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randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure (OUTSTEP-HF)

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ClinicalTrials.gov Identifier: NCT02900378
Recruitment Status : Completed
First Posted : September 14, 2016
Results First Posted : September 16, 2019
Last Update Posted : September 2, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Heart Failure With Reduced Ejection Fraction
Interventions Drug: LCZ696 (Sacubitril/Valsartan)
Drug: Placebo of LCZ696 (Sacubitril/Valsartan)
Drug: Enalapril
Drug: Placebo of Enalapril
Enrollment 621
Recruitment Details This study was conducted at 120 centers in 19 countries worldwide (Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Iceland, Ireland, Latvia, Lithuania, Netherlands, Norway, Poland, Spain, Sweden and UK).
Pre-assignment Details It was planned to recruit 300 patients per treatment arm, i.e. 600 patients in total. A total of 764 patients were screened, of whom 621 patients were randomized (310 in the sacubitril/valsartan group and 311 in the enalapril group).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme. Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Period Title: Randomization (Visit 2)
Started [1] 310 311
Completed 287 283
Not Completed 23 28
Reason Not Completed
Adverse Event             14             11
Death             1             4
Lost to Follow-up             1             0
Non-compliance with Study Drug             1             1
Protocol Deviation             1             7
Withdrawal by Parent/Guardian             5             3
Withdrawal of Informed Consent             0             2
[1]
All randomized patients
Period Title: Treatment Phase
Started [1] 309 310
Full Analysis Set [2] 302 302
Completed 309 310
Not Completed 0 0
[1]
All randomized patients with at least 1 dose of study treatment
[2]
At least 1 dose of study treatment and 1 post baseline safety assessment
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril Total
Hide Arm/Group Description LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme. Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme. Total of all reporting groups
Overall Number of Baseline Participants 310 311 621
Hide Baseline Analysis Population Description
All randomized patients are represented in the overall number of Baseline Participants. The Demographic and Baseline Characteristics were done in the Safety Analysis Set.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 309 participants 310 participants 619 participants
67.16  (11.04) 66.62  (10.45) 66.89  (10.74)
[1]
Measure Analysis Population Description: The Demographic and Baseline Characteristics were done in the Safety Analysis Set.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 309 participants 310 participants 619 participants
Female
71
  23.0%
61
  19.7%
132
  21.3%
Male
238
  77.0%
249
  80.3%
487
  78.7%
[1]
Measure Analysis Population Description: The Demographic and Baseline Characteristics were done in the Safety Analysis Set.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Black or African American Number Analyzed 309 participants 310 participants 619 participants
1 0 1
White Number Analyzed 309 participants 310 participants 619 participants
298 299 597
Missing Number Analyzed 309 participants 310 participants 619 participants
10 11 21
[1]
Measure Analysis Population Description: The Demographic and Baseline Characteristics were done in the Safety Analysis Set.
1.Primary Outcome
Title Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12)
Hide Description The impact of LCZ696 (Sacubitril/Valsartan) and Enalapril on functional exercise capacity was measured by the Six Minute Walk Test at 12 weeks. The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) and FAS population subset without AE/SAE were considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: meters
Baseline (FAS) Number Analyzed 301 participants 300 participants
365.37  (108.18) 371.08  (104.41)
Week 12 (FAS) Number Analyzed 292 participants 284 participants
395.80  (113.11) 395.33  (105.94)
Change from BL at Week 12 (FAS) Number Analyzed 291 participants 282 participants
31.57  (67.35) 24.89  (51.64)
Baseline (FAS without AE/SAE) Number Analyzed 289 participants 292 participants
364.72  (106.86) 371.18  (105.13)
Week 12 (FAS without AE/SAE) Number Analyzed 283 participants 277 participants
399.31  (110.54) 396.02  (106.39)
Change from BL at Week 12 (FAS without AE/SAE) Number Analyzed 282 participants 275 participants
35.75  (58.76) 25.87  (51.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12 (FAS)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2464
Comments The comparison of treatment groups were out using an analysis of covariance (ANCOVA) model adjusting for treatment and baseline NYHA class (NYHA II vs. III/IV) and the 6MWT baseline value as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences of least square means
Estimated Value 5.68
Confidence Interval (2-Sided) 95%
-3.93 to 15.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12 (FAS without AE/SAE)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0503
Comments The comparison of treatment groups were out using an analysis of covariance (ANCOVA) model adjusting for treatment and baseline NYHA class (NYHA II vs. III/IV) and the 6MWT baseline value as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences of least square means
Estimated Value 8.98
Confidence Interval (2-Sided) 97.5%
-1.31 to 19.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.58
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
Hide Description Non-sedentary physical activity is defined as >= 178.50 activity counts per minute; the average number of minutes per day spent in non-sedentary physical activity is being calculated over 14 days before randomization (baseline i.e. week -2 to week 0) and the last 14 days of treatment (i.e. week 10 to week 12).
