Study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function (BalanceD-HF): background and design

Background Despite available guideline-recommended medical therapies for HF there is an unmet need to reduce residual morbidity and mortality in patients with HF and kidney disease. Mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity in patients with HF, but they increase the risk of hyperkalaemia resulting in MRA underutilisation in patients with HF and impaired kidney function. Balcinrenone is a novel non-steroidal (ns)MRA (also known as modulator) with cardio-renal protection comparable to approved MRAs in animal models, but with a predicted reduced risk of hyperkalaemia. Dapagliflozin is indicated to reduce the risk of cardiovascular death (CV) or worsening HF in adults with HF across the left ventricular ejection fraction (LVEF) spectrum. A Phase 2 trial of the combination of balcinrenone and dapagliflozin in patients with CKD demonstrated a reduction in urinary albumin creatinine ratio and another Phase 2 trial in patients with HF identified a dose range with beneficial effects on surrogate cardio-renal biomarkers compared to dapagliflozin alone without increasing the risk of hyperkalaemia. Methods BalanceD-HF is an ongoing Phase 3, randomized, double-blind, parallel group, active controlled, event-driven trial in ambulatory or hospitalised patients with HF and impaired kidney function who had a recent HF event, to evaluate the efficacy and safety of combined balcinrenone/dapagliflozin vs dapagliflozin, in addition to standard of care. An estimated 4800 patients with symptomatic HF (NYHA class II to IV) across the LVEF range, elevated NT-proBNP (>300 pg/mL), eGFR >20 - <60 ml/min/1.73m2, potassium <5.0 mmol/L, a HF event in last 6 months and not taking an MRA will be randomized 1:1:1 to balcinrenone/dapagliflozin 15 mg/10 mg, 40 mg/10 mg or dapagliflozin 10 mg. The primary composite endpoint is the time to first occurrence of CV death, hospitalisation for HF or urgent HF visit (requiring intravenous therapies). Suspected endpoint events are adjudicated by a blinded Clinical Endpoint Committee. An independent Data Monitoring Committee is monitoring safety data. The study started in April 2024 and is targeting 1050 primary endpoint events. BalanceD-HF is underway across 700 sites in 39 countries. Results Not applicable; On-going study. Conclusions BalanceD-HF is a unique trial evaluating the efficacy and safety of the novel nsMRA balcinrenone combined with dapagliflozin in patients with HF and impaired kidney function across the LVEF spectrum and HF care continuum.BalanceD-HF figure