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)

Heart Failure Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951625
• Other study ID #: 15371
• Secondary ID: 2013-002287-11
• Status: Completed
• Phase: Phase 2
• Start date: November 29, 2013
• Est. completion date: June 9, 2015

Study information

• Verified date: March 2021
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 456
• Est. completion date: June 9, 2015
• Est. primary completion date: May 14, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
• Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets
• Placebo

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Ostrava	Ostrava

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (2)

Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Müller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. Effect of Vericiguat, a Soluble Guanyl — View Citation

Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Müller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cy — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Left Ventricular End-Diastolic Volume (LVEDV) and Left ventricular end-systolic volume (LVESV) are measured echocardiography parameter. These are acquired during a non-invasive echocardiography examination.	Baseline, Week 12
Other	Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12	The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a noninvasive echocardiography examination. Formula: LVEF = 100*(LVEDV - LVESV)/LVEDV.	Baseline, Week 12
Other	Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12	Blood pressure was measured by monitor measurements after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.	Baseline, Week 12
Other	Change From Baseline in Heart Rate to Week 12	Heart rate was measured after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.	Baseline, Week 12
Other	Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality)	Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.	Baseline until 16 weeks
Other	Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy	ICD / CRT with defibrillation therapy (CRT-D) included previous appropriate interventions such as shocks or anti-tachycardic pacing (ATP) when diagnostic of sustained ventricular tachycardias in pre defined rapid zone.	Baseline upto 16 weeks
Other	Number of Subjects With Treatment-Emergent Adverse Events	An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; and another medically important serious event as judged by the investigator. AEs are considered to be treatment-emergent if they have started or worsened after first application of study drug up to 5 days after end of treatment with study drug.	From the start of study treatment upto 5 days after the last dose of study drug
Other	Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)		Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)	TIMP-4: tissue inhibitor of matrix metalloproteinases 4	Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)	cGMP: cyclic guanosine monophosphate	Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)	PIIINP: pro-collagen III N-terminal peptide	Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)	GDF-15: growth differentiation factor 15	Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)	ST2: suppression of tumorigenicity 2	Baseline, Week 12
Other	Change in Biomarkers From Baseline to Week 12: Gal-3 (µg/mL)	Gal-3: Galectin-3	Baseline, Week 12
Primary	Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12	Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.	Baseline, Week 12

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