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population with Multiple Imputation (MI), with Last Observation Carried Forward (LOCF) and without MI/LOCF were considered.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline (FAS with MI) Number Analyzed 302 participants 302 participants
510.11  (128.08) 506.81  (139.60)
Week 12 (FAS with MI) Number Analyzed 302 participants 302 participants
479.69  (124.23) 487.53  (126.84)
Change from BL at Week 12 (FAS with MI) Number Analyzed 302 participants 302 participants
-30.42  (102.55) -19.28  (104.04)
Baseline (FAS with LOCF) Number Analyzed 259 participants 257 participants
512.07  (126.37) 505.31  (129.74)
Week 12 (FAS with LOCF) Number Analyzed 253 participants 256 participants
489.43  (127.36) 490.09  (127.82)
Change from BL at Week 12 (FAS with LOCF) Number Analyzed 253 participants 256 participants
-21.88  (68.55) -15.41  (74.45)
Baseline (FAS without MI/LOCF) Number Analyzed 259 participants 257 participants
512.07  (126.37) 505.31  (129.74)
Week 12 (FAS without MI/LOCF) Number Analyzed 234 participants 216 participants
479.81  (122.45) 486.85  (128.70)
Change from BL at Week 12 (FAS without MI/LOCF) Number Analyzed 203 participants 194 participants
-25.14  (69.11) -20.51  (72.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12 (FAS with MI)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4769
Comments The comparison of treatment groups were carried out using an ANCOVA model adjusting for treatment, baseline NYHA class (NYHA II vs. III/IV) and the daily non-sedentary daytime activity baseline value as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences of least square means
Estimated Value -6.14
Confidence Interval (2-Sided) 97.5%
-25.70 to 13.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12 (FAS with LOCF)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3463
Comments The comparison of treatment groups were carried out using an ANCOVA model adjusting for treatment, baseline NYHA class (NYHA II vs. III/IV) and the daily non-sedentary daytime activity baseline value as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences of least square means
Estimated Value -5.67
Confidence Interval (2-Sided) 95%
-17.48 to 6.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12 (FAS without MI/LOCF)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3513
Comments The comparison of treatment groups were carried out using an ANCOVA model adjusting for treatment, baseline NYHA class (NYHA II vs. III/IV) and the daily non-sedentary daytime activity baseline value as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences of least square means
Estimated Value -6.24
Confidence Interval (2-Sided) 95%
-19.39 to 6.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.69
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) was considered.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Measure Type: Count of Participants
Unit of Measure: Participants
No
142
  47.0%
153
  50.7%
Yes
149
  49.3%
129
  42.7%
Missing
11
   3.6%
20
   6.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS population
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.228
Confidence Interval (2-Sided) 95%
0.882 to 1.708
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population subset without AE/SAE was considered.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 290 294
Measure Type: Count of Participants
Unit of Measure: Participants
No
133
  45.9%
146
  49.7%
Yes
149
  51.4%
129
  43.9%
Missing
8
   2.8%
19
   6.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS subset without AE/SAE
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.251
Confidence Interval (2-Sided) 95%
0.895 to 1.748
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group in a subset of patients with baseline six-minute walk distance equal to or less than 300 meters.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) was considered for patients with Baseline 6MWT equal to or less than 300 meters.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 78 65
Measure Type: Count of Participants
Unit of Measure: Participants
No
35
  44.9%
31
  47.7%
Yes
41
  52.6%
29
  44.6%
Missing
2
   2.6%
5
   7.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS population
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.250
Confidence Interval (2-Sided) 95%
0.634 to 2.464
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS Subset Without AE/SAE
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group in a subset of patients with baseline six-minute walk distance equal to or less than 300 meters.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population subset without AE/SAE was considered for patients with Baseline 6MWT equal to or less than 300 meters.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 75 63
Measure Type: Count of Participants
Unit of Measure: Participants
No
33
  44.0%
30
  47.6%
Yes
41
  54.7%
29
  46.0%
Missing
1
   1.3%
4
   6.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS subset without AE/SAE
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.280
Confidence Interval (2-Sided) 95%
0.644 to 2.544
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group in a subset of patients with baseline six-minute walk distance from 100 to 450 meters.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) was considered for patients with Baseline 6MWT between 100 or above and less than 450 meters.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 238 238
Measure Type: Count of Participants
Unit of Measure: Participants
No
109
  45.8%
121
  50.8%
Yes
122
  51.3%
105
  44.1%
Missing
7
   2.9%
12
   5.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS population
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.250
Confidence Interval (2-Sided) 95%
0.863 to 1.811
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS Subset Without AE/SAE
Hide Description The proportion of patients with improved performance (>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group in a subset of patients with baseline six-minute walk distance from 100 to 450 meters.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population subset without AE/SAE was considered for patients with Baseline 6MWT between 100 or above and less than 450 meters.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 230 231
Measure Type: Count of Participants
Unit of Measure: Participants
No
103
  44.8%
115
  49.8%
Yes
122
  53.0%
105
  45.5%
Missing
5
   2.2%
11
   4.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments FAS subset without AE/SAE
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.260
Confidence Interval (2-Sided) 95%
0.865 to 1.834
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8
Hide Description The impact of LCZ696 (Sacubitril/Valsartan) and Enalapril on functional exercise capacity was measured by the Six Minute Walk Test at Weeks 4 and 8. The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway.
