IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)

Organon

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia; Myocardial Infarction

Treatments: Drug: simvastatin; Drug: ezetimibe/simvastatin; Drug: Placebo for simvastatin 40 mg; Drug: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination

Study type: Interventional

Funder types: Industry

Identifiers

NCT00202878

MK-0653A-080 (Other Identifier)

P04103

Details and patient eligibility

About

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. As per the original protocol, if low-density lipoprotein cholesterol (LDL-C) response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of cardiovascular (CV) death, major coronary events, and stroke.

Enrollment: 18,144 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinically stable participants may be eligible to enroll within 10 days following hospital admission with high-risk acute coronary syndrome (either ST-elevation myocardial infarction [STEMI] or Non-STEMI or unstable angina)
• Participants not taking a statin must have an LDL-C of 125 mg/dl or less. Participants 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
• Participant with active liver disease or persistent unexplained serum transaminase elevation
• History of alcohol or drug abuse
• History of sensitivity to statin or ezetimibe
• A participant for whom discontinuation of existing lipid lowering regimen poses an unacceptable risk.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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18,144 participants in 2 patient groups

ezetimibe/simvastatin

Experimental group

Description:

One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day.

Treatment:

Drug: Placebo for simvastatin 40 mg

Drug: ezetimibe/simvastatin

simvastatin

Active Comparator group

Description:

One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.

Treatment:

Drug: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination

Drug: Placebo for simvastatin 40 mg

Drug: simvastatin