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

Sponsor:	Novartis
Collaborator:	The TIMI Study Group
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00409578

Purpose

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.

Condition	Intervention	Phase
Post Acute Coronary Syndrome Myocardial Ischemia	Drug: Placebo Drug: Aliskiren 300 mg Drug: Valsartan 320 mg Drug: Aliskiren/valsartan 300/320 mg	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

Drug Information available for: Valsartan Aliskiren

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
Blood samples for the measurement of NT-proBNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.

Secondary Outcome Measures:

Change From Baseline in B-type Natriuretic Peptide (BNP) at Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
Blood samples for the measurement of BNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.
Percentage of Patients With a Cardiac Event [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
A cardiac event was defined as at least one of the following events: Cardiovascular death, recurrent myocardial infarction (MI), or hospitalization for congestive heart failure (CHF), all to be confirmed by adjudication.
Percentage of Patients With a Composite Clinical-biochemical Event [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
A composite clinical-biochemical event was defined as at least one of the following events: cardiovascular death confirmed by adjudication, recurrent MI confirmed by adjudication, hospitalization for CHF confirmed by adjudication, and/or NT-proBNP => 200 pg/mL.

Enrollment:	1101
Study Start Date:	February 2007
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Placebo tablets and capsules	Drug: Placebo 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.
Experimental: Aliskiren 300 mg 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.	Drug: Aliskiren 300 mg 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.
Experimental: Valsartan 320 mg 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.	Drug: Valsartan 320 mg 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.
Experimental: Aliskiren/valsartan 300/320 mg 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.	Drug: Aliskiren/valsartan 300/320 mg 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.

Eligibility

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409578

Locations

United States, New Jersey
Investigative Site
Investigative Site, New Jersey, United States
Belgium
Investigative Site
Investigative Site, Belgium
Canada
Investigative Site
Investigative Site, Canada
Czech Republic
Investigative Site
Investigative Site, Czech Republic
Germany
Investigative Site
Investigative Site, Germany
Hungary
Investigative Site
Investigative Site, Hungary
Netherlands
Investigative Site
Investigative Site, Netherlands
Poland
Investigative Site
Investigative Site, Poland
Russian Federation
Investigative Site
Investigative Site, Russian Federation
Spain
Investigative Site
Investigative Site, Spain
Sweden
Investigative Site
Investigative Site, Sweden

Sponsors and Collaborators

Novartis

The TIMI Study Group

Investigators

Study Chair:

Eugene Braunwald, MD

TIMI Study Group, Boston, MA

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00409578 History of Changes
Other Study ID Numbers:	CSPP100A2347
Study First Received:	December 7, 2006
Results First Received:	January 11, 2011
Last Updated:	April 15, 2011
Health Authority:	United States: Food and Drug Administration; Germany: Federal Institute for Drugs and Medical Devices; Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Novartis:

Post acute coronary syndrome
Acute
coronary syndrome
B-type natriuretic peptide

N-terminal
pro-B-type natriuretic peptide
myocardial infarctions

Additional relevant MeSH terms:

Myocardial Ischemia
Coronary Artery Disease
Ischemia
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Angina Pectoris
Chest Pain

Pain
Signs and Symptoms
Natriuretic Peptide, Brain
Valsartan
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on February 09, 2012