Hypertension
Conditions
Keywords
Hypertension, Aliskiren, Ramipril
Brief summary
This study is designed to investigate the efficacy, safety and tolerability of aliskiren 300 mg, 150 mg and 75 mg when compared to ramipril 5 mg in patients with essential hypertension.
Interventions
DRUGAliskiren
Aliskiren
DRUGRamipril
comparator
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have msDBP ≥ 90 mmHg and \< 110 mmHg at the visit immediately prior to Visit 3 * Patients must have msDBP \>OR= 95 mmHg and \< 110 mmHg at Visit 3 * Patients must have an absolute difference of \< or =10 mmHg in their mean sitting diastolic blood pressure (msDBP) from Visit 2 to Visit 3
Exclusion criteria
* Severe hypertension (grade 3 WHO classification; msDBP \>or= 110 mmHg and/or msSBP \>or = 180 mmHg). * History or evidence of a secondary form of hypertension. * History of transient ischemic cerebral attack within 12 months of visit 1. * Current angina pectoris requiring pharmacological therapy (other than those patients on a stable dose of oral or topical nitrates) * Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) \> 8% at Visit 1. * Known or suspected contraindications to the study medications, including history of allergy to ramipril or other ACE Inhibitors. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline and Week 8 | To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint |
| Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline and Week 8 | To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint |
| Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline and Week 8 | To evaluate the non-inferiority of aliskiren 75 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | Baseline and Week 8 | To evaluate the change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic blood Pressure (msDBP) from baseline to 8 week endpoint on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg in patients with essential hypertension. |
| Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg | Week 8 | To evaluate the percentage of patients controlled to a target blood pressure of \< 140/90 mmHg on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg. |
| Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP | Week 8 | To evaluate the percentage of responders on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg, defined as msDBP \< 90 mmHg or ≥ 10mmHg decrease from baseline in msDBP. |
Countries
China, India, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren 300 mg Aliskiren 300 mg once daily | 331 |
| Aliskiren 150 mg Aliskiren 150 mg once daily | 323 |
| Aliskiren 75 mg Aliskiren 75 mg once daily | 332 |
| Ramipril 5 mg Ramipril 5 mg once daily | 330 |
| Total | 1,316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative problems | 1 | 1 | 0 | 2 |
| Overall Study | Adverse Event | 9 | 16 | 14 | 8 |
| Overall Study | Lost to Follow-up | 4 | 7 | 4 | 4 |
| Overall Study | Protocol deviation | 1 | 1 | 4 | 1 |
| Overall Study | Subject withdrew consent | 16 | 21 | 13 | 12 |
| Overall Study | Unsatisfactory therapeutic response | 6 | 2 | 5 | 4 |
Baseline characteristics
| Characteristic | Aliskiren 300 mg | Aliskiren 150 mg | Aliskiren 75 mg | Ramipril 5 mg | Total |
|---|---|---|---|---|---|
| Age Continuous | 53.8 years STANDARD_DEVIATION 9.45 | 53.3 years STANDARD_DEVIATION 10.53 | 52.7 years STANDARD_DEVIATION 10.22 | 52.9 years STANDARD_DEVIATION 9.6 | 53.2 years STANDARD_DEVIATION 9.95 |
| Age, Customized < 65 years | 288 Participants | 273 Participants | 285 Participants | 296 Participants | 1142 Participants |
| Age, Customized ≥ 65 years | 43 Participants | 50 Participants | 47 Participants | 34 Participants | 174 Participants |
| Sex: Female, Male Female | 150 Participants | 140 Participants | 144 Participants | 151 Participants | 585 Participants |
| Sex: Female, Male Male | 181 Participants | 183 Participants | 188 Participants | 179 Participants | 731 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 | 4 / 331 | 3 / 323 | 2 / 332 | 17 / 329 |
| serious Total, serious adverse events | 1 / 331 | 2 / 323 | 3 / 332 | 1 / 329 |
Outcome results
Primary
Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time frame: Baseline and Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg | Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -10.04 mm Hg | Standard Error 0.44 |
| Aliskiren 150 mg | Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -9.19 mm Hg | Standard Error 0.44 |
95% CI: [-2.06, 0.34]
Primary
Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time frame: Baseline and Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg | Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -11.63 mm Hg | Standard Error 0.44 |
| Aliskiren 150 mg | Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -9.19 mm Hg | Standard Error 0.44 |
95% CI: [-3.63, -1.25]
Primary
Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
To evaluate the non-inferiority of aliskiren 75 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time frame: Baseline and Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg | Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -10.66 mm Hg | Standard Error 0.44 |
| Aliskiren 150 mg | Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) | -9.19 mm Hg | Standard Error 0.44 |
95% CI: [-2.67, -0.28]
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint
To evaluate the change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic blood Pressure (msDBP) from baseline to 8 week endpoint on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg in patients with essential hypertension.
Time frame: Baseline and Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren 300 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msDBP | -11.63 mm Hg | Standard Error 0.44 |
| Aliskiren 300 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msSBP | -14.39 mm Hg | Standard Error 0.66 |
| Aliskiren 150 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msDBP | -10.04 mm Hg | Standard Error 0.44 |
| Aliskiren 150 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msSBP | -12.16 mm Hg | Standard Error 0.67 |
| Aliskiren 75 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msDBP | -10.66 mm Hg | Standard Error 0.44 |
| Aliskiren 75 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msSBP | -12.24 mm Hg | Standard Error 0.66 |
| Ramipril 5 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msSBP | -11.46 mm Hg | Standard Error 0.66 |
| Ramipril 5 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint | msDBP | -9.19 mm Hg | Standard Error 0.44 |
Secondary
Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg
To evaluate the percentage of patients controlled to a target blood pressure of \< 140/90 mmHg on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg.
Time frame: Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 300 mg | Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg | 52.29 Percentage of participants |
| Aliskiren 150 mg | Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg | 48.11 Percentage of participants |
| Aliskiren 75 mg | Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg | 45.68 Percentage of participants |
| Ramipril 5 mg | Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg | 43.65 Percentage of participants |
Secondary
Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP
To evaluate the percentage of responders on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg, defined as msDBP \< 90 mmHg or ≥ 10mmHg decrease from baseline in msDBP.
Time frame: Week 8
Population: Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 300 mg | Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP | 67.89 Percentage of participants |
| Aliskiren 150 mg | Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP | 59.75 Percentage of participants |
| Aliskiren 75 mg | Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP | 59.57 Percentage of participants |
| Ramipril 5 mg | Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP | 53.87 Percentage of participants |