Moderate to Severe Hypertension
Conditions
Keywords
Hypertension, systolic blood pressure, cardiovascular disease, aliskiren, amlodipine
Brief summary
This study will compare the blood pressure (BP) lowering effect of the combination of aliskiren/amlodipine 300/10 mg versus amlodipine 10 mg monotherapy in patients with moderate to severe hypertension by testing the hypothesis that the combination of aliskiren/amlodipine produces a superior reduction from baseline in mean sitting systolic blood pressure (msSBP) after 8 weeks of treatment.
Interventions
Each dose was taken by mouth with water at approximately 8:00 in the morning with or without food, except on the morning of the next office/clinic visit, when the medication was taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of two tablets and one capsule of study medication per day throughout the study.
Each dose was taken by mouth with water at approximately 8:00 in the morning with or without food, except on the morning of the next office/clinic visit, when the medication was taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of two tablets and one capsule of study medication per day throughout the study.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients ≥ 18 years of age * Patients with a diagnosis of moderate to severe hypertension, defined as msSBP ≥ 160 mmHg and \< 200 mmHg at Visit 2
Exclusion criteria
* Mild to moderate hypertension * Pregnant or nursing (lactating) women * Women of child-bearing potential * Previous or current diagnosis of heart failure New York Heart Association(NYHA) Class II-IV. * Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1. * Uncontrolled Type 1 or Type 2 diabetes mellitus * Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with Similar chemical structures * History of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention * Patients on a combination of 3 or more antihypertensive medications Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sitting Systolic Blood Pressure (msSBP) | Baseline to end of study (Week 8) | Change in mean sitting systolic blood pressure (msSBP) from baseline to end of study (Week 8) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline to end of study (Week 8) | Change in mean sitting diastolic blood pressure (msDBP) from baseline to end of study (Week 8) |
| Systolic Blood Pressure Response | Baseline to end of study (Week 8) | Percentage of patients achieving a mean sitting systolic blood pressure response (msSBP \< 140 mmHg or a reduction =\> 20 mmHg from the baseline) from baseline to end of study (Week 8) |
| Diastolic Blood Pressure Response | Baseline to end of study (Week 8) | Percentage of patients achieving a mean sitting diastolic blood pressure response (msDBP \< 90 mmHg or a reduction ≥ 10 mmHg from the baseline) from baseline to end of study (Week 8) |
| Blood Pressure Control | End of study (Week 8) | Percentage of patients achieving blood pressure control (msSBP \< 140 mm Hg and msDBP \< 90 mm Hg) at end of study |
Countries
Germany, Philippines, Romania, Russia, Singapore, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet Aliskiren/amlodipine treatment regimen: At randomization, patients were treated with aliskiren/amlodipine 150/5 mg for one week. For the remaining 7 weeks of the study, patients were force-titrated to receive aliskiren/amlodipine 300/10 mg. | 244 |
| Amlodipine 10 mg Capsule Amlodipine treatment regimen: At randomization, patients were treated with amlodipine 5 mg for one week. For the remaining 7 weeks of the study, patients were force-titrated to receive amlodipine 10 mg. | 241 |
| Total | 485 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 0 | 1 |
| Overall Study | Administrative problems | 9 | 9 |
| Overall Study | Adverse Event | 7 | 16 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Misrandomized | 1 | 0 |
| Overall Study | Protocol Deviation | 0 | 1 |
| Overall Study | Subject withdrew consent | 2 | 4 |
Baseline characteristics
| Characteristic | Aliskiren/Amlodipine 300/10 mg Tablet | Amlodipine 10 mg Capsule | Total |
|---|---|---|---|
| Age Continuous | 59 years STANDARD_DEVIATION 10.38 | 59 years STANDARD_DEVIATION 10.82 | 59 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 136 Participants | 139 Participants | 275 Participants |
| Sex: Female, Male Male | 108 Participants | 102 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 243 | 56 / 241 |
| serious Total, serious adverse events | 0 / 243 | 3 / 241 |
Outcome results
Primary
Mean Sitting Systolic Blood Pressure (msSBP)
Change in mean sitting systolic blood pressure (msSBP) from baseline to end of study (Week 8)
Time frame: Baseline to end of study (Week 8)
Population: Full Analysis Set - analysis set was the FAS excluding patients from one center due to Good Clinical Practices (GCP) issues
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet | Mean Sitting Systolic Blood Pressure (msSBP) | -37.72 mm Hg | Standard Error 0.937 |
| Amlodipine 10 mg Capsule | Mean Sitting Systolic Blood Pressure (msSBP) | -30.63 mm Hg | Standard Error 0.941 |
Secondary
Blood Pressure Control
Percentage of patients achieving blood pressure control (msSBP \< 140 mm Hg and msDBP \< 90 mm Hg) at end of study
Time frame: End of study (Week 8)
Population: Full Analysis Set - analysis set was the FAS excluding patients from one center due to Good Clinical Practices (GCP) issues
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet | Blood Pressure Control | 67.0 Percentage of participants |
| Amlodipine 10 mg Capsule | Blood Pressure Control | 49.1 Percentage of participants |
Secondary
Diastolic Blood Pressure Response
Percentage of patients achieving a mean sitting diastolic blood pressure response (msDBP \< 90 mmHg or a reduction ≥ 10 mmHg from the baseline) from baseline to end of study (Week 8)
Time frame: Baseline to end of study (Week 8)
Population: Full Analysis Set - analysis set was the FAS excluding patients from one center due to Good Clinical Practices (GCP) issues All randomized patients who received the study medication. The measurement at Week 8 was used unless it was not available, in which case, the last observation carried forward was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet | Diastolic Blood Pressure Response | 92.7 Percentage of participants |
| Amlodipine 10 mg Capsule | Diastolic Blood Pressure Response | 86.5 Percentage of participants |
Secondary
Mean Sitting Diastolic Blood Pressure (msDBP)
Change in mean sitting diastolic blood pressure (msDBP) from baseline to end of study (Week 8)
Time frame: Baseline to end of study (Week 8)
Population: Full Analysis Set - analysis set was the FAS excluding patients from one center due to Good Clinical Practices (GCP) issues
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet | Mean Sitting Diastolic Blood Pressure (msDBP) | -16.10 mm Hg | Standard Error 0.557 |
| Amlodipine 10 mg Capsule | Mean Sitting Diastolic Blood Pressure (msDBP) | -12.27 mm Hg | Standard Error 0.559 |
Secondary
Systolic Blood Pressure Response
Percentage of patients achieving a mean sitting systolic blood pressure response (msSBP \< 140 mmHg or a reduction =\> 20 mmHg from the baseline) from baseline to end of study (Week 8)
Time frame: Baseline to end of study (Week 8)
Population: Full Analysis Set - analysis set was the FAS excluding patients from one center due to GCP issues
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/Amlodipine 300/10 mg Tablet | Systolic Blood Pressure Response | 88.8 Percentage of participants |
| Amlodipine 10 mg Capsule | Systolic Blood Pressure Response | 79.1 Percentage of participants |