Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy (IMPACT on IMT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Seoul National University Hospital
Sponsor:
Collaborator:
Korea Otsuka Pharmaceutical Co.,Ltd.
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01291641
First received: January 31, 2011
Last updated: July 1, 2013
Last verified: July 2013

January 31, 2011
July 1, 2013
March 2011
March 2014   (final data collection date for primary outcome measure)
Difference of Carotid artery IMT (mean IMT) between screening and treatment completion(3 years after) or discontinuation [ Time Frame: Baseline(screening), 3years ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01291641 on ClinicalTrials.gov Archive Site
  • Time from enrollment date to the onset of composite cerebrovascular events [ Time Frame: enrollment date, onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    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.

  • Number of composite cerebrovascular and cardiovascular events(including intervention) [ Time Frame: enrollment date, onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    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).

  • The change of Biomarkers(1) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    Metabolic index: Lipid profile (TC, LDL-C, HDL-C, TG)
  • The change of Biomarkers(2) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    Inflammatory index: High sensitive C-reactive protein (hsCRP)
  • The change of Biomarkers(3) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]

    Oxidation index:oxidized LDL

    The change of biomarkers, t-test will be done by treatment arm(Group A vs B, Group A vs C).

Same as current
Not Provided
Not Provided
 
Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy
Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy (IMPACT on IMT): A Randomized, Multicenter, Multinational Study

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

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Hyperlipidemias
  • Drug: HMGCoA reductase inhibitor

    During the study period, HMGCoA reductase inhibitor is continuously administered to the patients.

    Dosage regimen: following the package insert of each HMGCoA reductase inhibitor

  • Drug: HMGCoA reductase inhibitor + probucol

    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)

  • Drug: HMGCA reductase inhibitor + probucol + cilostazol

    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

  • Experimental: Group A
    HMGCoA reductase inhibitor continued
    Intervention: Drug: HMGCoA reductase inhibitor
  • Experimental: Group B
    HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID
    Intervention: Drug: HMGCoA reductase inhibitor + probucol
  • Experimental: Group C
    HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID + Cilostazol 100 mg PO, BID
    Intervention: Drug: HMGCA reductase inhibitor + probucol + cilostazol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
342
Not Provided
March 2014   (final data collection date for primary outcome measure)

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
Both
20 Years and older
No
Contact: Byung-Hee Oh, M.D +82-2-2072-3345 ohbhmed@snu.ac.kr
Contact: Hyun-Jae Kang, M.D. nowkang@snu.ac.kr
Korea, Republic of
 
NCT01291641
IMT-01
No
Byung Hee Oh/Professor, Department of Internal Medicine, Seoul National University Hospital, Seoul National University Hospital
Seoul National University Hospital
Korea Otsuka Pharmaceutical Co.,Ltd.
Study Chair: Byung-Hee Oh, M.D. Seoul National University Hospital
Principal Investigator: Cheol Ho Kim, M.D. Seoul National University Bundang Hospital
Principal Investigator: Sang-Hyun Kim, M.D. SMG-SNU Boramae Medical Center
Principal Investigator: Moo-Hyun Kim, M.D. Dong-A medical center
Seoul National University Hospital
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP