Premium
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
Author(s) -
Pitt Bertram,
Filippatos Gerasimos,
Gheorghiade Mihai,
Kober Lars,
Krum Henry,
Ponikowski Piotr,
Nowack Christina,
Kolkhof Peter,
Kim SoYoung,
Zannad Faiez
Publication year - 2012
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfs061
Subject(s) - medicine , tolerability , spironolactone , kidney disease , mineralocorticoid receptor , renal function , heart failure , placebo , aldosterone , urology , endocrinology , cardiology , adverse effect , pathology , alternative medicine
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.