Aliskiren in Combination With Losartan Compared to Losartan on the Regression of Left Ventricular Hypertrophy in Overweight Patients With Essential Hypertension (ALLAY)

A 36-week, Randomized, Double-blind, Multi-center, Parallel Group Study Comparing the Efficacy and Safety of Aliskiren in Combination With Losartan Compared to Losartan on the Regression of Left Ventricular Hypertrophy in Overweight Patients With Essential Hypertension

To compare the efficacy and safety of aliskiren in combination with losartan compared to losartan on the regression of the increased size of the left ventricle in overweight patients with high blood pressure.

Study Overview

• Status: Completed
• Conditions: Hypertension; Overweight; Left Ventricular Hypertrophy
• Intervention / Treatment: Drug: Aliskiren 150/300 mg; Drug: Aliskiren placebo; Drug: Losartan 50/100 mg placebo; Drug: Losartan 50/100 mg

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Argentina, Argentina
    • sites in Argentina
• Colombia
  • Colombia, Colombia
    • sites in Colombia
• Finland
  • Finland, Finland
    • sites in Finland
• Germany
  • Germany, Germany
    • Sites in germany
• Italy
  • Italy, Italy
    • Sites in Italy
• Russian Federation
  • Russia, Russian Federation
    • sites in Russia
• Spain
  • Spain, Spain
    • sites in Spain
• Sweden
  • Sweden, Sweden
    • sites in Sweden
• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with essential hypertension
• Patients with a BMI > 25 kg/m2
• Patients with LVH (LVWT ≥ 1.3 cm) confirmed by the ECHO

Exclusion Criteria:

• Patients treated with an ACE or an ARB within 3 months of study entry (Study Visit 1) who are unable or unwilling to undergo the 3 month washout period.
• Patients treated with an ACE and ARB combination at study entry.
• Known secondary hypertension of any etiology (e.g., uncorrected renal artery stenosis).

Other protocol related inclusion/exclusion criteria applied to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren 300 mg; Patients in this arm initially received 150 mg of aliskiren for two weeks and were then force-titrated up to 300 mg of aliskiren where they remained for 34 weeks. In order to adequately blind the study, patients were required to take a total of 2 tablets and 1 capsule of study medication or placebo per day. In the first 2 weeks, patients took 1 tablet of aliskiren 150 mg, 1 tablet of aliskiren 150 mg placebo, and 1 capsule of losartan placebo. In the remaining 34 weeks, patients took 2 tablets of aliskiren 150 mg and 1 capsule of losartan placebo. Each dose was to be taken by mouth with water at approximately 8:00 AM, except on the morning of study visit when the dose was taken after all procedures and assessments had been completed.	Drug: Aliskiren 150/300 mg; Aliskiren 150 mg tablets; Drug: Aliskiren placebo; Aliskiren 150 mg placebo tablet; Drug: Losartan 50/100 mg placebo; Losartan 50/100 mg placebo capsules
Active Comparator: Losartan 100 mg; Patients in this arm initially received 50 mg of losartan for two weeks and were then force-titrated up to 100 mg of losartan where they remained for 34 weeks. In order to adequately blind the study, patients were required to take a total of 2 tablets and 1 capsule of study medication or placebo per day. In the first 2 weeks, patients took 2 tablets of aliskiren 150 mg placebo and 1 capsule of losartan 50 mg. In the remaining 34 weeks, patients took 2 tablets of aliskiren 150 mg placebo and 1 capsule of losartan 100 mg. Each dose was to be taken by mouth with water at approximately 8:00 AM, except on the morning of study visit when the dose was taken after all procedures and assessments had been completed.	Drug: Aliskiren placebo; Aliskiren 150 mg placebo tablet; Drug: Losartan 50/100 mg; Losartan 50 or 100 mg capsules
Experimental: Aliskiren/losartan 300/100 mg; Patients in this arm initially received 150 mg of aliskiren in combination with 50 mg of losartan for two weeks and were then force-titrated up to 300 mg of aliskiren in combination with 100 mg of losartan where they remained for 34 weeks. In order to adequately blind the study, patients were required to take a total of 2 tablets and 1 capsule of study medication or placebo per day. In the first 2 weeks, patients took 1 tablet of aliskiren 150 mg, 1 tablet of aliskiren 150 mg placebo, and 1 capsule of losartan 50 mg. In the remaining 34 weeks, patients took 2 tablets of aliskiren 150 mg and 1 capsule of losartan 100 mg. Each dose was to be taken by mouth with water at approximately 8:00 AM, except on the morning of study visit when the dose was taken after all procedures and assessments had been completed.	Drug: Aliskiren 150/300 mg; Aliskiren 150 mg tablets; Drug: Aliskiren placebo; Aliskiren 150 mg placebo tablet; Drug: Losartan 50/100 mg; Losartan 50 or 100 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Ventricular Mass Index (LVMI) From Baseline to End of Study (Week 36)	Left ventricular mass index (LVMI) was measured by magnetic resonance imaging (MRI). An increase in LVMI indicates hypertrophy of the left ventricle. This could be a normal reversible response to cardiovascular conditioning (athletic heart) or an abnormal irreversible response to chronically increased volume load (preload) or increased pressure load (afterload). Thickening of the ventricular muscle results in increased left ventricular pressure, increased end-systolic volume, and decreased end-diastolic volume, causing an overall reduction in cardiac output.	Baseline to end of study (Week 36)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular Mass Index as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular End Diastolic Volume as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular End Systolic Volume as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular Anteroseptal Wall Thickness as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular Inferolateral Wall Thickness as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Diameter of Ascending Aorta as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular End Diastolic Mass as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular Ejection Fraction as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Left Ventricular Stroke Volume as Measured by MRI From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Sokolow-Lyon Voltage as Measured by Electrocardiogram From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change in the Left Ventricular Hypertrophy (LVH) Parameter Cornell Voltage Duration Product as Measured by Electrocardiogram From Baseline to End of Study (Week 36)		Baseline to end of study (Week 36)
Change From Baseline in Mean 24-hour Ambulatory Diastolic and Systolic Blood Pressure From Baseline to the End of the Study (Week 36)	Two 24-hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline and one at the end of the study. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. A correlation was made between the ABPM device readings and measurements taken with a mercury sphygmomanometer and stethoscope. Following the correlation procedure, blood pressure was measured at study specified intervals.	Baseline the end of study (Week 36)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Pouleur AC, Uno H, Prescott MF, Desai A, Appelbaum E, Lukashevich V, Smith BA, Dahlof B, Solomon SD; ALLAY Investigators. Suppression of aldosterone mediates regression of left ventricular hypertrophy in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):483-90. doi: 10.1177/1470320311414453. Epub 2011 Jul 11.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): May 26, 2011
• Last Update Submitted That Met QC Criteria: May 20, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Body Weight; Pathological Conditions, Anatomical; Cardiomegaly; Hypertension; Overweight; Hypertrophy; Essential Hypertension; Hypertrophy, Left Ventricular; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: CSPP100A2316