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A Study to Evaluate the Effect of LCZ696 on Aortic Stiffness in Subjects With Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01870739
Recruitment Status : Completed
First Posted : June 6, 2013
Results First Posted : September 1, 2016
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: sacubitril/valsartan (LCZ696)
Drug: olmesartan
Other: placebo to sacubitril/valsartan (LCZ696)
Other: placebo to olmesartan
Drug: Amlodipine (Optional)
Enrollment 115
Recruitment Details

A total of 115 patients were enrolled. One patient was discontinued after randomization before receiving any dose of study randomized medication.

A total of 114 patients received study randomized medication

Pre-assignment Details  
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target) Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Period Title: Single Drug Treatment (12 Weeks)
Started 57 [1] 57
Initiation Dose Completed 57 56
Maintenance Dose Started 57 56
Completed 54 [2] 53
Not Completed 3 4
Reason Not Completed
Protocol deviation             0             1
Adverse Event             0             1
Administrative problems             3             2
[1]
"Start" = Safety/Pharmacokinetic/Pharmacodynamic analysis set
[2]
"Completed" indicates maintenance dose complete
Period Title: Add-on Period (40 Weeks)
Started 54 53
Completed 51 51
Not Completed 3 2
Reason Not Completed
Adverse Event             0             1
Unsatisfactory therapeutic effect             1             0
Protocol deviation             1             1
Patient withdrew consent             1             0
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan Total
Hide Arm/Group Description LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target) Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target) Total of all reporting groups
Overall Number of Baseline Participants 57 57 114
Hide Baseline Analysis Population Description
Safety analysis set: All patients that received study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 57 participants 114 participants
60.5  (7.8) 59.2  (13.1) 59.8  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 57 participants 114 participants
Female
20
  35.1%
17
  29.8%
37
  32.5%
Male
37
  64.9%
40
  70.2%
77
  67.5%
1.Primary Outcome
Title Change From Baseline in Ascending Aorta Distensibility at 52 Week
Hide Description Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Ascending aorta distensibility was one of the 3 components for measuring local arota distensibility.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 49 53
Least Squares Mean (Standard Error)
Unit of Measure: 10^(-3) x mmHg^(-1)
0.269  (0.1283) 0.330  (0.1233)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sacubitril/Valsartan (LCZ696), Olmesartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7324
Comments [Not Specified]
Method Linear Model
Comments Treatment as fixed effect and corresponding baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0616
Confidence Interval (2-Sided) 95%
-0.4178 to 0.2947
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Proximal Descending Aorta Distensibility at 52 Weeks
Hide Description Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Proximal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 49 53
Least Squares Mean (Standard Error)
Unit of Measure: 10^(-3) x mmHg^(-1)
0.510  (0.1528) 0.547  (0.1469)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sacubitril/Valsartan (LCZ696), Olmesartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8614
Comments [Not Specified]
Method Linear Model
Comments Treatment as a fixed effect and corresponding baseline as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0371
Confidence Interval (2-Sided) 95%
-0.4582 to 0.3839
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Distal Descending Aorta Distensibility at 52 Weeks
Hide Description Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Distal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 49 53
Least Squares Mean (Standard Error)
Unit of Measure: 10^(-3) x mmHg^(-1)
0.417  (0.2242) 0.498  (0.2156)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sacubitril/Valsartan (LCZ696), Olmesartan
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7946
Comments [Not Specified]
Method Linear Model
Comments Treatment as a fixed effect and corresponding baseline as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0812
Confidence Interval (2-Sided) 95%
-0.6987 to 0.5362
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Local Aortic Strain at 52 Weeks
Hide Description Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic strain. Local aortic strain was measured by assessing ascending aorta strain, proximal descending aorta strain and distal descending aorta strain.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 49 53
Least Squares Mean (Standard Error)
Unit of Measure: percent
Ascending Aorta Strain -0.830  (0.7903) 0.453  (0.7598)
Proximal Descending Aorta Strain -0.284  (0.8940) -0.066  (0.8596)
Distal Descending Aorta Strain -1.092  (1.0956) 0.225  (1.0533)
5.Secondary Outcome
Title Change From Baseline in Regional Aortic Pulse Wave Velocity at 52 Weeks
Hide Description Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of regional aortic pulse wave velocity.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 49 53
Least Squares Mean (Standard Error)
Unit of Measure: meters per second (m/s)
-2.086  (0.5029) -1.085  (0.4835)
6.Secondary Outcome
Title Change From Baseline in Central Blood Pressure at 52 Weeks
Hide Description Central blood pressure was determined by measuring central systolic blood pressure , diastolic blood pressure and pulse pressure.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 50 50
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Central systolic blood pressure -16.655  (1.4968) -13.625  (1.4968)
Central diastolic blood pressure -10.318  (1.0578) -10.432  (1.0578)
Central pulse pressure -6.539  (0.9428) -3.041  (0.9428)
7.Secondary Outcome
Title Change From Baseline in Augmentation Pressure at 52 Weeks
Hide Description Augmentation pressure is the added pressure during systole due to wave reflection.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis.