Time Frame Baseline, Week 4 and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) and FAS population subset without AE/SAE were considered.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: meters
Baseline (FAS) Number Analyzed 301 participants 300 participants
365.37  (108.18) 371.08  (104.41)
Week 4 (FAS) Number Analyzed 295 participants 289 participants
385.22  (110.55) 385.02  (109.92)
Change from BL at Week 4 (FAS) Number Analyzed 295 participants 287 participants
19.13  (49.16) 13.72  (51.39)
Week 8 (FAS) Number Analyzed 291 participants 284 participants
395.28  (112.05) 391.72  (108.99)
Change from BL at Week 8 (FAS) Number Analyzed 290 participants 282 participants
28.72  (57.99) 21.15  (52.75)
Baseline (FAS without AE/SAE) Number Analyzed 289 participants 292 participants
364.72  (106.86) 371.18  (105.13)
Week 4 (FAS without AE/SAE) Number Analyzed 284 participants 283 participants
384.58  (107.69) 385.92  (110.81)
Change from BL at Week 4 (FAS without AE/SAE) Number Analyzed 284 participants 281 participants
18.91  (49.63) 14.45  (51.48)
Week 8 (FAS without AE/SAE) Number Analyzed 280 participants 278 participants
396.64  (110.65) 391.82  (109.72)
Change from BL at Week 8 (FAS without AE/SAE) Number Analyzed 279 participants 276 participants
30.38  (57.07) 21.51  (52.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4 (FAS)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1814
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4 (FAS without AE/SAE)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3315
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8 (FAS)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2414
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8 (FAS without AE/SAE)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1793
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline
Hide Description Non-sedentary physical activity is defined as >= 178.50 activity counts per minute; the average number of minutes per day spent in non-sedentary physical activity will be calculated over 14 days before randomization (baseline) and the last 14 days of treatment (i.e week 10 to week 12)
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Measure Type: Count of Participants
Unit of Measure: Participants
No
175
  57.9%
163
  54.0%
Yes
28
   9.3%
31
  10.3%
Missing
99
  32.8%
108
  35.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Increased levels (>= 10% increase) of non sedentary daytime physical activity at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.821
Confidence Interval (2-Sided) 95%
0.462 to 1.457
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12
Hide Description The Patient Global Assessment (PGA) is a self-reported tool to assess the patients' subjective rating of their disease activity widely used in HF research. The patients are asked to report functioning or response to an intervention by rating their current condition compared to their pre-intervention condition on a numerical scale: 1) much improved 2) moderately improved 3) a little improved 4) unchanged 5) a little worse 6) moderately worse or 7) much worse.
Time Frame Week 4, Week 8, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4 Has much improved
19
   6.3%
16
   5.3%
Has (moderately) improved
63
  20.9%
51
  16.9%
Has a little improved
94
  31.1%
64
  21.2%
Is unchanged
98
  32.5%
131
  43.4%
Is a little worse
13
   4.3%
15
   5.0%
Is (moderately) worse
3
   1.0%
5
   1.7%
Is much worse
1
   0.3%
1
   0.3%
Missing
11
   3.6%
19
   6.3%
Week 8 Has much improved
23
   7.6%
24
   7.9%
Has (moderately) improved
79
  26.2%
73
  24.2%
Has a little improved
88
  29.1%
82
  27.2%
Is unchanged
82
  27.2%
88
  29.1%
Is a little worse
14
   4.6%
11
   3.6%
Is (moderately) worse
2
   0.7%
3
   1.0%
Is much worse
0
   0.0%
1
   0.3%
Missing
14
   4.6%
20
   6.6%
Week 12 Has much improved
35
  11.6%
40
  13.2%
Has (moderately) improved
72
  23.8%
67
  22.2%
Has a little improved
82
  27.2%
74
  24.5%
Is unchanged
79
  26.2%
94
  31.1%
Is a little worse
12
   4.0%
7
   2.3%
Is (moderately) worse
5
   1.7%
3
   1.0%
Is much worse
2
   0.7%
2
   0.7%
Missing
15
   5.0%
15
   5.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0516
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9025
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6713
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
12.Secondary Outcome
Title Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)
Hide Description The Patient Global Assessment (PGA) is a self-reported tool to assess the patients' subjective rating of their disease activity widely used in HF research. The patients are asked to report functioning or response to an intervention by rating their current condition compared to their pre-intervention condition on a numerical scale: 1) much improved 2) moderately improved 3) a little improved 4) unchanged 5) a little worse 6) moderately worse or 7) much worse. Patients with improved symptoms were categorized as: Improvement, Is unchanged, Gets worse or Missing.
