Effect of Low-dose vs. High-dose Pitavastatin on In-stent Restenosis

Study Overview
=================
Brief Summary
-----------------
To compare low dose (1mg) pitavastatin and high dose (4mg) pitavastatin on neointimal hyperplasia and atherosclerosis progression by using optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) at 12 months follow-up and on clinical adverse cardiovascular events during 3-year follow-up.

Detailed Description
-----------------
Patients with non-ST elevation ACS will be randomized into pitavastatin 1mg or 4mg after everolimus-eluting stent implantation with OCT and NIRS study. 12 months follow-up coronary angiography with OCT and NIRS will be performed to compare neointimal hyperplasia and atherosclerosis progression. 36 months clinical follow-up for major adverse cardiovascular events (cardiac death, all-cause death, myocardial infarction, stroke, target lesion revascularization) will be compared. Safety issues such as bleeding rates, abnormal liver function will be compared

Official Title
-----------------
Effect of Low-dose vs. High-dose Pitavastatin on In-stent Restenosis, Endothelial Function, Circulating microRNAs, and Cardiovascular Events in Patients With Coronary Artery Disease Requiring Stent Implantation: OCT and NIRS Comparison

Conditions
-----------------
Atherosclerosis, Neointima, Angina

Intervention / Treatment
-----------------
* Drug: Pitavastatin 1mg
* Drug: Pitavastatin 4mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of informed consent prior to any study specific procedures Patients between the age of 30 to 79 Non-ST elevation Acute coronary syndrome with successful everolimus eluting stent implantation (with TIMI flow grade 3 after the procedure) Exclusion Criteria: Hypersensitivity to pitavastatin Unable to perform OCT and NIRS Serum creatinine > 2.0 mg/dL. Steroid or hormone replacement therapy Hemoglobin A1c >9% Type 1 diabetes Decreased serum platelet level (< 100,000/uL) Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin Life expectancy less than a year Renal failure requiring dialysis or anticipated need for dialysis during the course of the study Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the patient to participate in this study Involvement in the planning and/or conduct of the study Left ventricular ejection fraction < 40% Hepatic dysfunction (aspartate aminotransferase or alanine aminotransferase > twice the upper limit) Gastrointestinal disorder such as Crohn's disease Alcohol abuse Known pregnancy, breast-feeding, or intend to become pregnant during the study period

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose 1mg pitavastatin<br>pitavastatin 1mg which is considered low dose statin will be administered for 36 months | Drug: Pitavastatin 1mg<br>* To compare different doses of statins on atherosclerosis progression and neointimal hyperplasia<br>* Other names: Livalo 1mg;Drug: Placebo<br>* To compare different doses of statins on atherosclerosis progression and neointimal hyperplasia<br>|
| Active Comparator: High dose 4mg pitavastatin<br>pitavastatin 4mg which is considered high dose statin will be administered for 36 months | Drug: Pitavastatin 4mg<br>* To compare different doses of statins on atherosclerosis progression and neointimal hyperplasia<br>* Other names: Livalo 4mg;Drug: Placebo<br>* To compare different doses of statins on atherosclerosis progression and neointimal hyperplasia<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neointimal volume with OCT (mm3 per 1mm) and lipid volume with NIRS (the maximal lipid core burden index (LCBI) in 4 mm segment during 12 months of treatment | OCT will measure neointimal volume in every mm interval and will be averaged by dividing the total neointimal volume with the number of the segment analyzed. LCBI is the lipid volume index which is calculated automatically by the device, and LCBI > 400 is considered high lipid volume. | 12 months for OCT and NIRS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of major adverse cardiovascular events during 12 months follow-up | Major adverse cardiovascular events include all-cause death, cardiovascular death, myocardial infarction, stroke, target vessel revascularization | 12 months for clinical events |