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LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

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ClinicalTrials.gov Identifier: NCT00887588
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : August 13, 2015
Last Update Posted : August 25, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Heart Failure
Interventions Drug: LCZ696
Drug: Valsartan
Drug: Placebo
Enrollment 307
Recruitment Details A total of 308 participants were randomized to the core 12 week period, but 7 participants were excluded due to major Good Clinical Practice (GCP) violation. Of the 261 participants who completed the core, 252 participants entered the extension period.
Pre-assignment Details Eight participants, who completed the core, could not continue in the extension because the 36 week protocol amendment was not yet approved by health authorities; 1 participant, who completed the core, discontinued before the extension start due to an adverse event.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid. During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Period Title: Core Period
Started 149 152
Extension Efficacy Set 127 125
Full Analysis Set 148 146
Arterial Stiffness Set 86 94
Completed 130 131
Not Completed 19 21
Reason Not Completed
Death             1             1
Lost to Follow-up             3             1
Withdrawal by Subject             6             8
Adverse Event             9             11
Period Title: Extension Period
Started 127 125
Arterial Stiffness Set 86 94
Completed 121 120
Not Completed 6 5
Reason Not Completed
Adverse Event             4             4
Death             0             1
Protocol deviation             1             0
Lost to Follow-up             1             0
Arm/Group Title LCZ696 Valsartan Total
Hide Arm/Group Description During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid. During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid. Total of all reporting groups
Overall Number of Baseline Participants 149 152 301
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 149 participants 152 participants 301 participants
70.9  (9.38) 71.2  (8.94) 71.0  (9.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 152 participants 301 participants
Female
85
  57.0%
85
  55.9%
170
  56.5%
Male
64
  43.0%
67
  44.1%
131
  43.5%
1.Primary Outcome
Title Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Hide Description Evaluation of NT-proBNP was performed by a central laboratory. Change from baseline in NT-proBNP was presented as a ratio where the ratio was calculated as the NT-proBNP value at 12 weeks over the NT-proBNP value at baseline. A ratio < 1 indicates improvement.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set (FAS), who had both baseline and 12 week values, were included in the analysis. The FAS consisted of all randomized participants who had baseline and at least one post-baseline efficacy measurement during the double blind period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 134 132
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio: endpoint/baseline (pg/mL)
0.83
(0.68 to 1.01)
1.08
(0.89 to 1.32)
2.Secondary Outcome
Title Change From Baseline in NT-proBNP and Brain Natriuretic Peptide (BNP)
Hide Description Evaluation of NT-proBNP and BNP was performed by a central laboratory. Change from baseline in NT-proBNP and in BNP was presented as a ratio where the ratio for NT-proBNP was calculated as the NT-proBNP value at 36 weeks over the NT-proBNP value at baseline, and the ratio for BNP was calculated as the BNP value at 36 weeks over the BNP value at baseline. A ratio < 1 indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each parameter, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio: endpoint/baseline (pg/mL)
NT-proBNP (n=115,116)
0.78
(0.59 to 1.02)
0.92
(0.70 to 1.21)
BNP (n=116,113)
1.14
(0.88 to 1.47)
0.95
(0.73 to 1.23)
3.Secondary Outcome
Title Change From Baseline in Plasma Cyclic Guanine Monophosphate (cGMP)
Hide Description Evaluation of cGMP was performed by a central laboratory. Change from baseline in cGMP was presented as a ratio where the ratio was calculated as the cGMP value at 36 weeks over the cGMP value at baseline. A ratio < 1 indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 56 54
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio: endpoint/baseline (nmol/L)
0.90
(0.78 to 1.03)
0.85
(0.73 to 0.99)
4.Secondary Outcome
Title Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Relative Wall Thickness, Left Atrial Dimension
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each parameter, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: cm