Time Frame Week 4, Week 8, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4 Improvement
176
  58.3%
131
  43.4%
Is unchanged
98
  32.5%
131
  43.4%
Gets worse
17
   5.6%
21
   7.0%
Missing
11
   3.6%
19
   6.3%
Week 8 Improvement
190
  62.9%
179
  59.3%
Is unchanged
82
  27.2%
88
  29.1%
Gets worse
16
   5.3%
15
   5.0%
Missing
14
   4.6%
20
   6.6%
Week 12 Improvement
189
  62.6%
181
  59.9%
Is unchanged
79
  26.2%
94
  31.1%
Gets worse
19
   6.3%
12
   4.0%
Missing
15
   5.0%
15
   5.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7754
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2172
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals
Hide Description Non-sedentary physical activity is defined as >= 178.50 activity counts per minute; Mean daily non-sedentary daytime physical activity were being calculated over weekly and compared to before the inclusion.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 259 participants 257 participants
512.07  (126.37) 505.31  (129.74)
Week 1 Number Analyzed 290 participants 292 participants
527.34  (129.54) 509.28  (131.75)
Change from BL at Week 1 Number Analyzed 250 participants 250 participants
22.60  (62.33) 9.88  (50.17)
Week 2 Number Analyzed 285 participants 292 participants
531.19  (133.89) 508.70  (133.69)
Change from BL at Week 2 Number Analyzed 247 participants 250 participants
22.80  (70.25) 6.19  (55.14)
Week 3 Number Analyzed 275 participants 282 participants
525.98  (126.66) 513.63  (130.58)
Change from BL at Week 3 Number Analyzed 238 participants 241 participants
13.55  (66.74) 6.40  (62.63)
Week 4 Number Analyzed 273 participants 275 participants
519.45  (133.21) 503.25  (139.48)
Change from BL at Week 4 Number Analyzed 236 participants 234 participants
11.99  (60.10) -5.35  (72.35)
Week 5 Number Analyzed 241 participants 220 participants
507.46  (129.31) 501.70  (138.78)
Change from BL at Week 5 Number Analyzed 212 participants 190 participants
1.77  (71.74) -10.95  (81.39)
Week 6 Number Analyzed 232 participants 214 participants
504.15  (131.05) 500.39  (136.08)
Change from BL at Week 6 Number Analyzed 205 participants 185 participants
-0.44  (76.32) -7.91  (69.71)
Week 7 Number Analyzed 230 participants 215 participants
495.06  (127.80) 503.46  (139.69)
Change from BL at Week 7 Number Analyzed 202 participants 187 participants
-10.35  (76.94) -6.54  (75.77)
Week 8 Number Analyzed 230 participants 213 participants
497.62  (130.56) 496.45  (139.12)
Change from BL at Week 8 Number Analyzed 202 participants 186 participants
-9.49  (79.10) -9.21  (75.23)
Week 9 Number Analyzed 235 participants 222 participants
496.74  (128.90) 497.24  (131.02)
Change from BL at Week 9 Number Analyzed 205 participants 196 participants
-10.09  (69.93) -10.75  (75.82)
Week 10 Number Analyzed 239 participants 219 participants
495.53  (130.97) 500.88  (138.35)
Change from BL at Week 10 Number Analyzed 207 participants 194 participants
-9.46  (80.47) -7.52  (77.12)
Week 11 Number Analyzed 232 participants 214 participants
492.28  (127.19) 495.14  (135.54)
Change from BL at Week 11 Number Analyzed 201 participants 192 participants
-12.93  (74.12) -11.64  (75.35)
Week 12 Number Analyzed 232 participants 214 participants
492.28  (127.19) 495.14  (135.54)
Change from BL at Week 12 Number Analyzed 201 participants 192 participants
-12.93  (74.12) -11.64  (75.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0297
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2275
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3486
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6800
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7184
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5301
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6019
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8229
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8229
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals
Hide Description Non-sedentary physical activity is defined as >= 178.50 activity counts per minute; Mean daily non-sedentary daytime physical activity were being calculated over two-weekly intervals and compared to before the inclusion.
Time Frame Baseline, Weeks 0 to 2, Weeks 2 to 4, Weeks 4 to 6, Weeks 6 to 8, Weeks 8 to 10, Weeks 10 to 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 259 participants 257 participants
512.07  (126.37) 505.31  (129.74)
Weeks 0 to 2 Number Analyzed 286 participants 292 participants
529.63  (129.31) 509.02  (129.97)
Change from BL at Week 2 Number Analyzed 248 participants 250 participants
22.88  (60.90) 8.06  (45.65)
Weeks 2 to 4 Number Analyzed 275 participants 279 participants
522.30  (126.68) 508.57  (131.41)
Change from BL at Week 4 Number Analyzed 238 participants 238 participants
12.04  (54.84) 0.55  (60.23)
Weeks 4 to 6 Number Analyzed 236 participants 216 participants
505.54  (127.40) 500.49  (135.70)
Change from BL at Week 6 Number Analyzed 206 participants 186 participants
0.21  (68.47) -10.86  (72.76)
Weeks 6 to 8 Number Analyzed 231 participants 213 participants
495.94  (124.78) 500.92  (135.26)
Change from BL at Week 8 Number Analyzed 203 participants 186 participants
-10.11  (71.75) -7.62  (69.96)
Weeks 8 to 10 Number Analyzed 240 participants 221 participants
496.57  (126.68) 497.02  (132.96)
Change from BL at Week 10 Number Analyzed 209 participants 195 participants
-8.44  (68.35) -8.75  (71.50)
Weeks 10 to 12 Number Analyzed 226 participants 210 participants
483.20  (121.43) 493.41  (130.00)
Change from BL at Week 12 Number Analyzed 196 participants 188 participants
-21.17  (68.77) -13.93  (72.85)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2560
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5865
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5463
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3212
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity
