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Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure and Preserved Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-PRESERVED)

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ClinicalTrials.gov Identifier: NCT01951638
Recruitment Status : Completed
First Posted : September 26, 2013
Results First Posted : February 12, 2021
Last Update Posted : March 16, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Vericiguat (BAY1021189) (1.25 mg)
Drug: Vericiguat (BAY1021189) (5 mg)
Drug: Placebo
Enrollment 477
Recruitment Details The study was conducted at 158 centers in 25 countries between 06 November 2013 (first subject first visit) and 16 September 2015 (last subject last visit).
Pre-assignment Details Overall, 632 subjects were enrolled, of them 477 were randomized and 475 were treated. Among the 477 subjects who were randomized, 404 subjects completed both treatment and follow-up [FU] periods. All arms in FU period were mutually exclusive, this question below is ticked No because of database validation rule constraints.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Period Title: Treatment Period
Started 93 96 96 96 96
Completed 80 82 83 80 86
Not Completed 13 14 13 16 10
Reason Not Completed
Protocol Violation             0             0             0             2             0
Protocol-driven decision point             1             3             0             0             0
Logistical difficulties             0             1             1             0             0
Withdrawal by Subject             9             6             4             5             4
Death             0             0             0             3             1
Adverse Event             3             4             8             6             5
Period Title: Follow-up Period
Started 89 95 95 88 94
Completed 87 86 90 80 89
Not Completed 2 9 5 8 5
Reason Not Completed
Protocol Violation             0             0             0             1             0
Logistical difficulties             0             2             0             0             1
Withdrawal by Subject             1             5             2             1             2
Lost to Follow-up             0             1             0             1             0
Death             1             0             1             4             1
Adverse Event             0             1             2             1             1
Arm/Group Title BAY1021189 1.25 mg Placebo BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg Total
Hide Arm/Group Description Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days. Total of all reporting groups
Overall Number of Baseline Participants 96 93 96 96 96 477
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 96 participants 93 participants 96 participants 96 participants 96 participants 477 participants
73.8  (10) 73.7  (9.1) 72  (10.7) 73.9  (7.9) 72.5  (10.2) 73.2  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants 93 participants 96 participants 96 participants 96 participants 477 participants
Female
51
  53.1%
46
  49.5%
43
  44.8%
43
  44.8%
44
  45.8%
227
  47.6%
Male
45
  46.9%
47
  50.5%
53
  55.2%
53
  55.2%
52
  54.2%
250
  52.4%
1.Primary Outcome
Title Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Hide Description NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF).
Time Frame Baseline, Week 12 (end of treatment [EOT])
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS) NT-pro BNP: included all subjects randomized to treatment who had a valid measurement of NT-pro BNP at baseline and at Week 12 (Visit 5) and showed no major protocol deviations.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Overall Number of Participants Analyzed 73 77 78 57 60
Mean (Standard Deviation)
Unit of Measure: log-transformed picograms per milliliter
-0.098  (0.778) -0.047  (0.788) 0.071  (0.818) 0.057  (0.819) -0.023  (0.705)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments For the primary analysis, the three highest active treatment groups BAY1021189 (2.5mg, 2.5 to 5mg, 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test. The Hochberg procedure was used to test the two primary end points at study-wise significance level of 5%. Results are reported including 90% confidence intervals (CI) for the difference of means. The difference between the comparison groups is difference of means on the log scale.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.8991
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.137
Confidence Interval (2-Sided) 90%
-0.04 to 0.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg to 10 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.7194
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.076
Confidence Interval (2-Sided) 95%
-0.18 to 0.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg to 5 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.8653
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.156
Confidence Interval (2-Sided) 95%
-0.12 to 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9041
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.171
Confidence Interval (2-Sided) 95%
-0.09 to 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 1.25 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.6572
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.052
Confidence Interval (2-Sided) 95%
-0.2 to 0.3
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline to Week 12 in Left Atrial Volume (LAV)
Hide Description Left atrial volume was measured by echocardiography.
Time Frame Baseline, Week 12 (EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
PPS Left Atrial Volume (LAV) included all subjects randomized to treatment who had a valid measurement of LAV at baseline and at Week 12 (Visit 5) and showed no major protocol deviations.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Overall Number of Participants Analyzed 67 77 78 57 59
Mean (Standard Deviation)
Unit of Measure: milliliter
-3.361  (12.654) -2.163  (7.895) -2.142  (11.931) -1.252  (16.139) -1.654  (10.245)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments For the primary analysis, the three highest active treatment groups (BAY1021189 2.5mg, BAY1021189 2.5 to 5mg, BAY1021189 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test. The Hochberg procedure was used to test the two primary end points at study-wise significance level of 5%. Results are reported including 90% confidence intervals (CI) for the difference of means.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.8156
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.629
Confidence Interval (2-Sided) 90%
-1.36 to 4.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg to 10 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.7945
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.707
Confidence Interval (2-Sided) 95%
-2.39 to 5.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg to 5 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.7917
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.109
Confidence Interval (2-Sided) 95%
-3.01 to 7.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.7241
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.219
Confidence Interval (2-Sided) 95%
-2.82 to 5.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 1.25 mg
Comments Pairwise comparisons to placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In accordance with the specification in the protocol these secondary analyses are considered exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.7546
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.198
Confidence Interval (2-Sided) 95%
-2.23 to 4.63
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description Blood pressure was measured after at least 10 minutes resting in a sitting position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.