LVE diastolic diameter (n=98,107) -0.23  (0.051) -0.19  (0.051)
LVE systolic diameter (n=98,107) -0.12  (0.044) -0.11  (0.044)
Septal end diastolic thickness (n=98,106) 0.01  (0.020) 0.01  (0.020)
Post. LV wall end diastolic thickness (n=99,107) 0.00  (0.015) 0.01  (0.015)
Relative wall thickness (n=98,107) 0.02  (0.008) 0.02  (0.008)
Left atrial dimension (n=99,108) -0.21  (0.043) -0.12  (0.042)
5.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each parameter, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: ml
LVE diastolic volume (n=94,111) -12.66  (2.094) -14.31  (2.027)
LVE systolic volume (n=95,111) -8.49  (1.251) -9.64  (1.215)
LV stroke volume (n=94,111) -4.34  (1.448) -4.63  (1.400)
Left atrial volume (n=96,112) -8.08  (2.133) -2.38  (2.057)
6.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 94 111
Least Squares Mean (Standard Error)
Unit of Measure: Percent ejection fraction
2.62  (0.778) 2.90  (0.755)
7.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Left Ventricular Mass
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 97 106
Least Squares Mean (Standard Error)
Unit of Measure: grams (g)
-11.26  (4.145) -8.00  (4.106)
8.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 91 100
Least Squares Mean (Standard Error)
Unit of Measure: g/m^2
-3.95  (2.249) -1.94  (2.283)
9.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 90 106
Least Squares Mean (Standard Error)
Unit of Measure: ml/m^2
-4.02  (1.260) -0.88  (1.237)
10.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each parameter, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: cm/s
E wave velocity (n=100,112) -0.60  (2.947) 4.12  (2.897)
A wave velocity (n=60,68) -0.39  (4.199) 0.59  (4.265)
e' at septal mitral annulus (n=79,98) 1.00  (0.266) 0.98  (0.260)
e' at lateral mitral annulus (n=84,96) 0.71  (0.307) 0.95  (0.296)
11.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A ratio < 1 indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each parameter, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: ratio
E to A velocity (n=60,68) 0.01  (0.080) 0.07  (0.081)
E/e' (n=83,95) -1.18  (0.561) -0.75  (0.543)
12.Secondary Outcome
Title Change in Echocardiography Parameters: Isovolumic Relaxation Time
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 35 42
Least Squares Mean (Standard Error)
Unit of Measure: ms
0.01  (0.002) 0.01  (0.002)
13.Secondary Outcome
Title Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity
Hide Description A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time Frame Baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 35 42
Least Squares Mean (Standard Error)
Unit of Measure: m/s
-0.05  (0.081) 0.00  (0.079)
14.Secondary Outcome
Title Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and Individual Domain Summary Scores
Hide Description The KCCQ is a self-administered questionnaire. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and quality of life, each with different Likert scale wording, including limitations, frequency, bother, change in condition, understanding, levels of enjoyment and satisfaction. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A positive change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values for each domain, were included in the analysis for that domain. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Physical limitation (n=117,114) 9.27  (2.528) 9.88  (2.516)
Symptom stability (n=118,116) 6.43  (3.171) 7.94  (3.167)
Symptom frequency (n=118,116) 10.38  (2.582) 9.16  (2.577)
Symptom burden (n=118,116) 9.23  (2.528) 9.45  (2.527)
Total symptom score (n=118,116) 9.83  (2.386) 9.32  (2.384)
Self efficacy (n=118,116) 11.24  (2.427) 8.77  (2.419)
Quality of life (n=118,116) 13.13  (2.706) 12.50  (2.702)
Social limitation (n=113,107) 9.99  (2.878) 11.04  (2.936)
Overall summary score (n=118,116) 11.25  (2.185) 11.31  (2.183)
15.Secondary Outcome
Title Percentage of Participants With Clinical Composite Assessment of Improved, Unchanged or Worsened
Hide Description The clinical composite assessment is defined as follows: Improved = a) participant improved (markedly or moderately) in the global assessment of disease activity with no worsening of NYHA functional class and no major adverse cardiovascular event or b) participant improved in NYHA functional class with no worsening (markedly or moderately) in the global assessment of disease activity and no major adverse cardiovascular event. Worsened = participant worsened (markedly or moderately) in the global assessment of disease activity or in NYHA functional class or experienced a major adverse cardiovascular event. Unchanged = participant does not meet the definition for improved or worsened.