Hide Description The average number of minutes per day spent in light non-sedentary physical activity was being calculated over 7 day epochs. Non-sedentary physical activity is defined as >= 178.5 activity counts per minute and light physical activity is defined as 178.5 - 565.5 counts per minute.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 259 participants 257 participants
251.94  (50.54) 247.30  (58.70)
Week 1 Number Analyzed 290 participants 292 participants
263.17  (55.85) 251.37  (58.13)
Change from BL at Week 1 Number Analyzed 250 participants 250 participants
14.10  (31.15) 6.28  (27.98)
Week 2 Number Analyzed 285 participants 292 participants
262.42  (55.12) 248.33  (57.81)
Change from BL at Week 2 Number Analyzed 247 participants 250 participants
10.91  (36.10) 1.58  (28.80)
Week 3 Number Analyzed 275 participants 282 participants
261.80  (52.68) 251.12  (57.48)
Change from BL at Week 3 Number Analyzed 238 participants 241 participants
9.68  (33.10) 3.61  (31.85)
Week 4 Number Analyzed 273 participants 275 participants
256.10  (52.61) 246.97  (58.06)
Change from BL at Week 4 Number Analyzed 236 participants 234 participants
5.14  (31.12) -1.77  (33.49)
Week 5 Number Analyzed 241 participants 220 participants
253.98  (54.75) 243.71  (59.17)
Change from BL at Week 5 Number Analyzed 212 participants 190 participants
2.71  (37.90) -5.77  (37.14)
Week 6 Number Analyzed 232 participants 214 participants
252.10  (56.73) 244.25  (57.33)
Change from BL at Week 6 Number Analyzed 205 participants 185 participants
1.08  (38.80) -4.72  (36.44)
Week 7 Number Analyzed 230 participants 215 participants
251.02  (52.09) 244.85  (57.32)
Change from BL at Week 7 Number Analyzed 202 participants 187 participants
-0.88  (38.88) -3.18  (37.27)
Week 8 Number Analyzed 230 participants 213 participants
251.46  (52.21) 245.02  (59.31)
Change from BL at Week 8 Number Analyzed 202 participants 186 participants
-1.71  (38.69) -2.41  (36.53)
Week 9 Number Analyzed 235 participants 222 participants
250.04  (52.64) 254.84  (56.31)
Change from BL at Week 9 Number Analyzed 205 participants 196 participants
-2.54  (35.74) -4.52  (37.14)
Week 10 Number Analyzed 239 participants 219 participants
248.33  (54.44) 245.62  (58.69)
Change from BL at Week 10 Number Analyzed 207 participants 194 participants
-3.43  (42.11) -2.65  (36.76)
Week 11 Number Analyzed 232 participants 214 participants
248.19  (53.09) 244.83  (59.77)
Change from BL at Week 11 Number Analyzed 201 participants 192 participants
-3.86  (39.67) -3.13  (34.23)
Week 12 Number Analyzed 183 participants 173 participants
239.30  (52.76) 243.63  (56.92)
Change from BL at Week 12 Number Analyzed 161 participants 157 participants
-11.98  (42.07) -6.55  (35.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0301
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1557
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6461
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9759
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3941
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7209
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4444
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7247
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2933
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
Hide Description The average number of minutes per day spent in moderate to vigorous non-sedentary physical activity was being calculated over 7 day epochs. Non-sedentary physical activity is defined as >= 178.5 activity counts per minute and moderate-to-vigorous activity is defined as > 565.5 counts per minute.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 259 participants 257 participants
260.13  (110.94) 258.01  (111.73)
Week 1 Number Analyzed 290 participants 292 participants
264.16  (109.31) 257.92  (111.47)
Change from BL at Week 1 Number Analyzed 250 participants 250 participants
8.50  (45.86) 3.60  (39.79)
Week 2 Number Analyzed 285 participants 292 participants
268.77  (114.83) 260.37  (116.00)
Change from BL at Week 2 Number Analyzed 247 participants 250 participants
11.89  (50.98) 4.61  (45.53)
Week 3 Number Analyzed 275 participants 282 participants
264.19  (108.10) 262.51  (111.15)
Change from BL at Week 3 Number Analyzed 238 participants 241 participants
3.87  (49.53) 2.80  (51.23)
Week 4 Number Analyzed 273 participants 275 participants
263.35  (114.86) 256.28  (115.82)
Change from BL at Week 4 Number Analyzed 236 participants 234 participants
6.85  (43.45) -3.58  (56.76)
Week 5 Number Analyzed 241 participants 220 participants
253.48  (108.52) 257.99  (115.65)
Change from BL at Week 5 Number Analyzed 212 participants 190 participants
-0.93  (51.57) -5.18  (66.01)
Week 6 Number Analyzed 232 participants 214 participants
252.05  (108.75) 256.14  (115.35)
Change from BL at Week 6 Number Analyzed 205 participants 185 participants
-1.52  (55.23) -3.19  (54.72)
Week 7 Number Analyzed 230 participants 215 participants
244.04  (105.32) 258.61  (118.51)
Change from BL at Week 7 Number Analyzed 202 participants 187 participants
-9.47  (57.67) -3.35  (56.28)
Week 8 Number Analyzed 230 participants 213 participants
246.16  (109.03) 251.42  (113.84)
Change from BL at Week 8 Number Analyzed 202 participants 186 participants
-7.78  (57.13) -6.80  (57.90)
Week 9 Number Analyzed 235 participants 222 participants
246.70  (106.78) 251.40  (108.51)
Change from BL at Week 9 Number Analyzed 205 participants 196 participants
-7.55  (54.98) -6.23  (57.68)
Week 10 Number Analyzed 239 participants 219 participants
247.20  (107.41) 255.26  (116.88)
Change from BL at Week 10 Number Analyzed 207 participants 194 participants
-6.03  (57.08) -4.86  (59.50)
Week 11 Number Analyzed 232 participants 214 participants
244.09  (104.33) 250.31  (113.81)
Change from BL at Week 11 Number Analyzed 201 participants 192 participants
-9.07  (51.95) -8.51  (61.45)
Week 12 Number Analyzed 183 participants 173 participants
237.15  (100.32) 248.08  (113.51)
Change from BL at Week 12 Number Analyzed 161 participants 157 participants
-20.52  (58.37) -11.57  (64.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0854
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0528
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4137
