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

Purpose

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.

Condition	Intervention	Phase
Hypercholesterolemia Myocardial Infarction	Drug: ezetimibe/simvastatin Drug: simvastatin	Phase III

Genetics Home Reference related topics:

hypercholesterolemia

MedlinePlus related topics:

Cholesterol Heart Attack

ChemIDplus related topics:

Simvastatin Ezetimibe Cholest-5-en-3-ol (3beta)- Vytorin

U.S. FDA Resources

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

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)

Further study details as provided by Schering-Plough:

Primary Outcome 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. ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	18000
Study Start Date:	February 2006
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ezetimibe/simvastatin: Experimental	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)
simvastatin: Active Comparator	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)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00202878

Locations


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

Sponsors and Collaborators

Schering-Plough

Merck

More Information

Publications indexed to this study:

Drazen JM, Jarcho JA, Morrissey S, Curfman GD. Cholesterol lowering and ezetimibe. N Engl J Med. 2008 Apr 3;358(14):1507-8. Epub 2008 Mar 30. No abstract available.

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	P04103
First Received:	September 13, 2005
Last Updated:	May 1, 2008
ClinicalTrials.gov Identifier:	NCT00202878
Health Authority:	United States: Food and Drug Administration

Keywords provided by Schering-Plough:

hypercholesterolemia

myocardial infarction

cholesterol

randomized controlled trials

Study placed in the following topic categories:

Heart Diseases

Hyperlipidemias

Metabolic Diseases

Simvastatin

Myocardial Ischemia

Vascular Diseases

Ezetimibe

Ischemia

Signs and Symptoms

Necrosis

Pathologic Processes

Acute Coronary Syndrome

Metabolic disorder

Infarction

Myocardial Infarction

Hypercholesterolemia

Dyslipidemias

Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites

Molecular Mechanisms of Pharmacological Action

Therapeutic Uses

Antilipemic Agents

Enzyme Inhibitors

Cardiovascular Diseases

Nutritional and Metabolic Diseases

Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Pharmacologic Actions

Pathological Conditions, Signs and Symptoms

ClinicalTrials.gov processed this record on May 08, 2008

Sponsors and Collaborators:	Schering-Plough Merck
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00202878