A Phase III, Randomized, Open Label, Active Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Dapagliflozin and Sacubitril/Valsartan Tablets Versus Concomitant Administration of Dapagliflozin and Sacubitril/Valsartan Tablets in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF)

Background The management of heart failure with reduced ejection fraction (HFrEF) has advance significantly with the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2) and angiotensin receptor-neprilysin inhibitors (ARNI). This study aimed to compare the efficacy, safety, and tolerability of a fixed-dose combination (FDC) of Dapagliflozin and Sacubitril/Valsartan with their concomitant administration in patients with HFrEF. Methods This was a phase III, randomized, open label, active controlled, prospective, parallel group, comparative, multicentric clinical study conducted at 17 study centers across India between June 2024 and March 2025 (CTRI/2024/03/064908). Patients with symptomatic HFrEF (left ventricular ejection fraction LVEF ≤ 40% and New York Heart Association NYHA class II-III) receiving stable guideline-directed therapy were randomly assigned (1:1) to receive either a FDC of Dapagliflozin 5 mg plus Sacubitril/Valsartan 97/103 mg or concomitant administration of the same doses twice daily for 24 weeks. The primary endpoint was the mean change in ejection fraction from baseline to Week 24. Results A total of 232 patients were included in the study. Improvement in ejection fraction at Week 24 was comparable between the Arm A and Arm B (6.23% vs. 5.62%; P = 0.1557). Changes in NYHA functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, blood pressure, heart rate, and serum potassium were comparable between groups. Both regimens were well tolerated, with comparable adverse event (AEs) profiles and no serious AEs. Conclusion The FDC of Dapagliflozin and Sacubitril/Valsartan showed similar efficacy, safety, and tolerability to their concomitant administration in patients with HFrEF, supporting its use as a convenient therapeutic option without compromising clinical outcomes.