@article{3102846,
    title = "Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study",
    author = "Felker, G.M. and McMurray, J.J.V. and Cleland, J.G. and O'Connor, C.M. and Teerlink, J.R. and Voors, A.A. and Belohlavek, J. and Böhm, M. and Borentain, M. and Bueno, H. and Cole, R.T. and DeSouza, M.M. and Ezekowitz, J.A. and Filippatos, G. and Lang, N.N. and Kessler, P.D. and Martinez, F.A. and Mebazaa, A. and Metra, M. and Mosterd, A. and Pang, P.S. and Ponikowski, P. and Sato, N. and Seiffert, D. and Ye, J.",
    journal = "JACC: Heart Failure",
    year = "2021",
    volume = "9",
    number = "2",
    pages = "146-157",
    publisher = "HANLEY & BELFUS-ELSEVIER INC",
    issn = "2213-1779",
    doi = "10.1016/j.jchf.2020.10.012",
    keywords = "amino terminal pro brain natriuretic peptide;  angiotensin receptor antagonist;  beta adrenergic receptor blocking agent;  bilirubin;  cimlanod;  dipeptidyl carboxypeptidase inhibitor;  enkephalinase inhibitor;  loop diuretic agent;  mineralocorticoid antagonist;  placebo;  sacubitril plus valsartan, acute heart failure;  aged;  Article;  bilirubin blood level;  cohort analysis;  continuous infusion;  controlled study;  dose response;  double blind procedure;  drug dose comparison;  drug dose escalation;  drug dose reduction;  drug effect;  drug efficacy;  drug fatality;  drug safety;  drug tolerability;  drug withdrawal;  dyspnea;  female;  heart failure with reduced ejection fraction;  heart left ventricle ejection fraction;  heart rate;  human;  hypotension;  major clinical study;  male;  multicenter study;  phase 2 clinical trial;  priority journal;  protein blood level;  randomized controlled trial",
    abstract = "Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro–B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325) © 2021 The Authors"
}