Re-PERFUSE: Phase 1b study of AZD3427, a novel relaxin receptor agonist, on renal perfusion in HFrEF patients.

Aims: Renal impairment frequently coexists with heart failure (HF) and is associated with increased risk of poor clinical outcomes. This highlights the urgent need for therapies targeting both cardiac and renal dysfunction. AZD3427, a long-acting recombinant fusion protein and relaxin analogue that selectively activates the relaxin family peptide receptor 1 (RXFP1), showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients (NCT04630067). The hypothesis is that AZD3427 may enhance GFR by expanding the functional renal cortex volume and improving renal perfusion.

Methods and results: The Re-PERFUSE study (NCT06611423) is a Phase 1b, randomised, double-blind, placebo-controlled trial aimed at evaluating the effects of AZD3427 on renal perfusion in patients with HF and reduced ejection fraction (HFrEF) with reduced eGFR. Patients with HF, EF ≤ 40% and an eGFR of 30 to 90 mL/min/1.73 m², assessed by the CKD-EPI 2021, will receive a single dose of subcutaneous AZD3427 (n = 6) or placebo (n = 6). Intravenous dopamine will serve as a positive control for increased renal blood flow. Positron emission tomography (PET) imaging with [¹⁵O]-labelled water will be used to measure renal cortex blood flow pre- and post-treatment, allowing differentiation between global and focal renal blood flow changes and providing insights into potential nephron recruitment and increased filtration membrane area. Safety and tolerability will be assessed through monitoring of adverse events, clinical laboratory tests and vital signs.

Conclusions: This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment.