Hypertension
Conditions
Keywords
Hypertension, aliskiren, amlodipine, HCTZ, blood pressure
Brief summary
To assess the long-term (6 month and 12 month) safety of the combination of aliskiren 300 mg / amlodipine 10 mg in patients with essential hypertension (Mean Sitting Diastolic Blood Pressure \[msDBP\] ≥ 90 mmHg and \< 110 mmHg).
Interventions
DRUGAliskiren
All patients received aliskiren 150 mg for the first two weeks; dose was then force-titrated to aliskiren 300 mg for 52 weeks duration
DRUGAmlodipine
All patients received amlodipine 5 mg for the first two weeks; dose was then force-titrated to amlodipine 10 mg for 52 weeks duration
DRUGHydrochlorothiazide
Optional addition of Hydrochlorothiazide (HCTZ)of 12.5 mg with increase to 25 mg was allowed for patients not adequately controlled.
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients 18 years of age or older * Male or female patients are eligible * For newly diagnosed/untreated patients with essential hypertension defined as msDBP ≥ 90 and \< 110 mmHg at Visit 1 and Visit 4 * For previously treated patients with essential hypertension defined as msDBP ≥ 90 and \< 110 mmHg after 2 to 4 weeks of washout (Visit 4)
Exclusion criteria
* Severe hypertension * History or evidence of a secondary form of hypertension * History of Hypertensive encephalopathy or cerebrovascular accident. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Percentage of Patients With Adverse Events | 52 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Baseline, Week 2, Week 4, Week 6, Week 10, Week 14, Week 28, Week 41 and Week 54 |
| Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Baseline, Week 2, Week 10, Week 28 and Week 54 |
| Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline, Week 2, Week 10, Week 28 and Week 54 |
Countries
Belgium, Denmark, Finland, Germany, Iceland, India, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/Amlodipine Aliskiren and Amlodipine tablets once a day in the morning | 470 |
| Aliskiren/Amlodipine/HCTZ Aliskiren and Amlodipine tablets and HCTZ capsules once a day in the morning | 86 |
| Total | 556 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 2 | 0 |
| Overall Study | Adverse Event | 60 | 7 |
| Overall Study | Condition no longer requires study drug | 2 | 0 |
| Overall Study | Lost to Follow-up | 6 | 3 |
| Overall Study | Patient withdrew consent | 12 | 1 |
| Overall Study | Protocol Deviation | 8 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 2 |
Baseline characteristics
| Characteristic | Aliskiren/Amlodipine | Aliskiren/Amlodipine/HCTZ | Total |
|---|---|---|---|
| Age Continuous | 54.2 years STANDARD_DEVIATION 11.66 | 55.7 years STANDARD_DEVIATION 11.33 | 54.4 years STANDARD_DEVIATION 11.61 |
| Sex: Female, Male Female | 196 Participants | 30 Participants | 226 Participants |
| Sex: Female, Male Male | 274 Participants | 56 Participants | 330 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 | 14 / 556 | 138 / 546 | 21 / 86 |
| serious Total, serious adverse events | 0 / 556 | 13 / 546 | 2 / 86 |
Outcome results
Primary
Overall Percentage of Patients With Adverse Events
Time frame: 52 weeks
Population: Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 150mg/ Amlodipine 5mg Alone | Overall Percentage of Patients With Adverse Events | 23.6 Percentage of Participants |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Overall Percentage of Patients With Adverse Events | 71.2 Percentage of Participants |
| Aliskiren 300mg/ Amlodipine 10mg/ HCTZ | Overall Percentage of Patients With Adverse Events | 57.0 Percentage of Participants |
Secondary
Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points
Time frame: Baseline, Week 2, Week 4, Week 6, Week 10, Week 14, Week 28, Week 41 and Week 54
Population: Treated population, Last observation carried forward (LOCF). Total combined treated patients are 556 out of which 470 patients are treated with Aliskiren and Amlodipine combination only and 86 patients are treated with Ali/Amlo/HCTZ combination.