Hypertension; Hypertrophy, Left Ventricular
Conditions
Keywords
Left ventricular hypertrophy, hypertension, valsartan, amlodipine
Brief summary
This study will evaluate the safety and efficacy of amlodipine plus valsartan in patients with hypertension and left ventricular hypertrophy
Interventions
DRUGAmlodipine
5 mg or 10 mg tablets taken orally once daily in the morning.
DRUGHydrochlorothiazide
12.5 mg or 25 mg tablets taken orally once daily in the morning.
DRUGValsartan
160 mg film coated tablets taken orally once daily in the morning.
DRUGLosartan
100 mg tablets taken orally once daily in the morning.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Caucasian; male or female outpatients and age between 18-80 years of age, inclusive. * Patients with a history of essential hypertension and who are actually treated either with an antihypertensive monotherapy and with a diastolic blood pressure \>=90 and \<= 105mmHg or with a combination therapy (limited to two active compounds) and with a diastolic blood pressure of \>=90 and \<= 100mmHg. * Patients with Left Ventricular Hypertrophy
Exclusion criteria
* Severe hypertension * Symptomatic heart failure * History of stroke, heart attack, coronary bypass surgery etc. * Insulin-dependent diabetes mellitus or poorly controlled diabetes mellitus. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Left Ventricular Mass Index (LVMI) Measured Via Magnetic Resonance Imaging (MRI) | Baseline to week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of Study in Interventricular Septum Thickness (IVS) Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Posterior Wall Thickness Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Left Ventricular Ejection Fraction (LVEF) Assessed by MRI | Baseline to week 52 | Ejection fraction is a measurement of the percentage of blood that is pumped out of a filled ventricle with each heartbeat. |
| Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Normalized to Body Surface Area Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Left Ventricular Mass Index (LVMI) Normalized to Body Surface Area Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in Left Atrial (LA) Area Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to the End of Study in the Ascending Aortic Diameter Assessed by MRI | Baseline to week 52 | — |
| Change From Baseline to End of Study in Levels of N-terminal Pro-B Type Natriuretic Peptide (NT-proBNP) | Baseline to week 52 | — |
| Change From Baseline to End of Study in Levels of High-sensitivity C-reactive Protein (Hs-CRP) | Baseline to week 52 | — |
| Percentage of Participants Achieving Target Blood Pressure at Week 52 | Week 52 | Target blood pressure defined as having a mean sitting systolic blood pressure (MSSBP) \< 140 mm Hg and a mean sitting diastolic blood pressure (MSDBP) \< 90 mm Hg. |
| Percentage of Participants Who Experienced Adverse Events (AEs) | Baseline to week 52 | An adverse event was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after obtaining informed consent even if the event was not considered to be related to study drug. Medical conditions/diseases present before obtaining informed consent were only considered adverse events if they worsened after study start. Abnormal laboratory values or test results constituted adverse events only if they induced clinical signs or symptoms, required study drug discontinuation or required therapy. |
| Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Normalized to Body Surface Area Assessed by MRI | Baseline to week 52 | — |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valsartan and Amlodipine Participants received 160 mg Valsartan and 5 mg amlodipine orally once a day for 52 weeks. If blood pressure was not normalized at week 4, treatment was uptitrated to valsartan/amlodipine 160/10 mg. Participants with still uncontrolled hypertension could receive add-on antihypertensive medication. | 43 |
| Losartan and HCTZ Participants received 100 mg losartan and 12.5 mg Hydrochlorothiazide (HCT) orally once a day for 52 weeks. If blood pressure was not normalized at week 4, treatment was uptitrated to losartan/HCT 100/25 mg, respectively, until end of study. Participants with still uncontrolled hypertension could receive add-on antihypertensive medication. | 47 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 1 |
| Overall Study | Abnormal test procedure result(s) | 1 | 0 |
| Overall Study | Administrative problems | 0 | 1 |
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Valsartan and Amlodipine | Losartan and HCTZ | Total |
|---|---|---|---|
| Age Continuous | 58.2 years STANDARD_DEVIATION 12.2 | 57.2 years STANDARD_DEVIATION 10.9 | 57.7 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 31 Participants | 34 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 43 | 16 / 47 |
| serious Total, serious adverse events | 2 / 43 | 6 / 47 |
Outcome results
Primary
Change From Baseline in Left Ventricular Mass Index (LVMI) Measured Via Magnetic Resonance Imaging (MRI)
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline in Left Ventricular Mass Index (LVMI) Measured Via Magnetic Resonance Imaging (MRI) | -7.1 g/m˄2 | Standard Deviation 16.5 |
| Losartan and HCTZ | Change From Baseline in Left Ventricular Mass Index (LVMI) Measured Via Magnetic Resonance Imaging (MRI) | -9.1 g/m˄2 | Standard Deviation 18.89 |
Secondary
Change From Baseline to End of Study in Levels of High-sensitivity C-reactive Protein (Hs-CRP)
Time frame: Baseline to week 52
Population: The safety population consisted of the sample of all randomized patients who applied study medication at least once.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to End of Study in Levels of High-sensitivity C-reactive Protein (Hs-CRP) | 0.8 mg/l | Standard Deviation 6.09 |
| Losartan and HCTZ | Change From Baseline to End of Study in Levels of High-sensitivity C-reactive Protein (Hs-CRP) | -2.1 mg/l | Standard Deviation 9.9 |
Secondary
Change From Baseline to End of Study in Levels of N-terminal Pro-B Type Natriuretic Peptide (NT-proBNP)
Time frame: Baseline to week 52
Population: The safety population consisted of the sample of all randomized patients who applied study medication at least once.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to End of Study in Levels of N-terminal Pro-B Type Natriuretic Peptide (NT-proBNP) | -4.5 pg/ml | Standard Deviation 56.41 |
| Losartan and HCTZ | Change From Baseline to End of Study in Levels of N-terminal Pro-B Type Natriuretic Peptide (NT-proBNP) | -40.1 pg/ml | Standard Deviation 74.09 |
Secondary
Change From Baseline to the End of Study in Interventricular Septum Thickness (IVS) Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Interventricular Septum Thickness (IVS) Assessed by MRI | -1.1 mm | Standard Deviation 1.5 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Interventricular Septum Thickness (IVS) Assessed by MRI | -0.6 mm | Standard Deviation 1.3 |
Secondary
Change From Baseline to the End of Study in Left Atrial (LA) Area Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Atrial (LA) Area Assessed by MRI | -0.6 cm˄2 | Standard Deviation 3.2 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Atrial (LA) Area Assessed by MRI | -1.0 cm˄2 | Standard Deviation 4.5 |
Secondary
Change From Baseline to the End of Study in Left Ventricular Ejection Fraction (LVEF) Assessed by MRI
Ejection fraction is a measurement of the percentage of blood that is pumped out of a filled ventricle with each heartbeat.
