Clinical trial NCT01291641: Effect of Probucol and/or Cilostazol on Mean IMT in Patients With Coronary Heart dIsease
Official title: Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy: A Randomized, Multicenter, Multinational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperlipidemias
Keywords: Hyperlipidemias
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Probucol
Cilostazol
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Korea Otsuka Pharmaceutical Co., Ltd.
First posted: 2011-02-08
Enrollment: 342
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 1) Subjects who are at least 20 y of age at the time of informed consent (male or female)
* 2) Subjects with coronary heart disease longer than 3 months.
* 3) Subjects being treated with HMGCoA reductase inhibitors(Statins)
* 4) Subjects with an max IMT equal to or greater than 1.2 mm
* 5) Subjects with an LDL-Cholesterol less than 200mg/dl
* 6) Subjects whose voluntary written informed consent is obtained for participation in this study

Exclusion Criteria:

* 1) Subjects who took probucol within 6 months before participation of the study
* 2) Subjects who took cilostazol within 3 months before participation of the study
* 3) Subjects with a history of hypersensitivity to probucol or cilostazol
* 4) Subjects with homozygous familial hyperlipidemia\*
* 5) Subjects with a triglyceride ( TG) level greater than 400mg/dL at screening
* 6) Subjects with uncontrolled diabetes : HbA1c level greater than 9%
* 7) Subjects with New York Heart Association (NYHA) classification: Class Ⅲ and Ⅳ
* 8) Subjects with a QTc interval greater than 450msec(male) 470msec(female)
* 9) Subjects with serious ventricular arrythmias (frequent episodes of multifocal ventricular extrasystole)
* 10) Subjects with atrial fibrillation (including paroxysmal AF)
* 11) Subjects with unstable angina
* 12) Subjects with liver and kidney functions that satisfy the following criteria - AST or ALT \>100 IU/L, serum creatinine \>1.5 mg/dL
* 13) Subjects who are participating in another clinical trial
* 14) Subjects with pregnant or possibly pregnant without appropriate contraception control. Appropriate contraception control means that Oral contraception for greater than 4 weeks, surgical contraception including loop insertion, condom use etc. Women who has no possibility of pregnancy because of surgery or menopause should not be regarded the subject with possibly pregnant
* 15) Subjects with clinically significant disorders of blood coagulation
* 16) Subjects who are not considered by the physicians to be appropriate to participate in this trial for any other reason

Primary outcomes:
measure: Difference of Carotid artery IMT (mean IMT) between screening and treatment completion(3 years after) or discontinuation
timeFrame: Baseline(screening), 3years
Secondary outcomes:
measure: Time from enrollment date to the onset of composite cerebrovascular events
timeFrame: enrollment date, onset date(during study period, 3years)
measure: Number of composite cerebrovascular and cardiovascular events(including intervention)
timeFrame: enrollment date, onset date(during study period, 3years)
measure: The change of Biomarkers(1)
timeFrame: enrollment date ,onset date(during study period, 3years)
measure: The change of Biomarkers(2)
timeFrame: enrollment date ,onset date(during study period, 3years)
measure: The change of Biomarkers(3)
timeFrame: enrollment date ,onset date(during study period, 3years)
Other outcomes:
Locations:
city: Seogu
country: Korea, Republic of
facility: Dong-A Medical Center
state: Busan
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-Gu
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Boramae Medical Center
Study officials:
affiliation: Seoul National University Hospital
name: Byung-Hee Oh, M.D.
role: STUDY_CHAIR
affiliation: Seoul National University Bundang Hospital
name: Cheol Ho Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: SMG-SNU Boramae Medical Center
name: Sang-Hyun Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dong-A medical center
name: Moo-Hyun Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
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