title: 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: 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.affiliation: University of Michigan School of Medicine, Ann Arbor, MI 48109-0366, USA. bpitt@med.umich.edu
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Lars
authors.initials: L
authors.lastname: Kober
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Christina
authors.initials: C
authors.lastname: Nowack
authors.forename: Peter
authors.initials: P
authors.lastname: Kolkhof
authors.forename: So-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D000450:Aldosterone / Q000097:blood*; D016001:Confidence Intervals; D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D006305:Health Status Indicators; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid; D012107:Research Design; D012720:Severity of Illness Index; D013148:Spironolactone / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone