Hypertension
Conditions
Brief summary
Assess that for an equivalent brachial blood pressure (BP)lowering, a fixed dose combination amlodipine/valsartan based regimen reduces central aortic BP pressure to a larger extent than an atenolol/amlodipine combination based regimen.
Interventions
DRUGValsartan/amlodipine 80/5 mg tablets
DRUGAmlodipine 10 mg capsules
DRUGAtenolol 50 mg tablets
DRUGAtenolol 100 mg tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients 18 years of age or older * Hypertension defined by MSDBP \> 90 and or MSSBP \> 140 mmHg, MSDBP \> 80 mmHg, or/and MSSBP \> 130 mmHg if diabetes or chronic renal impairment uncontrolled under their previous therapy, or untreated , or experiencing unacceptable side effects * Written informed consent to participate in the study prior to any study procedures
Exclusion criteria
* Severe hypertension (grade 3 WHO classification MSDBP \> 110 mmHg and/or MSSBP \> 180 mmHg) * Evidence of a secondary form of hypertension * Type 1 diabetes mellitus * History of congestive heart failure, unstable coronary insufficiency, life threatening arrhythmia, significant valvular disease, second or third degree heart block etc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 24 (Radial Measurement) | Baseline and Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Central Pulse Pressure at Week 24 (Radial Measurement) | Baseline and Week 24 | — |
| Change From Baseline of Augmentation Index (Aix) at Week 8 | Baseline and Week 8 | To calculate the blood pressure augmentation index, the inflection point of the pressure curve corresponding to the return of the reflection wave was determined. The ratio between the pressure located above and below the inflection point was calculated. |
| Change From Baseline of Aix at Week 24 | Baseline and Week 24 | — |
| Change From Baseline of Aix Corrected to Heart Rate at Week 24 | Baseline and Week 24 | The heart rate correction was computed by a multivariate model analysis |
| Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 8 (Radial Measurement) | Baseline and Week 8 | — |
| Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) | Baseline and Week 24 | Applanation tonometry is a measurement of aortic pressure and vascular stiffness. To assess the central aortic blood pressure, it is necessary to calibrate the applanation tonometry device using the brachial blood pressure. |
| Change From Baseline of Brachial Pulse Pressure at Week 24 (Tonometry Center) | Baseline and Week 24 | — |
| Change From Baseline of SBP/DBP at Week 24 (Office BP) | Baseline and Week 24 | — |
| Change From Baseline of Pulse Pressure at Week 24 (Office BP) | Baseline and Week 24 | — |
| Change From Baseline of Pulse Wave Velocity at Week 24 (Radial Measurement) | Baseline and Week 24 | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valsartan/Amlodipine 160/10 mg Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled. | 193 |
| Atenolol/Amlodipine 100/10 mg Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled. | 200 |
| Total | 393 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reasons | 0 | 2 |
| Overall Study | Adverse Event | 18 | 28 |
| Overall Study | Lack of Efficacy | 2 | 3 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Valsartan/Amlodipine 160/10 mg | Atenolol/Amlodipine 100/10 mg | Total |
|---|---|---|---|
| Age Continuous | 57.5 years STANDARD_DEVIATION 9.94 | 56.2 years STANDARD_DEVIATION 11.09 | 56.9 years STANDARD_DEVIATION 10.55 |
| Region of Enrollment France | 193 participants | 200 participants | 393 participants |
| Sex: Female, Male Female | 82 Participants | 101 Participants | 183 Participants |
| Sex: Female, Male Male | 111 Participants | 99 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 393 | 30 / 193 | 31 / 200 |
| serious Total, serious adverse events | 3 / 393 | 4 / 193 | 4 / 200 |
Outcome results
Primary
Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 24 (Radial Measurement)
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 24 (Radial Measurement) | -13.65 mmHg | Standard Error 1.15 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 24 (Radial Measurement) | -9.7 mmHg | Standard Error 1.09 |
Secondary
Change From Baseline of Aix at Week 24
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Aix at Week 24 | -4.10 Ratio | Standard Error 0.72 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Aix at Week 24 | 2.40 Ratio | Standard Error 0.7 |
Secondary
Change From Baseline of Aix Corrected to Heart Rate at Week 24
The heart rate correction was computed by a multivariate model analysis
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Aix Corrected to Heart Rate at Week 24 | -4.12 Ratio | Standard Error 0.67 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Aix Corrected to Heart Rate at Week 24 | -2.43 Ratio | Standard Error 0.66 |
Secondary
Change From Baseline of Augmentation Index (Aix) at Week 8
To calculate the blood pressure augmentation index, the inflection point of the pressure curve corresponding to the return of the reflection wave was determined. The ratio between the pressure located above and below the inflection point was calculated.
