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Trial record 87 of 134 for:    OLMESARTAN

Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension

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ClinicalTrials.gov Identifier: NCT01692301
Recruitment Status : Completed
First Posted : September 25, 2012
Results First Posted : May 4, 2016
Last Update Posted : May 4, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: LCZ696
Drug: Olmesartan
Drug: LCZ696 matching placebo
Drug: Olmesartan matching placebo
Drug: amlodipine
Drug: hydrochlorothiazide
Enrollment 454
Recruitment Details  
Pre-assignment Details  
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 229 [1] 225
Completed 184 183
Not Completed 45 42
Reason Not Completed
Adverse Event             15             12
Death             1             2
Lack of Efficacy             0             5
Non-compliance with study treatment             1             2
Protocol deviation             9             2
Patient/guardian decision             16             15
Technical problems             0             1
Physician Decision             2             2
Lost to Follow-up             1             1
[1]
"Started" indicates patients in randomized, full analysis and safety set
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 229 225 454
Hide Baseline Analysis Population Description
Full analysis set - All patients who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 229 participants 225 participants 454 participants
68.2  (5.73) 67.2  (5.97) 67.7  (5.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 229 participants 225 participants 454 participants
Female
110
  48.0%
107
  47.6%
217
  47.8%
Male
119
  52.0%
118
  52.4%
237
  52.2%
1.Primary Outcome
Title Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
Hide Description

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.

Time Frame baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 207 206
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.57  (1.01) -8.90  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCZ696 (Sacubitril/Valsartan), Olmesartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.66
Confidence Interval (2-Sided) 95%
-6.45 to -0.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.42
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Central Pulse (CPP) Pressure
Hide Description [Not Specified]
Time Frame Baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to Week 12 (n = 207, 206) -6.41  (0.69) -3.96  (0.69)
Baseline to Week 52 (n = 209, 208) -7.16  (0.69) -6.65  (0.69)
3.Secondary Outcome
Title Change From Baseline in Mean Pulse Wave Velocity (PWV)
Hide Description

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.

Time Frame baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: meter/second
Baseline to week 12 (n= 192, 196) -0.68  (0.12) -0.57  (0.12)
Baseline to week 52 ( n= 199, 199) -0.83  (0.13) 0.77  (0.13)
4.Secondary Outcome
Title Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks
Hide Description

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.

