Chronic Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
sacubitril/valsartan, enalapril, physical activity, actigraphy, sleep, heart failure, reduced ejection fraction, randomized controlled trial, accelerometry
Brief summary
The purpose of this randomized, actively controlled, double-blind study with prospective data collection was to assess differences between sacubitril/valsartan versus enalapril in increasing exercise capacity and non-sedentary physical activity in HFrEF patients. Physical activity was assessed by the 6 minute walk test, and daily physical activity was continuously measured by means of a wrist-worn accelerometry device from 2 weeks before until 12 weeks after start of study therapy (sacubitril/valsartan or enalapril).
Interventions
LCZ696 (sacubitril/valsartan) was available in 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets
DRUGPlacebo of LCZ696 (Sacubitril/Valsartan)
Placebo of LCZ696 (sacubitril/valsartan) was available to match 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets
DRUGEnalapril
Enalapril was available in 2.5 mg, 5 mg and 10 mg film-coated tablets
Placebo of Enalapril was available to match 2.5 mg, 5 mg and 10 mg film-coated tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Written informed consent obtained before any study assessment is performed. * Ambulatory ≥ 18 years of age with a diagnosis of chronic symptomatic HF (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 40% AND one of the following two criteria: * Plasma NT-proBNP level of ≥ 300 pg/mL or BNP ≥ 100 pg/mL (measurement may be recorded no longer than past 12 months) OR * Confirmation of a heart failure hospitalization last 12 months. * Patients must be on stable HF medication for at least 4 weeks prior to Week - 2, where the minimal daily dose of current evidence based therapies is equivalent to at least 2.5 mg/d enalapril * Willingness to wear the accelerometer wristband continuously for the duration of the trial. * Patients must be living in a setting, allowing them to move about freely and where they are primarily self-responsible for scheduling their sleep and daily activities. Key
Exclusion criteria
* History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes * Use of sacubitril/valsartan prior to week - 2. * Bedridden patients, or patients with significantly impaired/limited physical activity and/or fatigue due to medical conditions other than HF, such as, but not limited to angina (chest pain at exertion), arthritis, gout, peripheral artery occlusive disease, obstructive or restrictive lung disease, malignant disease, neurological disorders (e.g. Parkinson's or Alzheimer's disease, central and peripheral neuroinflammatory and -degenerative disorders or functional central nervous lesions due to hemodynamic or traumatic incidents), injuries (incl. diabetic foot ulcers) or missing limbs * Patients with palsy, tremor or rigor affecting the non-dominant arm. * Patients with any skin or other condition of the non-dominant arm that would limit the ability to wear the actigraphy device continuously (24h/day) over 14 weeks. * Patients fully depending on a mobility support system, e.g. wheelchair, scooter or walker. Patients are allowed to use a cane as long as this is not used with the non-dominant arm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Baseline, Week 12 | 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. |
| Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline, Week 12 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Week 12 | 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. |
| 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 | Baseline, Week 12 | 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. |
| Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | Baseline, Week 12 | 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. |
| 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 | Baseline, Week 12 | 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. |
| Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Baseline, Week 4 and Week 8 | 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. |
| Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | Baseline, Week 12 | 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) |
| Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4, Week 8, Week 12 | 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. |
| Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4, Week 8, Week 12 | 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. |
| Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | Baseline, Week 12 | The proportion of patients with improved performance (\>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group. |
| Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | 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 | 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. |
| Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | 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 | 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. |
| Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | 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 | 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. |
| Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | 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 | 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. |
| Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | 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 | 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. |
| Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | 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 | 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. |
| Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Baseline, Week 2, Week 4, Week 6, Week 8 and Week 12 | 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. |
| Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | 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 | 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. |
| Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | Baseline, Week 12 | The proportion of patients with improved performance (\>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group. |
Countries
Belgium, Bulgaria, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Iceland, Ireland, Latvia, Lithuania, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| LCZ696 (Sacubitril/Valsartan) 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. | 310 |
| Enalapril 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. | 311 |
| Total | 621 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization (Visit 2) | Adverse Event | 14 | 11 |
| Randomization (Visit 2) | Death | 1 | 4 |
| Randomization (Visit 2) | Lost to Follow-up | 1 | 0 |
| Randomization (Visit 2) | Non-compliance with Study Drug | 1 | 1 |
| Randomization (Visit 2) | Protocol Deviation | 1 | 7 |
| Randomization (Visit 2) | Withdrawal by Parent/Guardian | 5 | 3 |
| Randomization (Visit 2) | Withdrawal of Informed Consent | 0 | 2 |
Baseline characteristics
| Characteristic | LCZ696 (Sacubitril/Valsartan) | Enalapril | Total |
|---|---|---|---|
| Age, Continuous | 67.16 Years STANDARD_DEVIATION 11.04 | 66.62 Years STANDARD_DEVIATION 10.45 | 66.89 Years STANDARD_DEVIATION 10.74 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 10 Participants | 11 Participants | 21 Participants |
| Race/Ethnicity, Customized White | 298 Participants | 299 Participants | 597 Participants |
| Sex: Female, Male Female | 71 Participants | 61 Participants | 132 Participants |
| Sex: Female, Male Male | 238 Participants | 249 Participants | 487 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 309 | 4 / 310 |
| other Total, other adverse events | 168 / 309 | 143 / 310 |
| serious Total, serious adverse events | 19 / 309 | 28 / 310 |
Outcome results
Primary
Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
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
