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

Study Overview
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Brief Summary
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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
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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

Official Title
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An Open-label, Multicenter Study to Evaluate the Efficacy and Safety of a 4 Week Therapy With Aliskiren 300 mg Plus Hydrochlorothiazide 25 mg in Hypertensive Patients Not Adequately Responding to a 4 Week Therapy With Candesartan 32 mg Plus Hydrochlorothiazide 25 mg

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Candesartan+HCTZ - Phase 1
* Drug: Aliskiren+HCTZ - Phase 2
* Drug: Aliskiren+HCTZ+amlodipine - Phase 3


Participation Criteria
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Eligibility Criteria
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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 Exclusion criteria for the Extension: Premature discontinuation in the core study or failure to comply with the core study protocol History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures, known or suspected contraindications to diuretics as described in the SmPC (particularly amlodipine 5 mg), e.g. severe hypotension, shock - including cardiogenic shock, obstructions impairing the flow out of the left ventricle (e.g. significant aortic stenosis) Any patient that the investigator decides should not participate in the extension study for medical reasons Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine<br> | Drug: Candesartan+HCTZ - Phase 1<br>* 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.<br>Drug: Aliskiren+HCTZ - Phase 2<br>* 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.<br>Drug: Aliskiren+HCTZ+amlodipine - Phase 3<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 2 to end of Phase 2 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 
| 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. | Baseline Phase 3 to end of Phase 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, aliskiren, cardiovascular diseases