Clinical trial

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)

NCT00202878

Name

P04103

Description

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.

Trial arms

Trial start

2005-10-17

Estimated PCD

2014-09-18

Trial end

2014-09-18

Status

Completed

Phase

Early phase I

Treatment

ezetimibe/simvastatin

Ezetimibe/simvastatin 10/40 mg per day from randomization through the end of participation. As per the original protocol, if 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).

Arms:

ezetimibe/simvastatin

Other names:

Vytorin, Inegy

simvastatin

Simvastatin 40 mg per day from randomization through the end of participation. As per the original protocol, if 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).

Arms:

simvastatin

Other names:

Zocor

Placebo for simvastatin 40 mg

one or two tablets orally daily

Arms:

ezetimibe/simvastatin, simvastatin

Placebo for ezetimibe 10 mg/simvastatin 40 mg combination

one tablet orally daily.

Arms:

simvastatin

Size

18144

Primary endpoint

Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

Up to approximately 9 years

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 18144, 'type': 'ACTUAL'}}

Updated at

2024-05-20

1 organization

4 products

2 indications

Organization

Organon and Co

Product

ezetimibe/simvastatin

Indication

Hypercholesterolemia

Indication

Heart Attack

Product

simvastatin

Product

Placebo for Simvastatin

Product

Placebo