Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F16%3A00066347" target="_blank" >RIV/65269705:_____/16:00066347 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/16:00092316

Result on the web

<a href="http://dx.doi.org/10.1016/S0140-6736(16)32049-9" target="_blank" >http://dx.doi.org/10.1016/S0140-6736(16)32049-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S0140-6736(16)32049-9" target="_blank" >10.1016/S0140-6736(16)32049-9</a>

Result language

angličtina

Original language name

Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial

Original language description

Background Impaired contractility is a feature of heart failure with reduced ejection fraction. We assessed the pharmacokinetics and eff ects 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. Findings From March 17, 2014, to March 5, 2015, we enrolled 150 patients in the fi xed-dose omecamtiv mecarbil group and 149 in the pharmacokinetic-titration and placebo groups. Mean maximum concentration of omecamtiv mecarbil at 12 weeks was 200 (SD 71) ng/mL in the fi xed-dose group and 318 (129) ng/mL in the pharmacokinetic-titration group. For the pharmacokinetic-titration group versus placebo group at 20 weeks, least square mean diff erences were as follows: systolic ejection time 25 ms (95% CI 18-32, p< 0.0001), stroke volume 3.6 mL (0.5-6.7, p= 0.0217), left ventricular end-systolic diameter -1.8 mm (-2.9 to -0.6, p= 0.0027), left ventricular end-diastolic diameter -1.3 mm, (-2.3 to 0.3, p= 0.0128), heart rate -3.0 beats per min (-5.1 to -0.8, p= 0.0070), and N-terminal pro B-type natriuretic peptide concentration in plasma -970 pg/mL (-1672 to -268, p= 0.0069).

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FA - Cardiovascular diseases including cardio-surgery

OECD FORD branch

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Project

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Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Lancet

ISSN

0140-6736

e-ISSN

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Volume of the periodical

388

Issue of the periodical within the volume

10062

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

2895-2903

UT code for WoS article

000389631700034

EID of the result in the Scopus database

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