Population: The FAS population with Multiple Imputation (MI), with Last Observation Carried Forward (LOCF) and without MI/LOCF were considered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS with MI) | 479.69 minutes | Standard Deviation 124.23 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS with LOCF) | -21.88 minutes | Standard Deviation 68.55 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS with LOCF) | 512.07 minutes | Standard Deviation 126.37 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS without MI/LOCF) | 512.07 minutes | Standard Deviation 126.37 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS with MI) | -30.42 minutes | Standard Deviation 102.55 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS without MI/LOCF) | 479.81 minutes | Standard Deviation 122.45 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS with LOCF) | 489.43 minutes | Standard Deviation 127.36 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS without MI/LOCF) | -25.14 minutes | Standard Deviation 69.11 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS with MI) | 510.11 minutes | Standard Deviation 128.08 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS without MI/LOCF) | -20.51 minutes | Standard Deviation 72.52 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS with MI) | 506.81 minutes | Standard Deviation 139.6 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS with MI) | 487.53 minutes | Standard Deviation 126.84 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS with MI) | -19.28 minutes | Standard Deviation 104.04 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS with LOCF) | 505.31 minutes | Standard Deviation 129.74 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS with LOCF) | 490.09 minutes | Standard Deviation 127.82 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Change from BL at Week 12 (FAS with LOCF) | -15.41 minutes | Standard Deviation 74.45 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Baseline (FAS without MI/LOCF) | 505.31 minutes | Standard Deviation 129.74 |
| Enalapril | Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) | Week 12 (FAS without MI/LOCF) | 486.85 minutes | Standard Deviation 128.7 |
Comparison: Change from BL at Week 12 (FAS with MI)p-value: 0.476997.5% CI: [-25.7, 13.41]ANCOVA
Comparison: Change from BL at Week 12 (FAS with LOCF)p-value: 0.346395% CI: [-17.48, 6.14]ANCOVA
Comparison: Change from BL at Week 12 (FAS without MI/LOCF)p-value: 0.351395% CI: [-19.39, 6.91]ANCOVA
Primary
Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12)
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
Population: The Full Analysis Set (FAS) and FAS population subset without AE/SAE were considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Baseline (FAS) | 365.37 meters | Standard Deviation 108.18 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Week 12 (FAS) | 395.80 meters | Standard Deviation 113.11 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Change from BL at Week 12 (FAS) | 31.57 meters | Standard Deviation 67.35 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Baseline (FAS without AE/SAE) | 364.72 meters | Standard Deviation 106.86 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Week 12 (FAS without AE/SAE) | 399.31 meters | Standard Deviation 110.54 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Change from BL at Week 12 (FAS without AE/SAE) | 35.75 meters | Standard Deviation 58.76 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Week 12 (FAS without AE/SAE) | 396.02 meters | Standard Deviation 106.39 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Baseline (FAS) | 371.08 meters | Standard Deviation 104.41 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Baseline (FAS without AE/SAE) | 371.18 meters | Standard Deviation 105.13 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Week 12 (FAS) | 395.33 meters | Standard Deviation 105.94 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Change from BL at Week 12 (FAS without AE/SAE) | 25.87 meters | Standard Deviation 51.73 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) | Change from BL at Week 12 (FAS) | 24.89 meters | Standard Deviation 51.64 |
Comparison: Change from BL at Week 12 (FAS)p-value: 0.246495% CI: [-3.93, 15.29]ANCOVA
Comparison: Change from BL at Week 12 (FAS without AE/SAE)p-value: 0.050397.5% CI: [-1.31, 19.27]ANCOVA
Secondary
Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 1 | 263.17 minutes | Standard Deviation 55.85 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 7 | 251.02 minutes | Standard Deviation 52.09 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 9.68 minutes | Standard Deviation 33.1 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -0.88 minutes | Standard Deviation 38.88 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 2 | 262.42 minutes | Standard Deviation 55.12 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 8 | 251.46 minutes | Standard Deviation 52.21 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 4 | 256.10 minutes | Standard Deviation 52.61 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -1.71 minutes | Standard Deviation 38.69 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Baseline | 251.94 minutes | Standard Deviation 50.54 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 9 | 250.04 minutes | Standard Deviation 52.64 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | 5.14 minutes | Standard Deviation 31.12 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -2.54 minutes | Standard Deviation 35.74 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 10.91 minutes | Standard Deviation 36.1 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 10 | 248.33 minutes | Standard Deviation 54.44 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 5 | 253.98 minutes | Standard Deviation 54.75 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -3.43 minutes | Standard Deviation 42.11 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | 2.71 minutes | Standard Deviation 37.9 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 11 | 248.19 minutes | Standard Deviation 53.09 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 14.10 minutes | Standard Deviation 31.15 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -3.86 minutes | Standard Deviation 39.67 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 6 | 252.10 minutes | Standard Deviation 56.73 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 12 | 239.30 minutes | Standard Deviation 52.76 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 3 | 261.80 minutes | Standard Deviation 52.68 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -11.98 minutes | Standard Deviation 42.07 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | 1.08 minutes | Standard Deviation 38.8 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -6.55 minutes | Standard Deviation 35.79 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Baseline | 247.30 minutes | Standard Deviation 58.7 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 1 | 251.37 minutes | Standard Deviation 58.13 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 6.28 minutes | Standard Deviation 27.98 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 2 | 248.33 minutes | Standard Deviation 57.81 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 1.58 minutes | Standard Deviation 28.8 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 3 | 251.12 minutes | Standard Deviation 57.48 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 3.61 minutes | Standard Deviation 31.85 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 4 | 246.97 minutes | Standard Deviation 58.06 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -1.77 minutes | Standard Deviation 33.49 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -5.77 minutes | Standard Deviation 37.14 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 6 | 244.25 minutes | Standard Deviation 57.33 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -4.72 minutes | Standard Deviation 36.44 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 7 | 244.85 minutes | Standard Deviation 57.32 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -3.18 minutes | Standard Deviation 37.27 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 8 | 245.02 minutes | Standard Deviation 59.31 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -2.41 minutes | Standard Deviation 36.53 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 9 | 254.84 minutes | Standard Deviation 56.31 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -4.52 minutes | Standard Deviation 37.14 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 10 | 245.62 minutes | Standard Deviation 58.69 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -2.65 minutes | Standard Deviation 36.76 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 11 | 244.83 minutes | Standard Deviation 59.77 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -3.13 minutes | Standard Deviation 34.23 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 12 | 243.63 minutes | Standard Deviation 56.92 |
