Hypertension
Conditions
Keywords
Hypertension, ≥ 65 years, aliskiren, placebo, light meal
Brief summary
This study will evaluate the efficacy and safety of aliskiren 75 mg, 150 mg, and 300 mg in elderly patients with essential hypertension when given with a light meal.
Interventions
DRUGPlacebo
Placebo tablet taken once daily in the morning with a light meal.
DRUGAliskiren 75 mg
Aliskiren 75 mg tablet taken once daily in the morning with a light meal.
DRUGAliskiren 150 mg
Aliskiren 150 mg tablet taken once daily in the morning with a light meal.
DRUGAliskiren 300 mg
Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients 65 years of age and older. * Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent). * At the randomization visit patients must have an office msSBP greater than or equal to 150 mmHg and \< 180 mmHg (msDBP \<110 mmHg) with a less than or equal to 15 mmHg difference during the last two visits of the single blind run-in period.
Exclusion criteria
* Severe hypertension \[Office msDBP ≥110 mmHg and/or mean sitting systolic blood pressure (msSBP) ≥ 180 mmHg\]. * History or evidence of a secondary form of hypertension. * Known Keith-Wagener grade III or IV hypertensive retinopathy. * History of hypertensive encephalopathy or cerebrovascular accident, including a history of transient ischemic cerebral attack (TIA). * Current diagnosis of heart failure (NYHA Class II-IV). * History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI). * Current angina pectoris requiring pharmacological therapy other than nitrates. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) | Baseline to end of study (Week 8) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | Baseline to end of study (Week 8) | — |
| Percentage of Patients Achieving Systolic Blood Pressure Response | Baseline to end of study (Week 8) | Patients achieving a systolic blood pressure response had to have a msSBP \< 140 mmHg at the end of the study and/or a ≥ 20 mmHg reduction in msSBP from baseline to the end of the study. |
| Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Baseline to end of study (Week 8) | Two 24-hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline and one at the end of the study. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. |
| Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | Baseline to end of study (Week 8) | Smoothness index (SI) is a measure of consistency of the BP reduction over 24 hours. The SI was obtained by first calculating the mean blood pressure value at each hour of the 24-hour ambulatory blood pressure monitoring period, both before and during treatment. Similarly, the change from baseline in blood pressure was calculated at each hour. The average hourly change from baseline (δh) and standard deviation (std δh) of the hourly changes were computed, and the SI was derived: SI = δh/std δh. A negative change score indicates improvement. |
| Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | Baseline to end of study (week 8) | The morning surge was defined as the average of the hourly means in the last three hours (hours 22, 23, 24) of the 24 hour ambulatory blood pressure monitoring assessment period. |
Countries
Argentina, Czechia, Germany, Iceland, Italy, Netherlands, Poland, Slovakia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet taken once daily in the morning with a light meal. | 189 |
| Aliskiren 75 mg Aliskiren 75 mg tablet taken once daily in the morning with a light meal. | 192 |
| Aliskiren 150 mg Aliskiren 150 mg tablet taken once daily in the morning with a light meal. | 189 |
| Aliskiren 300 mg Aliskiren 300 mg tablet taken once daily in the morning with a light meal. | 186 |
| Total | 756 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 | 2 | 3 |
| Overall Study | Did not meet study criteria | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 6 | 0 | 3 |
| Overall Study | Unsatisfactory therapeutic effect | 9 | 3 | 3 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Aliskiren 75 mg | Aliskiren 150 mg | Aliskiren 300 mg | Total |
|---|---|---|---|---|---|
| Age, Customized ≥ 65 and < 75 years of age | 128 Participants | 131 Participants | 129 Participants | 129 Participants | 517 Participants |
| Age, Customized ≥ 75 years of age | 61 Participants | 61 Participants | 60 Participants | 57 Participants | 239 Participants |
| Sex: Female, Male Female | 100 Participants | 109 Participants | 106 Participants | 102 Participants | 417 Participants |
| Sex: Female, Male Male | 89 Participants | 83 Participants | 83 Participants | 84 Participants | 339 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 186 | 0 / 191 | 0 / 189 | 0 / 188 |
| serious Total, serious adverse events | 1 / 186 | 2 / 191 | 3 / 189 | 0 / 188 |
Outcome results
Primary
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 (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) | -7.97 mmHg | Standard Error 1.043 |
| Aliskiren 75 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) | -12.51 mmHg | Standard Error 1.024 |
| Aliskiren 150 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) | -15.28 mmHg | Standard Error 1.035 |
| Aliskiren 300 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) | -14.14 mmHg | Standard Error 1.042 |
Secondary
Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study
Two 24-hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline and one at the end of the study. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient.
Time frame: Baseline to end of study (Week 8)
Population: Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Systolic Blood Pressure | -1.15 mmHg | Standard Error 1.28 |
| Placebo | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Diastolic Blood Pressure | 0.31 mmHg | Standard Error 0.99 |
| Aliskiren 75 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Diastolic Blood Pressure | -1.78 mmHg | Standard Error 0.877 |
| Aliskiren 75 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Systolic Blood Pressure | -3.33 mmHg | Standard Error 1.155 |
| Aliskiren 150 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Diastolic Blood Pressure | -3.26 mmHg | Standard Error 0.693 |
| Aliskiren 150 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Systolic Blood Pressure | -5.76 mmHg | Standard Error 1.128 |
| Aliskiren 300 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Diastolic Blood Pressure | -2.45 mmHg | Standard Error 0.823 |
| Aliskiren 300 mg | Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study | Ambulatory Systolic Blood Pressure | -5.83 mmHg | Standard Error 1.52 |
Secondary
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 (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -3.50 mmHg | Standard Error 0.579 |
| Aliskiren 75 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -5.33 mmHg | Standard Error 0.568 |
| Aliskiren 150 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -6.42 mmHg | Standard Error 0.575 |
| Aliskiren 300 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -6.66 mmHg | Standard Error 0.579 |
Secondary
Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8)
The morning surge was defined as the average of the hourly means in the last three hours (hours 22, 23, 24) of the 24 hour ambulatory blood pressure monitoring assessment period.
Time frame: Baseline to end of study (week 8)
Population: Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | 0.46 mmHg | Standard Error 1.782 |
| Aliskiren 75 mg | Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -3.04 mmHg | Standard Error 1.596 |
| Aliskiren 150 mg | Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -7.03 mmHg | Standard Error 1.539 |
| Aliskiren 300 mg | Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -3.96 mmHg | Standard Error 1.66 |
Secondary
Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8)
Smoothness index (SI) is a measure of consistency of the BP reduction over 24 hours. The SI was obtained by first calculating the mean blood pressure value at each hour of the 24-hour ambulatory blood pressure monitoring period, both before and during treatment. Similarly, the change from baseline in blood pressure was calculated at each hour. The average hourly change from baseline (δh) and standard deviation (std δh) of the hourly changes were computed, and the SI was derived: SI = δh/std δh. A negative change score indicates improvement.
Time frame: Baseline to end of study (Week 8)
Population: Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -0.11 Ratio | Standard Error 0.102 |
| Aliskiren 75 mg | Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -0.38 Ratio | Standard Error 0.092 |
| Aliskiren 150 mg | Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -0.50 Ratio | Standard Error 0.089 |
| Aliskiren 300 mg | Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) | -0.51 Ratio | Standard Error 0.096 |
Secondary
Percentage of Patients Achieving Systolic Blood Pressure Response
Patients achieving a systolic blood pressure response had to have a msSBP \< 140 mmHg at the end of the study and/or a ≥ 20 mmHg reduction in msSBP from baseline to the end of the study.
Time frame: Baseline to end of study (Week 8)
Population: Full analysis set (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients Achieving Systolic Blood Pressure Response | 28.8 Percentage of participants |
| Aliskiren 75 mg | Percentage of Patients Achieving Systolic Blood Pressure Response | 42.4 Percentage of participants |
| Aliskiren 150 mg | Percentage of Patients Achieving Systolic Blood Pressure Response | 44.1 Percentage of participants |
| Aliskiren 300 mg | Percentage of Patients Achieving Systolic Blood Pressure Response | 47.3 Percentage of participants |