Hypertension
Conditions
Keywords
Essential Hypertension, Stage II
Brief summary
This study will compare the efficacy and safety of once daily dosing of aliskiren monotherapy to once daily dosing of aliskiren and hydrochlorothiazide combination therapy in patients with Stage II hypertension over a period of 12 weeks.
Interventions
DRUGAliskiren/hydrochlorothiazide (HCTZ) (300/25 mg)
During the titration period, patients received aliskiren/hydrochlorothiazide (HCTZ) 150/12.5 mg for 1 week.
DRUGAliskiren (300 mg)
During the titration period, patients received aliskiren 150 mg for one week. Subsequently, patients were up-titrated and received aliskiren 300 mg.
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 Stage II hypertension, defined as mean sitting Systolic Blood Pressure (msSBP) ≥ 160 mmHg and \< 180 mmHg at Visit 2.
Exclusion criteria
* Severe hypertension defined as msSBP ≥ 180 mmHg and/or mean sitting Diastolic Blood Pressure (msDBP) ≥ 110 mmHg. * Secondary form of hypertension. * Current diagnosis of heart failure (New York Heart Association \[NYHA\] Class II-IV). * Current angina pectoris requiring pharmacological therapy (other than stable doses of oral or topical nitrates). * Second or third degree heart block without a pacemaker. * Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, atrial fibrillation or atrial flutter, during the 12 months prior to Visit 1. * Clinically significant valvular heart disease. * Previous history of hypertensive encephalopathy or stroke, Transcient Ischemic Attack (TIA), heart attack, coronary bypass surgery or any PCI. * Known Keith-Wagener grade III or IV hypertensive retinopathy. * In the month prior to Visit 1, patients on combination antihypertensive therapy that includes more than 2 classes of antihypertensive medications. * Patients on combined antihypertensive medication that contain two classes of antihypertensive medications are considered to take two antihypertensive medications. * Inability to discontinue prior antihypertensive or other CV medications as required by the protocol. * Patients with Type 1 diabetes mellitus. * Patients with Type 2 diabetes mellitus not well controlled . * Elevated Serum potassium (over 5.3 mEq/L (mmol/L). * Any surgical or medical condition or the use of any medication which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 12) | Baseline to end of study (Week 12) | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 | Baseline to Week 8 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | Baseline to Week 12 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. |
| Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | Baseline to Week 12 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. |
Countries
Argentina, Ecuador, Germany, Guatemala, Italy, Switzerland, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) During the titration period, patients received aliskiren/hydrochlorothiazide (HCTZ) 150/12.5 mg for 1 week. Subsequently, patients were up-titrated and received aliskiren/HCTZ 300/25 mg. | 349 |
| Aliskiren (300 mg) During the titration period, patients received aliskiren 150 mg for one week. Subsequently, patients were up-titrated and received aliskiren 300 mg. | 339 |
| Total | 688 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 3 |
| Overall Study | Abnormal test procedure result(s) | 2 | 12 |
| Overall Study | Adverse Event | 11 | 15 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Aliskiren (300 mg) | Total |
|---|---|---|---|
| Age Continuous | 57.4 years STANDARD_DEVIATION 10.33 | 56.4 years STANDARD_DEVIATION 10.73 | 56.9 years STANDARD_DEVIATION 10.53 |
| Sex: Female, Male Female | 169 Participants | 172 Participants | 341 Participants |
| Sex: Female, Male Male | 180 Participants | 167 Participants | 347 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 349 | 34 / 339 |
| serious Total, serious adverse events | 2 / 349 | 4 / 339 |
Outcome results
Primary
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 12)
At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings.
Time frame: Baseline to end of study (Week 12)
Population: Full analysis set (FAS): All randomized patients. For each patient, the last post-baseline measurement during the double-blind period was carried forward. n = number of patients with non-missing Week 12 measurement or last observation carried forward (LOCF) value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 12) | -30.01 mm Hg | Standard Error 1.053 |
| Aliskiren (300 mg) | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 12) | -20.29 mm Hg | Standard Error 1.067 |
Secondary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12
At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings.
Time frame: Baseline to Week 12
Population: Full analysis set (FAS): All randomized patients. For each patient, the last post-baseline measurement during the double-blind period was carried forward. n = number of patients with non-missing Week 8 or Week 12 measurement or last observation carried forward (LOCF) value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | Baseline to Week 8 | -13.69 mm Hg | Standard Error 0.599 |
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | Baseline to Week 12 | -12.64 mm Hg | Standard Error 0.59 |
| Aliskiren (300 mg) | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | Baseline to Week 8 | -7.99 mm Hg | Standard Error 0.607 |
| Aliskiren (300 mg) | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | Baseline to Week 12 | -8.18 mm Hg | Standard Error 0.598 |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings.
Time frame: Baseline to Week 8
Population: Full analysis set (FAS): All randomized patients. For each patient, the last post-baseline measurement during the double-blind period was carried forward. n = number of patients with non-missing Week 8 measurement or last observation carried forward (LOCF) value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 | -30.09 mm Hg | Standard Error 1.079 |
| Aliskiren (300 mg) | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 | -20.75 mm Hg | Standard Error 1.094 |
Secondary
Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12
At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings.
Time frame: Baseline to Week 12
Population: Full analysis set (FAS): All randomized patients. For each patient, the last post-baseline measurement during the double-blind period was carried forward. n = number of patients with non-missing Week 8 or Week 12 measurement or last observation carried forward (LOCF) value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | Baseline to Week 8 | 53.5 Percentage |
| Aliskiren/Hydrochlorothiazide (HCTZ) (300/25 mg) | Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | Baseline to Week 12 | 54.6 Percentage |
| Aliskiren (300 mg) | Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | Baseline to Week 8 | 30.4 Percentage |
| Aliskiren (300 mg) | Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | Baseline to Week 12 | 32.2 Percentage |