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 4 (Visit 6) | -14.0 mm Hg | Standard Deviation 6.88 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 28 (Visit 10) | -16.7 mm Hg | Standard Deviation 7.15 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 10 (Visit 8) | -16.3 mm Hg | Standard Deviation 6.69 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 41 (Visit 11) | -17.0 mm Hg | Standard Deviation 7.26 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 6 (Visit 7) | -15.7 mm Hg | Standard Deviation 6.96 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 54 (Visit 12) | -16.3 mm Hg | Standard Deviation 7.13 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 14 (Visit 9) | -17.1 mm Hg | Standard Deviation 6.84 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 54 (Visit 12) (LOCF) | -15.7 mm Hg | Standard Deviation 7.61 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 2 (Visit 5) | -8.7 mm Hg | Standard Deviation 6.94 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 54 (Visit 12) (LOCF) | -14.2 mm Hg | Standard Deviation 7.9 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 2 (Visit 5) | -5.9 mm Hg | Standard Deviation 6.05 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 4 (Visit 6) | -11.9 mm Hg | Standard Deviation 5.58 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 6 (Visit 7) | -11.5 mm Hg | Standard Deviation 7.36 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 10 (Visit 8) | -9.3 mm Hg | Standard Deviation 7.22 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 14 (Visit 9) | -13.1 mm Hg | Standard Deviation 7.64 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 28 (Visit 10) | -14.7 mm Hg | Standard Deviation 8.22 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 41 (Visit 11) | -15.4 mm Hg | Standard Deviation 6.86 |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Change in Mean Sitting Diastolic Blood Pressure (msDBP)From Baseline to the Indicated Time Points | Week 54 (Visit 12) | -15.3 mm Hg | Standard Deviation 6.55 |
Secondary
Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg
Time frame: Baseline, Week 2, Week 10, Week 28 and Week 54
Population: Treated Population, Last observation carried forward (LOCF). Total combined treated patients are 556 out of which 470 patients are treated with Aliskiren and Amlodipine combination only and 86 patients are treated with Ali/Amlo/HCTZ combination.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 2 (Visit 5) | 35.3 Percentage of patients | 88 |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 10 (Visit 8) | 88.0 Percentage of patients | — |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 28 (Visit 10) | 88.2 Percentage of patients | — |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 54 (Visit 12) | 82.0 Percentage of patients | — |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 54 (Visit 12) (LOCF) | 77.3 Percentage of patients | — |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 54 (Visit 12) (LOCF) | 58.1 Percentage of patients | — |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 54 (Visit 12) | 62.2 Percentage of patients | — |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 10 (Visit 8) | 16.3 Percentage of patients | — |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 2 (Visit 5) | 8.1 Percentage of patients | — |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Blood Pressure Control Target of <140/90 mmHg | Week 28 (Visit 10) | 56.8 Percentage of patients | — |
Secondary
Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP)
Time frame: Baseline, Week 2, Week 10, Week 28 and Week 54
Population: Treated Population, Last observation carried forward (LOCF). Total combined treated patients are 556 out of which 470 patients are treated with Aliskiren and Amlodipine combination only and 86 patients are treated with Ali/Amlo/HCTZ combination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 10 (Visit 8) | 96.8 Percentage of patients |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 54 (Visit 12) | 93.2 Percentage of patients |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 28 (Visit 10) | 95.9 Percentage of patients |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 54 (Visit 12) (LOCF) | 90.6 Percentage of patients |
| Aliskiren 150mg/ Amlodipine 5mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 2 (Visit 5) | 61.2 Percentage of patients |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 54 (Visit 12) (LOCF) | 84.9 Percentage of patients |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 2 (Visit 5) | 38.4 Percentage of patients |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 10 (Visit 8) | 61.6 Percentage of patients |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 28 (Visit 10) | 85.2 Percentage of patients |
| Aliskiren 300mg/ Amlodipine 10mg Alone | Percentage of Patients Achieving a Response in Mean Sitting Diastolic Blood Pressure (msDBP) | Week 54 (Visit 12) | 89.2 Percentage of patients |