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)

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01951638
Collaborator
(none)
477
158
5
22.3
3
0.1

Study Details

Study Description

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 diuretic and comorbidity treatment for heart failure with preserved ejection fraction (HFpEF)

Condition or Disease Intervention/Treatment Phase
  • Drug: Vericiguat (BAY1021189) (1.25 mg)
  • Drug: Vericiguat (BAY1021189) (5 mg)
  • Drug: Placebo
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
477 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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 and Preserved Ejection Fraction (HFpEF)
Actual Study Start Date :
Nov 6, 2013
Actual Primary Completion Date :
Aug 18, 2015
Actual Study Completion Date :
Sep 16, 2015

Arms and Interventions

Arm Intervention/Treatment
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

Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets

Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets

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)

Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets

Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets

Experimental: Vericiguat (BAY1021189) (2.5 mg)

2.5 mg orally once daily for 12 weeks (with sham titrations)

Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets

Experimental: Vericiguat (BAY1021189) (1.25 mg)

1.25 mg orally once daily for 12 weeks (with sham titrations)

Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets

Placebo Comparator: Placebo

Orally once daily for 12 weeks (with sham titrations)

Drug: Placebo

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [Baseline, Week 12 (end of treatment [EOT])]

    NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF).

  2. Change From Baseline to Week 12 in Left Atrial Volume (LAV) [Baseline, Week 12 (EOT)]

    Left atrial volume was measured by echocardiography.

Other Outcome Measures

  1. Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline, Week 12 (EOT)]

    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.

  2. Change From Baseline to Week 12 in Heart Rate [Baseline, Week 12 (EOT)]

    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.

  3. Number of Subjects With Clinical Events (Heart Failure Hospitalization and Cardio-vascular [CV] Mortality) [Baseline up to Week 16 including 12 week treatment period and 4 week follow-up period]

    Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Fountain Valley California United States 92708
2 Fort Lauderdale Florida United States 33308
3 Naples Florida United States 34102
4 Macon Georgia United States 31201
5 Chicago Illinois United States 60611-2908
6 Iowa City Iowa United States 52242
7 New Orleans Louisiana United States 70112-1396
8 Detroit Michigan United States 48202
9 Minneapolis Minnesota United States 55422
10 Jackson Mississippi United States 39216-4505
11 Newark New Jersey United States 07103
12 Buffalo New York United States 14215
13 Pittsburgh Pennsylvania United States 15212
14 Charleston South Carolina United States 29425
15 Germantown Tennessee United States 38138
16 Nashville Tennessee United States 37232-8802
17 Milwaukee Wisconsin United States 53215
18 Darlinghurst New South Wales Australia 2010
19 Brisbane Queensland Australia 4029
20 Brisbane Queensland Australia 4064
21 Redcliffe Queensland Australia 4020
22 Hobart Tasmania Australia 7000
23 St. Pölten Niederösterreich Austria 3100
24 Linz Oberösterreich Austria 4010
25 Linz Oberösterreich Austria 4020
26 Graz Steiermark Austria 8036
27 Salzburg Austria 5020
28 Wien Austria 1090
29 Wien Austria 1220
30 Brugge Belgium 8000
31 Bruxelles - Brussel Belgium 1200
32 Gent Belgium 9000
33 Gilly Belgium 6060
34 HUY Belgium 4500
35 Mechelen Belgium 2800
36 MOL Belgium 2400
37 Roeselare Belgium 8800
38 Burgas Bulgaria 8018
39 Sofia Bulgaria 1202
40 Sofia Bulgaria 1233
41 Sofia Bulgaria 1309
42 Sofia Bulgaria 1527
43 Stara Zagora Bulgaria 6000
44 Toronto Ontario Canada M5B 1W8
45 Montreal Quebec Canada H1T 1C8
46 Montreal Quebec Canada H2W 1T8
47 Saint-Jean-sur-Richelieu Quebec Canada J3A 1C3
48 Sherbrooke Quebec Canada J1G 2E8
49 Quebec Canada G1V 4G5
50 Kromeriz Czechia 767 01
51 Praha 10 Czechia 10034
52 Praha 2 Czechia 12808
53 Praha 4 Czechia 140 21
54 Praha 6 Czechia 169 02
55 Aalborg Denmark 9000
56 Holbaek Denmark 4300
57 Randers Denmark 8930
58 BRON Cedex France 69677
59 Pessac France 33604
60 Rouen France 76031
61 Toulouse France 31403
62 Bad Krozingen Baden-Württemberg Germany 79189
63 München Bayern Germany 80331
64 Bad Homburg Hessen Germany 61348
65 Greifswald Mecklenburg-Vorpommern Germany 17475
66 Hannover Niedersachsen Germany 30625
67 Köln Nordrhein-Westfalen Germany 50937
68 Münster Nordrhein-Westfalen Germany 48149
69 Homburg Saarland Germany 66421
70 Erfurt Thüringen Germany 99089
71 Hamburg Germany 20246
72 Athens Greece 11527
73 Chaidari Greece 12462
74 Nea Ionia / Athens Greece 142 33
75 Budapest Hungary 1097
76 Kistarcsa Hungary H-2143
77 Szekesfehervar Hungary 8000
78 Afula Israel 1834111
79 Ashkelon Israel 7830604
80 Hadera Israel 3810101
81 Haifa Israel 3109601
82 Jerusalem Israel 9103102
83 Petah Tikva Israel 4941492
84 Rehovot Israel 7610001
85 Tel Aviv Israel 6423906
86 Tiberias Israel 1528001
87 Zrifin Israel 7030000
88 Bergamo Lombardia Italy 24127
89 Brescia Lombardia Italy 25123
90 Milano Lombardia Italy 20017
91 Milano Lombardia Italy 20149
92 Pavia Lombardia Italy 27100
93 Ancona Marche Italy 60126
94 Arezzo Toscana Italy 52040
95 Iizuka Fukuoka Japan 820-8505
96 Himeji Hyogo Japan 670-0981
97 Higashiibaraki Ibaraki Japan 311-3193
98 Kanazawa Ishikawa Japan 920-8650
99 Takamatsu Kagawa Japan 760-0018
100 Sagamihara Kanagawa Japan 252-5188
101 Yokohama Kanagawa Japan 236-0051
102 Yokosuka Kanagawa Japan 238-8567
103 Uji Kyoto Japan 611-0041
104 Naha Okinawa Japan 902-8511
105 Sakai Osaka Japan 599-8247
106 Takatsuki Osaka Japan 569-1096
107 Komatsushima Tokushima Japan 773-8502
108 Meguro-ku Tokyo Japan 152-8902
109 Minato-ku Tokyo Japan 106-0031
110 Fukui Japan 910-8526
111 Hiroshima Japan 734-8530
112 Kumamoto Japan 862-8505
113 Nagasaki Japan 850-8555
114 Osaka Japan 558-8558
115 Tokushima Japan 770-8539
116 Toyama Japan 930-8550
117 Seoul Korea, Republic of 138-736
118 Amsterdam Netherlands 1105 AZ
119 Heerenveen Netherlands 8441 PW
120 Leeuwarden Netherlands 8934 AD
121 Sneek Netherlands 8601 ZR
122 Bialystok Poland 15-276
123 Krakow Poland 31-121
124 Krakow Poland 31-202
125 Lodz Poland 92-213
126 Lodz Poland 93-513
127 Olsztyn Poland 10-010
128 Poznan Poland 61-848
129 Szczecin Poland 70-965
130 Almada Portugal 2801-951
131 Lisboa Portugal 1449-005
132 Lisboa Portugal 1500-650
133 Lisboa Portugal 1649-035
134 Singapore Singapore 119228
135 Singapore Singapore 169609
136 Singapore Singapore 308433
137 Singapore Singapore 768828
138 Santander Cantabria Spain 39008
139 Majadahonda Madrid Spain 28222
140 El Palmar Murcia Spain 30120
141 Barcelona Spain 08003
142 Barcelona Spain 08023
143 Valencia Spain 46010
144 Valencia Spain 46026
145 Helsingborg Sweden 251 87
146 Karlstad Sweden 652 30
147 Linköping Sweden 581 85
148 Stockholm Sweden 118 83
149 Örebro Sweden 701 85
150 Lugano Ticino Switzerland 6900
151 Genève Switzerland 1205
152 Kaohsiung Taiwan 813
153 New Taipei City Taiwan 220
154 Taipei Taiwan 10016
155 Taipei Taiwan 11217
156 Taoyuan Taiwan 333423
157 Chesterfield Derbyshire United Kingdom S44 5DX
158 Stevenage Hertfordshire United Kingdom SG1 4AB

Sponsors and Collaborators

  • Bayer

Investigators

  • Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01951638
Other Study ID Numbers:
  • 15829
  • 2013-002288-25
First Posted:
Sep 26, 2013
Last Update Posted:
Mar 16, 2021
Last Verified:
Feb 1, 2021
Keywords provided by Bayer
Additional relevant MeSH terms:

Study Results

Participant Flow

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 Detail 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
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
Period Title: Treatment Period
STARTED 89 95 95 88 94
COMPLETED 87 86 90 80 89
NOT COMPLETED 2 9 5 8 5

Baseline Characteristics

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
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 Participants 96 93 96 96 96 477
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
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 (Count of 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%

Outcome Measures

1. Primary Outcome
Title Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
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])

Outcome Measure Data

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
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.
Measure Participants 73 77 78 57 60
Mean (Standard Deviation) [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)
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
Statistical Test of Hypothesis p-Value = 0.8991
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.137
Confidence Interval (2-Sided) 90%
-0.04 to 0.31
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.7194
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.076
Confidence Interval (2-Sided) 95%
-0.18 to 0.33
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.8653
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.156
Confidence Interval (2-Sided) 95%
-0.12 to 0.43
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.9041
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.171
Confidence Interval (2-Sided) 95%
-0.09 to 0.43
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.6572
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.052
Confidence Interval (2-Sided) 95%
-0.2 to 0.3
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Change From Baseline to Week 12 in Left Atrial Volume (LAV)
Description Left atrial volume was measured by echocardiography.
Time Frame Baseline, Week 12 (EOT)

Outcome Measure Data

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
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.
Measure Participants 67 77 78 57 59
Mean (Standard Deviation) [milliliter]
-3.361
(12.654)
-2.163
(7.895)
-2.142
(11.931)
-1.252
(16.139)
-1.654
(10.245)
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
Statistical Test of Hypothesis p-Value = 0.8156
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.629
Confidence Interval (2-Sided) 90%
-1.36 to 4.62
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.7945
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.707
Confidence Interval (2-Sided) 95%
-2.39 to 5.8
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.7917
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.109
Confidence Interval (2-Sided) 95%
-3.01 to 7.23
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.7241
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.219
Confidence Interval (2-Sided) 95%
-2.82 to 5.26
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value = 0.7546
Comments
Method t-test, 1 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.198
Confidence Interval (2-Sided) 95%
-2.23 to 4.63
Parameter Dispersion Type:
Value:
Estimation Comments
3. Other Pre-specified Outcome
Title Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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)

Outcome Measure Data

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
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.
Measure Participants 80 82 83 61 61
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
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)

Outcome Measure Data

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
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.
Measure Participants 80 82 83 61 61
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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
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.
Measure Participants 93 96 96 96 96
HF hospitalizations
8
8.3%
6
6.5%
11
11.5%
8
8.3%
5
5.2%
CV Mortality
1
1%
0
0%
0
0%
5
5.2%
1
1%

