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

Tracking Information
First Received Date ^ICMJE	September 13, 2005
Last Updated Date	October 29, 2009
Start Date ^ICMJE	October 2005
Estimated Primary Completion Date	June 2012 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: January 22, 2009)	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 ]
Original Primary Outcome Measures ^ICMJE (submitted: December 20, 2007)	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 an primary endpoint event and each subject is followed for a minimum of 2.5 years ] [ Designated as safety issue: No ]
Change History	Complete list of historical versions of study NCT00202878 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: January 22, 2009)	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 ]
Original Secondary Outcome Measures ^ICMJE (submitted: December 20, 2007)	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 ]

Descriptive Information
Brief Title ^ICMJE	IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (Study P04103AM3)
Official Title ^ICMJE	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)
Brief Summary	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.
Detailed Description
Study Phase	Phase III
Study Type ^ICMJE	Interventional
Study Design ^ICMJE	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Condition ^ICMJE	Hypercholesterolemia Myocardial Infarction
Intervention ^ICMJE	Drug: ezetimibe/simvastatin Drug: simvastatin
Study Arms / Comparison Groups
Publications *	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.
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Recruiting
Estimated Enrollment ^ICMJE	18000
Estimated Completion Date	June 2012
Estimated Primary Completion Date	June 2012 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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.
Gender	Both
Ages	18 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE
Location Countries ^ICMJE	United States

Administrative Information
NCT ID ^ICMJE	NCT00202878
Responsible Party	Head, Clinical Trials Registry & Results Disclosure Group, Schering-Plough
Study ID Numbers ^ICMJE	P04103
Study Sponsor ^ICMJE	Schering-Plough
Collaborators ^ICMJE	Merck
Investigators ^ICMJE
Information Provided By	Schering-Plough
Verification Date	October 2009
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP