Trial Outcomes & Findings for Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension (NCT NCT01692301)
NCT ID: NCT01692301
Last Updated: 2016-05-04
Results Overview
Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software. At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
COMPLETED
PHASE2
454 participants
baseline, 12 weeks
2016-05-04
Participant Flow
Participant milestones
| Measure |
LCZ696 (Sacubitril/Valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Overall Study
STARTED
|
229
|
225
|
|
Overall Study
COMPLETED
|
184
|
183
|
|
Overall Study
NOT COMPLETED
|
45
|
42
|
Reasons for withdrawal
| Measure |
LCZ696 (Sacubitril/Valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
12
|
|
Overall Study
Death
|
1
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
5
|
|
Overall Study
Non-compliance with study treatment
|
1
|
2
|
|
Overall Study
Protocol deviation
|
9
|
2
|
|
Overall Study
Patient/guardian decision
|
16
|
15
|
|
Overall Study
Technical problems
|
0
|
1
|
|
Overall Study
Physician Decision
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension
Baseline characteristics by cohort
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
Total
n=454 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68.2 Years
STANDARD_DEVIATION 5.73 • n=93 Participants
|
67.2 Years
STANDARD_DEVIATION 5.97 • n=4 Participants
|
67.7 Years
STANDARD_DEVIATION 5.87 • n=27 Participants
|
|
Sex: Female, Male
Female
|
110 Participants
n=93 Participants
|
107 Participants
n=4 Participants
|
217 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
119 Participants
n=93 Participants
|
118 Participants
n=4 Participants
|
237 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: baseline, 12 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12).
Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software. At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=207 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=206 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
|
-12.57 mmHg
Standard Error 1.01
|
-8.90 mmHg
Standard Error 1.01
|
SECONDARY outcome
Timeframe: Baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12, week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Central Pulse (CPP) Pressure
Baseline to Week 12 (n = 207, 206)
|
-6.41 mmHg
Standard Error 0.69
|
-3.96 mmHg
Standard Error 0.69
|
|
Change From Baseline in Mean Central Pulse (CPP) Pressure
Baseline to Week 52 (n = 209, 208)
|
-7.16 mmHg
Standard Error 0.69
|
-6.65 mmHg
Standard Error 0.69
|
SECONDARY outcome
Timeframe: baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12 , week 52).
Pulse wave velocity recordings were performed on patient while in a supine, face-up position. Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Pulse Wave Velocity (PWV)
Baseline to week 12 (n= 192, 196)
|
-0.68 meter/second
Standard Error 0.12
|
-0.57 meter/second
Standard Error 0.12
|
|
Change From Baseline in Mean Pulse Wave Velocity (PWV)
Baseline to week 52 ( n= 199, 199)
|
-0.83 meter/second
Standard Error 0.13
|
0.77 meter/second
Standard Error 0.13
|
SECONDARY outcome
Timeframe: baseline, 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis.
Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software. At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=209 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=208 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks
|
-16.18 mmHg
Standard Error 0.96
|
-14.70 mmHg
Standard Error 0.96
|
SECONDARY outcome
Timeframe: baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Baseline to week 12 (n=226, 222)
|
-20.84 mmHg
Standard Error 1.06
|
-14.57 mmHg
Standard Error 1.07
|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Baseline to week 52 (n=226,223)
|
-23.91 mmHg
Standard Error 0.98
|
-21.45 mmHg
Standard Error 0.99
|
SECONDARY outcome
Timeframe: baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Baseline to week 12 (n=226, 222)
|
-7.86 mmHg
Standard Error 0.58
|
-5.58 mmHg
Standard Error 0.59
|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Baseline to week 52 (n=226,223)
|
-8.92 mmHg
Standard Error 0.57
|
-7.85 mmHg
Standard Error 0.57
|
SECONDARY outcome
Timeframe: baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Sitting Pulse Pressure (msPP)
Baseline to week 12 (n=226,222)
|
-13.13 mmHg
Standard Error 0.82
|
-8.86 mmHg
Standard Error 0.82
|
|
Change From Baseline in Mean Sitting Pulse Pressure (msPP)
Baseline to week 52 (n= 226, 223)
|
-15.02 mmHg
Standard Error 0.79
|
-13.58 mmHg
Standard Error 0.80
|
SECONDARY outcome
Timeframe: baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 \* msDBP + msSBP)/3.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean Arterial Pressure (MAP)
Baseline to week 12 (n=226, 222)
|
-12.19 mmHg
Standard Error 0.68
|
-8.57 mmHg
Standard Error 0.68
|
|
Change From Baseline in Mean Arterial Pressure (MAP)
Baseline to week 52 (n=226, 223)
|
-13.92 mmHg
Standard Error 0.63
|
-12.38 mmHg
Standard Error 0.64
|
SECONDARY outcome
Timeframe: Baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)
Baseline to week 12 (n= 164, 162)
|
-13.25 mmHg
Standard Error 0.62
|
-9.14 mmHg
Standard Error 0.62
|
|
Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)
Baseline to week 52 (n= 174, 176)
|
-14.15 mmHg
Standard Error 0.59
|
-14.32 mmHg
Standard Error 0.58
|
SECONDARY outcome
Timeframe: Baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)
Baseline to week 12 (n= 164, 162)
|
-7.44 mmHg
Standard Error 0.37
|
-5.48 mmHg
Standard Error 0.36
|
|
Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)
Baseline to week 52 (n= 174, 176)
|
-8.85 mmHg
Standard Error 0.35
|
-8.44 mmHg
Standard Error 0.34
|
SECONDARY outcome
Timeframe: Baseline, 12 weeks, and 52 weeksPopulation: Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).
Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.
Outcome measures
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 Participants
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 Participants
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)
Baseline to Week 12 (n=164, 162 )
|
-5.77 mmHg
Standard Error 0.35
|
-3.69 mmHg
Standard Error 0.35
|
|
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)
Baseline to week 52 (n=174, 176)
|
-5.26 mmHg
Standard Error 0.36
|
-5.91 mmHg
Standard Error 0.35
|
Adverse Events
LCZ696 (Sacubitril/Valsartan)
Olmesartan
Serious adverse events
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 participants at risk
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 participants at risk
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
0.00%
0/229
|
0.44%
1/225
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.00%
0/229
|
0.44%
1/225
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/229
|
0.44%
1/225
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.00%
0/229
|
0.44%
1/225
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.87%
2/229
|
0.44%
1/225
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.00%
0/229
|
0.44%
1/225
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.44%
1/229
|
0.00%
0/225
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.44%
1/229
|
0.00%
0/225
|
|
Eye disorders
CATARACT
|
0.44%
1/229
|
0.00%
0/225
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.44%
1/229
|
0.00%
0/225
|
|
Hepatobiliary disorders
CHOLECYSTITIS CHRONIC
|
0.44%
1/229
|
0.00%
0/225
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.44%
1/229
|
0.00%
0/225
|
|
Infections and infestations
APPENDICITIS
|
0.44%
1/229
|
0.00%
0/225
|
|
Infections and infestations
DOUGLAS' ABSCESS
|
0.44%
1/229
|
0.00%
0/225
|
|
Infections and infestations
PERITONITIS
|
0.44%
1/229
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.00%
0/229
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
PULMONARY CONTUSION
|
0.00%
0/229
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.00%
0/229
|
0.89%
2/225
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.44%
1/229
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
SPINAL FRACTURE
|
0.00%
0/229
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
SUBDURAL HAEMORRHAGE
|
0.00%
0/229
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
TENDON RUPTURE
|
0.00%
0/229
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.44%
1/229
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
VASCULAR GRAFT OCCLUSION
|
0.44%
1/229
|
0.00%
0/225
|
|
Investigations
BLOOD PRESSURE INCREASED
|
0.44%
1/229
|
0.00%
0/225
|
|
Musculoskeletal and connective tissue disorders
OSTEOCHONDROSIS
|
0.44%
1/229
|
0.00%
0/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.44%
1/229
|
0.00%
0/225
|
|
Nervous system disorders
BRAIN STEM INFARCTION
|
0.00%
0/229
|
0.44%
1/225
|
|
Nervous system disorders
ISCHAEMIC STROKE
|
0.44%
1/229
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
ATELECTASIS
|
0.44%
1/229
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX
|
0.00%
0/229
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.44%
1/229
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY PNEUMATOCELE
|
0.00%
0/229
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/229
|
0.44%
1/225
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.00%
0/229
|
0.44%
1/225
|
|
Vascular disorders
ORTHOSTATIC HYPOTENSION
|
0.44%
1/229
|
0.00%
0/225
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.44%
1/229
|
0.00%
0/225
|
|
Blood and lymphatic system disorders
COAGULOPATHY
|
0.44%
1/229
|
0.00%
0/225
|
|
Blood and lymphatic system disorders
IRON DEFICIENCY ANAEMIA
|
0.44%
1/229
|
0.00%
0/225
|
Other adverse events
| Measure |
LCZ696 (Sacubitril/Valsartan)
n=229 participants at risk
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
|
Olmesartan
n=225 participants at risk
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
|
|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.2%
5/229
|
0.44%
1/225
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.6%
6/229
|
2.2%
5/225
|
|
Gastrointestinal disorders
NAUSEA
|
2.2%
5/229
|
0.89%
2/225
|
|
General disorders
OEDEMA PERIPHERAL
|
2.6%
6/229
|
0.89%
2/225
|
|
Infections and infestations
INFLUENZA
|
3.1%
7/229
|
2.2%
5/225
|
|
Infections and infestations
NASOPHARYNGITIS
|
7.0%
16/229
|
5.3%
12/225
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
2.6%
6/229
|
2.7%
6/225
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.2%
5/229
|
3.1%
7/225
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.3%
3/229
|
4.4%
10/225
|
|
Nervous system disorders
DIZZINESS
|
5.2%
12/229
|
5.3%
12/225
|
|
Nervous system disorders
HEADACHE
|
6.1%
14/229
|
4.4%
10/225
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
4.4%
10/229
|
0.89%
2/225
|
|
Vascular disorders
HYPOTENSION
|
0.87%
2/229
|
2.2%
5/225
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER