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

Eur J Heart Fail. 2012 Jun;14(6):668-75. doi: 10.1093/eurjhf/hfs061. Epub 2012 May 4.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Spironolactone / therapeutic use

Substances

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