Stage 2 Systolic Hypertension
Conditions
Keywords
Hypertension, combination therapy, valsartan, cardiovascular diseases
Brief summary
This study will compare the antihypertensive efficacy and safety of a valsartan/amlodipine-based treatment with a losartan-based treatment in patients with Stage 2 systolic hypertension (high blood pressure, mean systolic blood pressure greater than 160 and less than 200 mmHg).
Interventions
DRUGvalsartan, amlodipine, HCTZ
combination Valsartan/amlodipine160/5 mg tablet for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (6 weeks) of the study
DRUGLosartan, HCTZ followed by valsartan, amlodipine, HCTZ
losartan 100mg capsule for 3 weeks; losartan 100mg capsule +HCTZ 25 mg capsule for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (3 weeks) of the study
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
* Male or female outpatient of 18 years of age or greater * Stage 2 systolic hypertension defined as office Mean Sitting Systolic blood pressure (MSSBP) greater than or equal to 160 and \< 200 mmHg at randomization * Patients who were able to participate in the study, and who gave written informed consent before any study assessment was performed.
Exclusion criteria
* Office systolic blood pressure \>200 and/or mean sitting diastolic blood pressure (MSDBP) greater than or equal to 110 mmHg at Visit 1. * Use of four (4) or more antihypertensive medications within 30 days of Visit 1. * Refractory hypertension, defined as blood pressure \>140/90 mmHg while taking three (3) drugs at the maximum dose of each drug, one of which must be a diuretic. (Therapy with a fixed-dose combination of two active medications represents two drugs). * Inability to safely discontinue all antihypertensive medications for 1-2 weeks prior to randomization. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Baseline to Week 6 | To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Patients Achieving Blood Pressure Control | 3 and 6 weeks | To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP \< 140 mmHg and MSDBP \< 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. |
| Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Baseline to Week 6 | To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. |
| Cumulative Percentage of Treatment Responders | 3 and 6 weeks | To compare the percentage of treatment responders (defined as patients with MSSBP \< 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. |
| Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Baseline to week 12 | To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. |
| Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | 3, 6, 9 and 12 weeks | To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valsartan/Amlodipine/HCTZ Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study. | 241 |
| Losartan/HCTZ Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study. | 247 |
| Total | 488 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure results | 2 | 0 |
| Overall Study | Adverse Event | 16 | 10 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Patient withdrew consent | 4 | 9 |
| Overall Study | Protocol deviation | 1 | 2 |
| Overall Study | Unsatisfactory therapeutic effects | 5 | 12 |
Baseline characteristics
| Characteristic | Valsartan/Amlodipine/HCTZ | Losartan/HCTZ | Total |
|---|---|---|---|
| Age Continuous | 55.0 years STANDARD_DEVIATION 9.83 | 57.1 years STANDARD_DEVIATION 9.69 | 56.1 years STANDARD_DEVIATION 9.81 |
| Sex: Female, Male Female | 102 Participants | 111 Participants | 213 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 / 241 | 8 / 247 |
| serious Total, serious adverse events | 1 / 241 | 2 / 247 |
Outcome results
Primary
Change in Mean Sitting Systolic Blood Pressure After 6 Weeks
To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: Baseline to Week 6
Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Baseline | 166.8 mmHg | Standard Deviation 7.03 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Week 6 | 135.5 mmHg | Standard Deviation 16.26 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Change from Baseline to Week 6 | -31.3 mmHg | Standard Deviation 15.87 |
| Losartan/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Baseline | 168.5 mmHg | Standard Deviation 9.03 |
| Losartan/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Week 6 | 142.5 mmHg | Standard Deviation 18.89 |
| Losartan/HCTZ | Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | Change from Baseline to Week 6 | -26.0 mmHg | Standard Deviation 16.62 |
Secondary
Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks
To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: Baseline to Week 6
Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Baseline | 98.6 mmHg | Standard Deviation 7.71 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Week 6 | 85.1 mmHg | Standard Deviation 10.05 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Change from Baseline to Week 6 | -13.6 mmHg | Standard Deviation 9.48 |
| Losartan/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Baseline | 97.6 mmHg | Standard Deviation 7.88 |
| Losartan/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Week 6 | 88.5 mmHg | Standard Deviation 11.36 |
| Losartan/HCTZ | Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | Change from Baseline to Week 6 | -9.1 mmHg | Standard Deviation 10.03 |
Secondary
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: Baseline to week 12
Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Baseline MSSBP | 166.8 mmHg | Standard Deviation 7.03 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Week 12 MSSBP | 130.8 mmHg | Standard Deviation 16.22 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Change in MSSBP from baseline to Week 12 | -36.0 mmHg | Standard Deviation 16.08 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Baseline MSDBP | 98.6 mmHg | Standard Deviation 7.71 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Week 12 MSDBP | 82.5 mmHg | Standard Deviation 10.18 |
| Valsartan/Amlodipine/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Change in MSDBP from baseline to Week 12 | -16.1 mmHg | Standard Deviation 9.91 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Week 12 MSDBP | 82.5 mmHg | Standard Deviation 11.43 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Baseline MSSBP | 168.5 mmHg | Standard Deviation 9.03 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Baseline MSDBP | 97.6 mmHg | Standard Deviation 7.88 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Week 12 MSSBP | 134.3 mmHg | Standard Deviation 19.41 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Change in MSDBP from baseline to Week 12 | -15.1 mmHg | Standard Deviation 10.57 |
| Losartan/HCTZ | Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | Change in MSSBP from baseline to Week 12 | -34.2 mmHg | Standard Deviation 17.69 |
Secondary
Cumulative Percentage of Patients Achieving Blood Pressure Control
To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP \< 140 mmHg and MSDBP \< 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: 3 and 6 weeks
Population: Full Analysis Set (FAS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients Achieving Blood Pressure Control | Week 3 | 30.5 cumulative percentage of patients |
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients Achieving Blood Pressure Control | Week 6 | 61.5 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients Achieving Blood Pressure Control | Week 3 | 15.3 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients Achieving Blood Pressure Control | Week 6 | 47.1 cumulative percentage of patients |
Secondary
Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: 3, 6, 9 and 12 weeks
Population: Full Analysis Set (FAS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 3 | 0.8 cumulative percentage of patients |
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 6 | 0.8 cumulative percentage of patients |
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 9 | 1.3 cumulative percentage of patients |
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 12 | 2.9 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 12 | 4.5 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 3 | 0.8 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 9 | 0.8 cumulative percentage of patients |
| Losartan/HCTZ | Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | Week 6 | 0.8 cumulative percentage of patients |
Secondary
Cumulative Percentage of Treatment Responders
To compare the percentage of treatment responders (defined as patients with MSSBP \< 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time frame: 3 and 6 weeks
Population: Full Analysis Set (FAS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Treatment Responders | Week 3 | 65.3 Cumulative percentage of responders |
| Valsartan/Amlodipine/HCTZ | Cumulative Percentage of Treatment Responders | Week 6 | 87.0 Cumulative percentage of responders |
| Losartan/HCTZ | Cumulative Percentage of Treatment Responders | Week 3 | 34.3 Cumulative percentage of responders |
| Losartan/HCTZ | Cumulative Percentage of Treatment Responders | Week 6 | 71.5 Cumulative percentage of responders |