Hypertension
Conditions
Keywords
Hypertension, aliskiren, cardiovascular diseases
Brief summary
This study will assess the safety and efficacy of aliskiren plus hydrochlorothiazide (HCTZ) in patients who do not achieve controlled blood pressure levels after treatment with another specified antihypertensive medication. There was an optional study extension for the first eligible 60 patients who wanted to participate that contains the triple therapy with amlodipine 5 mg and aliskiren 300 mg plus HCTZ 25 mg.
Detailed description
Title of study extension: An open-label, multicenter extension to evaluate the efficacy and safety of a 4 week therapy with amlodipine 5 mg and aliskiren 300 mg plus HCTZ 25 mg in hypertensive patients not adequately responding to a 4 week therapy each with the combinations of candesartan 32 mg plus hydrochlorothiazide 25 mg followed by aliskiren 300mg plus hydrochlorothiazide 25 mg
Interventions
DRUGCandesartan+HCTZ - Phase 1
4 weeks treatment with candesartan 32 mg (two 16 mg tablets) plus hydrochlorothiazide 25 mg (two 12.5 mg tablets) taken orally with water in the morning between 7 and 10 am.
DRUGAliskiren+HCTZ - Phase 2
Patients with uncontrolled mean sitting diastolic blood pressure (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
DRUGAliskiren+HCTZ+amlodipine - Phase 3
The first 60 patients with uncontrolled mean sitting systolic or diastolic blood pressure (msDBP ≥ 90 mm Hg and/or msSBP ≥ 140 mm Hg) at the end of Phase 2 were offered 4 weeks treatment with aliskiren 300 mg plus HCTZ 25 mg in a single tablet plus an amlodipine 5 mg tablet taken orally with water in the morning between 7 and 10 am.
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Core Study: \- Patients with mean sitting diastolic blood pressure ≥ 100 mmHg and \< 110 mmHg Inclusion criteria for the Extension: \- msSBP ≥ 140 mm Hg and/or msDBP ≥ 90 mm Hg at Visit 5 of the core study
Exclusion criteria
for Core Study: * Patients with mean diastolic blood pressure ≥ 110 mmHg or mean systolic blood pressure ≥ 180 mmHg * Patients with prior stroke, hypertensive encephalopathy or heart attack * Patients with type 1 diabetes mellitus * Patients with type 2 diabetes mellitus with poor glucose control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | 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 patient in a sitting position for at least 5 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. |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study | Baseline Phase 3 to end of Phase 3 | 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 patient in a sitting position for at least 5 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sitting Pulse Rate During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. |
| Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | Normalized blood pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg. |
| Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 compared to Baseline in Phase 2 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2. |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | 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 patient in a sitting position for at least 5 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. |
| Change in Sitting Pulse Pressure During the Extension Phase of the Study | Baseline Phase 3 to end of Phase 3 | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs 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 patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
| Change in Sitting Pulse Rate During the Extension Phase of the Study | Baseline Phase 3 to end of Phase 3 | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study | Baseline Phase 3 to end of Phase 3 | 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 patient in a sitting position for at least 5 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. |
| Change in Sitting Pulse Pressure During the Core Phase of the Study | Baseline Phase 2 to end of Phase 2 | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs 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 patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Candesartan+HCTZ, Aliskiren+HCTZ, Aliskiren+HCTZ+Amlodipine 4 weeks treatment with candesartan 32 mg plus hydrochlorothiazide (HCTZ) 25 mg (Phase 1) followed by 4 weeks treatment with aliskiren 300 mg plus HCTZ 25 mg (Phase 2) in patients with uncontrolled diastolic blood pressure (BP) in Phase 1 followed by (optional) 4 weeks treatment with aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg (Phase 3) in patients with uncontrolled systolic or diastolic BP in Phase 2. | 186 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1 - Candesartan+HCTZ | Administrative Problems | 1 |
| Phase 1 - Candesartan+HCTZ | Adverse Event | 5 |
| Phase 1 - Candesartan+HCTZ | Withdrawal by Subject | 4 |
| Phase 2 - Aliskiren+HCTZ | Adverse Event | 2 |
| Phase 2 - Aliskiren+HCTZ | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Candesartan+HCTZ, Aliskiren+HCTZ, Aliskiren+HCTZ+Amlodipine |
|---|---|
| Age Continuous Phase I - Candesartan+HCTZ | 56.2 years STANDARD_DEVIATION 10.62 |
| Age Continuous Phase II - Aliskiren+HCTZ | 57.4 years STANDARD_DEVIATION 10.87 |
| Age Continuous Phase III - Aliskiren+HCTZ+amlodipine | 58.9 years STANDARD_DEVIATION 10.31 |
| Sex/Gender, Customized Phase I - Candesartan+HCTZ | 78 Participants |
| Sex/Gender, Customized Phase II - Aliskiren+HCTZ | 75 Participants |
| Sex/Gender, Customized Phase III - Aliskiren+HCTZ+amlodipine | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 186 | 0 / 123 | 0 / 61 |
| serious Total, serious adverse events | 1 / 186 | 2 / 123 | 0 / 61 |
Outcome results
Primary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study
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 patient in a sitting position for at least 5 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.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study | -3.12 mmHg |
Primary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study
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 patient in a sitting position for at least 5 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.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study | -5.87 mmHg |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study
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 patient in a sitting position for at least 5 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.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study | -2.81 mmHg |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study
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 patient in a sitting position for at least 5 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.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study | -9.20 mmHg |
Secondary
Change in Sitting Pulse Pressure During the Core Phase of the Study
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs 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 patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Sitting Pulse Pressure During the Core Phase of the Study | 0.31 mmHg |
Secondary
Change in Sitting Pulse Pressure During the Extension Phase of the Study
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs 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 patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Sitting Pulse Pressure During the Extension Phase of the Study | -3.33 mmHg |
Secondary
Change in Sitting Pulse Rate During the Core Phase of the Study
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Sitting Pulse Rate During the Core Phase of the Study | 0.27 BPM (beats per minute) |
Secondary
Change in Sitting Pulse Rate During the Extension Phase of the Study
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Change in Sitting Pulse Rate During the Extension Phase of the Study | 0.03 BPM (beats per minute) |
Secondary
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 compared to Baseline in Phase 2 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msSBP response | 37.4 Percentage of patients |
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msDBP response | 34.1 Percentage of patients |
Secondary
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 compared to Baseline in Phase 2 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msSBP response | 54.1 Percentage of patients |
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msDBP response | 47.5 Percentage of patients |
Secondary
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study
Normalized blood pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg.
Time frame: Baseline Phase 2 to end of Phase 2
Population: Intent-to-treat population (ITT): All patients who took at least one dose of aliskiren plus HCTZ who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msSBP < 140 mmHg | 37.4 Percentage of patients |
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msDBP < 90 mmHg | 33.3 Percentage of patients |
Secondary
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study
Normalized was defined as a msSBP \< 140 mm Hg and/or a msDBP \< 90 mm Hg.
Time frame: Baseline Phase 3 to end of Phase 3
Population: Safety population: All patients who took at least one dose of aliskiren 300 mg plus HCTZ 25 mg plus amlodipine 5 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msSBP < 140 mmHg | 54.1 Percentage of patients |
| Phase 2 - Aliskiren+HCTZ | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msDBP < 90 mmHg | 44.3 Percentage of patients |