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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Candesartan+HCTZ - Phase 1; Drug: Aliskiren+HCTZ - Phase 2; Drug: Aliskiren+HCTZ+amlodipine - Phase 3

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

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Chemnitz, Germany
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• 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. doi: 10.1185/03007995.2010.537318. Epub 2010 Nov 30.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (Estimate): March 23, 2009

Study Record Updates

• Last Update Posted (Estimate): May 6, 2011
• Last Update Submitted That Met QC Criteria: May 4, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Hypertension; cardiovascular diseases; aliskiren
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Hydrochlorothiazide; Candesartan
• Other Study ID Numbers: CSPH100ADE01