Hypertension
Conditions
Keywords
Hypertension, Aliskiren, Amlodipine, HCTZ, Systolic blood pressure, Diastolic blood pressure, Stage II, Combination
Brief summary
The purpose of the study is to compare the combination of aliskiren, amlodipine and Hydrochlorothiazide (HCTZ) versus the combination of aliskiren and amlodipine as therapy in minority Stage 2 hypertensive patients.
Interventions
Amlodipine capsule (5 mg) Aliskiren/Amlodipine tablets (150/5 mg, 300/5 mg, 300/10 mg)
DRUGAliskiren/Amlodipine and Hydrochlorothiazide (HCTZ)
Aliskiren/Amlodipine tablets (150/5 mg, 300/5 mg, 300/10 mg) HCTZ capsule (12.5 mg, 25mg)
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 newly diagnosed or have a history of hypertension, who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed. * Men or women 18 years and older of minority background; self-identified. * Patients with stage 2 hypertension defined as MSSBP ≥160 mmHg and \<200 mmHg at Visit 5 (randomization).
Exclusion criteria
* Patients with MSDBP ≥110 mmHg and/or MSSBP ≥200 mmHg as measured by office cuff at any visit. * Patients on 4 or more antihypertensive medications. * Patients with uncontrolled hypertension (MSSBP \>180 mmHg) taking more than 1 antihypertensive medication at Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Baseline and week 8 | To evaluate change from baseline in MSSBP after 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Baseline and week 8 | To evaluate change from baseline in MSDBP after 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. |
| Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | 8 weeks | To evaluate the cumulative percentage of patients achieving Blood Pressure control (defined as patients achieving an MSSBP \<140 mmHg and MSDBP \<90 mmHg) during 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. Cumulative refers to achieving BP control before or at the corresponding visit. |
| Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | 8 weeks | To compare the cumulative percentage of responders (defined as patients with MSSBP \<140 mmHg or a decrease from baseline ≥20 mmHg) during 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. Cumulative refers to achieving a response before or at the corresponding visit. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Baseline, Week 2 and Week 4 | Primary objective at additional timepoint. |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Baseline, Week 2 and Week 4 | Secondary objective at additional timepoint. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren / Amlodipine / HCTZ At week 0 patients were randomized to aliskiren/amlodipine 150/5 mg. At week 1, patients were force titrated to aliskiren/amlodipine/HCTZ 150/5/12.5 mg. At week 2, patients were force titrated to aliskiren/amlodipine/HCTZ 300/5/25 mg. At week 4, patients were force titrated to aliskiren/amlodipine/HCTZ 300/10/25 mg. | 202 |
| Aliskiren / Amlodipine At week 0 patients were randomized to amlodipine 5 mg. At week 1, patients were force titrated to aliskiren/amlodipine 150/5 mg. At week 2, patients were force titrated to aliskiren/amlodipine 300/5 mg. At week 4, patients were force titrated to aliskiren/amlodipine 300/10 mg. | 209 |
| Total | 411 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 | 0 |
| Overall Study | Adverse Event | 7 | 4 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Patient withdrew consent | 5 | 8 |
| Overall Study | Protocol deviation | 1 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 1 |
Baseline characteristics
| Characteristic | Aliskiren / Amlodipine / HCTZ | Aliskiren / Amlodipine | Total |
|---|---|---|---|
| Age Continuous | 55.7 years STANDARD_DEVIATION 9.79 | 54.7 years STANDARD_DEVIATION 10.19 | 55.2 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 107 Participants | 100 Participants | 207 Participants |
| Sex: Female, Male Male | 95 Participants | 109 Participants | 204 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 202 | 18 / 209 |
| serious Total, serious adverse events | 0 / 202 | 3 / 209 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
To evaluate change from baseline in MSSBP after 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension.
Time frame: Baseline and week 8
Population: Analysis was based on the Full Analysis Set consisting of all patients to whom study medication had been assigned. Last-observation-carried-forward was used. Baseline was not carried forward. In the Aliskiren/Amlodipine/HCTZ group, 5 patients did not have a post baseline measure. Hence, change from baseline to week 8 is reported for 197 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Baseline [N=202, 209] | 167.08 mmHg | Standard Deviation 7.277 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Week 8 [N=197, 209] | 130.73 mmHg | Standard Deviation 13.06 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Change from baseline to week 8 [N=197, 209] | -36.43 mmHg | Standard Deviation 13.904 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Baseline [N=202, 209] | 167.41 mmHg | Standard Deviation 7.118 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Week 8 [N=197, 209] | 137.87 mmHg | Standard Deviation 16.013 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Change from baseline to week 8 [N=197, 209] | -29.54 mmHg | Standard Deviation 15.674 |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
To evaluate change from baseline in MSDBP after 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension.
Time frame: Baseline and week 8
Population: Analysis was based on the Full Analysis Set consisting of all patients to whom study medication had been assigned. Last-observation-carried-forward was used. Baseline was not carried forward. In the Aliskiren/Amlodipine/HCTZ group, 5 patients did not have a post baseline measure. Hence, change from baseline to week 8 is reported for 197 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Baseline [N=202, 209] | 95.25 mmHg | Standard Deviation 8.985 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Change from baseline to week 8 [N=197, 209] | -15.10 mmHg | Standard Deviation 9.707 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Week 8 [N=197, 209] | 80.10 mmHg | Standard Deviation 10.317 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Change from baseline to week 8 [N=197, 209] | -12.08 mmHg | Standard Deviation 9.062 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Baseline [N=202, 209] | 95.25 mmHg | Standard Deviation 8.342 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Week 8 [N=197, 209] | 83.17 mmHg | Standard Deviation 10.116 |
Secondary
Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks
To evaluate the cumulative percentage of patients achieving Blood Pressure control (defined as patients achieving an MSSBP \<140 mmHg and MSDBP \<90 mmHg) during 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. Cumulative refers to achieving BP control before or at the corresponding visit.