Time Frame baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 209 208
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-16.18  (0.96) -14.70  (0.96)
5.Secondary Outcome
Title Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Hide Description 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.
Time Frame baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n=226, 222) -20.84  (1.06) -14.57  (1.07)
Baseline to week 52 (n=226,223) -23.91  (0.98) -21.45  (0.99)
6.Secondary Outcome
Title Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Hide Description 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.
Time Frame baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n=226, 222) -7.86  (0.58) -5.58  (0.59)
Baseline to week 52 (n=226,223) -8.92  (0.57) -7.85  (0.57)
7.Secondary Outcome
Title Change From Baseline in Mean Sitting Pulse Pressure (msPP)
Hide Description 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.
Time Frame baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n=226,222) -13.13  (0.82) -8.86  (0.82)
Baseline to week 52 (n= 226, 223) -15.02  (0.79) -13.58  (0.80)
8.Secondary Outcome
Title Change From Baseline in Mean Arterial Pressure (MAP)
Hide Description Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.
Time Frame baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n=226, 222) -12.19  (0.68) -8.57  (0.68)
Baseline to week 52 (n=226, 223) -13.92  (0.63) -12.38  (0.64)
9.Secondary Outcome
Title Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)
Hide Description 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.
Time Frame Baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n= 164, 162) -13.25  (0.62) -9.14  (0.62)
Baseline to week 52 (n= 174, 176) -14.15  (0.59) -14.32  (0.58)
10.Secondary Outcome
Title Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)
Hide Description 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.
Time Frame Baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to week 12 (n= 164, 162) -7.44  (0.37) -5.48  (0.36)
Baseline to week 52 (n= 174, 176) -8.85  (0.35) -8.44  (0.34)
11.Secondary Outcome
Title Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)
Hide Description 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.
Time Frame Baseline, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 229 225
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Baseline to Week 12 (n=164, 162 ) -5.77  (0.35) -3.69  (0.35)
Baseline to week 52 (n=174, 176) -5.26  (0.36) -5.91  (0.35)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LCZ696 (Sacubitril/Valsartan) Olmesartan
Hide Arm/Group Description 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. 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.
All-Cause Mortality
LCZ696 (Sacubitril/Valsartan) Olmesartan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
LCZ696 (Sacubitril/Valsartan) Olmesartan
Affected / at Risk (%) Affected / at Risk (%)
Total   16/229 (6.99%)   13/225 (5.78%) 
Blood and lymphatic system disorders     
ANAEMIA  1  1/229 (0.44%)  0/225 (0.00%) 
COAGULOPATHY  1  1/229 (0.44%)  0/225 (0.00%) 
IRON DEFICIENCY ANAEMIA  1  1/229 (0.44%)  0/225 (0.00%) 
Cardiac disorders     
ACUTE CORONARY SYNDROME  1  0/229 (0.00%)  1/225 (0.44%) 
ACUTE MYOCARDIAL INFARCTION  1  0/229 (0.00%)  1/225 (0.44%) 
ANGINA PECTORIS  1  0/229 (0.00%)  1/225 (0.44%) 
ANGINA UNSTABLE  1  0/229 (0.00%)  1/225 (0.44%) 
ATRIAL FIBRILLATION  1  2/229 (0.87%)  1/225 (0.44%) 
CARDIO-RESPIRATORY ARREST  1  0/229 (0.00%)  1/225 (0.44%) 
MYOCARDIAL INFARCTION  1  1/229 (0.44%)  0/225 (0.00%) 
SUPRAVENTRICULAR TACHYCARDIA  1  1/229 (0.44%)  0/225 (0.00%) 
Eye disorders     
CATARACT  1  1/229 (0.44%)  0/225 (0.00%) 
Gastrointestinal disorders     
INGUINAL HERNIA  1  1/229 (0.44%)  0/225 (0.00%) 
Hepatobiliary disorders     
CHOLECYSTITIS CHRONIC  1  1/229 (0.44%)  0/225 (0.00%) 
CHOLELITHIASIS  1  1/229 (0.44%)  0/225 (0.00%) 
Infections and infestations     
APPENDICITIS  1  1/229 (0.44%)  0/225 (0.00%) 
DOUGLAS' ABSCESS  1  1/229 (0.44%)  0/225 (0.00%) 
PERITONITIS  1  1/229 (0.44%)  0/225 (0.00%) 
Injury, poisoning and procedural complications     
HIP FRACTURE  1  0/229 (0.00%)  1/225 (0.44%) 
PULMONARY CONTUSION  1  0/229 (0.00%)  1/225 (0.44%) 
RIB FRACTURE  1  0/229 (0.00%)  2/225 (0.89%) 
ROAD TRAFFIC ACCIDENT  1  1/229 (0.44%)  0/225 (0.00%) 
SPINAL FRACTURE  1  0/229 (0.00%)  1/225 (0.44%) 
SUBDURAL HAEMORRHAGE  1  0/229 (0.00%)  1/225 (0.44%) 
TENDON RUPTURE  1  0/229 (0.00%)  1/225 (0.44%) 
UPPER LIMB FRACTURE  1  1/229 (0.44%)  0/225 (0.00%) 
VASCULAR GRAFT OCCLUSION  1  1/229 (0.44%)  0/225 (0.00%) 
Investigations     
BLOOD PRESSURE INCREASED  1  1/229 (0.44%)  0/225 (0.00%) 
Musculoskeletal and connective tissue disorders     
OSTEOCHONDROSIS  1  1/229 (0.44%)  0/225 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
SQUAMOUS CELL CARCINOMA  1  1/229 (0.44%)  0/225 (0.00%) 
Nervous system disorders     
BRAIN STEM INFARCTION  1  0/229 (0.00%)  1/225 (0.44%) 
ISCHAEMIC STROKE  1  1/229 (0.44%)  0/225 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
ATELECTASIS  1  1/229 (0.44%)  0/225 (0.00%) 
PNEUMOTHORAX  1  0/229 (0.00%)  1/225 (0.44%) 
PULMONARY EMBOLISM  1  1/229 (0.44%)  0/225 (0.00%) 
PULMONARY PNEUMATOCELE  1  0/229 (0.00%)  1/225 (0.44%) 
RESPIRATORY FAILURE  1  0/229 (0.00%)  1/225 (0.44%) 
Vascular disorders     
HYPERTENSIVE CRISIS  1  0/229 (0.00%)  1/225 (0.44%) 
ORTHOSTATIC HYPOTENSION  1  1/229 (0.44%)  0/225 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
LCZ696 (Sacubitril/Valsartan) Olmesartan
Affected / at Risk (%) Affected / at Risk (%)
Total   73/229 (31.88%)   55/225 (24.44%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  5/229 (2.18%)  1/225 (0.44%) 
DIARRHOEA  1  6/229 (2.62%)  5/225 (2.22%) 
NAUSEA  1  5/229 (2.18%)  2/225 (0.89%) 
General disorders     
OEDEMA PERIPHERAL  1  6/229 (2.62%)  2/225 (0.89%) 
Infections and infestations     
INFLUENZA  1  7/229 (3.06%)  5/225 (2.22%) 
NASOPHARYNGITIS  1  16/229 (6.99%)  12/225 (5.33%) 
UPPER RESPIRATORY TRACT INFECTION  1  6/229 (2.62%)  6/225 (2.67%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  5/229 (2.18%)  7/225 (3.11%) 
BACK PAIN  1  3/229 (1.31%)  10/225 (4.44%) 
Nervous system disorders     
DIZZINESS  1  12/229 (5.24%)  12/225 (5.33%) 
HEADACHE  1  14/229 (6.11%)  10/225 (4.44%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  10/229 (4.37%)  2/225 (0.89%) 
Vascular disorders     
HYPOTENSION  1  2/229 (0.87%)  5/225 (2.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Directors
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01692301     History of Changes
Other Study ID Numbers: CLCZ696A2216
2012-002899-14 ( EudraCT Number )
First Submitted: September 20, 2012
First Posted: September 25, 2012
Results First Submitted: March 31, 2016
Results First Posted: May 4, 2016
Last Update Posted: May 4, 2016