Adverse Events

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
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
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/93 (1.1%) 0/96 (0%) 1/95 (1.1%) 7/95 (7.4%) 2/96 (2.1%)
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 (21.5%) 20/96 (20.8%) 24/95 (25.3%) 18/95 (18.9%) 21/96 (21.9%)
Blood and lymphatic system disorders
Anaemia 2/93 (2.2%) 3 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Anaemia of chronic disease 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Cardiac disorders
Angina unstable 1/93 (1.1%) 1 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Atrial fibrillation 1/93 (1.1%) 1 0/96 (0%) 0 2/95 (2.1%) 3 1/95 (1.1%) 1 1/96 (1%) 2
Cardiac arrest 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Cardiac failure 6/93 (6.5%) 6 4/96 (4.2%) 4 7/95 (7.4%) 12 5/95 (5.3%) 8 2/96 (2.1%) 2
Cardiac failure acute 1/93 (1.1%) 1 1/96 (1%) 1 3/95 (3.2%) 3 0/95 (0%) 0 0/96 (0%) 0
Cardiac failure chronic 2/93 (2.2%) 3 4/96 (4.2%) 4 3/95 (3.2%) 3 2/95 (2.1%) 2 4/96 (4.2%) 5
Cardiac failure congestive 2/93 (2.2%) 2 0/96 (0%) 0 1/95 (1.1%) 1 3/95 (3.2%) 3 0/96 (0%) 0
Cardiogenic shock 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Myocardial infarction 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Right ventricular failure 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Tachyarrhythmia 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Acute coronary syndrome 0/93 (0%) 0 2/96 (2.1%) 2 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Ear and labyrinth disorders
Vertigo 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Eye disorders
Vitreous haemorrhage 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Gastrointestinal disorders
Diarrhoea 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 1/95 (1.1%) 1 1/96 (1%) 1
Gastrointestinal haemorrhage 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Large intestine polyp 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Intestinal haemorrhage 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
General disorders
Chest pain 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Pain 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Pyrexia 1/93 (1.1%) 2 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Sudden death 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Hepatobiliary disorders
Cholelithiasis 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Jaundice cholestatic 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Infections and infestations
Carbuncle 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Diabetic gangrene 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Erysipelas 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Gangrene 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Gastroenteritis 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Hepatitis C 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Osteomyelitis 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Pneumonia 1/93 (1.1%) 2 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 3/96 (3.1%) 3
Respiratory syncytial virus bronchiolitis 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Urinary tract infection 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Urosepsis 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Urinary tract infection bacterial 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Enterococcal sepsis 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Chlamydial infection 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Respiratory tract infection 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Injury, poisoning and procedural complications
Femoral neck fracture 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Radius fracture 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Ulna fracture 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Vascular pseudoaneurysm 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Contusion 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Post procedural haematoma 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Investigations
