Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01951625
Recruitment Status : Completed
First Posted : September 26, 2013
Results First Posted : March 25, 2021
Last Update Posted : March 25, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE September 24, 2013
First Posted Date  ICMJE September 26, 2013
Results First Submitted Date  ICMJE January 20, 2021
Results First Posted Date  ICMJE March 25, 2021
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE November 29, 2013
Actual Primary Completion Date May 14, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2021)
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12 [ Time Frame: Baseline, Week 12 ]
Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.
Original Primary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
Change in log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: Baseline and 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 4 months ]
Current Other Pre-specified Outcome Measures
 (submitted: March 2, 2021)
  • 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 [ Time Frame: Baseline, 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.
  • Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12 [ Time Frame: Baseline, 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.
  • Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12 [ Time Frame: Baseline, 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.
  • Change From Baseline in Heart Rate to Week 12 [ Time Frame: Baseline, 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.
  • Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality) [ Time Frame: Baseline until 16 weeks ]
    Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
  • Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy [ Time Frame: Baseline upto 16 weeks ]
    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.
  • Number of Subjects With Treatment-Emergent Adverse Events [ Time Frame: From the start of study treatment upto 5 days after the last dose of study drug ]
    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.
  • Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL) [ Time Frame: Baseline, Week 12 ]
  • Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL) [ Time Frame: Baseline, Week 12 ]
    TIMP-4: tissue inhibitor of matrix metalloproteinases 4
  • Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL) [ Time Frame: Baseline, Week 12 ]
    cGMP: cyclic guanosine monophosphate
  • Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L) [ Time Frame: Baseline, Week 12 ]
    PIIINP: pro-collagen III N-terminal peptide
  • Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL) [ Time Frame: Baseline, Week 12 ]
    GDF-15: growth differentiation factor 15
  • Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL) [ Time Frame: Baseline, Week 12 ]
    ST2: suppression of tumorigenicity 2
  • Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL) [ Time Frame: Baseline, Week 12 ]
    Gal-3: Galectin-3
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure
Intervention  ICMJE
  • Drug: Vericiguat (BAY1021189) (1.25 mg)
    1.25 mg BAY1021189 tablets
  • Drug: Vericiguat (BAY1021189) (5 mg)
    5 mg BAY1021189 tablets
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Vericiguat (BAY1021189) (10 mg)
    2.5 mg orally once daily for 2 weeks, up-titration to 5 mg orally once daily for 2 weeks, up-titration to 10 mg orally once daily for 8 weeks
    Interventions:
    • Drug: Vericiguat (BAY1021189) (1.25 mg)
    • Drug: Vericiguat (BAY1021189) (5 mg)
  • Experimental: Vericiguat (BAY1021189) (5 mg)
    2.5 mg orally once daily for 2 weeks, then 5 mg orally once daily for 10 weeks (with sham titration)
    Interventions:
    • Drug: Vericiguat (BAY1021189) (1.25 mg)
    • Drug: Vericiguat (BAY1021189) (5 mg)
  • Experimental: Vericiguat (BAY1021189) (2.5 mg)
    2.5 mg orally once daily for 12 weeks (with sham titrations)
    Intervention: Drug: Vericiguat (BAY1021189) (1.25 mg)
  • Experimental: Vericiguat (BAY1021189) (1.25 mg)
    1.25 mg orally once daily for 12 weeks (with sham titrations)
    Intervention: Drug: Vericiguat (BAY1021189) (1.25 mg)
  • Placebo Comparator: Placebo
    Orally once daily for 12 weeks (with sham titrations)
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 7, 2015)
456
Original Estimated Enrollment  ICMJE
 (submitted: September 24, 2013)
410
Actual Study Completion Date  ICMJE June 9, 2015
Actual Primary Completion Date May 14, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries China,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01951625
Other Study ID Numbers  ICMJE 15371
2013-002287-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP