Rationale and design of ARTS: a randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease.

Abstract

AIMS:

BAY 94-8862 is a novel, non-steroidal, mineralocorticoid receptor antagonist with greater selectivity than spironolactone and stronger mineralocorticoid receptor binding affinity than eplerenone. The aims of the MinerAlocorticoid Receptor Antagonist Tolerability Study (ARTS; NCT01345656) are to evaluate the safety and tolerability of BAY 94-8862 in patients with heart failure associated with a reduced left ventricular ejection fraction (HFREF) and chronic kidney disease (CKD), and to examine the effects on biomarkers of cardiac and renal function. Methods ARTS is a multicentre, randomized, double-blind, placebo-controlled, parallel-group study divided into two parts. In part A, oral BAY 94-8862 [2.5, 5, or 10 mg once daily (o.d.)] is compared with placebo in ∼60 patients with HFREF and mild CKD. Outcome measures include serum potassium concentration, biomarkers of renal injury, estimated glomerular filtration rate (eGFR), and albuminuria. Part B compares BAY 94-8862 (2.5, 5, or 10 mg o.d., or 5 mg twice daily), placebo, and open-label spironolactone (25-50 mg o.d.) in ∼360 patients with HFREF and moderate CKD. Outcome measures include the change in serum potassium concentration with BAY 94-8862 vs. placebo (primary endpoint) and vs. spironolactone, safety and tolerability, biomarkers of cardiac and renal function or injury, eGFR, and albuminuria. BAY 94-8862 pharmacokinetics are also assessed. Perspectives ARTS is the first phase II clinical trial of BAY 94-8862 and is expected to provide a wealth of information on BAY 94-8862 in patients with HFREF and CKD, including the optimal dose range for further studies.

• Authors: Bertram Pitt, Gerasimos Filippatos, Mihai Gheorghiade, Lars Kober, Henry Krum, Piotr Ponikowski, Christina Nowack, Peter Kolkhof, So-Young Kim, Faiez Zannad
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 14 Issue 6 Pg. 668-75 (Jun 2012) ISSN: 1879-0844 [Electronic] England
• PMID: 22562554 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Spironolactone
• Aldosterone
• Eplerenone

Topics

• Aldosterone (blood)
• Confidence Intervals
• Double-Blind Method
• Eplerenone
• Female
• Health Status Indicators
• Heart Failure (drug therapy)
• Humans
• Kidney Failure, Chronic (pathology)
• Male
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Receptors, Mineralocorticoid
• Research Design
• Severity of Illness Index
• Spironolactone (analogs & derivatives, therapeutic use)