Time frame: 8 weeks
Population: Analysis was based on the Full Analysis Set (FAS) consisting of all patients to whom study medication had been assigned.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 2 | 50.5 Percentage of Participants |
| Aliskiren / Amlodipine / HCTZ | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 4 | 74.8 Percentage of Participants |
| Aliskiren / Amlodipine / HCTZ | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 8 | 81.7 Percentage of Participants |
| Aliskiren / Amlodipine | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 2 | 40.2 Percentage of Participants |
| Aliskiren / Amlodipine | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 4 | 57.4 Percentage of Participants |
| Aliskiren / Amlodipine | Percentage of Patients Achieving Blood Pressure Control (Defined as MSSBP < 140 mmHg and MSDBP < 90 mmHg) During 8 Weeks | Week 8 | 67.9 Percentage of Participants |
Secondary
Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks.
To compare the cumulative percentage of responders (defined as patients with MSSBP \<140 mmHg or a decrease from baseline ≥20 mmHg) during 8 weeks of treatment with an aliskiren, amlodipine, and HCTZ treatment regimen versus an aliskiren and amlodipine treatment regimen in minority patients with Stage 2 hypertension. Cumulative refers to achieving a response before or at the corresponding visit.
Time frame: 8 weeks
Population: Analysis was based on the Full Analysis Set (FAS) consisting of all patients to whom study medication had been assigned.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 2 | 79.2 Percentage of Responders |
| Aliskiren / Amlodipine / HCTZ | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 4 | 91.1 Percentage of Responders |
| Aliskiren / Amlodipine / HCTZ | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 8 | 92.6 Percentage of Responders |
| Aliskiren / Amlodipine | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 2 | 72.2 Percentage of Responders |
| Aliskiren / Amlodipine | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 4 | 84.7 Percentage of Responders |
| Aliskiren / Amlodipine | Percentage of Responders (Defined as Patients With MSSBP < 140 mmHg or a Reduction From Baseline in MSSBP of ≥20 mmHg) During 8 Weeks. | Week 8 | 91.9 Percentage of Responders |
Other Pre-specified
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4
Secondary objective at additional timepoint.
Time frame: Baseline, Week 2 and Week 4
Population: Analysis was based on the Full Analysis Set consisting of all patients to whom study medication had been assigned. Last-observation-carried-forward was used. Baseline was not carried forward. In the Aliskiren/Amlodipine/HCTZ group, 5 patients did not have a post baseline measure. Hence, change from baseline is reported for 197 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Baseline [N=202, 209] | 95.25 mmHg | Standard Deviation 8.985 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Week 2 [N=197, 209] | 84.26 mmHg | Standard Deviation 9.597 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Change from baseline to week 2 [N=197, 209] | -10.95 mmHg | Standard Deviation 8.569 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Week 4 [N=197, 209] | 81.29 mmHg | Standard Deviation 9.177 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Change from baseline to week 4 [N=197, 209] | -13.92 mmHg | Standard Deviation 8.891 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Change from baseline to week 4 [N=197, 209] | -9.91 mmHg | Standard Deviation 7.606 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Baseline [N=202, 209] | 95.25 mmHg | Standard Deviation 8.342 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Change from baseline to week 2 [N=197, 209] | -9.01 mmHg | Standard Deviation 7.872 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Week 2 [N=197, 209] | 86.24 mmHg | Standard Deviation 8.908 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 2 and Week 4 | Week 4 [N=197, 209] | 85.35 mmHg | Standard Deviation 9.567 |
Other Pre-specified
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4
Primary objective at additional timepoint.
Time frame: Baseline, Week 2 and Week 4
Population: Analysis was based on the Full Analysis Set consisting of all patients to whom study medication had been assigned. Last-observation-carried-forward was used. Baseline was not carried forward. In the Aliskiren/Amlodipine/HCTZ group, 5 patients did not have a post baseline measure. Hence, change from baseline is reported for 197 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Baseline [N=202, 209] | 167.08 mmHg | Standard Deviation 7.277 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Week 2 [N=197, 209] | 138.35 mmHg | Standard Deviation 12.578 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Change from baseline to week 4 [N=197, 209] | -34.74 mmHg | Standard Deviation 12.145 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Change from baseline to week 2 [N=197, 209] | -28.81 mmHg | Standard Deviation 12.64 |
| Aliskiren / Amlodipine / HCTZ | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Week 4 [N=197, 209] | 132.42 mmHg | Standard Deviation 12.027 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Change from baseline to week 4 [N=197, 209] | -26.98 mmHg | Standard Deviation 13.389 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Baseline [N=202, 209] | 167.41 mmHg | Standard Deviation 7.118 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Week 2 [N=197, 209] | 143.77 mmHg | Standard Deviation 13.922 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Week 4 [N=197, 209] | 140.43 mmHg | Standard Deviation 13.961 |
| Aliskiren / Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 2 and Week 4 | Change from baseline to week 2 [N=197, 209] | -23.64 mmHg | Standard Deviation 13.673 |