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0082
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7908
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6499
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5547
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6961
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5946
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8957
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8468
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1711
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Total Weekly Time Spent in Non-sedentary Daytime Physical Activity
Hide Description Non-sedentary physical activity is defined as >= 178.5 activity counts per minute; The total time spent in non-sedentary physical activity was being calculated for each patient in weekly intervals and the temporal course for each patient was assessed.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 264 participants 263 participants
3616.87  (964.92) 3528.56  (993.10)
Week 1 Number Analyzed 290 participants 292 participants
3676.46  (923.85) 3560.10  (916.16)
Change from BL at Week 1 Number Analyzed 255 participants 256 participants
103.29  (509.20) 82.48  (588.19)
Week 2 Number Analyzed 285 participants 292 participants
3691.24  (953.03) 3557.71  (940.60)
Change from BL at Week 2 Number Analyzed 251 participants 256 participants
76.23  (563.79) 52.38  (600.08)
Week 3 Number Analyzed 275 participants 282 participants
3668.25  (894.91) 3580.54  (922.70)
Change from BL at Week 3 Number Analyzed 242 participants 246 participants
25.28  (571.36) 34.56  (663.68)
Week 4 Number Analyzed 273 participants 275 participants
3608.39  (936.87) 3482.15  (991.15)
Change from BL at Week 4 Number Analyzed 240 participants 239 participants
5.10  (497.55) -56.23  (748.35)
Week 5 Number Analyzed 241 participants 220 participants
3488.43  (944.87) 3458.65  (973.75)
Change from BL at Week 5 Number Analyzed 214 participants 196 participants
-116.74  (607.31) -79.18  (817.71)
Week 6 Number Analyzed 232 participants 214 participants
3519.12  (922.58) 3489.15  (962.55)
Change from BL at Week 6 Number Analyzed 207 participants 191 participants
-72.08  (569.61) -21.73  (724.96)
Week 7 Number Analyzed 230 participants 215 participants
3444.52  (892.15) 3502.67  (977.43)
Change from BL at Week 7 Number Analyzed 205 participants 192 participants
-143.38  (605.25) -36.18  (709.43)
Week 8 Number Analyzed 230 participants 213 participants
3466.82  (936.51) 3457.74  (993.56)
Change from BL at Week 8 Number Analyzed 205 participants 190 participants
-130.59  (631.30) -59.92  (716.74)
Week 9 Number Analyzed 235 participants 222 participants
3470.69  (913.06) 3447.28  (932.67)
Change from BL at Week 9 Number Analyzed 208 participants 199 participants
-131.28  (549.54) -108.48  (719.58)
Week 10 Number Analyzed 239 participants 219 participants
3444.77  (947.18) 3489.68  (964.08)
Change from BL at Week 10 Number Analyzed 212 participants 197 participants
-119.41  (648.17) -68.93  (711.22)
Week 11 Number Analyzed 232 participants 214 participants
3406.56  (910.84) 3436.96  (971.78)
Change from BL at Week 11 Number Analyzed 205 participants 194 participants
-170.14  (632.53) -120.35  (707.11)
Week 12 Number Analyzed 183 participants 173 participants
3093.96  (913.14) 3234.90  (991.50)
Change from BL at Week 12 Number Analyzed 165 participants 158 participants
-506.82  (792.71) -339.15  (786.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0316
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1342
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0252
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9052
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2870
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3174
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5020
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4037
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4823
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1090
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
18.Secondary Outcome
Title Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity
Hide Description Light non-sedentary daytime physical activity is defined as between 178.5 - 565.5 counts per minute; The time spent in light non-sedentary physical activity was being calculated for each patient in weekly intervals and the temporal course for each patient was assessed.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 264 participants 263 participants
1773.14  (392.22) 1721.50  (452.26)
Week 1 Number Analyzed 290 participants 292 participants
1834.71  (400.46) 1757.76  (407.14)
Change from BL at Week 1 Number Analyzed 255 participants 256 participants
81.84  (255.91) 53.74  (282.22)
Week 2 Number Analyzed 285 participants 292 participants
1823.86  (396.55) 1736.64  (407.45)
Change from BL at Week 2 Number Analyzed 251 participants 256 participants
46.26  (301.74) 17.26  (280.12)
Week 3 Number Analyzed 275 participants 282 participants
1826.38  (376.72) 1751.95  (410.11)
Change from BL at Week 3 Number Analyzed 242 participants 246 participants
46.05  (281.11) 24.88  (313.52)
Week 4 Number Analyzed 273 participants 275 participants
1778.88  (372.86) 1707.68  (410.73)
Change from BL at Week 4 Number Analyzed 240 participants 239 participants
9.17  (275.92) -18.74  (346.02)
Week 5 Number Analyzed 241 participants 220 participants
1745.87  (406.21) 1683.08  (429.50)
Change from BL at Week 5 Number Analyzed 214 participants 196 participants
-36.66  (307.01) -37.98  (369.53)
Week 6 Number Analyzed 232 participants 214 participants
1759.09  (397.67) 1701.89  (405.01)
Change from BL at Week 6 Number Analyzed 207 participants 191 participants
-17.85  (290.75) -16.56  (343.51)
Week 7 Number Analyzed 230 participants 215 participants
1747.03  (366.43) 1702.58  (399.11)
Change from BL at Week 7 Number Analyzed 205 participants 192 participants
-32.03  (307.16) -17.71  (322.33)
Week 8 Number Analyzed 230 participants 213 participants
