Vicadrostat-Empagliflozin Combination Reduces Albuminuria in Chronic Kidney Disease

The combination of vicadrostat and empagliflozin (VicaEmpa) was well tolerated by patients with chronic kidney disease (CKD) and demonstrated the largest reductions in albuminuria compared with either agent alone or placebo, according to study findings published in the American Journal of Kidney Diseases.

The phase 2 multinational, randomized, dose-finding trial, led by Peter Rossing, MD, DMSc, of Steno Diabetes Center, Copenhagen, Denmark, evaluated vicadrostat, a highly selective aldosterone synthase inhibitor, alone or in combination with the sodium-glucose co-transporter 2 inhibitor empagliflozin in adults with CKD with or without type 2 diabetes (T2D). All patients had received prior renin-angiotensin system inhibition.

Cumulative effects of combination therapy compared with monotherapy or placebo were measured from week −8 (first randomization [R1]) through week 14 via two rounds of randomization.

The R1 set included 714 patients who received either empagliflozin 10 mg daily or placebo for an 8-week run-in period. Participants had a mean age of 63.9 years; 60.2% were White, and 69.5% had T2D. At R1 baseline, the mean estimated glomerular filtration rate (eGFR) was 53.3 mL/min/1.73 m², and the median urinary albumin-to-creatinine ratio (UACR) was 691.5 mg/g.

At the second randomization (R2; week 0), 586 patients were randomly selected to receive vicadrostat at 3 mg, 10 mg, or 20 mg daily or vicadrostat-matched placebo in addition to treatment they were receiving from R1.

The primary outcome was the change in UACR from R2 baseline to week 14.

At week 14, the largest reduction in UACR was observed in those who received VicaEmpa (61%) compared with vicadrostat (40%) or empagliflozin alone (26%) or dual-matched placebo (3%). Furthermore, mean UACR reductions exceeded 30% across all VicaEmpa groups, which the researchers indicated as being clinically meaningful for long-term kidney outcomes.

VicaEmpa also showed larger decreases in eGFR from R1 to week 14 and larger reductions in systolic BP.

“Interventions to lower potassium and treatment discontinuations were infrequent,” the researchers wrote. They also mentioned that overall, no unexpected safety signals were observed during treatment with vicadrostat or VicaEmpa.