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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00409578
First Posted: December 11, 2006
Last Update Posted: April 19, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
The TIMI Study Group
Information provided by:
Novartis
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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:


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 ]
    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 ]
    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 ]
    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 ]
    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00409578     History of Changes
Other Study ID Numbers: CSPP100A2347
First Submitted: December 7, 2006
First Posted: December 11, 2006
Results First Submitted: January 11, 2011
Results First Posted: February 2, 2011
Last Update Posted: April 19, 2011
Last Verified: April 2011

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:
Syndrome
Ischemia
Acute Coronary Syndrome
Myocardial Ischemia
Coronary Artery Disease
Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Valsartan
Natriuretic Peptide, Brain
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs