RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases (RACING Trial)

Study Overview
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Brief Summary
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The clinical efficacy of LDL-lowering therapy have been proven with strong evidences and more emphasized. However, there are also growing concerns that high-intensity statin would be related to increased risk of adverse effects. In addition, there was an inconsistency of efficacy of statin according to ethnic population. Asian population showed more profound LDL reduction not only from high potent statin but from moderate to low potent statin. Conventional strategies for lowering LDL-cholesterol was focused on statins, therefore doubling of previously described dose of statin would be common way in patients with inadequate lowering LDL-cholesterol level. Additive ezetimibe will also an alternative strategy not only to lower LDL-cholesterol level and also to reduce the need of dosage of high-intensity statin to fulfill sufficient LDL-cholesterol lowering effect. We will evaluate whether additive ezetimibe with rosuvastatin will have comparable clinical efficacy in terms of clinical outcomes and goal attainment of LDL-C compared to rosuvastatin monotherapy.

Official Title
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RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases (RACING Trial)

Conditions
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Cardiovascular Diseases, Cerebrovascular Disease, Peripheral Atherosclerotic Disease

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Rosuvastatin plus ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-80 years Documented CVD (cardiovascular disease), previous MI(Myocardial Infarction), ACS (Acute Coronary Syndrome), coronary revascularization and other arterial revascularization procedures, ischemic stroke, or PAD (peripheral artery disease) Exclusion Criteria: Active liver disease or persistent unexplained serum AST or ALT elevation more than 2 times the upper limit of normal range Allergy or hypersensitivity to any statin or ezetimibe Solid organ transplantation recipient History of any adverse drug reaction requiring discontinuation of statin Pregnant women, women with potential childbearing, or lactating women Life expectancy less than 3 years Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator Inability to understand or read the informed content

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-intensity statin monotherapy<br>Statin monotherapy | Drug: Rosuvastatin<br>* Subjects will start rosuvastatin 20 mg a day irrespective of previous lipid-lowering treatment or LDL-cholesterol level as current US guideline.<br>|
| Experimental: Statin plus ezetimibe combination therapy<br>Statin plus ezetimibe combination therapy | Drug: Rosuvastatin plus ezetimibe<br>* Subjects will start single combination pill of rosuvastatin 10 mg plus ezetimibe 10 mg a day irrespective of previous lipid-lowering treatment or LDL-cholesterol level.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of cardiovascular death | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 2 months. | 
| Composite of cardiovascular death | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 6 months. | 
| Composite of cardiovascular death | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at every years until 3 years. | 
| Major cardiovascular event | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 2 months. | 
| Major cardiovascular event | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 6 months. | 
| Major cardiovascular event | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at every years until 3 years. | 
| Composite of nonfatal stroke | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 2 months. | 
| Composite of nonfatal stroke | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at 6 months. | 
| Composite of nonfatal stroke | Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) | Clinical status including medication and clinical events will be evaluated at every years until 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of lipid lowering treatment | The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment) Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) Statin discontinuation or dose-reduction caused by intolerance new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery | 3years | 
| Clinical safety of lipid lowering treatment | The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment) Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) Statin discontinuation or dose-reduction caused by intolerance new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery | 3years | 
| statin discontinuation and intolerance | The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment) Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) Statin discontinuation or dose-reduction caused by intolerance new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery | 3years | 
| Clinical adverse events | The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment) Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.) Statin discontinuation or dose-reduction caused by intolerance new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery | 3years |