Hypertension
Conditions
Keywords
Hypertension, African Americans, Aliskiren, Amlodipine, Systolic blood pressure, Diastolic blood pressure, Stage II, Combination
Brief summary
The purpose of the study is to evaluate the BP-lowering efficacy of the combination of aliskiren and amlodipine, as initial therapy, compared to amlodipine monotherapy in African American patients with Stage II hypertension.
Interventions
Aliskiren/Amlodipine 150 mg/5 mg titrated to 300 mg/10 mg
DRUGAmlodipine
Amlodipine 5 mg titrated to 10mg
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
* Men or women of African American background; self identified * Patients with stage 2 hypertension defined as MSSBP ≥ 160 mmHg and \< 200 mmHg at Visit 5 (randomization
Exclusion criteria
* Office blood pressure measured by cuff (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 200 mmHg) * Patients on 4 or more antihypertensive medications. * Patients with uncontrolled hypertension (MSSBP \>180 mmHg) taking more than 1 antihypertensive medication at Visit 1 * 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 (140/90 mmHg). Therapy with a fixed dose combination of two active substances represent two drugs. * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. * Evidence of a secondary form of hypertension, including but not limited to any of the following: * coarctation of the aorta * hyperaldosteronism * unilateral or bilateral renal artery stenosis * Cushing's disease * polycystic kidney disease * pheochromocytoma * Known Keith-Wagener grade III or IV hypertensive retinopathy. * History of angioedema due to usage of an ARB or ACE inhibitor. * History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, heart failure (NYHA Class II-IV), coronary bypass graft surgery (CABG), percutaneous coronary intervention (PCI), unstable angina pectoris, or myocardial infarction in the last 12 months Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline, 8 weeks | To compare the change from baseline in mean sitting systolic blood pressure (msSBP) after 8 weeks of treatment with a combination of aliskiren and amlodipine treatment regimen (150/5 mg, 300/10 mg) versus an amlodipine treatment regimen (5 mg, 10 mg) in African American patients with Stage 2 hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Peripheral Edema by Visit | 8 weeks | Cumulative percentage of patients with peripheral edema was calculated. 'Cumulative' refers to patients with peripheral edema before or at the corresponding visit. If peripheral edema occurred more than once, only the first occurrence was counted. Peripheral edema is the swelling of tissues due to the accumulation of fluids. Peripheral edema was assessed by investigators during physical examination. |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline, 8 weeks | To compare the change from baseline in mean sitting diastolic blood pressure (msDBP) after 8 weeks of treatment with a combination of aliskiren and amlodipine treatment regimen (150/5 mg, 300/10 mg) versus an amlodipine treatment regimen (5 mg, 10 mg). |
| Percentage of Patients Achieving Blood Pressure (BP) Control (<140/90 mmHg) | 8 weeks | Cumulative percentage of patients achieving BP control (\<140/90 mmHg)for both treatment arms was calculated. Cumulative refers to achieving blood pressure control before or at the corresponding visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted. |
| Percentage of Responders (Patients With MSSBP < 140 mmHg or Decrease From Baseline of Greater Than or Equal to 20 mmHg) | 8 weeks | Cumulative percentage of responders (Responders are defined as patients with MSSBP \<140 mmHg or a decrease from baseline ≥20 mmHg) during 8 weeks of treatment was calculated. Cumulative refers to achieving blood pressure control before or at the corresponding visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted. |
| Change From Baseline in MSSBP at Week 1 and 4 | Baseline, 1 and 4 weeks | Compare the change from baseline in MSSBP at week 1 and 4 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren/Amlodipine Aliskiren/Amlodipine 150 mg/5 mg titrated to 300 mg/10 mg | 220 |
| Amlodipine Amlodipine 5mg titrated to 10 mg | 223 |
| Total | 443 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 |
| Overall Study | Lost to Follow-up | 1 | 6 |
| Overall Study | Protocol deviation | 0 | 3 |
| Overall Study | Subject withdrew consent | 4 | 5 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 2 |
Baseline characteristics
| Characteristic | Aliskiren/Amlodipine | Amlodipine | Total |
|---|---|---|---|
| Age Continuous | 53.2 years STANDARD_DEVIATION 9.33 | 52.4 years STANDARD_DEVIATION 10.57 | 52.8 years STANDARD_DEVIATION 9.97 |
| Age, Customized <55 years | 123 participants | 127 participants | 250 participants |
| Age, Customized ≥55 years | 97 participants | 96 participants | 193 participants |
| Sex: Female, Male Female | 123 Participants | 115 Participants | 238 Participants |
| Sex: Female, Male Male | 97 Participants | 108 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 220 | 31 / 223 |
| serious Total, serious adverse events | 1 / 220 | 1 / 223 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
To compare the change from baseline in mean sitting systolic blood pressure (msSBP) after 8 weeks of treatment with a combination of aliskiren and amlodipine treatment regimen (150/5 mg, 300/10 mg) versus an amlodipine treatment regimen (5 mg, 10 mg) in African American patients with Stage 2 hypertension.
