Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial | Chronic Kidney Disease | JAMA | JAMA Network
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Original Investigation
September 1, 2015

Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial

Author Affiliations
  • 1University of Chicago Medicine, Chicago, Illinois
  • 2Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis
  • 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
  • 4Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  • 5Department of Nephrology, University Medical Center Groeningen, Groeningen, the Netherlands
  • 6Departments of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
  • 7Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases “Aldo e Cele Daccò,” Ranica (Bergamo), Italy
  • 8Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
  • 9Steno Diabetes Center, Gentofte, Denmark
  • 10University of Copenhagen, Copenhagen, Denmark
  • 11Aarhus University, Aarhus, Denmark
  • 12Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany
  • 13Global Clinical Development, Bayer HealthCare AG, Wuppertal, Germany
  • 14Heart Diseases Research, Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany
  • 15Global Clinical Development, Bayer PLC, Newbury, England
  • 16MARCO GmbH & Co KG, Düsseldorf, Germany
  • 17Global Research and Development Statistics, Bayer HealthCare AG, Leverkusen, Germany
  • 18Institute of Investigation and Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain
JAMA. 2015;314(9):884-894. doi:10.1001/jama.2015.10081

Importance  Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events.

Objective  To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled, parallel-group study conducted at 148 sites in 23 countries. Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014. Of 1501 screened patients, 823 were randomized and 821 received study drug.

Interventions  Participants were randomly assigned to receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5 mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d, n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or matching placebo (n = 94) for 90 days.

Main Outcomes and Measures  The primary outcome was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 vs at baseline. Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate.

Results  The mean age of the participants was 64.2 years; 78% were male. At baseline, 36.7% of patients treated had very high albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone demonstrated a dose-dependent reduction in UACR. The primary outcome, the placebo-corrected mean ratio of the UACR at day 90 relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and 20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for 10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90% CI, 0.58-0.77; P<.001]; for 20 mg/d, 0.62 [90% CI, 0.54-0.72; P < .001]). The prespecified secondary outcome of hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10-mg/d groups; incidences in the finerenone 7.5-, 15-, and 20-mg/d groups were 2.1%, 3.2%, and 1.7%, respectively. There were no differences in the incidence of the prespecified secondary outcome of an estimated glomerular filtration rate decrease of 30% or more or in incidences of adverse events and serious adverse events between the placebo and finerenone groups.

Conclusions and Relevance  Among patients with diabetic nephropathy, most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, the addition of finerenone compared with placebo resulted in improvement in the urinary albumin-creatinine ratio. Further trials are needed to compare finerenone with other active medications.

Trial Registration  clinicaltrials.gov Identifier: NCT1874431