Time Frame 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Extension efficacy set: the extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Measure Type: Number
Unit of Measure: Percentage of participants
Improved 41.7 32.8
Unchanged 45.7 53.6
Worsened 12.6 13.6
16.Secondary Outcome
Title Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV
Hide Description The NYHA Functional Classification classifies patients' heart failure according to the severity of their symptoms. The classification is as follows: Class I: no limitation of physical activity, ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath); Class II: slight limitation to physical activity, comfortable at rest, ordinary physical activity results in fatigue, palpitation or dyspnea; Class III: marked limitation of physical activity, comfortable at rest, less than ordinary activity causes fatigue, palpitation or dyspnea; Class IV: unable to carry on any physical activity without discomfort, symptoms of heart failure at rest, if any physical activity is undertaken, discomfort increases.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Extension efficacy set: the extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline, Class I 0.8 0.8
Baseline, Class II 78.7 81.6
Baseline, Class III 20.5 17.6
Baseline, Class IV 0 0
Week 36, Class I 12.6 7.2
Week 36, Class II 74.0 78.4
Week 36, Class III 13.4 14.4
Week 36, Class IV 0 0
17.Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Hide Description eGFR was calculated from the serum creatinine concentration determined by central laboratory assessment. A positive change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 126 123
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73m^2
-3.68  (1.493) -7.14  (1.517)
18.Secondary Outcome
Title Change From Baseline in Serum Creatinine
Hide Description Evaluation of serum creatinine was performed by central laboratory. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Extension efficacy set: the extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 127 125
Least Squares Mean (Standard Error)
Unit of Measure: µmol/L
5.82  (2.136) 10.65  (2.183)
19.Secondary Outcome
Title Change From Baseline in Albumin/Creatinine Ratio
Hide Description Evaluation of albumin/creatinine was performed by central laboratory. A ratio < 1 indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the extension efficacy set, who had both baseline and 36 week values, were included in the analysis for that parameter. The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 100 101
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
1.19
(0.85 to 1.66)
0.74
(0.52 to 1.06)
20.Secondary Outcome
Title Change From Baseline in Arterial Stiffness Parameters: Brachial Systolic Blood Pressure (SBP), Brachial Diastolic Blood Pressure (DBP), Central Augmentation Pressure, Central Pressure at T1-DP, Central SBP, Central DBP, Central Mean Pressure
Hide Description A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the arterial stiffness set, who had values for both baseline and week 36, were analyzed. The arterial stiffness set included randomized participants who participated in the arterial stiffness sub-study.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 86 94
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Brachial SBP(n=36,44) -1.27  (3.935) 1.47  (3.670)
Brachial DBP (n=36,44) 1.68  (2.279) 0.79  (2.165)
Central augmentation pressure (n=36,44) -0.21  (1.824) -0.24  (1.705)
Central pressure at T1-DP (n=36,44) -1.92  (2.071) 0.02  (1.941)
Central SBP (n=36,44) -0.71  (3.856) 0.86  (3.594)
Central DBP (n=36,44) 1.40  (2.319) 0.24  (2.204)
Central mean pressure (n=36,44) 0.84  (2.565) -0.13  (2.436)
21.Secondary Outcome
Title Change From Baseline in Arterial Stiffness Parameters: Heart Rate Correct Cen Aug/Pulse Ht
Hide Description A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the arterial stiffness set, who had values for both baseline and week 36, were analyzed. The arterial stiffness set included randomized participants who participated in the arterial stiffness sub-study.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 36 43
Least Squares Mean (Standard Error)
Unit of Measure: Percent
-0.74  (2.392) -2.16  (2.250)
22.Secondary Outcome
Title Change From Baseline in Arterial Stiffness Parameters: Heart Rate
Hide Description A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the arterial stiffness set, who had values for both baseline and week 36, were analyzed. The arterial stiffness set included randomized participants who participated in the arterial stiffness sub-study.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 36 44
Least Squares Mean (Standard Error)
Unit of Measure: bpm
-0.64  (2.026) -1.32  (1.905)
23.Secondary Outcome
Title Change From Baseline in Arterial Stiffness Parameters: Pulse Wave Velocity
Hide Description A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the arterial stiffness set, who had values for both baseline and week 36, were analyzed. The arterial stiffness set included randomized participants who participated in the arterial stiffness sub-study.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 32 42
Least Squares Mean (Standard Error)
Unit of Measure: cm/s
-0.44  (0.731) -0.74  (0.631)
24.Secondary Outcome
Title Change From Baseline in Sitting SBP, Sitting DBP and Sitting Pulse Pressure (PP)
Hide Description Sitting blood pressure and sitting pulse pressure were assessed. A negative change from baseline indicates improvement.
