Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES)
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Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). / Pieske, Burkert; Butler, Javed; Filippatos, Gerasimos; Lam, Carolyn; Maggioni, Aldo Pietro; Ponikowski, Piotr; Shah, Sanjiv; Solomon, Scott; Kraigher-Krainer, Elisabeth; Samano, Eliana Tibana; Scalise, Andrea Viviana; Müller, Katharina; Roessig, Lothar; Gheorghiade, Mihai; SOCRATES Investigators and Coordinators.
In: EUR J HEART FAIL, Vol. 16, No. 9, 09.2014, p. 1026-1038.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES)
AU - Pieske, Burkert
AU - Butler, Javed
AU - Filippatos, Gerasimos
AU - Lam, Carolyn
AU - Maggioni, Aldo Pietro
AU - Ponikowski, Piotr
AU - Shah, Sanjiv
AU - Solomon, Scott
AU - Kraigher-Krainer, Elisabeth
AU - Samano, Eliana Tibana
AU - Scalise, Andrea Viviana
AU - Müller, Katharina
AU - Roessig, Lothar
AU - Gheorghiade, Mihai
AU - SOCRATES Investigators and Coordinators
AU - Westermann, Dirk
N1 - © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.
PY - 2014/9
Y1 - 2014/9
N2 - AIMS: The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement.METHODS: The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥ 45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks.PERSPECTIVES: SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population.
AB - AIMS: The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement.METHODS: The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥ 45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks.PERSPECTIVES: SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population.
KW - Administration, Oral
KW - Aged
KW - Double-Blind Method
KW - Female
KW - Guanylate Cyclase/administration & dosage
KW - Heart Failure/blood
KW - Humans
KW - Male
KW - Natriuretic Peptide, Brain/blood
KW - Peptide Fragments/blood
KW - Prognosis
KW - Protein Precursors
KW - Receptors, Cytoplasmic and Nuclear/administration & dosage
KW - Soluble Guanylyl Cyclase
KW - Stroke Volume/physiology
KW - Treatment Outcome
U2 - 10.1002/ejhf.135
DO - 10.1002/ejhf.135
M3 - SCORING: Journal article
C2 - 25056511
VL - 16
SP - 1026
EP - 1038
JO - EUR J HEART FAIL
JF - EUR J HEART FAIL
SN - 1388-9842
IS - 9
ER -