Time frame: Baseline, 8 weeks
Population: Full analysis set, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -33.1 mm Hg | Standard Deviation 14.53 |
| Amlodipine | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -27.8 mm Hg | Standard Deviation 13.45 |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
To compare the change from baseline in mean sitting diastolic blood pressure (msDBP) after 8 weeks of treatment with a combination of aliskiren and amlodipine treatment regimen (150/5 mg, 300/10 mg) versus an amlodipine treatment regimen (5 mg, 10 mg).
Time frame: Baseline, 8 weeks
Population: Full analysis set, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren/Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | -13.7 mm Hg | Standard Deviation 9.6 |
| Amlodipine | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | -10.4 mm Hg | Standard Deviation 9.08 |
Secondary
Change From Baseline in MSSBP at Week 1 and 4
Compare the change from baseline in MSSBP at week 1 and 4
Time frame: Baseline, 1 and 4 weeks
Population: Full analysis set, Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren/Amlodipine | Change From Baseline in MSSBP at Week 1 and 4 | Baseline to Week 1 | -20.5 mm Hg | Standard Deviation 12.53 |
| Aliskiren/Amlodipine | Change From Baseline in MSSBP at Week 1 and 4 | baseline to Week 4 | -30.9 mm Hg | Standard Deviation 13.3 |
| Amlodipine | Change From Baseline in MSSBP at Week 1 and 4 | Baseline to Week 1 | -18.2 mm Hg | Standard Deviation 13.01 |
| Amlodipine | Change From Baseline in MSSBP at Week 1 and 4 | baseline to Week 4 | -27.3 mm Hg | Standard Deviation 13.58 |
Secondary
Percentage of Patients Achieving Blood Pressure (BP) Control (<140/90 mmHg)
Cumulative percentage of patients achieving BP control (\<140/90 mmHg)for both treatment arms was calculated. Cumulative refers to achieving blood pressure control before or at the corresponding visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted.
Time frame: 8 weeks
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/Amlodipine | Percentage of Patients Achieving Blood Pressure (BP) Control (<140/90 mmHg) | 71.4 Percentage of participants |
| Amlodipine | Percentage of Patients Achieving Blood Pressure (BP) Control (<140/90 mmHg) | 57.4 Percentage of participants |
Secondary
Percentage of Patients With Peripheral Edema by Visit
Cumulative percentage of patients with peripheral edema was calculated. 'Cumulative' refers to patients with peripheral edema before or at the corresponding visit. If peripheral edema occurred more than once, only the first occurrence was counted. Peripheral edema is the swelling of tissues due to the accumulation of fluids. Peripheral edema was assessed by investigators during physical examination.
Time frame: 8 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 1 | 1.4 Percentage of participants |
| Aliskiren/Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 4 | 4.1 Percentage of participants |
| Aliskiren/Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 8 | 6.8 Percentage of participants |
| Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 8 | 8.5 Percentage of participants |
| Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 1 | 1.3 Percentage of participants |
| Amlodipine | Percentage of Patients With Peripheral Edema by Visit | Week 4 | 5.8 Percentage of participants |
Secondary
Percentage of Responders (Patients With MSSBP < 140 mmHg or Decrease From Baseline of Greater Than or Equal to 20 mmHg)
Cumulative percentage of responders (Responders are defined as patients with MSSBP \<140 mmHg or a decrease from baseline ≥20 mmHg) during 8 weeks of treatment was calculated. Cumulative refers to achieving blood pressure control before or at the corresponding visit. If achieving blood pressure control occurred more than once, only the first occurrence was counted.
Time frame: 8 weeks
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren/Amlodipine | Percentage of Responders (Patients With MSSBP < 140 mmHg or Decrease From Baseline of Greater Than or Equal to 20 mmHg) | 92.3 Percentage of participants |
| Amlodipine | Percentage of Responders (Patients With MSSBP < 140 mmHg or Decrease From Baseline of Greater Than or Equal to 20 mmHg) | 86.5 Percentage of participants |