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

Primary Purpose

ST-Segment Elevation Myocardial Infarction

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Ezetimibe
Placebo
Sponsored by
Odense University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for ST-Segment Elevation Myocardial Infarction focused on measuring 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

Eligibility Criteria

18 Years - 81 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Cardiology, Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Atorvastatin plus Placebo

Atorvastatin plus Ezetimibe

Arm Description

50/100 patients are randomized to Atorvastatin 80 mg per day plus 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.

Outcomes

Primary Outcome Measures

Plaque volume and composition in a non-significant coronary plaque
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.
Change in percent of the plaque volume in the native coronary vessel with a non-significant stenosis.
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.
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.
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.
Change in percent of the plaque burden in a native coronary vessel with a non-significant lesion.
Incomplete stent apposition.
Edge response in stented segment.
Stent expansion.
Evaluation of the OCT-technique in clinical use compared to IVUS.
Evaluation of the Resolute stents effect on neointima growth and apposition.

Full Information

First Posted
June 28, 2011
Last Updated
September 1, 2014
Sponsor
Odense University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01385631
Brief Title
Ezetimibe In Addition To Atorvastatin Therapy On The Plaque Composition In Patients With Acute Myocardial Infarction.
Acronym
OCTIVUS
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Odense University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST-Segment Elevation Myocardial Infarction
Keywords
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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atorvastatin plus Placebo
Arm Type
Placebo Comparator
Arm Description
50/100 patients are randomized to Atorvastatin 80 mg per day plus placebo.
Arm Title
Atorvastatin plus Ezetimibe
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ezetimibe
Other Intervention Name(s)
Ezetrol, Zarator
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Ezetrol, Zarator
Intervention Description
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.
Primary Outcome Measure Information:
Title
Plaque volume and composition in a non-significant coronary plaque
Description
Plaque volume assessed by intravascular ultrasound and Optical Coherence Tomography
Time Frame
After 12 months of follow-up
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
Incomplete stent apposition.
Time Frame
After 12 months of follow-up
Title
Edge response in stented segment.
Time Frame
After 12 months of follow-up
Title
Stent expansion.
Time Frame
After 12 months of follow-up
Title
Evaluation of the OCT-technique in clinical use compared to IVUS.
Time Frame
After 12 months of follow-up
Title
Evaluation of the Resolute stents effect on neointima growth and apposition.
Time Frame
After 12 months of follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
81 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikkel Hougaard, MD
Organizational Affiliation
Department of Cardiology, Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology, Odense University Hospital
City
Odense C
ZIP/Postal Code
5000
Country
Denmark

12. IPD Sharing Statement

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

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