Time Frame Baseline, Week 12 (EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF) with evaluable subjects for this endpoint.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Overall Number of Participants Analyzed 80 82 83 61 61
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury
Change in SBP 1.458  (18.865) 0.703  (16.993) -1.819  (19.438) -1.486  (17.179) -0.913  (15.498)
Change in DBP 1.887  (11.435) 0.911  (10.037) -2.173  (11.249) -1.142  (11.4) -0.629  (10.271)
4.Other Pre-specified Outcome
Title Change From Baseline to Week 12 in Heart Rate
Hide Description Heart rate was measured after 10 minutes resting in a sitting position (3 measurements taken approximatly 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.
Time Frame Baseline, Week 12 (EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF) with evaluable subjects for this endpoint.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Overall Number of Participants Analyzed 80 82 83 61 61
Mean (Standard Deviation)
Unit of Measure: beats per minute
3.287  (13.582) 1.776  (11.42) -0.373  (9.845) 1.055  (13.331) -2.623  (9.639)
5.Other Pre-specified Outcome
Title Number of Subjects With Clinical Events (Heart Failure Hospitalization and Cardio-vascular [CV] Mortality)
Hide Description Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Time Frame Baseline up to Week 16 including 12 week treatment period and 4 week follow-up period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all subjects who were randomized to treatment.
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 2.5 mg to 5 mg BAY1021189 2.5 mg to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Overall Number of Participants Analyzed 93 96 96 96 96
Measure Type: Count of Participants
Unit of Measure: Participants
HF hospitalizations
8
   8.6%
6
   6.3%
11
  11.5%
8
   8.3%
5
   5.2%
CV Mortality
1
   1.1%
0
   0.0%
0
   0.0%
5
   5.2%
1
   1.0%
Time Frame Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28. Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
All-Cause Mortality
Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/93 (1.08%)      0/96 (0.00%)      1/95 (1.05%)      7/95 (7.37%)      2/96 (2.08%)    
Hide Serious Adverse Events
Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/93 (21.51%)      20/96 (20.83%)      24/95 (25.26%)      18/95 (18.95%)      21/96 (21.88%)    
Blood and lymphatic system disorders           
Anaemia * 1  2/93 (2.15%)  3 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Anaemia of chronic disease * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Cardiac disorders           
Angina unstable * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Atrial fibrillation * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 2/95 (2.11%)  3 1/95 (1.05%)  1 1/96 (1.04%)  2
Cardiac arrest * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Cardiac failure * 1  6/93 (6.45%)  6 4/96 (4.17%)  4 7/95 (7.37%)  12 5/95 (5.26%)  8 2/96 (2.08%)  2
Cardiac failure acute * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 3/95 (3.16%)  3 0/95 (0.00%)  0 0/96 (0.00%)  0
Cardiac failure chronic * 1  2/93 (2.15%)  3 4/96 (4.17%)  4 3/95 (3.16%)  3 2/95 (2.11%)  2 4/96 (4.17%)  5
Cardiac failure congestive * 1  2/93 (2.15%)  2 0/96 (0.00%)  0 1/95 (1.05%)  1 3/95 (3.16%)  3 0/96 (0.00%)  0
Cardiogenic shock * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Myocardial infarction * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Right ventricular failure * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Tachyarrhythmia * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Acute coronary syndrome * 1  0/93 (0.00%)  0 2/96 (2.08%)  2 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Ear and labyrinth disorders           
Vertigo * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Eye disorders           
Vitreous haemorrhage * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Gastrointestinal disorders           
Diarrhoea * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 1/95 (1.05%)  1 1/96 (1.04%)  1
Gastrointestinal haemorrhage * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Large intestine polyp * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Intestinal haemorrhage * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
General disorders           
Chest pain * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Pain * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Pyrexia * 1  1/93 (1.08%)  2 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Sudden death * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Hepatobiliary disorders           
Cholelithiasis * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Jaundice cholestatic * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Infections and infestations           
Carbuncle * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Diabetic gangrene * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Erysipelas * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Gangrene * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Gastroenteritis * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Hepatitis C * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Osteomyelitis * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Pneumonia * 1  1/93 (1.08%)  2 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 3/96 (3.13%)  3
Respiratory syncytial virus bronchiolitis * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Urinary tract infection * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Urosepsis * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Urinary tract infection bacterial * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Enterococcal sepsis * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Chlamydial infection * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Respiratory tract infection * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Injury, poisoning and procedural complications           
