Efficacy and Safety of Combination Therapy of Moderate-intensity Statin and Ezetimibe Compared to High-intensity Statin

Study Overview
=================
Brief Summary
-----------------
This study is a multicenter, randomized, open-label, parallel, phase IV trial. The purpose of this study efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin.

Detailed Description
-----------------
The study is planned to include 272 patients with a clinical atherosclerotic cardiovascular disease requiring optimal statin therapy. After enrollment, subjects are randomized into two groups in a 1:1 manner. The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily. The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily. Subjects will visit at weeks 12 and 24 to identify medication adherence and clinical side effects. The primary endpoint of this study is a % change of low-density lipoprotein cholesterol at 12 weeks.

Official Title
-----------------
Efficacy and Safety of Combination Therapy of Moderate-intensity Statin and Ezetimibe Compared to High-intensity Statin: Study Protocol for a Randomized Controlled Trial

Conditions
-----------------
Cardiovascular Diseases

Intervention / Treatment
-----------------
* Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged between 19 and 75 years Presence of atherosclerotic cardiovascular disease Coronary artery disease History of acute coronary syndrome Stable or unstable angina History of coronary revascularization Stroke or TIA Peripheral arterial disease, history of peripheral arterial revascularization Patients who have been taking lipid-lowering agents (statin or ezetimibe) for ≥4 weeks at the time of randomization Patients who gave informed consent Exclusion Criteria: Patients who have used lipid-lowering agents other than statin or ezetimibe within the last 3 months A serum triglyceride on fasting >400 mg/dL A history of muscular symptoms or rhabdomyolysis due to the use of statin Hypersensitivity to rosuvastatin or ezetimibe Labeled contraindications to rosuvastatin or rosuvastatin Severe renal impairment (CrCl <30 mL/min by Cockcroft-Gault formula or estimated GFR <30 mL/min / 1.73 m2 by MDRD equation) ALT, AST ≥3 × ULN or active liver disease CPK ≥3 × ULN Enrollment of other clinical trials within 30 days Any other issues that the treating physician assumes ineligible for participation in the trial

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: combination therapy group<br>The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily. | Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin<br>* This study is a multicenter, randomized, open-label, parallel, phase IV trial. The study is planned to include 272 patients with clinical ASCVD requiring optimal statin therapy. After enrollment, subjects are randomized into two groups in a 1:1 manner. patients in combination therapy group(rosuvastation 10mg and ezetimibe 10mg daily) will be provided a fixed-dose single pill comibation and patients in the intensive statin group will receive rosuvastatin 20mg daily.<br>|
| Other: intensive statin group<br>The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily. | Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin<br>* This study is a multicenter, randomized, open-label, parallel, phase IV trial. The study is planned to include 272 patients with clinical ASCVD requiring optimal statin therapy. After enrollment, subjects are randomized into two groups in a 1:1 manner. patients in combination therapy group(rosuvastation 10mg and ezetimibe 10mg daily) will be provided a fixed-dose single pill comibation and patients in the intensive statin group will receive rosuvastatin 20mg daily.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % change of low-density lipoprotein cholesterol | %change of LDL-C = (LDL-C at 12 weeks) - (LDL-C at baseline)/LDL-C at baseline * 100 | at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % change of serum cholesterol level | total cholesterol, LDL, HDL cholesterol, triglyceride (mg/dL) | at 12 and 24 weeks | 
| % change of high-sensitivity C-reactive protein | hs-CRP(mg/dL) | at 12 and 24 weeks | 
| % change of fasting glucose | fasting plasma glucose(mg/dL) | at 12 and 24 weeks | 
| % change of homeostatic model assessment for insulin resistance(HOMA-IR) | HOMA-IR = glucose * insulin / 405(glucose mg/dL , insulin uIU/mL) | at 12 and 24 weeks | 
| proportion of participant with statin-associated muscle symptoms | occurrence of statin-associated muscle symptoms | at 12 and 24 weeks | 
| proportion of participant with creatinine phosphokinase elevation | proportion of CPK elevation ≥4 or ≥10 upper normal of limit | at 12 and 24 weeks | 
| proportion of participant with liver function test abnormality | proportion of AST/ALT elevation ≥4 or ≥10 upper normal of limit | at 12 and 24 weeks | 
| proportion of participant with major adverse cardiovascular and cerebrovascular events(MACCE) | MACCE defined as a composite of the followings : cardiovascular death, acute myocardial infarction, unstable angina, stroke | at 12 and 24 weeks |