The purpose of this study is to evaluate the additional effect of probucol or concomitant administration of cilostazol and probucol on mean carotid artery intima-media thickness (mean IMT) at year 1, 2, and 3.
Hyperlipidemic patients who are currently receiving HMGCoA reductase inhibitors(Statins) will be randomized Group A(Control), Group B(Probucol only added group) or Group C(Probucol and cilostazol added group) . Randomization will be done by the minimization method, controlling for the following factors: Country(Korea vs China) and max IMT (≥2.0mm vs.\<2.0mm). Group A : HMGCoA reductase inhibitor continued Group B : HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID Group C : HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID +Cilostazol 100 mg PO, BID
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
342
During the study period, HMGCoA reductase inhibitor is continuously administered to the patients. Dosage regimen: following the package insert of each HMGCoA reductase inhibitor
In addition to the continued HMGCoA reductase inhibitor treatment, probucol is administered. Dosage regimen: probucol 250-mg tablet, oral administration twice daily with meal(breakfast and dinner)
In addition to the continued HMGCoA reductase inhibitor treatment, probucol and cilostazol are administered. Dosage regimen: probucol 250-mg tablet, oral administration twice daily with meal(breakfast and dinner) Cilostazol 100-mg tablet, twice daily by the oral route
Dong-A Medical Center
Seogu, Busan, South Korea
Samsung Medical Center
Seoul, Gangnam-Gu, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, South Korea
Seoul National University Hospital
Seoul, South Korea
Difference of Carotid artery IMT (mean IMT) between screening and treatment completion(3 years after) or discontinuation
For primary endpoint of Carotid artery IMT, t-test will be conducted for the mean IMT and variation by treatment arm(Group A vs B, Group A vs C). The 2-sided significance level is 5%. Morever, Mantel - Haenszel method can be accepted considering stratification factor or Sub-analysis can be done by each stratum in case of categorical variables.
Time frame: Baseline(screening), 3years
Time from enrollment date to the onset of composite cerebrovascular events
1. Cardiovascular death 2. Myocardial infarction 3. Cerebral infarction 4. Unstable angina and cardiac failure, required hospitalization 5. Coronary revascularization, required hospitalization 6. PCI and coronary artery bypass grafting \[CABG\] Kaplan-Meier method will be conducted for the time from enrollment date to the onset of composite cerebrovascular and cardiovascular events by treatment arm(Group A vs B, Group A vs C). Overall survival curves and progression-free survival curves are estimated per treatment arm.
Time frame: enrollment date, onset date(during study period, 3years)
Number of composite cerebrovascular and cardiovascular events(including intervention)
1. Cardiovascular death 2. Myocardial infarction 3. Cerebral infarction 4. Unstable angina and cardiac failure, required hospitalization 5. Coronary revascularization, required hospitalization 6. PCI and coronary artery bypass grafting \[CABG\] For the number of composite cerebrovascular and cardiovascular events (including intervention) t-test will be done by treatment arm(Group A vs B, Group A vs C).
Time frame: enrollment date, onset date(during study period, 3years)
The change of Biomarkers(1)
Metabolic index: Lipid profile (TC, LDL-C, HDL-C, TG)
Time frame: enrollment date ,onset date(during study period, 3years)
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Boramae Medical Center
Seoul, South Korea
The change of Biomarkers(2)
Inflammatory index: High sensitive C-reactive protein (hsCRP)
Time frame: enrollment date ,onset date(during study period, 3years)
The change of Biomarkers(3)
Oxidation index:oxidized LDL The change of biomarkers, t-test will be done by treatment arm(Group A vs B, Group A vs C).
Time frame: enrollment date ,onset date(during study period, 3years)