Time Frame baseline, 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Extension efficacy set: The extension efficacy set included all randomized participants who had baseline and at least one post-baseline efficacy measurement during the extension period.
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description:
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Overall Number of Participants Analyzed 125 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
mean SBP -7.47  (1.909) -2.18  (1.936)
mean DBP -5.28  (1.188) -1.39  (1.204)
Pulse pressure -2.24  (1.482) -1.17  (1.497)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LCZ696 Valsartan
Hide Arm/Group Description During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid. During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
All-Cause Mortality
LCZ696 Valsartan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
LCZ696 Valsartan
Affected / at Risk (%) Affected / at Risk (%)
Total   22/149 (14.77%)   30/152 (19.74%) 
Blood and lymphatic system disorders     
Anaemia  1  2/149 (1.34%)  1/152 (0.66%) 
Cardiac disorders     
Acute myocardial infarction  1  1/149 (0.67%)  0/152 (0.00%) 
Angina pectoris  1  1/149 (0.67%)  2/152 (1.32%) 
Angina unstable  1  3/149 (2.01%)  1/152 (0.66%) 
Atrial fibrillation  1  1/149 (0.67%)  1/152 (0.66%) 
Atrioventricular block complete  1  0/149 (0.00%)  1/152 (0.66%) 
Bradyarrhythmia  1  1/149 (0.67%)  0/152 (0.00%) 
Bradycardia  1  1/149 (0.67%)  0/152 (0.00%) 
Cardiac failure  1  3/149 (2.01%)  2/152 (1.32%) 
Cardiac failure acute  1  1/149 (0.67%)  3/152 (1.97%) 
Cardiac failure congestive  1  0/149 (0.00%)  1/152 (0.66%) 
Cardio-respiratory arrest  1  0/149 (0.00%)  1/152 (0.66%) 
Cardiogenic shock  1  0/149 (0.00%)  1/152 (0.66%) 
Coronary artery stenosis  1  0/149 (0.00%)  1/152 (0.66%) 
Myocardial infarction  1  1/149 (0.67%)  0/152 (0.00%) 
Palpitations  1  1/149 (0.67%)  0/152 (0.00%) 
Sick sinus syndrome  1  0/149 (0.00%)  1/152 (0.66%) 
Tachyarrhythmia  1  0/149 (0.00%)  1/152 (0.66%) 
Ear and labyrinth disorders     
Vertigo  1  1/149 (0.67%)  0/152 (0.00%) 
Gastrointestinal disorders     
Ascites  1  1/149 (0.67%)  0/152 (0.00%) 
Diarrhoea  1  1/149 (0.67%)  0/152 (0.00%) 
Diarrhoea haemorrhagic  1  0/149 (0.00%)  1/152 (0.66%) 
Duodenal ulcer  1  1/149 (0.67%)  0/152 (0.00%) 
Gastric haemorrhage  1  0/149 (0.00%)  2/152 (1.32%) 
Gastritis  1  0/149 (0.00%)  1/152 (0.66%) 
Gastritis erosive  1  0/149 (0.00%)  1/152 (0.66%) 
Ileus  1  0/149 (0.00%)  1/152 (0.66%) 
Melaena  1  0/149 (0.00%)  1/152 (0.66%) 
General disorders     
Asthenia  1  2/149 (1.34%)  0/152 (0.00%) 
Chest discomfort  1  1/149 (0.67%)  0/152 (0.00%) 
Device malfunction  1  0/149 (0.00%)  1/152 (0.66%) 
Non-cardiac chest pain  1  1/149 (0.67%)  1/152 (0.66%) 
