Ezetimibe In Addition To Atorvastatin Therapy On The Plaque Composition In Patients With Acute Myocardial Infarction. - Full Text View

Purpose

The purpose of the study is to examine the effect of the cholesterol lowering agent Ezetimibe when used in addition to optimal treatment with Atorvastatin in patients with acute ST-Elevation Myocardial Infarction (STEMI) who have not been in prior statin therapy.

An area with arteriosclerosis not demanding intervention in a coronary vessel other than the infarct related is used as measuring point and is examined at time of the infarction and after 12 month using intravascular ultrasound and optical coherence tomography. At the same time the same techniques are used to examine the implanted stent.

Condition	Intervention	Phase
ST-Segment Elevation Myocardial Infarction	Drug: Ezetimibe Drug: Placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Diagnostic
Official Title:	The Effect Of Ezetimibe In Addition To Optimal Cholesterol-Lowering Statin Therapy On The Plaque Composition In Patients With Acute Myocardial Infarction - Assessed By Optical Coherence Tomography And Intravascular Ultrasound.

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Heart Attack Statins

Drug Information available for: Atorvastatin calcium Ezetimibe

U.S. FDA Resources

Further study details as provided by Odense University Hospital:

Primary Outcome Measures:

Plaque volume and composition in a non-significant coronary plaque [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Plaque volume assessed by intravascular ultrasound and Optical Coherence Tomography

Secondary Outcome Measures:

Change in plaque-composition (measured with Tissue Characterization) in a 10 mm segment of a native coronary vessel with a non-significant stenosis where plaque-volume at baseline is greatest. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Change in percent of the plaque volume in the native coronary vessel with a non-significant stenosis. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Change in percent of the plaque volume in the 10 mm segment of a native coronary vessel with a non-significant lesion where plaque volume at baseline is greatest. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Change in absolute numbers of the plaque volume in the 10 mm segment of a native coronary vessel with a non-significant lesion where plaque volume at baseline is greatest. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Change in percent of the plaque burden in the 10 mm segment of a native coronary vessel with a non-significant lesion where plaque volume at baseline is greatest. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Change in percent of the plaque burden in a native coronary vessel with a non-significant lesion. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Incomplete stent apposition. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Edge response in stented segment. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Stent expansion. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Evaluation of the OCT-technique in clinical use compared to IVUS. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]
Evaluation of the Resolute stents effect on neointima growth and apposition. [ Time Frame: After 12 months of follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	June 2011
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Atorvastatin plus Placebo 50/100 patients are randomized to Atorvastatin 80 mg per day plus placebo.	Drug: Placebo 100 patients with ST elevation myocardial infarction are randomized 1:1 to either placebo or Ezetimibe 10 mg per day in addition to treatment with Atorvastatin 80 mg in both arms. Other Names: Ezetrol Zarator
Experimental: Atorvastatin plus Ezetimibe 100 patients with ST elevation myocardial infarction are randomized 1:1 to either placebo or Ezetimibe 10 mg per day in addition to treatment with Atorvastatin 80 mg in both arms.	Drug: Ezetimibe 100 patients with ST elevation myocardial infarction are randomized 1:1 to either placebo or Ezetimibe 10 mg per day in addition to treatment with Atorvastatin 80 mg in both arms. Other Names: Ezetrol Zarator

Detailed Description:

Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) with tissue characterization (IVUS-TC) are relatively new expansions to intravascular assessments, and has the capacity to assess plaque composition and, potentially, to identify vulnerable plaques. One of the mechanisms by which statins improve patient outcomes may be by changing the composition of a "vulnerable" plaque. The main effect is believed to rely on a lowering of LDL-c. The question is whether a further reduction of LDL by adding ezetimibe to optimal cholesterol lowering therapy using statins may result in further plaque stabilization or reduction. This is the hypothesis of the current study.

100 patients are randomized to Ezetimibe 10 mg per day or placebo. All patients are treated with Atorvastatin 80 mg. OCT and IVUS are performed at inclusion (typically the day after Primary PCI) and again at follow-up after 12 month.

Eligibility

Ages Eligible for Study:	18 Years to 81 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

ST segment elevation acute myocardial infarction
20% < angiographic diameter stenosis < 50% on a not previously revascularized native coronary artery
Statin naïve
In fertile women: Ongoing contraception with IUD or hormonal contraception.

Exclusion Criteria:

Pharmacologic lipid lowering treatment before index hospitalization
Atrial fibrillation, not well rate-controlled
Ventricle frequency variation with more than a factor 2 over 1 minute
Unconscious patients
History of statin induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins) including Atorvastatin.
Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test (a serum-human chorionic gonadotrophin [Beta-HCG] analysis)
History of malignancy (unless a documented disease free period exceeding 5-years is present) with the exception of basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia would be permitted to enter the study provided they had 3 consecutive clear Papanicolaou (Pap) smears
Uncontrolled hypothyroidism (TSH > 1.5xULN)
Abnormal LFT's
History of alcohol or drug abuse within the last 5 years (this may affect compliance)
Current active liver disease (ALT/SGPT >2xULN or severe hepatic impairment (to protect patient safety as directed on the labels of currently approved statins)
Unexplained creatine kinase (CK > 3xULN) (To protect patient safety) (will be increased at baseline because of acute ST segment elevation myocardial infarction a few days before enrolment)
Serum creatinine >176mmol/L (2.0mg/dL) (unless the protocol specifically aims to investigate a chronic renal disease population)
Participation in another investigational drug study less than 4 weeks before enrolment in the study, or according to subjects local ethics committee requirements where a larger period is stipulated (to avoid potential misinterpretation of overlapping adverse events)
Treatments with cyclosporine
Treatment with gemfibrozil

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385631

Locations

Denmark
Department of Cardiology, Odense University Hospital	Recruiting
Odense C, Denmark, 5000
Contact: Mikkel Hougaard, MD +45-21955150 octivus@candmed.dk
Principal Investigator: Mikkel Hougaard, MD

Sponsors and Collaborators

Odense University Hospital

Investigators

Principal Investigator:

Mikkel Hougaard, MD

Department of Cardiology, Odense University Hospital

More Information

No publications provided

Responsible Party:	Henrik Steen Hansen, Odense University Hospital
ClinicalTrials.gov Identifier:	NCT01385631 History of Changes
Other Study ID Numbers:	OUH-OCTIVUS
Study First Received:	June 28, 2011
Last Updated:	June 30, 2011
Health Authority:	Denmark: Danish Medicines Agency

Keywords provided by Odense University Hospital:

ST-Segment Elevation Myocardial Infarction
Intravascular ultrasound
IVUS
Optical coherence tomography
OCT
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atorvastatin

Randomized trial
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Hypolipidemic Agents

Atorvastatin
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Pharmacologic Actions
Therapeutic Uses
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013

Ezetimibe In Addition To Atorvastatin Therapy On The Plaque Composition In Patients With Acute Myocardial Infarction. (OCTIVUS)