Hypertension
Conditions
Keywords
Hypertension, Metabolic Syndrome, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, stage 2
Brief summary
The purpose of the study is to evaluate the blood pressure lowering effect and safety of aliskiren in combination with Hydrochlorothiazide (HCTZ) compared to aliskiren monotherapy when given to metabolic syndrome patients with stage 2 systolic hypertension (mean sitting systolic blood pressure \[msSBP\] ≥ 160 mm Hg and \< 200 mm Hg).
Interventions
DRUGAliskiren
Aliskiren 150 mg or 300 mg taken once daily in oral form
DRUGHydrochlorothiazide
Hydrochlorothiazide 12.5 mg or 25 mg taken once daily in oral form.
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 old. * Patients with stage 2 systolic hypertension. Patients must have a msSBP ≥160 mmHg and \<200 mmHg at Study Visit 5 (randomization). * Patients who have stage 2 systolic hypertension that meet at least 2 additional components of the metabolic syndrome as defined by the National \*Cholesterol Education program (NCEP) criteria: * Abdominal obesity (waist circumference \> than 102 cm for men and \> 88 cm for women) * Current triglycerides ≥ 150 mg/dL or medical treatment for this condition. * Current HDL- Cholesterol \<40 mg/dL in men and \<50 mg/dL in women or medical treatment for this condition. * Fasting glucose \>100 mg/dL and \<126 mg/dL
Exclusion criteria
* Office blood pressure measured by cuff (msDBP ≥ 110 mmHg and or msSBP ≥ 200 mmHg) at any visit. * Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever 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 medications or to drugs belonging to a similar therapeutic class (diuretics or renin inhibitors) as the study drugs. * History or evidence of 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 (140/90mmHg). Therapy with a fixed dose combination of two active substances represent two drugs. * Patients on 4 or more antihypertensive medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 8 in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline and Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Mean Sitting Diastolic Blood Pressure (msDBP) | 8 weeks | — |
| Percentage of Participants With Blood Pressure Response at Week 8 | 8 weeks | Response is defined as a patient with msSBP \< 140 mmHg or a decrease from baseline ≥ 20 mmHg in msSBP during eight weeks of treatment. |
| Percentage of Patients Achieving Blood Pressure Control at Week 8 | 8 weeks | Blood pressure control is defined as a patient who achieves a target Blood Pressure of mean sitting Systolic Blood Pressure / mean sitting Diastolic Blood pressure \< 140/90 mmHg. |
| Change From Baseline to Week 8 in Pulse Pressure | Baseline and Week 8 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/HCTZ Aliskiren (150 mg) plus Hydrochlorothiazide (12.5 mg) for one week. Subsequently up-titrated to Aliskiren (300 mg) plus Hydrochlorothiazide (25 mg). Medication was taken once daily in oral form. | 267 |
| Aliskiren Aliskiren (150 mg) for one week. Subsequently up-titrated to Aliskiren (300 mg). Medication was taken once daily in oral form. | 265 |
| Total | 532 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Patient withdrew consent | 12 | 6 |
| Overall Study | Protocol Deviation | 1 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 13 |
Baseline characteristics
| Characteristic | Aliskiren/HCTZ | Aliskiren | Total |
|---|---|---|---|
| Age Continuous | 54.4 years STANDARD_DEVIATION 11.09 | 53.5 years STANDARD_DEVIATION 10.87 | 53.9 years STANDARD_DEVIATION 10.98 |
| Age, Customized < 65 | 217 participants | 233 participants | 450 participants |
| Age, Customized >= 65 | 50 participants | 32 participants | 82 participants |
| Sex: Female, Male Female | 128 Participants | 129 Participants | 257 Participants |
| Sex: Female, Male Male | 139 Participants | 136 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 267 | 18 / 265 |
| serious Total, serious adverse events | 3 / 267 | 4 / 265 |
Outcome results
Primary
Change From Baseline to Week 8 in Mean Sitting Systolic Blood Pressure (msSBP)
Time frame: Baseline and Week 8
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/HCTZ | Change From Baseline to Week 8 in Mean Sitting Systolic Blood Pressure (msSBP) | -30.38 mm Hg | Standard Error 1.01 |
| Aliskiren | Change From Baseline to Week 8 in Mean Sitting Systolic Blood Pressure (msSBP) | -20.15 mm Hg | Standard Error 1.01 |
Secondary
Change From Baseline to Week 8 in Mean Sitting Diastolic Blood Pressure (msDBP)
Time frame: 8 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/HCTZ | Change From Baseline to Week 8 in Mean Sitting Diastolic Blood Pressure (msDBP) | -11.26 mm Hg | Standard Error 0.59 |
| Aliskiren | Change From Baseline to Week 8 in Mean Sitting Diastolic Blood Pressure (msDBP) | -6.90 mm Hg | Standard Error 0.6 |
Secondary
Change From Baseline to Week 8 in Pulse Pressure
Time frame: Baseline and Week 8
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/HCTZ | Change From Baseline to Week 8 in Pulse Pressure | -18.96 mm Hg | Standard Error 0.74 |
| Aliskiren | Change From Baseline to Week 8 in Pulse Pressure | -13.33 mm Hg | Standard Error 0.74 |
Secondary
Percentage of Participants With Blood Pressure Response at Week 8
Response is defined as a patient with msSBP \< 140 mmHg or a decrease from baseline ≥ 20 mmHg in msSBP during eight weeks of treatment.
Time frame: 8 weeks
Population: full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/HCTZ | Percentage of Participants With Blood Pressure Response at Week 8 | 78.4 Percentage of Participants |
| Aliskiren | Percentage of Participants With Blood Pressure Response at Week 8 | 55.2 Percentage of Participants |
Secondary
Percentage of Patients Achieving Blood Pressure Control at Week 8
Blood pressure control is defined as a patient who achieves a target Blood Pressure of mean sitting Systolic Blood Pressure / mean sitting Diastolic Blood pressure \< 140/90 mmHg.
Time frame: 8 weeks
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/HCTZ | Percentage of Patients Achieving Blood Pressure Control at Week 8 | 58.7 Percentage of Participants |
| Aliskiren | Percentage of Patients Achieving Blood Pressure Control at Week 8 | 34.5 Percentage of Participants |