Clinical trial NCT01951625: Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure With Reduced Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-REDUCED)
Official title: A Randomized Parallel-group, Placebo-controlled, Double-blind, Multi-center Dose Finding Phase II Trial Exploring the Pharmacodynamic Effects, Safety and Tolerability, and Pharmacokinetics of Four Dose Regimens of the Oral sGC Stimulator BAY1021189 Over 12 Weeks in Patients With Worsening Heart Failure With Reduced Ejection Fraction (HFrEF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Worsening Heart Failure
Heart Failure with Reduced Ejection Fraction
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-09-26
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objective of the study is to find the optimal dose of the once daily oral soluble guanylate cyclase stimulator (sGC) BAY1021189 for Phase III that can be given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).


Eligibility criteria: Inclusion Criteria:

* Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
* Left ventricular ejection fraction (LVEF) \<45% by echocardiography at randomization

Exclusion Criteria:

* Intravenous inotropes at any time after hospitalization

Primary outcomes:
measure: Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
Other outcomes:
measure: Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12
timeFrame: Baseline, Week 12
measure: Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Heart Rate to Week 12
timeFrame: Baseline, Week 12
measure: Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality)
timeFrame: Baseline until 16 weeks
measure: Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy
timeFrame: Baseline upto 16 weeks
measure: Number of Subjects With Treatment-Emergent Adverse Events
timeFrame: From the start of study treatment upto 5 days after the last dose of study drug
measure: Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)
timeFrame: Baseline, Week 12
measure: Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL)
timeFrame: Baseline, Week 12
Locations:
city: Fountain Valley
country: United States
state: California
city: Wilmington
country: United States
state: Delaware
city: Fort Lauderdale
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: New Orleans
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Buffalo
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Fairfield
country: United States
state: Ohio
city: Charleston
country: United States
state: South Carolina
city: Germantown
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Milwaukee
country: United States
state: Wisconsin
city: Darlinghurst
country: Australia
state: New South Wales
city: Hobart
country: Australia
state: Tasmania
city: Prahran
country: Australia
state: Victoria
city: St. Pölten
country: Austria
state: Niederösterreich
city: Linz
country: Austria
state: Oberösterreich
city: Graz
country: Austria
state: Steiermark
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Brugge
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Gilly
country: Belgium
city: HUY
country: Belgium
city: Mechelen
country: Belgium
city: MOL
country: Belgium
city: Roeselare
country: Belgium
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Saint-Jean-sur-Richelieu
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Hradec kralove
country: Czechia
city: Kromeriz
country: Czechia
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Praha 4
country: Czechia
city: Praha 6
country: Czechia
city: Slany
country: Czechia
city: Aalborg
country: Denmark
city: Aarhus N
country: Denmark
city: Hellerup
country: Denmark
city: Viborg
country: Denmark
city: BRON Cedex
country: France
city: La Tronche
country: France
city: Lille Cedex
country: France
city: Paris Cedex 15
country: France
city: Pessac
country: France
city: Rouen
country: France
city: München
country: Germany
state: Bayern
city: Bad Homburg
country: Germany
state: Hessen
city: Frankfurt
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
state: Niedersachsen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Erfurt
country: Germany
state: Thüringen
city: Hamburg
country: Germany
city: Athens
country: Greece
city: Nea Ionia
country: Greece
city: Budapest
country: Hungary
city: Kistarcsa
country: Hungary
city: Szekesfehervar
country: Hungary
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Hadera
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Tiberias
country: Israel
city: Zrifin
country: Israel
city: Bergamo
country: Italy
state: Lombardia
city: Brescia
country: Italy
state: Lombardia
city: Como
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Ancona
country: Italy
state: Marche
city: Arezzo
country: Italy
state: Toscana
city: Verona
country: Italy
state: Veneto
city: Iizuka
country: Japan
state: Fukuoka
city: Himeji
country: Japan
state: Hyogo
city: Kanazawa
country: Japan
state: Ishikawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Yokosuka
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Naha
country: Japan
state: Okinawa
city: Takatsuki
country: Japan
state: Osaka
city: Yao
country: Japan
state: Osaka
city: Ureshino
country: Japan
state: Saga
city: Komatsushima
country: Japan
state: Tokushima
city: Meguro-ku
country: Japan
state: Tokyo
city: Minato-ku
country: Japan
state: Tokyo
city: Fukui
country: Japan
city: Hiroshima
country: Japan
city: Kumamoto
country: Japan
city: Nagasaki
country: Japan
city: Tokushima
country: Japan
city: Toyama
country: Japan
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Deventer
country: Netherlands
city: Heerenveen
country: Netherlands
city: Leeuwarden
country: Netherlands
city: Veldhoven
country: Netherlands
city: Bialystok
country: Poland
city: Krakow
country: Poland
city: Legnica
country: Poland
city: Lodz
country: Poland
city: Olsztyn
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Santander
country: Spain
state: Cantabria
city: Majadahonda
country: Spain
state: Madrid
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Helsingborg
country: Sweden
city: Karlstad
country: Sweden
city: Linköping
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Örebro
country: Sweden
city: Liestal
country: Switzerland
state: Basel-Landschaft
city: Bruderholz
country: Switzerland
city: Lugano
country: Switzerland
city: Zürich
country: Switzerland
city: Kaohsiung
country: Taiwan
city: New Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Chesterfield
country: United Kingdom
state: Derbyshire
city: Stevenage
country: United Kingdom
state: Hertfordshire
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Muller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026-38. doi: 10.1002/ejhf.135. Epub 2014 Jul 24.
citation: Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Muller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. 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. JAMA. 2015 Dec 1;314(21):2251-62. doi: 10.1001/jama.2015.15734.
citation: Ruehs H, Klein D, Frei M, Grevel J, Austin R, Becker C, Roessig L, Pieske B, Garmann D, Meyer M. Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Clin Pharmacokinet. 2021 Nov;60(11):1407-1421. doi: 10.1007/s40262-021-01024-y. Epub 2021 Jun 4.
citation: Kramer F, Voss S, Roessig L, Igl BW, Butler J, Lam CSP, Maggioni AP, Shah SJ, Pieske B. Evaluation of high-sensitivity C-reactive protein and uric acid in vericiguat-treated patients with heart failure with reduced ejection fraction. Eur J Heart Fail. 2020 Sep;22(9):1675-1683. doi: 10.1002/ejhf.1787. Epub 2020 Mar 25.