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

Myocardial Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00409578
• Other study ID #: CSPP100A2347
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2006
• Last updated: April 15, 2011
• Start date: February 2007
• Est. completion date: April 2009

Study information

• Verified date: April 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1101
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Artery Disease
• Myocardial Ischemia
• Post Acute Coronary Syndrome
• Syndrome

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
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	Investigative Site	Investigative Site
United States	Investigative Site	Investigative Site	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	The TIMI Study Group

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czech Republic,  Germany,  Hungary,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Week 8	No
Secondary	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.	Baseline to Week 8	No
Secondary	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.	Baseline to Week 8	No
Secondary	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.	Baseline to Week 8	No