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

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

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

Drug Information available for: Simvastatin Ezetimibe 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 occurrance. ] [ 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 a 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 a 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 a 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:	October 2005
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 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.

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

No publications provided by Schering-Plough

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Cannon CP, Giugliano RP, Blazing MA, Harrington RA, Peterson JL, Sisk CM, Strony J, Musliner TA, McCabe CH, Veltri E, Braunwald E, Califf RM; IMPROVE-IT Investigators. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008 Nov;156(5):826-32. Epub 2008 Sep 2.

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
Study First Received:	September 13, 2005
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00202878 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Schering-Plough:

hypercholesterolemia
myocardial infarction
cholesterol

randomized controlled trials
acute coronary syndrome
angina

Study placed in the following topic categories:

Antimetabolites
Hyperlipidemias
Metabolic Diseases
Heart Diseases
Simvastatin
Antilipemic Agents
Myocardial Ischemia
Vascular Diseases
Angina Pectoris
Ezetimibe
Anticholesteremic Agents

Ischemia
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Necrosis
Acute Coronary Syndrome
Infarction
Metabolic Disorder
Myocardial Infarction
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Myocardial Ischemia
Ezetimibe
Necrosis
Pathologic Processes
Syndrome
Therapeutic Uses
Cardiovascular Diseases
Myocardial Infarction
Hypercholesterolemia
Dyslipidemias
Metabolic Diseases
Hyperlipidemias

Heart Diseases
Disease
Simvastatin
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors
Anticholesteremic Agents
Ischemia
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Acute Coronary Syndrome
Infarction
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 07, 2009