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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216224:14110/16:00092316

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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).

Název v anglickém jazyce

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

Popis výsledku anglicky

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).

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FA - Kardiovaskulární nemoci včetně kardiochirurgie

OECD FORD obor

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Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Lancet

ISSN

0140-6736

e-ISSN

—

Svazek periodika

388

Číslo periodika v rámci svazku

10062

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

2895-2903

Kód UT WoS článku

000389631700034

EID výsledku v databázi Scopus

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