Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial

• Authors: TEERLINK John R.; FELKER Michael G.; MCMURRAY John J.V.; SOLOMON Scott D.; ADAMS Kirkwood F. Jr.; CLELAND John G.F.; EZEKOWITZ Justin A.; GOUDEV Assen; MACDONALD Peter; METRA Marco; MITROVIC Veselin; PONIKOWSKI Piotr; SERPYTIS Pranas; ŠPINAR Jindřich; TOMCSÁNYI János; VANDEKERCKHOVE Hans J.; VOORS Adriaan A.; MONSALVO Maria Laura; JOHNSTON James; MALIK Fady I.; HONARPOUR Narimon
• Year of publication: 2016
• Type: Article in Periodical
• Magazine / Source: Lancet
• MU Faculty or unit: Faculty of Medicine
• web: http://www.sciencedirect.com/science/article/pii/S0140673616320499
• Doi: https://doi.org/10.1016/S0140-6736(16)32049-9
• Field: Cardiovascular diseases incl. cardiosurgery
• Keywords: COSMIC-HF
• Description: Impaired contractility is a feature of heart failure with reduced ejection fraction. We assessed the pharmacokinetics and effects on cardiac function and structure of the cardiac myosin activator, omecamtiv mecarbil. Methods In this randomised, double-blind study, done at 87 sites in 13 countries, we recruited patients with stable, symptomatic chronic heart failure and left ventricular ejection fraction 40% or lower. Patients were randomly assigned equally, via an interactive web response system, to receive 25 mg oral omecamtiv mecarbil twice daily (fixed-dose group), 25 mg twice daily titrated to 50 mg twice daily guided by pharmacokinetics (pharmacokinetic-titration group), or placebo for 20 weeks. We assessed the maximum concentration of omecamtiv mecarbil in plasma (primary endpoint) and changes in cardiac function and ventricular diameters. This trial is registered with ClinicalTrials.gov, number NCT01786512.