Oedema peripheral  1  1/149 (0.67%)  0/152 (0.00%) 
Pyrexia  1  0/149 (0.00%)  2/152 (1.32%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/149 (0.67%)  0/152 (0.00%) 
Infections and infestations     
Appendicitis  1  0/149 (0.00%)  1/152 (0.66%) 
Bacterial sepsis  1  0/149 (0.00%)  1/152 (0.66%) 
Bronchitis  1  0/149 (0.00%)  1/152 (0.66%) 
Endocarditis  1  1/149 (0.67%)  0/152 (0.00%) 
Gastroenteritis  1  1/149 (0.67%)  0/152 (0.00%) 
Pneumonia  1  1/149 (0.67%)  1/152 (0.66%) 
Postoperative wound infection  1  1/149 (0.67%)  0/152 (0.00%) 
Sepsis  1  0/149 (0.00%)  1/152 (0.66%) 
Urinary tract infection  1  0/149 (0.00%)  2/152 (1.32%) 
Injury, poisoning and procedural complications     
Humerus fracture  1  1/149 (0.67%)  0/152 (0.00%) 
Lower limb fracture  1  0/149 (0.00%)  1/152 (0.66%) 
Spinal fracture  1  1/149 (0.67%)  0/152 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/149 (0.00%)  1/152 (0.66%) 
Hyperglycaemia  1  1/149 (0.67%)  0/152 (0.00%) 
Hyperkalaemia  1  2/149 (1.34%)  1/152 (0.66%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/149 (0.00%)  1/152 (0.66%) 
Muscular weakness  1  1/149 (0.67%)  0/152 (0.00%) 
Osteoarthritis  1  1/149 (0.67%)  0/152 (0.00%) 
Osteonecrosis  1  0/149 (0.00%)  1/152 (0.66%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adrenal carcinoma  1  0/149 (0.00%)  1/152 (0.66%) 
Pancreatic carcinoma  1  1/149 (0.67%)  0/152 (0.00%) 
Nervous system disorders     
Carotid artery stenosis  1  0/149 (0.00%)  1/152 (0.66%) 
Cerebrovascular insufficiency  1  0/149 (0.00%)  1/152 (0.66%) 
Syncope  1  0/149 (0.00%)  1/152 (0.66%) 
Transient ischaemic attack  1  0/149 (0.00%)  1/152 (0.66%) 
Renal and urinary disorders     
Hyperuricosuria  1  0/149 (0.00%)  1/152 (0.66%) 
Renal colic  1  0/149 (0.00%)  1/152 (0.66%) 
Renal failure  1  0/149 (0.00%)  1/152 (0.66%) 
Renal failure acute  1  2/149 (1.34%)  1/152 (0.66%) 
Urinary retention  1  1/149 (0.67%)  0/152 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/149 (0.00%)  1/152 (0.66%) 
Bronchiectasis  1  1/149 (0.67%)  0/152 (0.00%) 
Dyspnoea  1  2/149 (1.34%)  4/152 (2.63%) 
Productive cough  1  0/149 (0.00%)  3/152 (1.97%) 
Pulmonary oedema  1  0/149 (0.00%)  1/152 (0.66%) 
Respiratory failure  1  0/149 (0.00%)  2/152 (1.32%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  1/149 (0.67%)  0/152 (0.00%) 
Vascular disorders     
Arterial thrombosis limb  1  0/149 (0.00%)  1/152 (0.66%) 
Femoral arterial stenosis  1  0/149 (0.00%)  1/152 (0.66%) 
Hypotension  1  2/149 (1.34%)  1/152 (0.66%) 
Peripheral arterial occlusive disease  1  0/149 (0.00%)  1/152 (0.66%) 
Peripheral embolism  1  0/149 (0.00%)  1/152 (0.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
LCZ696 Valsartan
Affected / at Risk (%) Affected / at Risk (%)
Total   79/149 (53.02%)   92/152 (60.53%) 
