Hypertension
Conditions
Keywords
Hypertension, Obese, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, ramipril, stage 2
Brief summary
Study to Evaluate the Efficacy and Safety of Aliskiren Hydrochlorothiazide (HCTZ) vs Ramipril in Obese patients (BMI ≥ 30) with Stage 2 Hypertension
Interventions
DRUGAliskiren Hydrochlorothiazide
Aliskiren HCTZ 150/12.5 mg: 1 week; Aliskiren HCTZ 300/25 mg: 7 weeks
DRUGRamipril
Ramipril 5mg: 1 week; Ramipril 10 mg: 7 weeks
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 who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed. * Male or female outpatients, 18 years of age and older. * Patients with Stage 2 hypertension. Patients must have a MSSBP ≥ 160 mmHg and \< 200 mmHg at Study Visit 5 (randomization). * Patients must have a BMI ≥ 30 kg/m2 but ≤ 45 kg/m2.
Exclusion criteria
* Office blood pressure measured by cuff (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 200 mmHg) at any visit. * Use of other investigational drugs within 30 days of enrollment, or 5 half-lives, which ever is longer. * Use of aliskiren and/or a fixed dose combination of aliskiren HCTZ or participation in a clinical trial that had aliskiren and/or aliskiren HCTZ as treatment within 30 days of Visit 1. * History of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (ACE inhibitors or renin inhibitors) as the study drugs. * History or evidence of a secondary form of hypertension. * Refractory hypertension, defined as, unresponsive to triple drug therapy at the maximum dose of each drug, one of which must be a diuretic, and not at blood pressure goal (140/90 mmHg). Therapy with a fixed dose combination of two active substances represent two drugs. * Patients on 4 or more antihypertensive medications. * Long QT syndrome or QTc \> 450 msec for males and \> 470 msec for females at screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Baseline to week 8 | To assess the change in mean sitting systolic blood pressure (MSSBP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Baseline to week 8 | To evaluate the difference in mean sitting diastolic blood pressure (MSDBP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). |
| Percentage of Patients Achieving Blood Pressure Control During 8 Weeks | 8 weeks | The percentage of patients achieving the Blood Pressure control (defined as patients achieving a MSSBP \< 140 mm Hg and MSDBP \< 90 mm Hg) during 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). Data presented are cumulative. Cumulative refers to achieving blood pressure control before or at the 8 week visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted. |
| Percentage of Responders (MSSBP < 140 mmHg or ≥ 20 mmHg Decrease From Baseline in MSSBP) | 8 weeks | To compare the percentage of responders (as defined by patients with MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg) during 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). Data presented are cumulative. Cumulative refers to achieving the response before or at the 8 week visit. If response occurred more than once, only the first occurrence was counted. |
| Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Baseline to week 8 | To compare the change in mean sitting pulse pressure (MSPP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren HCTZ Aliskiren HCTZ 150/12.5 mg: 1 week; Aliskiren HCTZ 300/25 mg: 7 weeks | 193 |
| Ramipril Ramipril 5mg: 1 week; Ramipril 10 mg: 7 weeks | 193 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory values | 0 | 1 |
| Overall Study | Administrative problems | 2 | 1 |
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Patient withdrew consent | 8 | 5 |
| Overall Study | Protocol Deviation | 3 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 8 |
Baseline characteristics
| Characteristic | Aliskiren HCTZ | Ramipril | Total |
|---|---|---|---|
| Age Continuous | 55.4 years STANDARD_DEVIATION 11.15 | 54.4 years STANDARD_DEVIATION 10.9 | 54.9 years STANDARD_DEVIATION 11.02 |
| Sex: Female, Male Female | 107 Participants | 99 Participants | 206 Participants |
| Sex: Female, Male Male | 86 Participants | 94 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 193 | 17 / 193 |
| serious Total, serious adverse events | 4 / 193 | 2 / 193 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)
To assess the change in mean sitting systolic blood pressure (MSSBP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg).
Time frame: Baseline to week 8
Population: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable). Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Baseline | 167.0 mm Hg | Standard Deviation 7.05 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Week 8 | 138.9 mm Hg | Standard Deviation 16.56 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Change from baseline to week 8 | -28.1 mm Hg | Standard Deviation 15.54 |
| Ramipril | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Baseline | 168.2 mm Hg | Standard Deviation 7.86 |
| Ramipril | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Week 8 | 151.6 mm Hg | Standard Deviation 17.44 |
| Ramipril | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Change from baseline to week 8 | -16.6 mm Hg | Standard Deviation 14.76 |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)
To evaluate the difference in mean sitting diastolic blood pressure (MSDBP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg).
Time frame: Baseline to week 8
Population: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable). Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Baseline | 94.3 mm Hg | Standard Deviation 8.41 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Week 8 | 84.2 mm Hg | Standard Deviation 9.8 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Change from baseline to week 8 | -10.1 mm Hg | Standard Deviation 9.04 |
| Ramipril | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Baseline | 96.3 mm Hg | Standard Deviation 8.48 |
| Ramipril | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Week 8 | 92.7 mm Hg | Standard Deviation 11.07 |
| Ramipril | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Change from baseline to week 8 | -3.6 mm Hg | Standard Deviation 9.48 |
Secondary
Change From Baseline in Mean Sitting Pulse Pressure (MSPP)
To compare the change in mean sitting pulse pressure (MSPP) after 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg).
Time frame: Baseline to week 8
Population: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable). Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Baseline | 72.7 mm Hg | Standard Deviation 10.44 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Week 8 | 54.7 mm Hg | Standard Deviation 13.87 |
| Aliskiren HCTZ | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Change from baseline to week 8 | -18.0 mm Hg | Standard Deviation 12.14 |
| Ramipril | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Baseline | 71.9 mm Hg | Standard Deviation 9.85 |
| Ramipril | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Week 8 | 58.9 mm Hg | Standard Deviation 13.98 |
| Ramipril | Change From Baseline in Mean Sitting Pulse Pressure (MSPP) | Change from baseline to week 8 | -13.0 mm Hg | Standard Deviation 12.12 |
Secondary
Percentage of Patients Achieving Blood Pressure Control During 8 Weeks
The percentage of patients achieving the Blood Pressure control (defined as patients achieving a MSSBP \< 140 mm Hg and MSDBP \< 90 mm Hg) during 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). Data presented are cumulative. Cumulative refers to achieving blood pressure control before or at the 8 week visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted.
Time frame: 8 weeks
Population: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren HCTZ | Percentage of Patients Achieving Blood Pressure Control During 8 Weeks | 63.7 Percentage of patients |
| Ramipril | Percentage of Patients Achieving Blood Pressure Control During 8 Weeks | 30.0 Percentage of patients |
Secondary
Percentage of Responders (MSSBP < 140 mmHg or ≥ 20 mmHg Decrease From Baseline in MSSBP)
To compare the percentage of responders (as defined by patients with MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg) during 8 weeks of treatment with aliskiren HCTZ (150/12.5 mg, 300/25 mg) versus ramipril (5 mg, 10 mg). Data presented are cumulative. Cumulative refers to achieving the response before or at the 8 week visit. If response occurred more than once, only the first occurrence was counted.
Time frame: 8 weeks
Population: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren HCTZ | Percentage of Responders (MSSBP < 140 mmHg or ≥ 20 mmHg Decrease From Baseline in MSSBP) | 87.9 Percentage of patients |
| Ramipril | Percentage of Responders (MSSBP < 140 mmHg or ≥ 20 mmHg Decrease From Baseline in MSSBP) | 63.2 Percentage of patients |