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 50 50
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-2.443  (0.5950) -1.437  (0.5950)
8.Secondary Outcome
Title Change From Baseline in Augmentation Index at 52 Weeks
Hide Description Augmentation index (Alx) is the percentage of the central pulse pressure due to wave reflection.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 50 50
Least Squares Mean (Standard Error)
Unit of Measure: percent
-2.385  (1.1805) -1.515  (1.1805)
9.Secondary Outcome
Title Change From Baseline in Carotid-femoral Pulse Wave Velocity at 52 Weeks
Hide Description For pulse wave velocity calculation, the pressure waveform at the femoral site (using a partially inflated custom blood pressure cuff) and the carotid site (using hand -held applanation tonometry) were measured simultaneously. Pulse wave analysis was performed on the central aortic pressure waveform as derived from the brachial pressure waveform recorded in a partially-inflated blood pressure cuff around the upper arm.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: All patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data. Patients with both baseline and week 52 data were included in this analysis
Arm/Group Title Sacubitril/Valsartan (LCZ696) Olmesartan
Hide Arm/Group Description:
LCZ696 based treatment strategy (LCZ696 200 mg for 2 weeks as initiation dose, LCZ696 400 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Olmesartan based treatment strategy (olmesartan 20 mg for 2 weeks as initiation dose, olmesartan 40 mg for additional 50 weeks as maintenance dose. Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target)
Overall Number of Participants Analyzed 50 50
Least Squares Mean (Standard Error)
Unit of Measure: meters per second (m/s)
-0.428  (0.1663) -0.434  (0.1663)
10.Secondary Outcome
Title Number of Patients With Reported Adverse Events, Serious Adverse Events and Death
Hide Description This outcome measure summarizes patients with any adverse events, serious adverse events and death.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All patients that received study drug
Arm/Group Title Initiation Dose : Sacubitril/Valsartan (LCZ696 200mg) Initiation Dose: Olmesartan 20mg Maintenance Dose: Sacubitril/Valsartan (LCZ696 400mg) Maintenance Dose: Olmesartan 40 mg Sacubitril/Valsartan (LCZ696 400mg) +/- Amlodipine Olmesartan 40mg +/- Amlodipine
Hide Arm/Group Description:
Patients received LCZ696 200 mg for 2 weeks as initiation dose for 2 weeks
Patients received olmesartan 20 mg for 2 weeks as initiation dose for 2 weeks
After 2 weeks on initiation dose, patients were dosed at the maintenance dose level of LCZ696 400 mg for 10 weeks
After 2 weeks on initiation dose, patients were dosed at the maintenance dose level of olmesartan 40 mg for 10 weeks
Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target
Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target
Overall Number of Participants Analyzed 57 57 57 56 54 53
Measure Type: Number
Unit of Measure: Patients
Any Adverse events 13 16 21 28 31 38
Serious Adverse Events 0 2 0 2 6 5
Death 0 0 0 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Initiation Dose : Sacubitril/Valsartan (LCZ696 200mg) Initiation Dose: Olmesartan 20mg Maintenance Dose: Sacubitril/Valsartan (LCZ696 400mg) Maintenance Dose: Olmesartan 40 mg Sacubitril/Valsartan (LCZ696 400mg) +/- Amlodipine Olmesartan 40mg +/- Amlodipine
Hide Arm/Group Description Patients received LCZ696 200 mg for 2 weeks as initiation dose for 2 weeks Patients received olmesartan 20 mg for 2 weeks as initiation dose for 2 weeks After 2 weeks on initiation dose, patients were dosed at the maintenance dose level of LCZ696 400 mg for 10 weeks After 2 weeks on initiation dose, patients were dosed at the maintenance dose level of olmesartan 40 mg for 10 weeks Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target Optional amlodipine 2.5 to 10 mg add-on after Week 12 to reach blood pressure target
All-Cause Mortality