| Enalapril | Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity | Week 5 | 243.71 minutes | Standard Deviation 59.17 |
Comparison: Change from BL at Week 1p-value: 0.0004Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.0009Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.0094Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0301Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.1557Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.6461Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.9759Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.3941Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.7209Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.4444Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.7247Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.2933Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 8.50 minutes | Standard Deviation 45.86 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 7 | 244.04 minutes | Standard Deviation 105.32 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 4 | 263.35 minutes | Standard Deviation 114.86 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -9.47 minutes | Standard Deviation 57.67 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 11.89 minutes | Standard Deviation 50.98 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 8 | 246.16 minutes | Standard Deviation 109.03 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | 6.85 minutes | Standard Deviation 43.45 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -7.78 minutes | Standard Deviation 57.13 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Baseline | 260.13 minutes | Standard Deviation 110.94 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 9 | 246.70 minutes | Standard Deviation 106.78 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 5 | 253.48 minutes | Standard Deviation 108.52 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -7.55 minutes | Standard Deviation 54.98 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 3 | 264.19 minutes | Standard Deviation 108.1 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 10 | 247.20 minutes | Standard Deviation 107.41 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -0.93 minutes | Standard Deviation 51.57 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -6.03 minutes | Standard Deviation 57.08 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 2 | 268.77 minutes | Standard Deviation 114.83 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 11 | 244.09 minutes | Standard Deviation 104.33 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 6 | 252.05 minutes | Standard Deviation 108.75 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -9.07 minutes | Standard Deviation 51.95 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 3.87 minutes | Standard Deviation 49.53 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 12 | 237.15 minutes | Standard Deviation 100.32 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -1.52 minutes | Standard Deviation 55.23 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -20.52 minutes | Standard Deviation 58.37 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 1 | 264.16 minutes | Standard Deviation 109.31 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -11.57 minutes | Standard Deviation 64.9 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Baseline | 258.01 minutes | Standard Deviation 111.73 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 1 | 257.92 minutes | Standard Deviation 111.47 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 3.60 minutes | Standard Deviation 39.79 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 2 | 260.37 minutes | Standard Deviation 116 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 4.61 minutes | Standard Deviation 45.53 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 3 | 262.51 minutes | Standard Deviation 111.15 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 2.80 minutes | Standard Deviation 51.23 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 4 | 256.28 minutes | Standard Deviation 115.82 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -3.58 minutes | Standard Deviation 56.76 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 5 | 257.99 minutes | Standard Deviation 115.65 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -5.18 minutes | Standard Deviation 66.01 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 6 | 256.14 minutes | Standard Deviation 115.35 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -3.19 minutes | Standard Deviation 54.72 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 7 | 258.61 minutes | Standard Deviation 118.51 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -3.35 minutes | Standard Deviation 56.28 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 8 | 251.42 minutes | Standard Deviation 113.84 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -6.80 minutes | Standard Deviation 57.9 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 9 | 251.40 minutes | Standard Deviation 108.51 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -6.23 minutes | Standard Deviation 57.68 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 10 | 255.26 minutes | Standard Deviation 116.88 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -4.86 minutes | Standard Deviation 59.5 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 11 | 250.31 minutes | Standard Deviation 113.81 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -8.51 minutes | Standard Deviation 61.45 |
| Enalapril | Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 12 | 248.08 minutes | Standard Deviation 113.51 |
Comparison: Change from BL at Week 1p-value: 0.0854Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.0528Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.4137Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0082Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.7908Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.6499Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.5547Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.6961Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.5946Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.8957Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.8468Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.1711Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 2 | 22.88 minutes | Standard Deviation 60.9 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 6 to 8 | 495.94 minutes | Standard Deviation 124.78 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 4 | 12.04 minutes | Standard Deviation 54.84 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 8 | -10.11 minutes | Standard Deviation 71.75 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 0 to 2 | 529.63 minutes | Standard Deviation 129.31 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 8 to 10 | 496.57 minutes | Standard Deviation 126.68 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 4 to 6 | 505.54 minutes | Standard Deviation 127.4 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 10 | -8.44 minutes | Standard Deviation 68.35 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 2 to 4 | 522.30 minutes | Standard Deviation 126.68 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 10 to 12 | 483.20 minutes | Standard Deviation 121.43 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 6 | 0.21 minutes | Standard Deviation 68.47 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 12 | -21.17 minutes | Standard Deviation 68.77 