IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (Study P04103AM3)

Condition(s) targeted: Hypercholesterolemia; Myocardial Infarction

Intervention: ezetimibe/simvastatin (Drug); simvastatin (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Schering-Plough

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.

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)

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

Primary outcome: 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

Secondary outcome:

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

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

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 a 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

- History of alcohol or drug abuse

- History of sensitivity to statin or ezetimibe

- A subject for whom discontinuation of existing lipid lowering regimen poses an

unacceptable risk.

TIMI Study Group, Boston, Massachusetts 02115, United States; Recruiting
Amy McCagg, Phone: 800-385-4444, Email: amccagg@partners.org

Starting date: October 2005
Ending date: June 2012
Last updated: September 16, 2009