Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multinational Clinical Trial to Evaluate the Efficacy of Aliskiren and Valsartan Versus Placebo in Lowering Levels on NT-proBNP in Stabilized Patients Post Acute Coronary Syndromes

Sponsors

Lead Sponsor: Novartis

Collaborator: The TIMI Study Group

Source Novartis
Brief Summary

The purpose of this study is to test the hypothesis that the inhibition of the renin-angiotensin-aldosterone system (RAAS) with the angiotensin receptor blocker valsartan or the renin antagonist aliskiren will improve ventricular hemodynamics, as reflected by a greater reduction in levels of N-terminal proB-type natriuretic peptide (NT-proBNP) compared to placebo in subjects stabilized following acute coronary syndrome (ACS) who are determined to be at high risk due to an elevated concentration of natriuretic peptides.

Overall Status Completed
Start Date 2007-02-01
Completion Date 2009-04-01
Primary Completion Date 2009-04-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at Week 8 Baseline to Week 8
Secondary Outcome
Measure Time Frame
Change From Baseline in B-type Natriuretic Peptide (BNP) at Week 8 Baseline to Week 8
Percentage of Patients With a Cardiac Event Baseline to Week 8
Percentage of Patients With a Composite Clinical-biochemical Event Baseline to Week 8
Enrollment 1101
Condition
Intervention

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo tablets and capsules. In order to adequately blind the study, patients were required to take a total of 1 tablet and 2 capsules during the first 4 weeks of the study. During the remainder of the study, patients were required to take 2 tablets and 2 capsules. Each dose was taken by mouth with water at approximately 8:00 AM with or without food.

Arm Group Label: Placebo

Intervention Type: Drug

Intervention Name: Aliskiren 300 mg

Description: Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study. If a patient was not up-titrated or required down-titration, the patient continued on that dose for the remainder of the study. If 2 down-titrations were required, they stopped study drug. In order to adequately blind the study, patients were required to take 1 tablet and 2 capsules during the first 4 weeks of the study and 2 tablets and 2 capsules for the remainder of the study. Each dose was taken by mouth with water at approximately 8:00 AM.

Arm Group Label: Aliskiren 300 mg

Intervention Type: Drug

Intervention Name: Valsartan 320 mg

Description: Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. If a patient was not up-titrated or required down-titration, the patient continued on that dose for the remainder of the study. If 2 down-titrations were required, they stopped study drug. In order to adequately blind the study, patients were required to take 1 tablet and 2 capsules during the first 4 weeks of the study and 2 tablets and 2 capsules for the remainder of the study. Each dose was taken by mouth with water at approximately 8:00 AM.

Arm Group Label: Valsartan 320 mg

Intervention Type: Drug

Intervention Name: Aliskiren/valsartan 300/320 mg

Description: Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study. If a patient was not up-titrated or required down-titration, the patient continued on that dose for the remainder of the study. If 2 down-titrations were required, they stopped study drug. In order to adequately blind the study, patients were required to take 1 tablet and 2 capsules during the first 4 weeks of the study and 2 tablets and 2 capsules for the remainder of the study. Each dose was taken by mouth with water at approximately 8:00 AM.

Arm Group Label: Aliskiren/valsartan 300/320 mg

Eligibility

Criteria:

Inclusion Criteria: - Male or female outpatients 18 years old or older - Subjects who are hospitalized for ischemic chest discomfort at rest lasting at least 10 minutes and consistent with cardiac ischemia - Final diagnosis of acute coronary syndrome - Elevated concentrations of natriuretic peptide 3-10 days after admission for their qualifying acute coronary syndrome event Exclusion Criteria: - Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARBs), renin antagonists, or to drugs with similar chemical structures. - Presence of clinically overt heart failure - Known evidence of left ventricular systolic dysfunction - Percutaneous coronary intervention (PCI) less than 24 hours before randomization. - Patients on chronic ACEI or ARB therapy for whom therapy with an ACEI or ARB is clinically required with no reasonable alternative therapy available. Other protocol-defined inclusion/exclusion criteria applied to the study.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Eugene Braunwald, MD Study Chair TIMI Study Group, Boston, MA
Location
Facility:
Investigative Site | Investigative Site, New Jersey, United States
Investigative Site | Investigative Site, Belgium
Investigative Site | Investigative Site, Canada
Investigative Site | Investigative Site, Czech Republic
Investigative Site | Investigative Site, Germany
Investigative Site | Investigative Site, Hungary
Investigative Site | Investigative Site, Netherlands
Investigative Site | Investigative Site, Poland
Investigative Site | Investigative Site, Russian Federation
Investigative Site | Investigative Site, Spain
Investigative Site | Investigative Site, Sweden
Location Countries

Belgium

Canada

Czech Republic

Germany

Hungary

Netherlands

Poland

Russian Federation

Spain

Sweden

United States

Verification Date

2011-04-01

Responsible Party

Name Title: External Affairs

Organization: Novartis

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Placebo

Type: Placebo Comparator

Description: Placebo tablets and capsules

Label: Aliskiren 300 mg

Type: Experimental

Description: Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.

Label: Valsartan 320 mg

Type: Experimental

Description: Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.

Label: Aliskiren/valsartan 300/320 mg

Type: Experimental

Description: Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News