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Baseline | 512.07 minutes | Standard Deviation 126.37 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 12 | -13.93 minutes | Standard Deviation 72.85 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Baseline | 505.31 minutes | Standard Deviation 129.74 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 0 to 2 | 509.02 minutes | Standard Deviation 129.97 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 2 | 8.06 minutes | Standard Deviation 45.65 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 2 to 4 | 508.57 minutes | Standard Deviation 131.41 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 4 | 0.55 minutes | Standard Deviation 60.23 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 4 to 6 | 500.49 minutes | Standard Deviation 135.7 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 6 | -10.86 minutes | Standard Deviation 72.76 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 6 to 8 | 500.92 minutes | Standard Deviation 135.26 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 8 | -7.62 minutes | Standard Deviation 69.96 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 8 to 10 | 497.02 minutes | Standard Deviation 132.96 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Change from BL at Week 10 | -8.75 minutes | Standard Deviation 71.5 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals | Weeks 10 to 12 | 493.41 minutes | Standard Deviation 130 |
Comparison: Change from BL at Week 2p-value: 0.0001Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0123Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.256Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.5865Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.5463Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.3212Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 1 | 22.60 minutes | Standard Deviation 62.33 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 7 | 495.06 minutes | Standard Deviation 127.8 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 4 | 519.45 minutes | Standard Deviation 133.21 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 7 | -10.35 minutes | Standard Deviation 76.94 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 2 | 22.80 minutes | Standard Deviation 70.25 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 8 | 497.62 minutes | Standard Deviation 130.56 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 4 | 11.99 minutes | Standard Deviation 60.1 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 8 | -9.49 minutes | Standard Deviation 79.1 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 1 | 527.34 minutes | Standard Deviation 129.54 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 9 | 496.74 minutes | Standard Deviation 128.9 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 5 | 507.46 minutes | Standard Deviation 129.31 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 9 | -10.09 minutes | Standard Deviation 69.93 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 3 | 525.98 minutes | Standard Deviation 126.66 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 10 | 495.53 minutes | Standard Deviation 130.97 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 5 | 1.77 minutes | Standard Deviation 71.74 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 10 | -9.46 minutes | Standard Deviation 80.47 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 2 | 531.19 minutes | Standard Deviation 133.89 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 11 | 492.28 minutes | Standard Deviation 127.19 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 6 | 504.15 minutes | Standard Deviation 131.05 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 11 | -12.93 minutes | Standard Deviation 74.12 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 3 | 13.55 minutes | Standard Deviation 66.74 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 12 | 492.28 minutes | Standard Deviation 127.19 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 6 | -0.44 minutes | Standard Deviation 76.32 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 12 | -12.93 minutes | Standard Deviation 74.12 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Baseline | 512.07 minutes | Standard Deviation 126.37 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 12 | -11.64 minutes | Standard Deviation 75.35 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Baseline | 505.31 minutes | Standard Deviation 129.74 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 1 | 509.28 minutes | Standard Deviation 131.75 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 1 | 9.88 minutes | Standard Deviation 50.17 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 2 | 508.70 minutes | Standard Deviation 133.69 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 2 | 6.19 minutes | Standard Deviation 55.14 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 3 | 513.63 minutes | Standard Deviation 130.58 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 3 | 6.40 minutes | Standard Deviation 62.63 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 4 | 503.25 minutes | Standard Deviation 139.48 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 4 | -5.35 minutes | Standard Deviation 72.35 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 5 | 501.70 minutes | Standard Deviation 138.78 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 5 | -10.95 minutes | Standard Deviation 81.39 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 6 | 500.39 minutes | Standard Deviation 136.08 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 6 | -7.91 minutes | Standard Deviation 69.71 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 7 | 503.46 minutes | Standard Deviation 139.69 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 7 | -6.54 minutes | Standard Deviation 75.77 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 8 | 496.45 minutes | Standard Deviation 139.12 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 8 | -9.21 minutes | Standard Deviation 75.23 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 9 | 497.24 minutes | Standard Deviation 131.02 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 9 | -10.75 minutes | Standard Deviation 75.82 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 10 | 500.88 minutes | Standard Deviation 138.35 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 10 | -7.52 minutes | Standard Deviation 77.12 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 11 | 495.14 minutes | Standard Deviation 135.54 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Change from BL at Week 11 | -11.64 minutes | Standard Deviation 75.35 |
| Enalapril | Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals | Week 12 | 495.14 minutes | Standard Deviation 135.54 |
Comparison: Change from BL at Week 1p-value: 0.0008Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.0008Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.0297Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0069Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.2275Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.3486Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.68Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.7184Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.5301Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.6019Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.8229Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.8229Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Peak Six Minutes of Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 12 | 184.42 minutes | Standard Deviation 67.09 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Baseline | 189.08 minutes | Standard Deviation 67.75 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 2 | 193.54 minutes | Standard Deviation 77.3 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 2 | 6.18 minutes | Standard Deviation 46.72 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 4 | 191.86 minutes | Standard Deviation 80.21 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 4 | 5.47 minutes | Standard Deviation 50.93 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 6 | 191.21 minutes | Standard Deviation 77.38 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 6 | 2.69 minutes | Standard Deviation 42.51 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 8 | 183.96 minutes | Standard Deviation 70.54 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 8 | -2.71 minutes | Standard Deviation 41.43 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 12 | -1.07 minutes | Standard Deviation 49.32 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 12 | -2.45 minutes | Standard Deviation 39.15 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 6 | 181.11 minutes | Standard Deviation 55.07 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Baseline | 182.52 minutes | Standard Deviation 60.09 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 8 | -0.22 minutes | Standard Deviation 38.05 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 2 | 184.46 minutes | Standard Deviation 59.49 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 6 | -1.02 minutes | Standard Deviation 38.82 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 2 | 3.52 minutes | Standard Deviation 32.16 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 12 | 180.44 minutes | Standard Deviation 55.36 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 4 | 181.11 minutes | Standard Deviation 61.75 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Week 8 | 180.92 minutes | Standard Deviation 57.28 |
| Enalapril | Change From Baseline in Peak Six Minutes of Daytime Physical Activity | Change from BL at Week 4 | -0.23 minutes | Standard Deviation 40.44 |
Comparison: Change from BL at Week 2p-value: 0.4525Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0445Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.1158Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.3901Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.7725Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8
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
Population: The Full Analysis Set (FAS) and FAS population subset without AE/SAE were considered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Baseline (FAS) | 365.37 meters | Standard Deviation 108.18 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 4 (FAS) | 385.22 meters | Standard Deviation 110.55 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 4 (FAS) | 19.13 meters | Standard Deviation 49.16 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 8 (FAS) | 395.28 meters | Standard Deviation 112.05 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 8 (FAS) | 28.72 meters | Standard Deviation 57.99 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Baseline (FAS without AE/SAE) | 364.72 meters | Standard Deviation 106.86 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 4 (FAS without AE/SAE) | 384.58 meters | Standard Deviation 107.69 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 4 (FAS without AE/SAE) | 18.91 meters | Standard Deviation 49.63 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 8 (FAS without AE/SAE) | 396.64 meters | Standard Deviation 110.65 |
| LCZ696 (Sacubitril/Valsartan) | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 8 (FAS without AE/SAE) | 30.38 meters | Standard Deviation 57.07 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 4 (FAS without AE/SAE) | 14.45 meters | Standard Deviation 51.48 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Baseline (FAS) | 371.08 meters | Standard Deviation 104.41 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Baseline (FAS without AE/SAE) | 371.18 meters | Standard Deviation 105.13 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 4 (FAS) | 385.02 meters | Standard Deviation 109.92 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 8 (FAS without AE/SAE) | 21.51 meters | Standard Deviation 52.99 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 4 (FAS) | 13.72 meters | Standard Deviation 51.39 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 4 (FAS without AE/SAE) | 385.92 meters | Standard Deviation 110.81 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 8 (FAS) | 391.72 meters | Standard Deviation 108.99 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Week 8 (FAS without AE/SAE) | 391.82 meters | Standard Deviation 109.72 |
| Enalapril | Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 | Change from BL at Week 8 (FAS) | 21.15 meters | Standard Deviation 52.75 |
Comparison: Change from BL at Week 4 (FAS)p-value: 0.1814Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4 (FAS without AE/SAE)p-value: 0.3315Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8 (FAS)p-value: 0.2414Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8 (FAS without AE/SAE)p-value: 0.1793Wilcoxon (Mann-Whitney)
Secondary
Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is a little worse | 14 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is much worse | 1 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is (moderately) worse | 2 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is unchanged | 98 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is much worse | 0 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has much improved | 19 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Missing | 14 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has much improved | 23 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has much improved | 35 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is a little worse | 13 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has (moderately) improved | 72 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has (moderately) improved | 79 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has a little improved | 82 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has a little improved | 94 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is unchanged | 79 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has a little improved | 88 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is a little worse | 12 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is (moderately) worse | 3 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is (moderately) worse | 5 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is unchanged | 82 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is much worse | 2 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has (moderately) improved | 63 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Missing | 15 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Missing | 11 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Missing | 15 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has much improved | 16 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has (moderately) improved | 51 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Has a little improved | 64 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is unchanged | 131 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is a little worse | 15 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is (moderately) worse | 5 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Is much worse | 1 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 4 | Missing | 19 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has much improved | 24 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has (moderately) improved | 73 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Has a little improved | 82 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is unchanged | 88 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is a little worse | 11 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is (moderately) worse | 3 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Is much worse | 1 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 8 | Missing | 20 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has much improved | 40 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has (moderately) improved | 67 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Has a little improved | 74 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is unchanged | 94 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is a little worse | 7 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is (moderately) worse | 3 Participants |