Coagulation time prolonged 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Intraocular pressure increased 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Metabolism and nutrition disorders
Diabetes mellitus 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Failure to thrive 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Hypoglycaemia 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Musculoskeletal and connective tissue disorders
Osteochondrosis 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Gastrointestinal stromal tumour 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Nervous system disorders
Carotid artery stenosis 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Cerebral haemorrhage 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Presyncope 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 2
Syncope 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 2
Cervicogenic headache 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Renal and urinary disorders
Renal impairment 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Acute kidney injury 2/93 (2.2%) 2 1/96 (1%) 1 1/95 (1.1%) 1 4/95 (4.2%) 4 3/96 (3.1%) 3
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Chronic obstructive pulmonary disease 0/93 (0%) 0 1/96 (1%) 1 1/95 (1.1%) 1 1/95 (1.1%) 1 2/96 (2.1%) 2
Dyspnoea 1/93 (1.1%) 1 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Epistaxis 0/93 (0%) 0 0/96 (0%) 0 1/95 (1.1%) 1 0/95 (0%) 0 0/96 (0%) 0
Pleural effusion 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Pulmonary hypertension 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Respiratory failure 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Skin and subcutaneous tissue disorders
Diabetic foot 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Surgical and medical procedures
Eyelid operation 0/93 (0%) 0 1/96 (1%) 1 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Vascular disorders
Circulatory collapse 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Hypotension 0/93 (0%) 0 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 1/96 (1%) 1
Orthostatic hypotension 1/93 (1.1%) 1 0/96 (0%) 0 0/95 (0%) 0 0/95 (0%) 0 0/96 (0%) 0
Other (Not Including 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 21/93 (22.6%) 33/96 (34.4%) 40/95 (42.1%) 38/95 (40%) 33/96 (34.4%)
Cardiac disorders
Cardiac failure 5/93 (5.4%) 5 1/96 (1%) 1 3/95 (3.2%) 4 3/95 (3.2%) 3 2/96 (2.1%) 2
Gastrointestinal disorders
Abdominal pain upper 1/93 (1.1%) 1 1/96 (1%) 1 5/95 (5.3%) 5 2/95 (2.1%) 2 0/96 (0%) 0
Nausea 2/93 (2.2%) 2 2/96 (2.1%) 2 4/95 (4.2%) 5 5/95 (5.3%) 5 4/96 (4.2%) 5
General disorders
Fatigue 2/93 (2.2%) 3 2/96 (2.1%) 2 3/95 (3.2%) 3 6/95 (6.3%) 6 4/96 (4.2%) 4
Oedema peripheral 2/93 (2.2%) 3 3/96 (3.1%) 4 2/95 (2.1%) 3 6/95 (6.3%) 7 1/96 (1%) 1
Infections and infestations
Bronchitis 1/93 (1.1%) 1 1/96 (1%) 1 2/95 (2.1%) 2 4/95 (4.2%) 4 6/96 (6.3%) 6
Nasopharyngitis 3/93 (3.2%) 3 4/96 (4.2%) 4 6/95 (6.3%) 8 1/95 (1.1%) 1 5/96 (5.2%) 5
Metabolism and nutrition disorders
Hyperkalaemia 0/93 (0%) 0 6/96 (6.3%) 6 2/95 (2.1%) 2 3/95 (3.2%) 3 3/96 (3.1%) 3
Nervous system disorders
Dizziness 3/93 (3.2%) 3 2/96 (2.1%) 4 10/95 (10.5%) 11 6/95 (6.3%) 6 7/96 (7.3%) 7
Headache 1/93 (1.1%) 1 1/96 (1%) 1 6/95 (6.3%) 6 4/95 (4.2%) 4 4/96 (4.2%) 4
Renal and urinary disorders
Renal failure 2/93 (2.2%) 3 5/96 (5.2%) 5 0/95 (0%) 0 1/95 (1.1%) 1 0/96 (0%) 0
Acute kidney injury 1/93 (1.1%) 1 1/96 (1%) 1 0/95 (0%) 0 5/95 (5.3%) 5 1/96 (1%) 1
Respiratory, thoracic and mediastinal disorders
Cough 1/93 (1.1%) 1 5/96 (5.2%) 5 6/95 (6.3%) 6 2/95 (2.1%) 2 2/96 (2.1%) 2
Dyspnoea 3/93 (3.2%) 3 6/96 (6.3%) 7 9/95 (9.5%) 10 5/95 (5.3%) 6 3/96 (3.1%) 3
Vascular disorders
Hypotension 1/93 (1.1%) 1 4/96 (4.2%) 4 4/95 (4.2%) 6 5/95 (5.3%) 5 2/96 (2.1%) 2

Limitations/Caveats

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.

More Information

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

Name/Title Therapeutic Area Head
Organization Bayer AG
Phone
Email clinical-trials-contact@bayer.com
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01951638
Other Study ID Numbers:
  • 15829
  • 2013-002288-25
First Posted:
Sep 26, 2013
Last Update Posted:
Mar 16, 2021
Last Verified:
Feb 1, 2021