1750.02  (377.35) 1705.09  (424.99)
Change from BL at Week 8 Number Analyzed 205 participants 190 participants
-37.50  (323.19) -17.49  (318.83)
Week 9 Number Analyzed 235 participants 222 participants
1746.73  (375.07) 1706.26  (407.89)
Change from BL at Week 9 Number Analyzed 208 participants 199 participants
-36.47  (289.67) -43.21  (341.30)
Week 10 Number Analyzed 239 participants 219 participants
1724.72  (395.95) 1712.55  (412.82)
Change from BL at Week 10 Number Analyzed 212 participants 197 participants
-46.95  (339.81) -22.01  (314.65)
Week 11 Number Analyzed 232 participants 214 participants
1717.08  (386.33) 1697.81  (429.44)
Change from BL at Week 11 Number Analyzed 205 participants 194 participants
-60.08  (319.85) -40.52  (313.76)
Week 12 Number Analyzed 183 participants 173 participants
1559.62  (428.02) 1607.33  (449.83)
Change from BL at Week 12 Number Analyzed 165 participants 158 participants
-210.49  (390.17) -144.96  (339.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0143
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0708
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0750
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8017
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7956
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3499
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1192
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5237
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3902
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4228
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1571
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
19.Secondary Outcome
Title Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
Hide Description Moderate-to-vigorous non-sedentary physical activity is defined as > 565.5 counts per minute. The total time spent in moderate-to-vigorous non-sedentary physical activity was being calculated for each patient in weekly intervals and the temporal course for each patient was assessed.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 264 participants 263 participants
1843.73  (830.30) 1807.07  (815.89)
Week 1 Number Analyzed 290 participants 292 participants
1841.76  (769.54) 1802.34  (775.36)
Change from BL at Week 1 Number Analyzed 255 participants 256 participants
21.45  (373.16) 28.75  (404.20)
Week 2 Number Analyzed 285 participants 292 participants
1867.37  (806.56) 1821.07  (813.27)
Change from BL at Week 2 Number Analyzed 251 participants 256 participants
29.97  (383.31) 35.13  (432.43)
Week 3 Number Analyzed 275 participants 282 participants
1841.87  (755.88) 1828.59  (777.65)
Change from BL at Week 3 Number Analyzed 242 participants 246 participants
-20.77  (425.19) 9.68  (458.99)
Week 4 Number Analyzed 273 participants 275 participants
1829.51  (801.93) 1774.46  (815.93)
Change from BL at Week 4 Number Analyzed 240 participants 239 participants
-4.07  (344.29) -37.49  (506.27)
Week 5 Number Analyzed 241 participants 220 participants
1742.56  (767.53) 1775.57  (798.92)
Change from BL at Week 5 Number Analyzed 214 participants 196 participants
-80.08  (423.07) -41.20  (577.49)
Week 6 Number Analyzed 232 participants 214 participants
1760.03  (763.64) 1787.26  (810.30)
Change from BL at Week 6 Number Analyzed 207 participants 191 participants
-54.23  (416.05) -5.17  (509.74)
Week 7 Number Analyzed 230 participants 215 participants
1697.49  (732.18) 1800.09  (829.37)
Change from BL at Week 7 Number Analyzed 205 participants 192 participants
-111.35  (438.85) -18.47  (505.11)
Week 8 Number Analyzed 230 participants 213 participants
1716.80  (769.31) 1752.65  (802.46)
Change from BL at Week 8 Number Analyzed 205 participants 190 participants
-93.09  (429.65) -42.43  (522.80)
Week 9 Number Analyzed 235 participants 222 participants
1723.96  (750.60) 1741.02  (757.26)
Change from BL at Week 9 Number Analyzed 208 participants 199 participants
-94.81  (407.63) -65.27  (492.38)
Week 10 Number Analyzed 239 participants 219 participants
1720.06  (760.72) 1777.14  (811.27)
Change from BL at Week 10 Number Analyzed 212 participants 197 participants
-72.46  (442.80) -46.92  (514.49)
Week 11 Number Analyzed 232 participants 214 participants
1689.48  (731.77) 1739.15  (803.36)
Change from BL at Week 11 Number Analyzed 205 participants 194 participants
-110.06  (432.47) -79.83  (516.05)
Week 12 Number Analyzed 183 participants 173 participants
1534.35  (678.12) 1627.57  (778.70)
Change from BL at Week 12 Number Analyzed 165 participants 158 participants
-296.33  (525.81) -194.19  (564.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3231
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3519
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 3
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8335
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0465
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 5
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5016
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5941
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 7
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2019
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4125
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5702
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4752
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 11
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5343
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0985
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in Peak Six Minutes of Daytime Physical Activity
Hide Description The peak 6 min walk (M6min) is a parameter derived by validated algorithms of the software that are used to preprocess actigraphy data. The parameter reflected the peak 6 minutes of day time physical activity. The mean daily 6-minute walking test was being calculated over 14 day intervals.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set was considered
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description:
LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme.
Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
Overall Number of Participants Analyzed 302 302
Mean (Standard Deviation)
Unit of Measure: minutes
Baseline Number Analyzed 259 participants 257 participants
189.08  (67.75) 182.52  (60.09)
Week 2 Number Analyzed 285 participants 292 participants
193.54  (77.30) 184.46  (59.49)
Change from BL at Week 2 Number Analyzed 247 participants 250 participants
6.18  (46.72) 3.52  (32.16)
Week 4 Number Analyzed 273 participants 275 participants
191.86  (80.21) 181.11  (61.75)
Change from BL at Week 4 Number Analyzed 236 participants 234 participants
5.47  (50.93) -0.23  (40.44)
Week 6 Number Analyzed 232 participants 214 participants
191.21  (77.38) 181.11  (55.07)
Change from BL at Week 6 Number Analyzed 205 participants 185 participants
2.69  (42.51) -1.02  (38.82)
Week 8 Number Analyzed 230 participants 213 participants
183.96  (70.54) 180.92  (57.28)
Change from BL at Week 8 Number Analyzed 202 participants 186 participants
-2.71  (41.43) -0.22  (38.05)
Week 12 Number Analyzed 183 participants 173 participants
184.42  (67.09) 180.44  (55.36)
Change from BL at Week 12 Number Analyzed 161 participants 157 participants
-1.07  (49.32) -2.45  (39.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4525
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0445
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1158
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3901
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Enalapril
Comments Change from BL at Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7725
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Adverse Events were collected for the maximum duration of participants' treatment exposure plus any follow up period, approximately 4 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Enalapril
Hide Arm/Group Description LCZ696 (Sacubitril/Valsartan) or its matching placebo twice a day for 12 weeks. Patients began study treatment (Sacubitril/Valsartan) at a specific dose level according to their pre-study ACEI/ARB dose (1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ)) or matching placebo and were up-titrated according to an up-titration scheme. Enalapril or its matching placebo twice a day for 12 weeks. Patients began study treatment (Enalapril) at a specific dose level according to their pre-study ACEI/ARB dose (1 (2.5 mg), 2a (5 mg)) or matching placebo and were up-titrated according to an up-titration scheme.
All-Cause Mortality
LCZ696 (Sacubitril/Valsartan) Enalapril
Affected / at Risk (%) Affected / at Risk (%)
Total   1/309 (0.32%)   4/310 (1.29%) 
Hide Serious Adverse Events
LCZ696 (Sacubitril/Valsartan) Enalapril
Affected / at Risk (%) Affected / at Risk (%)
Total   19/309 (6.15%)   28/310 (9.03%) 
Blood and lymphatic system disorders     
Anaemia  1  1/309 (0.32%)  0/310 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  0/309 (0.00%)  1/310 (0.32%) 
Acute myocardial infarction  1  0/309 (0.00%)  1/310 (0.32%) 
Angina pectoris  1  1/309 (0.32%)  0/310 (0.00%) 
Atrial fibrillation  1  4/309 (1.29%)  2/310 (0.65%) 
Atrial flutter  1  0/309 (0.00%)  1/310 (0.32%) 
Cardiac arrest  1  0/309 (0.00%)  2/310 (0.65%) 
Cardiac failure  1  4/309 (1.29%)  7/310 (2.26%) 
Cardiac failure congestive  1  1/309 (0.32%)  0/310 (0.00%) 
Coronary artery disease  1  1/309 (0.32%)  0/310 (0.00%) 
Myocardial infarction  1  0/309 (0.00%)  1/310 (0.32%) 
Tachycardia  1  0/309 (0.00%)  1/310 (0.32%) 
Ventricular arrhythmia  1  0/309 (0.00%)  1/310 (0.32%) 
Ventricular fibrillation  1  1/309 (0.32%)  0/310 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/309 (0.00%)  1/310 (0.32%) 
Gastric haemorrhage  1  1/309 (0.32%)  0/310 (0.00%) 
Inguinal hernia  1  0/309 (0.00%)  1/310 (0.32%) 
Intestinal perforation  1  0/309 (0.00%)  1/310 (0.32%) 
General disorders     
Death  1  0/309 (0.00%)  1/310 (0.32%) 
Pyrexia  1  0/309 (0.00%)  2/310 (0.65%) 
Infections and infestations     
Diverticulitis  1  0/309 (0.00%)  1/310 (0.32%) 
Epididymitis  1  1/309 (0.32%)  0/310 (0.00%) 
Pneumonia  1  0/309 (0.00%)  2/310 (0.65%) 
Respiratory tract infection  1  1/309 (0.32%)  0/310 (0.00%) 
Sepsis  1  1/309 (0.32%)  0/310 (0.00%) 
Upper respiratory tract infection  1  1/309 (0.32%)  0/310 (0.00%) 
Urinary tract infection  1  1/309 (0.32%)  0/310 (0.00%) 
Injury, poisoning and procedural complications     
Coronary bypass thrombosis  1  0/309 (0.00%)  1/310 (0.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/309 (0.00%)  1/310 (0.32%) 
Bladder cancer  1  0/309 (0.00%)  1/310 (0.32%) 
Metastatic bronchial carcinoma  1  0/309 (0.00%)  1/310 (0.32%) 
Nervous system disorders     
Paraesthesia  1  0/309 (0.00%)  1/310 (0.32%) 
Stroke in evolution  1  1/309 (0.32%)  0/310 (0.00%) 
Syncope  1  0/309 (0.00%)  1/310 (0.32%) 
Renal and urinary disorders     
Haematuria  1  0/309 (0.00%)  1/310 (0.32%) 
Renal failure  1  2/309 (0.65%)  0/310 (0.00%) 
Urinary retention  1  0/309 (0.00%)  1/310 (0.32%) 
Urogenital haemorrhage  1  1/309 (0.32%)  0/310 (0.00%) 
Reproductive system and breast disorders