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular Ejection Fraction (LVEF) Assessed by MRI | -0.8 Percentage | Standard Deviation 6.7 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular Ejection Fraction (LVEF) Assessed by MRI | -0.4 Percentage | Standard Deviation 5.9 |
Secondary
Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Assessed by MRI | 0.1 ml | Standard Deviation 19.9 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Assessed by MRI | -6.4 ml | Standard Deviation 22.9 |
Secondary
Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Normalized to Body Surface Area Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Normalized to Body Surface Area Assessed by MRI | 0.0 ml | Standard Deviation 9.6 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular End-diastolic Volume (LVEDV) Normalized to Body Surface Area Assessed by MRI | -3.0 ml | Standard Deviation 11.2 |
Secondary
Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Assessed by MRI | 0.4 ml | Standard Deviation 10.3 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Assessed by MRI | -1.5 ml | Standard Deviation 10.3 |
Secondary
Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Normalized to Body Surface Area Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Normalized to Body Surface Area Assessed by MRI | 0.2 ml | Standard Deviation 5.1 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular End-Systolic Volume (LVESV) Normalized to Body Surface Area Assessed by MRI | -0.8 ml | Standard Deviation 5.1 |
Secondary
Change From Baseline to the End of Study in Left Ventricular Mass Index (LVMI) Normalized to Body Surface Area Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Left Ventricular Mass Index (LVMI) Normalized to Body Surface Area Assessed by MRI | -3.5 g/m˄2 | Standard Deviation 7.4 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Left Ventricular Mass Index (LVMI) Normalized to Body Surface Area Assessed by MRI | -4.4 g/m˄2 | Standard Deviation 9.3 |
Secondary
Change From Baseline to the End of Study in Posterior Wall Thickness Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in Posterior Wall Thickness Assessed by MRI | -0.4 mm | Standard Deviation 1.1 |
| Losartan and HCTZ | Change From Baseline to the End of Study in Posterior Wall Thickness Assessed by MRI | -0.3 mm | Standard Deviation 1.2 |
Secondary
Change From Baseline to the End of Study in the Ascending Aortic Diameter Assessed by MRI
Time frame: Baseline to week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valsartan and Amlodipine | Change From Baseline to the End of Study in the Ascending Aortic Diameter Assessed by MRI | 0.1 mm | Standard Deviation 1.9 |
| Losartan and HCTZ | Change From Baseline to the End of Study in the Ascending Aortic Diameter Assessed by MRI | -0.8 mm | Standard Deviation 1.6 |
Secondary
Percentage of Participants Achieving Target Blood Pressure at Week 52
Target blood pressure defined as having a mean sitting systolic blood pressure (MSSBP) \< 140 mm Hg and a mean sitting diastolic blood pressure (MSDBP) \< 90 mm Hg.
Time frame: Week 52
Population: The intention-to-treat (ITT) population consisted of all patients from the safety population who had a baseline MRI assessment. If patients dropped out prior to the scheduled observation period, every effort should have been taken to get a final MRI scan which could then be used for the ITT analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan and Amlodipine | Percentage of Participants Achieving Target Blood Pressure at Week 52 | 53.5 Percentage of participants |
| Losartan and HCTZ | Percentage of Participants Achieving Target Blood Pressure at Week 52 | 14.9 Percentage of participants |
Secondary
Percentage of Participants Who Experienced Adverse Events (AEs)
An adverse event was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after obtaining informed consent even if the event was not considered to be related to study drug. Medical conditions/diseases present before obtaining informed consent were only considered adverse events if they worsened after study start. Abnormal laboratory values or test results constituted adverse events only if they induced clinical signs or symptoms, required study drug discontinuation or required therapy.
Time frame: Baseline to week 52
Population: The safety population consisted of the sample of all randomized patients who applied study medication at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan and Amlodipine | Percentage of Participants Who Experienced Adverse Events (AEs) | 69.8 Percentage of participants |
| Losartan and HCTZ | Percentage of Participants Who Experienced Adverse Events (AEs) | 68.1 Percentage of participants |