Essential Hypertension
Conditions
Keywords
Essential hypertension, High blood pressure
Brief summary
This study tested the safety of the combination of aliskiren/amlodipine/hydrochlorothiazide in participants with essential hypertension.
Interventions
DRUGAliskiren
300 mg tablet
DRUGAmlodipine
5 mg tablet
DRUGHydrochlorothiazide
12.5 mg and 25 mg capsule
Sponsors
Novartis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients 18 years of age or older * Male or female participants are eligible. * Mean sitting diastolic blood pressure (msDBP) and mean sitting systolic blood pressure (msSBP) Requirements: * For newly diagnosed/untreated participants, msDBP ≥ 100 and \< 120 millimeters of mercury (mmHg), and/or msSBP ≥ 160 and \< 200 mmHg at Visit 1 and Visit 2. * For previously treated participants, msDBP ≥ 100 and \< 120 mmHg, and/or msSBP ≥ 160 and \< 200 mmHg at Visit 2, Visit 3, or Visit 4. * For participants requiring tapering off their previous antihypertensive medication, they must meet the above criteria and completely discontinue all antihypertensive treatment prior to entering the treatment phase of the study. * Participants who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent).
Exclusion criteria
* Inability to discontinue all prior antihypertensive medications safely for a period of 1 week to 4 weeks as required by the protocol. * Participants on three antihypertensive drugs with msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg at Visit 1. * Participants on four or more antihypertensive drugs at Visit 1. * Participants with an msSBP ≥ 200 and msDBP ≥ 120 mmHg anytime during the washout period of the study Visit 1-4 must be discontinued from the study. * 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 human chorionic gonadotropin (hCG) laboratory test (\>= 5 milli-international units per milliliter mIU/mL).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | 54 weeks | An AE was defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, even if the event is not considered to be related to study drug. An SAE was defined as an event which was fatal or life-threatening, resulted in persistent or significant disability/incapacity, constituted a congenital anomaly/birth defect, required inpatient hospitalization or prolongation of existing hospitalization, was medically significant, i.e. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline, Weeks 28 and 54 endpoint | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28. |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline, Weeks 28 and 54 endpoints | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28. |
| Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg | Weeks 28 and 54 endpoints | Blood pressure control was defined as having a mean sitting diastolic blood pressure \<90 mmHg and a mean sitting systolic blood pressure \<140 mmHg. Percentage of participants achieving the blood pressure control of \< 140/90 mmHg were reported. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28 and Week 54 Endpoint was the last non-missing measurement value after Week 28. |
| Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure | Weeks 28 and 54 endpoints | Diastolic Blood pressure response was defined as a mean sitting diastolic blood pressure \<90 mmHg or a \>=10 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28. |
| Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure | Weeks 28 and 54 endpoints | Systolic blood pressure response was defined as a mean sitting systolic blood pressure \<140 mmHg or a \>=20 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28. |
Countries
Belgium, Egypt, Germany, Poland, Slovakia, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants with essential hypertension were enrolled in the study at 82 investigative sites worldwide from 5 June 2008 to 5 October 2009.
Pre-assignment details
A total of 635 participants entered the washout period, of which 564 participants met the study entry criteria and entered the study treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren /Amlodipine/Hydrochlorothiazide Participants received aliskiren 300 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 1 followed by combination of aliskiren 300 mg plus amlodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. Following Week 2, participants were force titrated up to aliskiren 300 mg plus amlodipine 10 mg plus hydrochlorothiazide 25 mg for 26 to 52 weeks (Weeks 28 to 54). All study medications were taken orally with water, once daily in the morning. | 564 |
| Total | 564 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal Test Procedure | 1 |
| Overall Study | Adverse Event | 39 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Unsatisfactory Therapeutic Effect | 3 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Aliskiren /Amlodipine/Hydrochlorothiazide |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 11.34 |
| Sex: Female, Male Female | 238 Participants |
| Sex: Female, Male Male | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 564 | 0 / 561 | 0 / 556 |
| other Total, other adverse events | 21 / 564 | 14 / 561 | 141 / 556 |
| serious Total, serious adverse events | 0 / 564 | 1 / 561 | 14 / 556 |
Outcome results
Primary
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death
An AE was defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, even if the event is not considered to be related to study drug. An SAE was defined as an event which was fatal or life-threatening, resulted in persistent or significant disability/incapacity, constituted a congenital anomaly/birth defect, required inpatient hospitalization or prolongation of existing hospitalization, was medically significant, i.e. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: 54 weeks
Population: Treated Population consisted of all participants who received at least one dose of trial medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Death | 0 Participants |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Any Adverse Events | 57 Participants |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Serious Adverse Events | 0 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Death | 0 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Any Adverse Events | 54 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/5/12.5 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Serious Adverse Events | 1 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Death | 0 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Serious Adverse Events | 14 Participants |
| Aliskiren/Amlodipine/Hydrochlorothiazide 300/10/25 mg | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Any Adverse Events | 255 Participants |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.
Time frame: Baseline, Weeks 28 and 54 endpoint
Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at both baseline and post-baseline time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline | 101.8 mmHg | Standard Deviation 7.74 |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Change from Baseline to Week 28 Endpoint | -20.3 mmHg | Standard Deviation 8.92 |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Change from Baseline to Week 54 Endpoint | -21.8 mmHg | Standard Deviation 8.66 |
Secondary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the participant in a sitting position for five minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.
Time frame: Baseline, Weeks 28 and 54 endpoints
Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at both baseline and post-baseline time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline | 166.1 millimeters of mercury | Standard Deviation 11.59 |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Change from baseline to Week 28 Endpoint | -34.2 millimeters of mercury | Standard Deviation 14.16 |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Change from Baseline to Week 54 Endpoint | -37.3 millimeters of mercury | Standard Deviation 14.63 |
Secondary
Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg
Blood pressure control was defined as having a mean sitting diastolic blood pressure \<90 mmHg and a mean sitting systolic blood pressure \<140 mmHg. Percentage of participants achieving the blood pressure control of \< 140/90 mmHg were reported. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28 and Week 54 Endpoint was the last non-missing measurement value after Week 28.
Time frame: Weeks 28 and 54 endpoints
Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg | Week 28 Endpoint | 69.1 percentage of participants |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Achieving the Blood Pressure Control Target of <140/90 mmHg | Week 54 Endpoint | 77.1 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure
Diastolic Blood pressure response was defined as a mean sitting diastolic blood pressure \<90 mmHg or a \>=10 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.
Time frame: Weeks 28 and 54 endpoints
Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at both baseline and post-baseline time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure | Week 28 Endpoint | 91.8 percentage of participants |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Diastolic Blood Pressure | Week 54 Endpoint | 96.6 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure
Systolic blood pressure response was defined as a mean sitting systolic blood pressure \<140 mmHg or a \>=20 mmHg reduction from baseline value. Week 28 Endpoint was the last non-missing post-baseline measurement value on or before Week 28, and Week 54 Endpoint was the last non-missing measurement value after Week 28.
Time frame: Weeks 28 and 54 endpoints
Population: Treated Population consisted of all participants who received at least one dose of trial medication. Number analyzed is the number of participants with data available at both baseline and post-baseline time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure | Week 28 Endpoint | 90.2 percentage of participants |
| Aliskiren/Hydrochlorothiazide 300/12.5 mg | Percentage of Participants Who Achieved a Blood Pressure Response in Mean Sitting Systolic Blood Pressure | Week 54 Endpoint | 93.7 percentage of participants |