Trial Outcomes & Findings for Safety and Efficacy of Aliskiren + Hydrochlorothiazide (± Amlodipine 5 mg) in Patients With Moderate Hypertension (NCT NCT00867490)

NCT ID: NCT00867490

Last Updated: 2011-05-06

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 186 participants
• Primary outcome timeframe: Baseline Phase 2 to end of Phase 2
• Results posted on: 2011-05-06

Participant Flow

Participant milestones

Measure	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.
Phase 1 - Candesartan+HCTZ STARTED	186
Phase 1 - Candesartan+HCTZ COMPLETED	176
Phase 1 - Candesartan+HCTZ NOT COMPLETED	10
Phase 2 - Aliskiren+HCTZ STARTED	123
Phase 2 - Aliskiren+HCTZ COMPLETED	120
Phase 2 - Aliskiren+HCTZ NOT COMPLETED	3
Phase 3 - Aliskiren+HCTZ+Amlodipine STARTED	61
Phase 3 - Aliskiren+HCTZ+Amlodipine COMPLETED	61
Phase 3 - Aliskiren+HCTZ+Amlodipine NOT COMPLETED	0

Reasons for withdrawal

Measure	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.
Phase 1 - Candesartan+HCTZ Adverse Event	5
Phase 1 - Candesartan+HCTZ Withdrawal by Subject	4
Phase 1 - Candesartan+HCTZ Administrative Problems	1
Phase 2 - Aliskiren+HCTZ Adverse Event	2
Phase 2 - Aliskiren+HCTZ Withdrawal by Subject	1

Baseline Characteristics

Safety and Efficacy of Aliskiren + Hydrochlorothiazide (± Amlodipine 5 mg) in Patients With Moderate Hypertension

Baseline characteristics by cohort

Measure	Candesartan+HCTZ, Aliskiren+HCTZ, Aliskiren+HCTZ+Amlodipine n=186 Participants 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.
Age Continuous Phase I - Candesartan+HCTZ	56.2 years STANDARD_DEVIATION 10.62 • n=5 Participants
Age Continuous Phase II - Aliskiren+HCTZ	57.4 years STANDARD_DEVIATION 10.87 • n=5 Participants
Age Continuous Phase III - Aliskiren+HCTZ+amlodipine	58.9 years STANDARD_DEVIATION 10.31 • n=5 Participants
Sex/Gender, Customized Phase I - Candesartan+HCTZ	108 Participants n=5 Participants
Sex/Gender, Customized Phase II - Aliskiren+HCTZ	75 Participants n=5 Participants
Sex/Gender, Customized Phase III - Aliskiren+HCTZ+amlodipine	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study	-3.12 mmHg Interval -4.29 to -1.95

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study	-5.87 mmHg Interval -7.48 to -4.26

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study	-2.81 mmHg Interval -4.81 to -0.81

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Sitting Pulse Pressure During the Core Phase of the Study	0.31 mmHg Interval -1.39 to 2.01

SECONDARY outcome

Timeframe: 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.

Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Sitting Pulse Rate During the Core Phase of the Study	0.27 BPM (beats per minute) Interval -1.15 to 1.69

SECONDARY outcome

Timeframe: 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.

Normalized blood pressure was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study msSBP < 140 mmHg	37.4 Percentage of patients
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study msDBP < 90 mmHg	33.3 Percentage of patients

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=123 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study	-9.20 mmHg Interval -11.86 to -6.54

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Sitting Pulse Pressure During the Extension Phase of the Study	-3.33 mmHg Interval -5.4 to -1.27

SECONDARY outcome

Timeframe: 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.

Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Change in Sitting Pulse Rate During the Extension Phase of the Study	0.03 BPM (beats per minute) Interval -1.82 to 1.89

SECONDARY outcome

Timeframe: 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.

Normalized was defined as a msSBP < 140 mm Hg and/or a msDBP < 90 mm Hg.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study msSBP < 140 mmHg	54.1 Percentage of patients
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study msDBP < 90 mmHg	44.3 Percentage of patients

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Phase 2 - Aliskiren+HCTZ n=61 Participants Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.
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
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

Adverse Events

Phase 1 - Candesartan+HCTZ

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase 2 - Aliskiren+HCTZ

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase 3 - Aliskiren+HCTZ+Amlodipine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase 1 - Candesartan+HCTZ n=186 participants at risk 4 weeks treatment with candesartan 32 mg (two 16 mg tablets) plus hydrochlorothiazide (HCTZ) 25 mg (two 12.5 mg tablets) taken orally with water in the morning between 7 and 10 am.	Phase 2 - Aliskiren+HCTZ n=123 participants at risk Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.	Phase 3 - Aliskiren+HCTZ+Amlodipine n=61 participants at risk 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 a 4 week treatment extension with aliskiren 300 mg plus hydrochlorothiazide (HCTZ) 25 mg in a single tablet plus amlodipine 5 mg tablet taken orally with water in the morning between 7 and 10 am.
Cardiac disorders Acute myocardial infarction	0.54% 1/186	0.00% 0/123	0.00% 0/61
Gastrointestinal disorders Colitis ischaemic	0.00% 0/186	0.81% 1/123	0.00% 0/61
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/186	0.81% 1/123	0.00% 0/61

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER