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

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00867490

Purpose

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.

Condition	Intervention	Phase
Hypertension	Drug: Candesartan+HCTZ - Phase 1 Drug: Aliskiren+HCTZ - Phase 2 Drug: Aliskiren+HCTZ+amlodipine - Phase 3	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Hydrochlorothiazide Amlodipine Amlodipine besylate Candesartan Candesartan cilexetil Aliskiren

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
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 Outcome Measures:

Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 Core Phase of the Study [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 2 to end of Phase 2 ] [ Designated as safety issue: No ]
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 Extension Phase of the Study [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
Normalized was defined as a msSBP < 140 mm Hg and/or a msDBP < 90 mm Hg.
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study [ Time Frame: Baseline Phase 3 to end of Phase 3 ] [ Designated as safety issue: No ]
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.

Enrollment:	186
Study Start Date:	March 2009
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine	Drug: Candesartan+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. Drug: Aliskiren+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. Drug: Aliskiren+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.

Arms

Assigned Interventions

Experimental: Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine

Drug: Candesartan+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.

Drug: Aliskiren+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.

Drug: Aliskiren+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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00867490

Locations

Germany
Investigative Site
Chemnitz, Germany

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schweizer J, Ulmer HJ, Benduhn H, Klebs S. Efficacy and tolerability of aliskiren 300 ?mg/hydrochlorothiazide 25 ?mg (± amlodipine 5? mg) in hypertensive patients not controlled by candesartan 32 ?mg plus HCT 25? mg. Curr Med Res Opin. 2011 Jan;27(1):131-40. Epub 2010 Nov 30.

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00867490 History of Changes
Other Study ID Numbers:	CSPH100ADE01
Study First Received:	March 20, 2009
Results First Received:	January 7, 2011
Last Updated:	May 4, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:

Hypertension
aliskiren
cardiovascular diseases

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Candesartan
Candesartan cilexetil
Amlodipine
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions

Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Calcium Channel Blockers
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 24, 2012