Blood and lymphatic system disorders     
Anaemia  1  2/149 (1.34%)  5/152 (3.29%) 
Cardiac disorders     
Angina pectoris  1  4/149 (2.68%)  2/152 (1.32%) 
Atrial fibrillation  1  2/149 (1.34%)  8/152 (5.26%) 
Bradycardia  1  0/149 (0.00%)  4/152 (2.63%) 
Cardiac failure  1  3/149 (2.01%)  4/152 (2.63%) 
Cardiac failure chronic  1  1/149 (0.67%)  4/152 (2.63%) 
Palpitations  1  5/149 (3.36%)  5/152 (3.29%) 
Ear and labyrinth disorders     
Vertigo  1  5/149 (3.36%)  1/152 (0.66%) 
Eye disorders     
Cataract  1  3/149 (2.01%)  1/152 (0.66%) 
Gastrointestinal disorders     
Abdominal pain  1  3/149 (2.01%)  3/152 (1.97%) 
Constipation  1  2/149 (1.34%)  5/152 (3.29%) 
Diarrhoea  1  9/149 (6.04%)  4/152 (2.63%) 
Dyspepsia  1  4/149 (2.68%)  2/152 (1.32%) 
Nausea  1  3/149 (2.01%)  4/152 (2.63%) 
General disorders     
Asthenia  1  7/149 (4.70%)  10/152 (6.58%) 
Fatigue  1  3/149 (2.01%)  6/152 (3.95%) 
Non-cardiac chest pain  1  3/149 (2.01%)  0/152 (0.00%) 
Oedema peripheral  1  4/149 (2.68%)  9/152 (5.92%) 
Pyrexia  1  4/149 (2.68%)  0/152 (0.00%) 
Infections and infestations     
Bronchitis  1  6/149 (4.03%)  2/152 (1.32%) 
Gastroenteritis  1  4/149 (2.68%)  1/152 (0.66%) 
Influenza  1  4/149 (2.68%)  5/152 (3.29%) 
Nasopharyngitis  1  3/149 (2.01%)  5/152 (3.29%) 
Respiratory tract infection  1  1/149 (0.67%)  4/152 (2.63%) 
Upper respiratory tract infection  1  3/149 (2.01%)  1/152 (0.66%) 
Urinary tract infection  1  6/149 (4.03%)  9/152 (5.92%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  3/149 (2.01%)  0/152 (0.00%) 
Gout  1  0/149 (0.00%)  4/152 (2.63%) 
Hyperkalaemia  1  10/149 (6.71%)  8/152 (5.26%) 
Hypokalaemia  1  3/149 (2.01%)  1/152 (0.66%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/149 (3.36%)  2/152 (1.32%) 
Back pain  1  5/149 (3.36%)  4/152 (2.63%) 
Pain in extremity  1  5/149 (3.36%)  2/152 (1.32%) 
Nervous system disorders     
Dizziness  1  11/149 (7.38%)  7/152 (4.61%) 
Headache  1  3/149 (2.01%)  4/152 (2.63%) 
Psychiatric disorders     
Insomnia  1  1/149 (0.67%)  4/152 (2.63%) 
Renal and urinary disorders     
Renal impairment  1  1/149 (0.67%)  5/152 (3.29%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  9/149 (6.04%)  8/152 (5.26%) 
Dyspnoea  1  4/149 (2.68%)  11/152 (7.24%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  2/149 (1.34%)  5/152 (3.29%) 
Vascular disorders     
Hypertension  1  3/149 (2.01%)  6/152 (3.95%) 
Hypotension  1  19/149 (12.75%)  14/152 (9.21%) 
Orthostatic hypotension  1  2/149 (1.34%)  5/152 (3.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00887588     History of Changes
Other Study ID Numbers: CLCZ696B2214
2009-010208-27
First Submitted: April 22, 2009
First Posted: April 24, 2009
Results First Submitted: July 16, 2015
Results First Posted: August 13, 2015
Last Update Posted: August 25, 2015