| Enalapril | Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 | Week 12 | Is much worse | 2 Participants |
Comparison: Week 4p-value: 0.0516Chi-squared
Comparison: Week 8p-value: 0.9025Chi-squared
Comparison: Week 12p-value: 0.6713Chi-squared
Secondary
Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline
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
Population: The Full Analysis Set was considered
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | No | 175 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | Yes | 28 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | Missing | 99 Participants |
| Enalapril | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | No | 163 Participants |
| Enalapril | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | Yes | 31 Participants |
| Enalapril | Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline | Missing | 108 Participants |
Comparison: Increased levels (\>= 10% increase) of non sedentary daytime physical activity at Week 1295% CI: [0.462, 1.457]
Secondary
Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS
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
Population: The Full Analysis Set (FAS) was considered for patients with Baseline 6MWT between 100 or above and less than 450 meters.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | No | 109 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | Yes | 122 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | Missing | 7 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | No | 121 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | Yes | 105 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS | Missing | 12 Participants |
Comparison: FAS population95% CI: [0.863, 1.811]
Secondary
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
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | 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 | No | 103 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Yes | 122 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Missing | 5 Participants |
| Enalapril | 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 | No | 115 Participants |
| Enalapril | 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 | Yes | 105 Participants |
| Enalapril | 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 | Missing | 11 Participants |
Comparison: FAS subset without AE/SAE95% CI: [0.865, 1.834]
Secondary
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
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
Population: The Full Analysis Set (FAS) was considered for patients with Baseline 6MWT equal to or less than 300 meters.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | 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 | No | 35 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Yes | 41 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Missing | 2 Participants |
| Enalapril | 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 | No | 31 Participants |
| Enalapril | 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 | Yes | 29 Participants |
| Enalapril | 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 | Missing | 5 Participants |
Comparison: FAS population95% CI: [0.634, 2.464]
Secondary
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
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | 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 | No | 33 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Yes | 41 Participants |
| LCZ696 (Sacubitril/Valsartan) | 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 | Missing | 1 Participants |
| Enalapril | 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 | No | 30 Participants |
| Enalapril | 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 | Yes | 29 Participants |
| Enalapril | 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 | Missing | 4 Participants |
Comparison: FAS subset without AE/SAE95% CI: [0.644, 2.544]
Secondary
Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS
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
Population: The Full Analysis Set (FAS) was considered.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | No | 142 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | Yes | 149 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | Missing | 11 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | No | 153 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | Yes | 129 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS | Missing | 20 Participants |
Comparison: FAS population95% CI: [0.882, 1.708]
Secondary
Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE
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
Population: The Full Analysis Set (FAS) population subset without AE/SAE was considered.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | No | 133 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | Yes | 149 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | Missing | 8 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | No | 146 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | Yes | 129 Participants |
| Enalapril | Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE | Missing | 19 Participants |
Comparison: FAS subset without AE/SAE95% CI: [0.895, 1.748]
Secondary
Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Improvement | 189 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Is unchanged | 98 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Gets worse | 19 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Gets worse | 17 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Missing | 14 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Missing | 11 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Missing | 15 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Improvement | 190 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Is unchanged | 79 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Is unchanged | 82 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Improvement | 176 Participants |
| LCZ696 (Sacubitril/Valsartan) | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Gets worse | 16 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Improvement | 131 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Missing | 20 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Improvement | 181 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Is unchanged | 94 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Gets worse | 12 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 12 | Missing | 15 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Gets worse | 15 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Is unchanged | 131 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Gets worse | 21 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 4 | Missing | 19 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Improvement | 179 Participants |
| Enalapril | Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA) | Week 8 | Is unchanged | 88 Participants |
Comparison: Week 4p-value: 0.0029Chi-squared
Comparison: Week 8p-value: 0.7754Chi-squared
Comparison: Week 12p-value: 0.2172Chi-squared
Secondary
Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -17.85 minutes | Standard Deviation 290.75 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 46.05 minutes | Standard Deviation 281.11 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 7 | 1747.03 minutes | Standard Deviation 366.43 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 2 | 1823.86 minutes | Standard Deviation 396.55 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -32.03 minutes | Standard Deviation 307.16 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 4 | 1778.88 minutes | Standard Deviation 372.86 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 8 | 1750.02 minutes | Standard Deviation 377.35 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -37.50 minutes | Standard Deviation 323.19 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Baseline | 1773.14 minutes | Standard Deviation 392.22 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 9 | 1746.73 minutes | Standard Deviation 375.07 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | 9.17 minutes | Standard Deviation 275.92 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -36.47 minutes | Standard Deviation 289.67 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 46.26 minutes | Standard Deviation 301.74 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 10 | 1724.72 minutes | Standard Deviation 395.95 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 5 | 1745.87 minutes | Standard Deviation 406.21 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -46.95 minutes | Standard Deviation 339.81 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 81.84 minutes | Standard Deviation 255.91 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 11 | 1717.08 minutes | Standard Deviation 386.33 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -36.66 minutes | Standard Deviation 307.01 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -60.08 minutes | Standard Deviation 319.85 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 3 | 1826.38 minutes | Standard Deviation 376.72 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 12 | 1559.62 minutes | Standard Deviation 428.02 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 6 | 1759.09 minutes | Standard Deviation 397.67 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -210.49 minutes | Standard Deviation 390.17 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 1 | 1834.71 minutes | Standard Deviation 400.46 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -144.96 minutes | Standard Deviation 339.29 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Baseline | 1721.50 minutes | Standard Deviation 452.26 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 1 | 1757.76 minutes | Standard Deviation 407.14 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 53.74 minutes | Standard Deviation 282.22 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 2 | 1736.64 minutes | Standard Deviation 407.45 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 17.26 minutes | Standard Deviation 280.12 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 3 | 1751.95 minutes | Standard Deviation 410.11 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 24.88 minutes | Standard Deviation 313.52 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 4 | 1707.68 minutes | Standard Deviation 410.73 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -18.74 minutes | Standard Deviation 346.02 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 5 | 1683.08 minutes | Standard Deviation 429.5 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -37.98 minutes | Standard Deviation 369.53 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 6 | 1701.89 minutes | Standard Deviation 405.01 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -16.56 minutes | Standard Deviation 343.51 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 7 | 1702.58 minutes | Standard Deviation 399.11 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -17.71 minutes | Standard Deviation 322.33 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -17.49 minutes | Standard Deviation 318.83 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 9 | 1706.26 minutes | Standard Deviation 407.89 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -43.21 minutes | Standard Deviation 341.3 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 10 | 1712.55 minutes | Standard Deviation 412.82 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -22.01 minutes | Standard Deviation 314.65 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 11 | 1697.81 minutes | Standard Deviation 429.44 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -40.52 minutes | Standard Deviation 313.76 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 12 | 1607.33 minutes | Standard Deviation 449.83 |
| Enalapril | Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity | Week 8 | 1705.09 minutes | Standard Deviation 424.99 |
Comparison: Change from BL at Week 1p-value: 0.0061Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.0143Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.0708Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.075Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.8017Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.7956Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.3499Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.1192Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.5237Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.3902Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.4228Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.1571Wilcoxon (Mann-Whitney)
Secondary
Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -296.33 minutes | Standard Deviation 525.81 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Baseline | 1843.73 minutes | Standard Deviation 830.3 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 1 | 1841.76 minutes | Standard Deviation 769.54 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 21.45 minutes | Standard Deviation 373.16 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 2 | 1867.37 minutes | Standard Deviation 806.56 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 3 | 1841.87 minutes | Standard Deviation 755.88 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | -20.77 minutes | Standard Deviation 425.19 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 4 | 1829.51 minutes | Standard Deviation 801.93 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -4.07 minutes | Standard Deviation 344.29 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 5 | 1742.56 minutes | Standard Deviation 767.53 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -80.08 minutes | Standard Deviation 423.07 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 6 | 1760.03 minutes | Standard Deviation 763.64 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -54.23 minutes | Standard Deviation 416.05 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 7 | 1697.49 minutes | Standard Deviation 732.18 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -111.35 minutes | Standard Deviation 438.85 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 8 | 1716.80 minutes | Standard Deviation 769.31 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -93.09 minutes | Standard Deviation 429.65 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 9 | 1723.96 minutes | Standard Deviation 750.6 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -94.81 minutes | Standard Deviation 407.63 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 10 | 1720.06 minutes | Standard Deviation 760.72 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -72.46 minutes | Standard Deviation 442.8 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 11 | 1689.48 minutes | Standard Deviation 731.77 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -110.06 minutes | Standard Deviation 432.47 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 12 | 1534.35 minutes | Standard Deviation 678.12 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 29.97 minutes | Standard Deviation 383.31 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -79.83 minutes | Standard Deviation 516.05 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -194.19 minutes | Standard Deviation 564.53 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -5.17 minutes | Standard Deviation 509.74 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Baseline | 1807.07 minutes | Standard Deviation 815.89 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -65.27 minutes | Standard Deviation 492.38 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 1 | 1802.34 minutes | Standard Deviation 775.36 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 7 | 1800.09 minutes | Standard Deviation 829.37 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 28.75 minutes | Standard Deviation 404.2 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 11 | 1739.15 minutes | Standard Deviation 803.36 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 2 | 1821.07 minutes | Standard Deviation 813.27 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 35.13 minutes | Standard Deviation 