Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction The SOCRATES-REDUCED Randomized Trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F15%3AN0000012" target="_blank" >RIV/00064173:_____/15:N0000012 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1001/jama.2015.15734" target="_blank" >http://dx.doi.org/10.1001/jama.2015.15734</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1001/jama.2015.15734" target="_blank" >10.1001/jama.2015.15734</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction The SOCRATES-REDUCED Randomized Trial

Popis výsledku v původním jazyce

OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic. INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point. RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15).

Název v anglickém jazyce

Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction The SOCRATES-REDUCED Randomized Trial

Popis výsledku anglicky

OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic. INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point. RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15).

Druh

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

CEP obor

FA - Kardiovaskulární nemoci včetně kardiochirurgie

OECD FORD obor

—

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

JAMA: The Journal of the American Medical Association

ISSN

0098-7484

e-ISSN

—

Svazek periodika

314

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

2251-2262

Kód UT WoS článku

000365515700017

EID výsledku v databázi Scopus

2-s2.0-84949489402