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

Primary Purpose

Post Acute Coronary Syndrome, Myocardial Ischemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Aliskiren 300 mg
Valsartan 320 mg
Aliskiren/valsartan 300/320 mg
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Acute Coronary Syndrome focused on measuring Post acute coronary syndrome, Acute, coronary syndrome, B-type natriuretic peptide, N-terminal, pro-B-type natriuretic peptide, myocardial infarctions

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo

Aliskiren 300 mg

Valsartan 320 mg

Aliskiren/valsartan 300/320 mg

Arm Description

Placebo tablets and capsules

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.

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at 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
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
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
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.

Full Information

First Posted
December 7, 2006
Last Updated
April 15, 2011
Sponsor
Novartis
Collaborators
The TIMI Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT00409578
Brief Title
Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis
Collaborators
The TIMI Study Group

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Acute Coronary Syndrome, Myocardial Ischemia
Keywords
Post acute coronary syndrome, Acute, coronary syndrome, B-type natriuretic peptide, N-terminal, pro-B-type natriuretic peptide, myocardial infarctions

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1101 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablets and capsules
Arm Title
Aliskiren 300 mg
Arm Type
Experimental
Arm 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.
Arm Title
Valsartan 320 mg
Arm Type
Experimental
Arm 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.
Arm Title
Aliskiren/valsartan 300/320 mg
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Aliskiren 300 mg
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Valsartan 320 mg
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Aliskiren/valsartan 300/320 mg
Intervention 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.
Primary Outcome Measure Information:
Title
Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at Week 8
Description
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.
Time Frame
Baseline to Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline in B-type Natriuretic Peptide (BNP) at Week 8
Description
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.
Time Frame
Baseline to Week 8
Title
Percentage of Patients With a Cardiac Event
Description
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.
Time Frame
Baseline to Week 8
Title
Percentage of Patients With a Composite Clinical-biochemical Event
Description
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.
Time Frame
Baseline to Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugene Braunwald, MD
Organizational Affiliation
TIMI Study Group, Boston, MA
Official's Role
Study Chair
Facility Information:
Facility Name
Investigative Site
City
Investigative Site
State/Province
New Jersey
Country
United States
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City
Investigative Site
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Belgium
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City
Investigative Site
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Canada
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Czech Republic
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Germany
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Hungary
Facility Name
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Netherlands
Facility Name
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Poland
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Russian Federation
Facility Name
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Investigative Site
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Spain
Facility Name
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City
Investigative Site
Country
Sweden

12. IPD Sharing Statement

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

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