432.43 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -18.47 minutes | Standard Deviation 505.11 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 3 | 1828.59 minutes | Standard Deviation 777.65 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 10 | 1777.14 minutes | Standard Deviation 811.27 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 9.68 minutes | Standard Deviation 458.99 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 8 | 1752.65 minutes | Standard Deviation 802.46 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 4 | 1774.46 minutes | Standard Deviation 815.93 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 12 | 1627.57 minutes | Standard Deviation 778.7 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -37.49 minutes | Standard Deviation 506.27 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -42.43 minutes | Standard Deviation 522.8 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 5 | 1775.57 minutes | Standard Deviation 798.92 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -46.92 minutes | Standard Deviation 514.49 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -41.20 minutes | Standard Deviation 577.49 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 9 | 1741.02 minutes | Standard Deviation 757.26 |
| Enalapril | Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity | Week 6 | 1787.26 minutes | Standard Deviation 810.3 |
Comparison: Change from BL at Week 1p-value: 0.3231Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.3519Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.8335Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0465Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.5016Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.5941Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.2019Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.4125Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.5702Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.4752Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.5343Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.0985Wilcoxon (Mann-Whitney)
Secondary
Total Weekly Time Spent in Non-sedentary Daytime Physical Activity
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
Population: The Full Analysis Set was considered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 4 | 3608.39 minutes | Standard Deviation 936.87 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 103.29 minutes | Standard Deviation 509.2 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 2 | 3691.24 minutes | Standard Deviation 953.03 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 76.23 minutes | Standard Deviation 563.79 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 3 | 3668.25 minutes | Standard Deviation 894.91 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 25.28 minutes | Standard Deviation 571.36 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -131.28 minutes | Standard Deviation 549.54 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | 5.10 minutes | Standard Deviation 497.55 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 5 | 3488.43 minutes | Standard Deviation 944.87 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -116.74 minutes | Standard Deviation 607.31 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 6 | 3519.12 minutes | Standard Deviation 922.58 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -72.08 minutes | Standard Deviation 569.61 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Baseline | 3616.87 minutes | Standard Deviation 964.92 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 1 | 3676.46 minutes | Standard Deviation 923.85 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 7 | 3444.52 minutes | Standard Deviation 892.15 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -143.38 minutes | Standard Deviation 605.25 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 8 | 3466.82 minutes | Standard Deviation 936.51 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -130.59 minutes | Standard Deviation 631.3 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 9 | 3470.69 minutes | Standard Deviation 913.06 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 10 | 3444.77 minutes | Standard Deviation 947.18 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -119.41 minutes | Standard Deviation 648.17 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 11 | 3406.56 minutes | Standard Deviation 910.84 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -170.14 minutes | Standard Deviation 632.53 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 12 | 3093.96 minutes | Standard Deviation 913.14 |
| LCZ696 (Sacubitril/Valsartan) | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -506.82 minutes | Standard Deviation 792.71 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 12 | 3234.90 minutes | Standard Deviation 991.5 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 1 | 3560.10 minutes | Standard Deviation 916.16 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 6 | -21.73 minutes | Standard Deviation 724.96 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 1 | 82.48 minutes | Standard Deviation 588.19 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 10 | 3489.68 minutes | Standard Deviation 964.08 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 2 | 3557.71 minutes | Standard Deviation 940.6 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 7 | 3502.67 minutes | Standard Deviation 977.43 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 2 | 52.38 minutes | Standard Deviation 600.08 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 11 | -120.35 minutes | Standard Deviation 707.11 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 3 | 3580.54 minutes | Standard Deviation 922.7 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 7 | -36.18 minutes | Standard Deviation 709.43 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 3 | 34.56 minutes | Standard Deviation 663.68 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 10 | -68.93 minutes | Standard Deviation 711.22 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 4 | 3482.15 minutes | Standard Deviation 991.15 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 8 | 3457.74 minutes | Standard Deviation 993.56 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 4 | -56.23 minutes | Standard Deviation 748.35 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 12 | -339.15 minutes | Standard Deviation 786.06 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 5 | 3458.65 minutes | Standard Deviation 973.75 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 8 | -59.92 minutes | Standard Deviation 716.74 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 5 | -79.18 minutes | Standard Deviation 817.71 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 11 | 3436.96 minutes | Standard Deviation 971.78 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 6 | 3489.15 minutes | Standard Deviation 962.55 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Week 9 | 3447.28 minutes | Standard Deviation 932.67 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Change from BL at Week 9 | -108.48 minutes | Standard Deviation 719.58 |
| Enalapril | Total Weekly Time Spent in Non-sedentary Daytime Physical Activity | Baseline | 3528.56 minutes | Standard Deviation 993.1 |
Comparison: Change from BL at Week 1p-value: 0.0065Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 2p-value: 0.0316Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 3p-value: 0.1342Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 4p-value: 0.0252Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 5p-value: 0.9024Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 6p-value: 0.9052Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 7p-value: 0.287Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 8p-value: 0.3174Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 9p-value: 0.502Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 10p-value: 0.4037Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 11p-value: 0.4823Wilcoxon (Mann-Whitney)
Comparison: Change from BL at Week 12p-value: 0.109Wilcoxon (Mann-Whitney)