Initiation Dose : Sacubitril/Valsartan (LCZ696 200mg) Initiation Dose: Olmesartan 20mg Maintenance Dose: Sacubitril/Valsartan (LCZ696 400mg) Maintenance Dose: Olmesartan 40 mg Sacubitril/Valsartan (LCZ696 400mg) +/- Amlodipine Olmesartan 40mg +/- Amlodipine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Initiation Dose : Sacubitril/Valsartan (LCZ696 200mg) Initiation Dose: Olmesartan 20mg Maintenance Dose: Sacubitril/Valsartan (LCZ696 400mg) Maintenance Dose: Olmesartan 40 mg Sacubitril/Valsartan (LCZ696 400mg) +/- Amlodipine Olmesartan 40mg +/- Amlodipine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/57 (0.00%)   2/57 (3.51%)   0/57 (0.00%)   2/56 (3.57%)   6/54 (11.11%)   5/53 (9.43%) 
Gastrointestinal disorders             
Enterocolitis  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Inguinal hernia  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
General disorders             
Fat necrosis  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/53 (0.00%) 
Nodule  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/53 (0.00%) 
Infections and infestations             
Appendicitis  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  1/56 (1.79%)  0/54 (0.00%)  0/53 (0.00%) 
Gastroenteritis  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  1/53 (1.89%) 
Injury, poisoning and procedural complications             
Abdominal injury  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Fall  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Road traffic accident  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  1/53 (1.89%) 
Tendon rupture  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  2/53 (3.77%) 
Metabolism and nutrition disorders             
Dehydration  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Adenocarcinoma of colon  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Intraductal proliferative breast lesion  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Metastases to bone  1  0/57 (0.00%)  1/57 (1.75%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/53 (0.00%) 
Prostate cancer metastatic  1  0/57 (0.00%)  1/57 (1.75%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/53 (0.00%) 
Nervous system disorders             
Syncope  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  0/53 (0.00%) 
Renal and urinary disorders             
Acute kidney injury  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  1/53 (1.89%) 
Haematuria  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  1/53 (1.89%) 
Vascular disorders             
Hypertension  1  0/57 (0.00%)  1/57 (1.75%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  0/53 (0.00%) 
Hypertensive crisis  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  1/53 (1.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Initiation Dose : Sacubitril/Valsartan (LCZ696 200mg) Initiation Dose: Olmesartan 20mg Maintenance Dose: Sacubitril/Valsartan (LCZ696 400mg) Maintenance Dose: Olmesartan 40 mg Sacubitril/Valsartan (LCZ696 400mg) +/- Amlodipine Olmesartan 40mg +/- Amlodipine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/57 (5.26%)   6/57 (10.53%)   10/57 (17.54%)   14/56 (25.00%)   16/54 (29.63%)   24/53 (45.28%) 
General disorders             
Oedema peripheral  1  0/57 (0.00%)  0/57 (0.00%)  1/57 (1.75%)  0/56 (0.00%)  1/54 (1.85%)  4/53 (7.55%) 
Infections and infestations             
Influenza  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  3/53 (5.66%) 
Nasopharyngitis  1  0/57 (0.00%)  2/57 (3.51%)  4/57 (7.02%)  5/56 (8.93%)  11/54 (20.37%)  10/53 (18.87%) 
Investigations             
Blood creatine phosphokinase increased  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  0/54 (0.00%)  3/53 (5.66%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/57 (0.00%)  0/57 (0.00%)  0/57 (0.00%)  0/56 (0.00%)  1/54 (1.85%)  3/53 (5.66%) 
Back pain  1  1/57 (1.75%)  0/57 (0.00%)  0/57 (0.00%)  5/56 (8.93%)  1/54 (1.85%)  5/53 (9.43%) 
Nervous system disorders             
Dizziness  1  1/57 (1.75%)  2/57 (3.51%)  4/57 (7.02%)  1/56 (1.79%)  1/54 (1.85%)  0/53 (0.00%) 
Headache  1  0/57 (0.00%)  2/57 (3.51%)  2/57 (3.51%)  6/56 (10.71%)  2/54 (3.70%)  2/53 (3.77%) 
Renal and urinary disorders             
Haematuria  1  1/57 (1.75%)  0/57 (0.00%)  0/57 (0.00%)  2/56 (3.57%)  3/54 (5.56%)  0/53 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01870739     History of Changes
Other Study ID Numbers: CLCZ696A2224
2012-005720-15 ( EudraCT Number )
First Submitted: June 3, 2013
First Posted: June 6, 2013
Results First Submitted: May 31, 2016
Results First Posted: September 1, 2016
Last Update Posted: April 9, 2019