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

NCT00219141 | Completed Phase 3 Results

• 1 other identifier: CSPP100A2316
• Study Type: interventional
• Target: 460
• Locations: 9 countries
• Sites: 9

Brief Summary

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.

Conditions

Hypertension; Left Ventricular Hypertrophy; Overweight

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• 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)

Study Arms (3)

Aliskiren 300 mg

EXPERIMENTAL

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; Drug: Aliskiren placebo; Drug: Losartan 50/100 mg placebo

Losartan 100 mg

ACTIVE COMPARATOR

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: Losartan 50/100 mg; Drug: Aliskiren placebo

Aliskiren/losartan 300/100 mg

EXPERIMENTAL

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; Drug: Losartan 50/100 mg; Drug: Aliskiren placebo

Interventions

Aliskiren 150/300 mg DRUG

Aliskiren 150 mg tablets

Aliskiren 300 mg; Aliskiren/losartan 300/100 mg

Losartan 50/100 mg DRUG

Losartan 50 or 100 mg capsules

Aliskiren/losartan 300/100 mg; Losartan 100 mg

Aliskiren placebo DRUG

Aliskiren 150 mg placebo tablet

Aliskiren 300 mg; Aliskiren/losartan 300/100 mg; Losartan 100 mg

Losartan 50/100 mg placebo DRUG

Losartan 50/100 mg placebo capsules

Aliskiren 300 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Pharmaceuticals

East Hanover, New Jersey, 07936, United States

Location

sites in Argentina

Argentina, Argentina

Location

sites in Colombia

Colombia, Colombia

Location

sites in Finland

Finland, Finland

Location

sites in Germany

Germany, Germany

Location

sites in Italy

Italy, Italy

Location

sites in Russia

Russia, Russia

Location

sites in Spain

Spain, Spain

Location

sites in Sweden

Sweden, Sweden

Location

Related Publications (2)

• Wang GM, Li LJ, Fan L, Xu M, Tang WL, Wright JM. Renin inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD012570. doi: 10.1002/14651858.CD012570.pub2.

  PMID: 40013543 DERIVED

• 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.

  PMID: 21746765 DERIVED

MeSH Terms

Conditions

Hypertension; Hypertrophy, Left Ventricular; Overweight

Interventions

aliskiren; Losartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 22, 2005
• Study Start: October 1, 2005
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: May 26, 2011
• Results First Posted: May 10, 2011

Record last verified: 2011-05

Locations

ES (1); IT (1); US (1); RU (1); CO (1); SE (1); FI (1); DE (1); AR (1)