Official Title: “A Multicenter, Double-Blind, Randomized Study to Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting With Acute Coronary Syndrome (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial - IMPROVE IT)”

This is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome (ACS). The primary objective is to evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet, under the brand VYTORIN in the United States) compared with Simvastatin 40 mg. If LDL-C response is inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, as appropriate, may be increased to 80 mg. Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of CV death, major coronary events, and stroke.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2012

Intervention(s) in this Clinical Trial

• Drug: ezetimibe/simvastatin
  • ezetimibe/simvastatin 10/40 mg per day from randomization through the end of participation (if LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg)
• Drug: simvastatin
  • simvastatin 40 mg per day from randomization through the end of participation (if LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: ezetimibe/simvastatin
• Active Comparator: simvastatin

Primary Measures

• To measure the effect of treatment with ezetimibe/simvastatin compared with simvastatin monotherapy on death due to any cardiovascular events, non-fatal coronary events (such as heart attack), and non-fatal strokes
  • Time Frame: Trial will continue until a minimum of 5,250 subjects have a primary endpoint event and each subject is followed for a minimum of 2.5 years. Thus, the anticipated completion dates below may be adjusted on the basis of actual event occurrence.
    Safety Issue?: No

Secondary Measures

• To measure the effect of treatment with ezetimibe/simvastatin compared with simvastatin monotherapy on death due to any cause, non-fatal coronary events (such as heart attack), and non-fatal stroke
  • Time Frame: Trial will continue until a minimum of 5,250 subjects have an primary endpoint event and each subject is followed for a minimum of 2.5 years
    Safety Issue?: No
• To measure the effect of treatment with ezetimibe/simvastatin compared with simvastatin monotherapy on coronary heart disease-related death, non-fatal heart attack, and by-pass surgery
  • Time Frame: Trial will continue until a minimum of 5,250 subjects have an primary endpoint event and each subject is followed for a minimum of 2.5 years
    Safety Issue?: No
• To measure the effect of treatment with ezetimibe/simvastatin compared with simvastatin monotherapy on death due to any cardiovascular events, non-fatal heart attack, angina leading to hospitalization, by-pass surgery, and non-fatal stroke
  • Time Frame: Trial will continue until a minimum of 5,250 subjects have an primary endpoint event and each subject is followed for a minimum of 2.5 years
    Safety Issue?: No

Inclusion Criteria:

• Clinically stable subjects may be eligible to enroll within 10 days following hospital admission with high-risk acute coronary syndrome (either STEMI or Non-STEMI or unstable angina) .
• Subjects not taking a statin must have an LDL-C of 125 mg/dl or less. Subjects taking s statin must have an LDL-C of 100 mg/dl or less.

Exclusion Criteria:

• Pregnant or lactating woman, or intending to become pregnant
• Subject with active liver disease or persistent unexplained serum transaminase elevation
• Subject with a history of alcohol or drug abuse,
• Subject with a history of sensitivity to statin or ezetimibe
• A subject for whom discontinuation of existing lipid lowering regimen poses an unacceptable risk.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00202878

Study ID Number: P04103

ClinicalTrials.gov Identifier: NCT00202878

Health Authority: United States: Food and Drug Administration