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Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies ( SOCRATES )
Author(s) -
Pieske Burkert,
Butler Javed,
Filippatos Gerasimos,
Lam Carolyn,
Maggioni Aldo Pietro,
Ponikowski Piotr,
Shah Sanjiv,
Solomon Scott,
KraigherKrainer Elisabeth,
Samano Eliana Tibana,
Scalise Andrea Viviana,
Müller Katharina,
Roessig Lothar,
Gheorghiade Mihai
Publication year - 2014
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.135
Subject(s) - medicine , heart failure , tolerability , ejection fraction , pharmacodynamics , placebo , clinical endpoint , socrates , guanylate cyclase , pharmacology , clinical trial , cardiology , pharmacokinetics , adverse effect , receptor , pathology , philosophy , alternative medicine , epistemology
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. Trial registration NCT01951625 (SOCRATES‐REDUCED) and NCT01951638 (SOCRATES‐PRESERVED)