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

Condition	Intervention	Phase
Hypercholesterolemia Myocardial Infarction	Drug: ezetimibe/simvastatin Drug: simvastatin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Angina Cholesterol Heart Attack

Drug Information available for: Simvastatin Ezetimibe

U.S. FDA Resources

Further study details as provided by Merck:

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 ]

Enrollment:	18141
Study Start Date:	October 2005
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

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

Arms

Assigned Interventions

Experimental: ezetimibe/simvastatin

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

Active Comparator: simvastatin

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

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

No Contacts or Locations Provided

More Information

No publications provided by Merck

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00202878 History of Changes
Other Study ID Numbers:	P04103
Study First Received:	September 13, 2005
Last Updated:	September 7, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

hypercholesterolemia
myocardial infarction
cholesterol

randomized controlled trials
acute coronary syndrome
angina

Additional relevant MeSH terms:

Hypercholesterolemia
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Simvastatin
Ezetimibe
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013