose underlying cause has been completely corrected by surgical or procedural intervention. Adults with a preoperative left ventricular ejection fraction (LVEF) ≤40% who have undergone successful correction of a reversible cause of heart failure-either revascularization (PCI or CABG) for ischemic cardiomyopathy or valvular surgery (including TAVI) for left-sided valvular heart disease causing volume overload-will be randomized 1:1 to (1) delayed initiation, in which ARNI/SGLT2i are withheld for 6 months and started only in patients whose LVEF remains ≤40% at the 6-month assessment, versus (2) immediate guideline-directed medical therapy (GDMT) including ARNI/SGLT2i started shortly after the corrective procedure. All patients are followed for 12 months. The primary outcome is the absolute change in LVEF from baseline at 12 months. Key secondary outcomes include cardiovascular mortality, heart failure hospitalization, additional echocardiographic indices, NT-proBNP, KCCQ quality-of-life score, 6-minute walk distance, and a cost-effectiveness analysis. By comparing these two strategies, this trial will clarify the incremental contribution of ARNI and SGLT2i-both to further LVEF recovery and to clinical outcomes-in patients who have already demonstrated spontaneous improvement in cardiac function after correction of the underlying cause, and will thereby help define whether these agents are truly necessary in this population.