Time frame: Baseline and Week 8
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Augmentation Index (Aix) at Week 8 | -2.21 Ratio | Standard Error 0.78 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Augmentation Index (Aix) at Week 8 | 3.61 Ratio | Standard Error 0.76 |
Secondary
Change From Baseline of Brachial Pulse Pressure at Week 24 (Tonometry Center)
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Brachial Pulse Pressure at Week 24 (Tonometry Center) | -5.02 mmHg | Standard Error 0.72 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Brachial Pulse Pressure at Week 24 (Tonometry Center) | -3.66 mmHg | Standard Error 0.7 |
Secondary
Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center)
Applanation tonometry is a measurement of aortic pressure and vascular stiffness. To assess the central aortic blood pressure, it is necessary to calibrate the applanation tonometry device using the brachial blood pressure.
Time frame: Baseline and Week 24
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) | SBP | -12.93 mmHg | Standard Error 1.14 |
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) | DBP | -7.85 mmHg | Standard Error 0.7 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) | SBP | -11.78 mmHg | Standard Error 1.11 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) | DBP | -7.94 mmHg | Standard Error 0.68 |
Secondary
Change From Baseline of Central Pulse Pressure at Week 24 (Radial Measurement)
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Central Pulse Pressure at Week 24 (Radial Measurement) | -5.5 mmHg | Standard Error 0.65 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Central Pulse Pressure at Week 24 (Radial Measurement) | -1.7 mmHg | Standard Error 0.63 |
Secondary
Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 8 (Radial Measurement)
Time frame: Baseline and Week 8
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 8 (Radial Measurement) | -10.92 mmHg | Standard Error 1.18 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 8 (Radial Measurement) | -8.3 mmHg | Standard Error 1.12 |
Secondary
Change From Baseline of Pulse Pressure at Week 24 (Office BP)
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Pulse Pressure at Week 24 (Office BP) | -6.32 mmHg | Standard Deviation 0.81 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Pulse Pressure at Week 24 (Office BP) | -6.48 mmHg | Standard Deviation 0.81 |
Secondary
Change From Baseline of Pulse Wave Velocity at Week 24 (Radial Measurement)
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of Pulse Wave Velocity at Week 24 (Radial Measurement) | -0.98 m/s | Standard Error 0.18 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of Pulse Wave Velocity at Week 24 (Radial Measurement) | -0.95 m/s | Standard Error 0.17 |
Secondary
Change From Baseline of SBP/DBP at Week 24 (Office BP)
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of SBP/DBP at Week 24 (Office BP) | SBP | -14.49 mmHg | Standard Error 1.08 |
| Valsartan/Amlodipine 160/10 mg | Change From Baseline of SBP/DBP at Week 24 (Office BP) | DBP | -8.17 mmHg | Standard Error 0.72 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of SBP/DBP at Week 24 (Office BP) | SBP | -16.94 mmHg | Standard Error 1.07 |
| Atenolol/Amlodipine 100/10 mg | Change From Baseline of SBP/DBP at Week 24 (Office BP) | DBP | -10.45 mmHg | Standard Error 0.71 |