IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103 AM5)

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Merck

ClinicalTrials.gov Identifier:

NCT00202878

First received: September 13, 2005

Last updated: September 7, 2012

Last verified: September 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	September 13, 2005
Last Updated Date	September 7, 2012
Start Date ^ICMJE	October 2005
Estimated Primary Completion Date	September 2014 (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	Not Provided
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	Not Provided
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103 AM5)
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. 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 CV death, major coronary events, and stroke.
Detailed Description	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 3
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Condition ^ICMJE	Hypercholesterolemia Myocardial Infarction
Intervention ^ICMJE	Drug: 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). Other Names: Vytorin Inegy Drug: 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). Other Name: Zocor
Study Arm (s)	Experimental: ezetimibe/simvastatin Intervention: Drug: ezetimibe/simvastatin Active Comparator: simvastatin Intervention: Drug: simvastatin
Publications *	Azar RR, Badaoui G, Sarkis A, Azar M, Aydanian H, Harb S, Achkouty G, Kassab R. Effect of ezetimibe/atorvastatin combination on oxidized low density lipoprotein cholesterol in patients with coronary artery disease or coronary artery disease equivalent. Am J Cardiol. 2010 Jul 15;106(2):193-7. 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 ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Active, not recruiting
Enrollment ^ICMJE	18141
Estimated Completion Date	September 2014
Estimated Primary Completion Date	September 2014 (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	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Not Provided

Administrative Information
NCT Number ^ICMJE	NCT00202878
Other Study ID Numbers ^ICMJE	P04103
Has Data Monitoring Committee	Yes
Responsible Party	Merck
Study Sponsor ^ICMJE	Merck
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Merck
Verification Date	September 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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