Effect of Probucol and/or Cilostazol on Mean IMT in Patients With Coronary Heart dIsease (IMPACTonIMT)

September 18, 2019 updated by: Byung-Hee Oh, Seoul National University Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

342

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 156-707
        • Boramae Medical Center
    • Busan
      • Seogu, Busan, Korea, Republic of, 602-715
        • Dong-A Medical Center
    • Gangnam-Gu
      • Seoul, Gangnam-Gu, Korea, Republic of, 135-710
        • Samsung Medical Center
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
        • Seoul National University Bundang Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Group A
HMGCoA reductase inhibitor continued
Drug: HMG-CoA 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
Active Comparator: Group B
HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID
Drug: 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)

Other Names:
  • HMG-CoA Reductase Inhibitor
Active Comparator: Group C
HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID + Cilostazol 100 mg PO, BID
Drug: 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

Other Names:
  • HMG-CoA Reductase Inhibitor
  • Probucol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference of Carotid artery IMT (mean IMT) between screening and treatment completion(3 years after) or discontinuation
Time Frame: Baseline(screening), 3years
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.
Baseline(screening), 3years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from enrollment date to the onset of composite cerebrovascular events
Time Frame: enrollment date, onset date(during study period, 3years)
  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.
enrollment date, onset date(during study period, 3years)
Number of composite cerebrovascular and cardiovascular events(including intervention)
Time Frame: enrollment date, onset date(during study period, 3years)
  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).
enrollment date, onset date(during study period, 3years)
The change of Biomarkers(1)
Time Frame: enrollment date ,onset date(during study period, 3years)
Metabolic index: Lipid profile (TC, LDL-C, HDL-C, TG)
enrollment date ,onset date(during study period, 3years)
The change of Biomarkers(2)
Time Frame: enrollment date ,onset date(during study period, 3years)
Inflammatory index: High sensitive C-reactive protein (hsCRP)
enrollment date ,onset date(during study period, 3years)
The change of Biomarkers(3)
Time Frame: enrollment date ,onset date(during study period, 3years)

Oxidation index:oxidized LDL

The change of biomarkers, t-test will be done by treatment arm(Group A vs B, Group A vs C).
enrollment date ,onset date(during study period, 3years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Collaborators

Korea Otsuka Pharmaceutical Co., Ltd.

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

January 31, 2011

First Submitted That Met QC Criteria

February 6, 2011

First Posted (Estimate)

February 8, 2011

Study Record Updates

Last Update Posted (Actual)

September 20, 2019

Last Update Submitted That Met QC Criteria

September 18, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMT-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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