Hypertension
Conditions
Keywords
Systolic hypertension, hypertension, aliskiren, blood pressure, ramipril, HTN
Brief summary
Evaluate the systolic blood pressure lowering effect of aliskiren 150mg and 300mg compared to ramipril 5mg and 10mg in elderly patients with essential systolic hypertension.
Interventions
DRUGAliskiren
Aliskiren 150 mg and 300 mg tablets taken orally, once a day in the morning
DRUGRamipril
Ramipril 5 mg and 10 mg capsules taken orally, once a day in the morning
DRUGHydrochlorothiazide
Hydrochlorothiazide 12.5 or 25 mg capsules taken orally, once a day in the morning
DRUGAmlodipine
Amlodipine 5 mg or 10 mg tablets taken orally, once a day in the morning
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients ≥ 65 years old. * Patients with essential hypertension with an msSBP ≥ 140 mmHg and \< 180 mmHg, and msDBP \< 110 mmHg at Visits 2 and 3. (Visit 201 was deleted by the Administrative Changes document.) * Patients must have had a difference in msSBP of ≤ 20 mmHg between Visit 3 and the visit immediately prior to Visit 3. * Patients who were eligible and able to participate in the study, and who consented to do so after the purpose and nature of the investigation had been explained to them (written informed consent).
Exclusion criteria
* History of renal artery stenosis. * Known Keith-Wagener grade III or IV hypertensive retinopathy. * History of hypertensive encephalopathy. * Current diagnosis of heart failure (New York Heart Association Class III-IV). * History of transient ischemic cerebral attack or cerebrovascular accident within 6 months. * History of myocardial infarction, bypass surgery, or any percutaneous coronary intervention within 6 months. * Current unstable angina pectoris. Patients on a stable dose of oral or topical nitrates or beta blockers for angina were acceptable. * Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. * Clinically significant valvular heart disease. * Concurrent use of any antihypersensitive medications except a stable dose 3 months prior to visit 1 of alpha adrenergic blockers for benign prostatic hypertrophy (e.g., Flomax for BPH), beta blockers for angina, or beta blockers ophthalmic preparations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12 | Baseline and Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Cough | Weeks 12 and 36 | — |
| Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints | Weeks 12 and 36 | Blood pressure control is defined as a mean sitting blood pressure \< 140/90 mm Hg |
| Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36 | Baseline and week 36 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Based Treatment Regimen Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg | 457 |
| Ramipril Based Treatment Regimen Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg | 444 |
| Total | 901 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 33 | 49 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 8 | 6 |
| Overall Study | Patient withdrew consent | 32 | 28 |
| Overall Study | Protocol deviation | 7 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 31 | 24 |
Baseline characteristics
| Characteristic | Aliskiren Based Treatment Regimen | Ramipril Based Treatment Regimen | Total |
|---|---|---|---|
| Age Continuous | 72.0 years STANDARD_DEVIATION 5.56 | 72.2 years STANDARD_DEVIATION 5.62 | 72.1 years STANDARD_DEVIATION 5.58 |
| Age, Customized 65 - 74 years | 312 participants | 296 participants | 608 participants |
| Age, Customized 75 years and older | 145 participants | 148 participants | 293 participants |
| Sex: Female, Male Female | 235 Participants | 237 Participants | 472 Participants |
| Sex: Female, Male Male | 222 Participants | 207 Participants | 429 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 170 / 452 | 181 / 444 |
| serious Total, serious adverse events | 35 / 452 | 27 / 444 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12
Time frame: Baseline and Week 12
Population: Intent to treat (ITT), Last Observation Carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren Based Treatment Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12 | -13.96 mm Hg | Standard Error 0.754 |
| Ramipril Based Treatment Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12 | -11.64 mm Hg | Standard Error 0.759 |
Secondary
Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36
Time frame: Baseline and week 36
Population: Intent to treat (ITT), Last Observation Carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren Based Treatment Regimen | Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36 | -8.24 mm Hg | Standard Error 0.409 |
| Ramipril Based Treatment Regimen | Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36 | -7.02 mm Hg | Standard Error 0.411 |
Secondary
Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints
Blood pressure control is defined as a mean sitting blood pressure \< 140/90 mm Hg
Time frame: Weeks 12 and 36
Population: intent to treat (ITT), last observation carried forward (LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren Based Treatment Regimen | Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints | week 12 endpoint | 46.3 Percentage of participants |
| Aliskiren Based Treatment Regimen | Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints | week 36 endpoint | 65.6 Percentage of participants |
| Ramipril Based Treatment Regimen | Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints | week 36 endpoint | 57.5 Percentage of participants |
| Ramipril Based Treatment Regimen | Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints | week 12 endpoint | 39.3 Percentage of participants |
Secondary
Percentage of Patients With Cough
Time frame: Weeks 12 and 36
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Aliskiren Based Treatment Regimen | Percentage of Patients With Cough | Week 12 | 3.1 Percentage of Participants | 0.788 |
| Aliskiren Based Treatment Regimen | Percentage of Patients With Cough | Week 36 | 4.4 Percentage of Participants | — |
| Ramipril Based Treatment Regimen | Percentage of Patients With Cough | Week 12 | 9.9 Percentage of Participants | 0.794 |
| Ramipril Based Treatment Regimen | Percentage of Patients With Cough | Week 36 | 14.2 Percentage of Participants | — |