Femoral neck fracture * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Radius fracture * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Ulna fracture * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Vascular pseudoaneurysm * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Contusion * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Post procedural haematoma * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Investigations           
Coagulation time prolonged * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Intraocular pressure increased * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Metabolism and nutrition disorders           
Diabetes mellitus * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Failure to thrive * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Hypoglycaemia * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Osteochondrosis * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Non-Hodgkin's lymphoma * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Gastrointestinal stromal tumour * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Nervous system disorders           
Carotid artery stenosis * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Cerebral haemorrhage * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Presyncope * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  2
Syncope * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  2
Cervicogenic headache * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Renal and urinary disorders           
Renal impairment * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Acute kidney injury * 1  2/93 (2.15%)  2 1/96 (1.04%)  1 1/95 (1.05%)  1 4/95 (4.21%)  4 3/96 (3.13%)  3
Respiratory, thoracic and mediastinal disorders           
Acute pulmonary oedema * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Chronic obstructive pulmonary disease * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 1/95 (1.05%)  1 1/95 (1.05%)  1 2/96 (2.08%)  2
Dyspnoea * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Epistaxis * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 1/95 (1.05%)  1 0/95 (0.00%)  0 0/96 (0.00%)  0
Pleural effusion * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Pulmonary hypertension * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Respiratory failure * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Skin and subcutaneous tissue disorders           
Diabetic foot * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Surgical and medical procedures           
Eyelid operation * 1  0/93 (0.00%)  0 1/96 (1.04%)  1 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
Vascular disorders           
Circulatory collapse * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Hypotension * 1  0/93 (0.00%)  0 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 1/96 (1.04%)  1
Orthostatic hypotension * 1  1/93 (1.08%)  1 0/96 (0.00%)  0 0/95 (0.00%)  0 0/95 (0.00%)  0 0/96 (0.00%)  0
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo BAY1021189 1.25 mg BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/93 (22.58%)      33/96 (34.38%)      40/95 (42.11%)      38/95 (40.00%)      33/96 (34.38%)    
Cardiac disorders           
Cardiac failure * 1  5/93 (5.38%)  5 1/96 (1.04%)  1 3/95 (3.16%)  4 3/95 (3.16%)  3 2/96 (2.08%)  2
Gastrointestinal disorders           
Abdominal pain upper * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 5/95 (5.26%)  5 2/95 (2.11%)  2 0/96 (0.00%)  0
Nausea * 1  2/93 (2.15%)  2 2/96 (2.08%)  2 4/95 (4.21%)  5 5/95 (5.26%)  5 4/96 (4.17%)  5
General disorders           
Fatigue * 1  2/93 (2.15%)  3 2/96 (2.08%)  2 3/95 (3.16%)  3 6/95 (6.32%)  6 4/96 (4.17%)  4
Oedema peripheral * 1  2/93 (2.15%)  3 3/96 (3.13%)  4 2/95 (2.11%)  3 6/95 (6.32%)  7 1/96 (1.04%)  1
Infections and infestations           
Bronchitis * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 2/95 (2.11%)  2 4/95 (4.21%)  4 6/96 (6.25%)  6
Nasopharyngitis * 1  3/93 (3.23%)  3 4/96 (4.17%)  4 6/95 (6.32%)  8 1/95 (1.05%)  1 5/96 (5.21%)  5
Metabolism and nutrition disorders           
Hyperkalaemia * 1  0/93 (0.00%)  0 6/96 (6.25%)  6 2/95 (2.11%)  2 3/95 (3.16%)  3 3/96 (3.13%)  3
Nervous system disorders           
Dizziness * 1  3/93 (3.23%)  3 2/96 (2.08%)  4 10/95 (10.53%)  11 6/95 (6.32%)  6 7/96 (7.29%)  7
Headache * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 6/95 (6.32%)  6 4/95 (4.21%)  4 4/96 (4.17%)  4
Renal and urinary disorders           
Renal failure * 1  2/93 (2.15%)  3 5/96 (5.21%)  5 0/95 (0.00%)  0 1/95 (1.05%)  1 0/96 (0.00%)  0
Acute kidney injury * 1  1/93 (1.08%)  1 1/96 (1.04%)  1 0/95 (0.00%)  0 5/95 (5.26%)  5 1/96 (1.04%)  1
Respiratory, thoracic and mediastinal disorders           
Cough * 1  1/93 (1.08%)  1 5/96 (5.21%)  5 6/95 (6.32%)  6 2/95 (2.11%)  2 2/96 (2.08%)  2
Dyspnoea * 1  3/93 (3.23%)  3 6/96 (6.25%)  7 9/95 (9.47%)  10 5/95 (5.26%)  6 3/96 (3.13%)  3
Vascular disorders           
Hypotension * 1  1/93 (1.08%)  1 4/96 (4.17%)  4 4/95 (4.21%)  6 5/95 (5.26%)  5 2/96 (2.08%)  2
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
End points, "Health-related quality of life, Composite Congestion Score, NYHA function class, echo parameters other than LAV, biomarker and background HF therapies" were exploratory. "Incidence of atrial fibrillation" is reported in AE section.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer AG
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01951638    
Other Study ID Numbers: 15829
2013-002288-25 ( EudraCT Number )
First Submitted: September 24, 2013
First Posted: September 26, 2013
Results First Submitted: January 20, 2021
Results First Posted: February 12, 2021
Last Update Posted: March 16, 2021