Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease.

Abstract

AIMS:

To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.

METHODS AND RESULTS:

The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline.

CONCLUSIONS:

ARTS-HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT-proBNP in a high-risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.

• Authors: Bertram Pitt, Stefan D Anker, Michael Böhm, Mihai Gheorghiade, Lars Køber, Henry Krum, Aldo P Maggioni, Piotr Ponikowski, Adriaan A Voors, Faiez Zannad, Christina Nowack, So-Young Kim, Alexander Pieper, Nina Kimmeskamp-Kirschbaum, Gerasimos Filippatos
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 17 Issue 2 Pg. 224-32 (Feb 2015) ISSN: 1879-0844 [Electronic] England
• PMID: 25678098 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Chemical References

• Mineralocorticoid Receptor Antagonists
• Naphthyridines
• Natriuretic Agents
• Peptide Fragments
• finerenone
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Spironolactone
• Eplerenone

Topics

• Comorbidity
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Eplerenone
• Heart Failure (blood, drug therapy)
• Humans
• Mineralocorticoid Receptor Antagonists (adverse effects, therapeutic use)
• Naphthyridines (adverse effects, therapeutic use)
• Natriuretic Agents (blood)
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Renal Insufficiency, Chronic (blood, drug therapy)
• Spironolactone (adverse effects, analogs & derivatives, therapeutic use)