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

NCT00409578 | Completed Phase 2 Results

• 1 other identifier: CSPP100A2347
• Study Type: interventional
• Target: 1,101
• Locations: 11 countries
• Sites: 11

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo tablets and capsules

Drug: Placebo

Aliskiren 300 mg

EXPERIMENTAL

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

Valsartan 320 mg

EXPERIMENTAL

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

Aliskiren/valsartan 300/320 mg

EXPERIMENTAL

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

Interventions

Placebo DRUG

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.

Placebo

Aliskiren 300 mg DRUG

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.

Aliskiren 300 mg

Valsartan 320 mg DRUG

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.

Valsartan 320 mg

Aliskiren/valsartan 300/320 mg DRUG

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.

Aliskiren/valsartan 300/320 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead
• The TIMI Study Group: collaborator

Study Sites (11)

Investigative Site

Investigative Site, New Jersey, United States

Location

Investigative Site

Investigative Site, Belgium

Location

Investigative Site

Investigative Site, Canada

Location

Investigative Site

Investigative Site, Czechia

Location

Investigative Site

Investigative Site, Germany

Location

Investigative Site

Investigative Site, Hungary

Location

Investigative Site

Investigative Site, Netherlands

Location

Investigative Site

Investigative Site, Poland

Location

Investigative Site

Investigative Site, Russia

Location

Investigative Site

Investigative Site, Spain

Location

Investigative Site

Investigative Site, Sweden

Location

MeSH Terms

Conditions

Myocardial Ischemia; Angina, Unstable; Myocardial Infarction

Interventions

aliskiren; Valsartan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Eugene Braunwald, MD

  TIMI Study Group, Boston, MA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 7, 2006
• First Posted: December 11, 2006
• Study Start: February 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: April 19, 2011
• Results First Posted: February 2, 2011

Record last verified: 2011-04

Locations

BE (1); DE (1); NL (1); US (1); PL (1); RU (1); ES (1); SE (1); HU (1); CA (1); CZ (1)