Hypertension
Conditions
Keywords
Hypertension, older population, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, amlodipine, stage 2
Brief summary
The purpose of the study is to evaluate the efficacy and safety of initial use of a fixed dose combination of aliskiren Hydrochlorothiazide (HCTZ) compared to Hydrochlorothiazide in older population with Stage 2 systolic hypertension.
Interventions
DRUGAliskiren
Aliskiren 150 mg for 1 week, Aliskiren 300 mg (with or without amlodipine)for 7 weeks
DRUGHydrochlorothiazide
Hydrochlorothiazide (HCTZ) 12.5 mg for week 1; Hydrochlorothiazide (HCTZ) 25 mg (with or without amlodipine)for 7 weeks
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female outpatients, ≥ 55 years old 2. Patients with essential hypertension 3. Prior to randomization: Patients must have an office cuff mean sitting Systolic Blood Pressure ≥ 160 mm Hg and \< 200 mm Hg 4. Patients who are eligible and able to participate in the study, and who are willing to give informed consent before any assessment is performed
Exclusion criteria
1. Office blood pressure measured by cuff (msSBP ≥ 200 mm Hg and/or msDBP ≥ 110 mm Hg) at Visits 1-5 2. History or evidence of a secondary hypertension of any etiology (e.g., uncorrected renal artery stenosis, pheochromocytoma). 3. History of hypertensive encephalopathy or heart failure (New York Heart Association \[NYHA\] Class II-IV) 4. Cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 1 year prior to Visit 1 5. Serum sodium less than the lower limit of normal, serum potassium \< 3.5 mEq/L (corresponding to 3.5 mmol/L) or ≥ 5.3 mEq/L (corresponding to 5.3 mmol/L), or dehydration at Visit 1. 6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL) 7. Use of other investigational drugs within 30 days of enrollment. Other exclusions may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4 | Baseline and Week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4 | Baseline and Week 4 | — |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 | Baseline and Week 8 | — |
| Percentage of Responders at Week 4 and Week 8 | At 4 weeks and 8 weeks | Responders defined as mean sitting Systolic Blood Pressure \< 140 mmHg or reduction of ≥ 20 mmHg from baseline |
| Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 | At Weeks 4 and 8 | Blood pressure control defined as mean sitting Systolic Blood Pressure \< 140 mm Hg and mean sitting Diastolic Blood Pressure \< 90 mm Hg |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/HCTZ Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks | 228 |
| HCTZ Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks | 223 |
| Total | 451 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 | 0 |
| Overall Study | Abnormal test procedure result(s) | 1 | 0 |
| Overall Study | Administrative Problems | 0 | 1 |
| Overall Study | Adverse Event | 13 | 7 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Patient withdrew consent | 3 | 3 |
| Overall Study | Protocol deviation | 2 | 4 |
Baseline characteristics
| Characteristic | Aliskiren/HCTZ | HCTZ | Total |
|---|---|---|---|
| Age Continuous | 64.5 years STANDARD_DEVIATION 7.57 | 65.1 years STANDARD_DEVIATION 6.96 | 64.8 years STANDARD_DEVIATION 7.27 |
| Sex: Female, Male Female | 127 Participants | 100 Participants | 227 Participants |
| Sex: Female, Male Male | 101 Participants | 123 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 227 | 26 / 223 |
| serious Total, serious adverse events | 4 / 227 | 3 / 223 |
Outcome results
Primary
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4
Time frame: Baseline and Week 4
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4 | -29.6 mm Hg | Standard Error 1 |
| HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4 | -22.3 mm Hg | Standard Error 1 |
Secondary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4
Time frame: Baseline and Week 4
Population: Full analysis set, restricted to baseline msDBP \>= 90 mmHg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/HCTZ | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4 | -11.1 mm Hg | Standard Error 0.8 |
| HCTZ | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4 | -9.2 mm Hg | Standard Error 0.8 |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8
Time frame: Baseline and Week 8
Population: Full analysis set, restricted for msDBP to those with baseline msDBP at least 90 mm Hg)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren/HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 | msSBP | -33.2 mm Hg | Standard Error 1 |
| Aliskiren/HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 | msDBP (N = 130 , 133) | -13.3 mm Hg | Standard Error 0.8 |
| HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 | msSBP | -25.7 mm Hg | Standard Error 1 |
| HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 | msDBP (N = 130 , 133) | -10.1 mm Hg | Standard Error 0.8 |
Secondary
Percentage of Responders at Week 4 and Week 8
Responders defined as mean sitting Systolic Blood Pressure \< 140 mmHg or reduction of ≥ 20 mmHg from baseline
Time frame: At 4 weeks and 8 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/HCTZ | Percentage of Responders at Week 4 and Week 8 | Week 4 | 73.3 Percentage of Participants |
| Aliskiren/HCTZ | Percentage of Responders at Week 4 and Week 8 | Week 8 | 83.1 Percentage of Participants |
| HCTZ | Percentage of Responders at Week 4 and Week 8 | Week 4 | 55.9 Percentage of Participants |
| HCTZ | Percentage of Responders at Week 4 and Week 8 | Week 8 | 67.6 Percentage of Participants |
Secondary
Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8
Blood pressure control defined as mean sitting Systolic Blood Pressure \< 140 mm Hg and mean sitting Diastolic Blood Pressure \< 90 mm Hg
Time frame: At Weeks 4 and 8
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/HCTZ | Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 | week 4 | 49.8 Percentage of Participants |
| Aliskiren/HCTZ | Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 | week 8 | 62.2 Percentage of Participants |
| HCTZ | Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 | week 4 | 33.3 Percentage of Participants |
| HCTZ | Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 | week 8 | 39.2 Percentage of Participants |