AzTrials
AzTrials

HyperlipidemiasPhase 4IMPACTonIMTNCT01291641

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

A Phase 4 study testing HMG-CoA Reductase Inhibitor, Probucol and Cilostazol in people with Hyperlipidemias, run by Seoul National University Hospital at 5 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Hyperlipidemias
What is being tested?
HMG-CoA Reductase Inhibitor, Probucol and Cilostazol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
342 participants
Where
5 sitesSouth Korea
Study dates
Mar 2011to Mar 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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%
Show all 16Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

South Korea5 sites
  • Dong-A Medical Center

    Seogu, Busan, 602-715

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 463-707

  • Samsung Medical Center

    Seoul, Gangnam-Gu, 135-710

  • Seoul National University Hospital

    Seoul, 110-744

  • Boramae Medical Center

    Seoul, 156-707

Other trials in South Korea

About this study

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

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.

Read the 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

Conditions
Hyperlipidemias
Being tested
HMG-CoA Reductase Inhibitor, Probucol, Cilostazol
Keywords
Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Probucol, Cilostazol
Medical subject headings
Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HMG-CoA Reductase InhibitorDrug

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

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

  • ProbucolDrug

    Also called HMG-CoA 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)

  • CilostazolDrug

    Also called Probucol, HMG-CoA Reductase Inhibitor

    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

Study groups in NCT01291641
Study groupRoleWhat they receive
Group APlacebo comparatorHMGCoA reductase inhibitor continued
Receives: Drug: HMG-CoA Reductase Inhibitor
Group BActive comparatorHMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID
Receives: Drug: Probucol
Group CActive comparatorHMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID + Cilostazol 100 mg PO, BID
Receives: Drug: Cilostazol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline(screening), 3years

Secondary outcomes (5)
  1. 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.

    Measured: enrollment date, onset date(during study period, 3years)

  2. 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).

    Measured: enrollment date, onset date(during study period, 3years)

  3. The change of Biomarkers(1)

    Metabolic index: Lipid profile (TC, LDL-C, HDL-C, TG)

    Measured: enrollment date ,onset date(during study period, 3years)

  4. The change of Biomarkers(2)

    Inflammatory index: High sensitive C-reactive protein (hsCRP)

    Measured: enrollment date ,onset date(during study period, 3years)

  5. 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).

    Measured: enrollment date ,onset date(during study period, 3years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionDec 2016
  4. Study completionMar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
342 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01291641
Sponsor's protocol ID
IMT-01
Acronym
IMPACTonIMT
Status last verified
Sep 2019
First submitted
31 Jan 2011
Last updated
20 Sep 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Manzato E. Scandinavian simvastatin study (4S). Lancet. 1994 Dec 24-31;344(8939-8940):1767; author reply 1767-8. No abstract available.

    PubMed 7997016
  • Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V, Cuddy TE, Moye LA, Piller LB, Rutherford J, Simpson LM, Braunwald E. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators. Circulation. 1999 Jan 19;99(2):216-23. doi: 10.1161/01.cir.99.2.216.

    PubMed 9892586
  • Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57. doi: 10.1056/NEJM199811053391902.

    PubMed 9841303
  • Barnhart JW, Sefranka JA, McIntosh DD. Hypocholesterolemic effect of 4,4'-(isopropylidenedithio)-bis(2,6-di-t-butylphenol) (probucol). Am J Clin Nutr. 1970 Sep;23(9):1229-33. doi: 10.1093/ajcn/23.9.1229. No abstract available.

    PubMed 5450842
  • Tomikawa M, Nakayasu T, Tawara K, Abiko Y. Effect of probucol on serum lipoprotein levels in normal and dyslipoproteinemic mice. Atherosclerosis. 1981 Oct;40(2):101-13. doi: 10.1016/0021-9150(81)90029-0.

    PubMed 6946776
  • Tawara K, Tomikawa M, Abiko Y. Mode of action of probucol in reducing serum cholesterol in mice. Jpn J Pharmacol. 1986 Jan;40(1):123-33. doi: 10.1254/jjp.40.123.

    PubMed 3959347
  • Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, Yoshida H, Kawai C. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5928-31. doi: 10.1073/pnas.84.16.5928.

    PubMed 3475709
  • Ishigami M, Yamashita S, Sakai N, Hirano K, Arai T, Maruyama T, Takami S, Koyama M, Kameda-Takemura K, Matsuzawa Y. High-density lipoproteins from probucol-treated patients have increased capacity to promote cholesterol efflux from mouse peritoneal macrophages loaded with acetylated low-density lipoproteins. Eur J Clin Invest. 1997 Apr;27(4):285-92. doi: 10.1046/j.1365-2362.1997.1040657.x.

    PubMed 9134376
  • Rinninger F, Wang N, Ramakrishnan R, Jiang XC, Tall AR. Probucol enhances selective uptake of HDL-associated cholesteryl esters in vitro by a scavenger receptor B-I-dependent mechanism. Arterioscler Thromb Vasc Biol. 1999 May;19(5):1325-32. doi: 10.1161/01.atv.19.5.1325.

    PubMed 10323786
  • Matsuzawa Y, Yamashita S, Funahashi T, Yamamoto A, Tarui S. Selective reduction of cholesterol in HDL2 fraction by probucol in familial hypercholesterolemia and hyperHDL2 cholesterolemia with abnormal cholesteryl ester transfer. Am J Cardiol. 1988 Jul 25;62(3):66B-72B. doi: 10.1016/s0002-9149(88)80055-9.

    PubMed 3394656
  • Daida H, Kuwabara Y, Yokoi H, Nishikawa H, Takatsu F, Nakata Y, Kutsumi Y, Oshima S, Nishiyama S, Ishiwata S, Kato K, Nishimura S, Miyauchi K, Kanoh T, Yamaguchi H. Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART]). Am J Cardiol. 2000 Sep 1;86(5):550-2, A9. doi: 10.1016/s0002-9149(00)01013-4.

    PubMed 11009277
  • Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probucol Study Group. N Engl J Med. 1997 Aug 7;337(6):365-72. doi: 10.1056/NEJM199708073370601.

    PubMed 9241125
  • Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995 Feb 23;332(8):488-93. doi: 10.1056/NEJM199502233320802.

    PubMed 7830729
  • Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, Kashiwagi S, Hayashi J. Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). J Am Coll Cardiol. 2002 Feb 20;39(4):610-6. doi: 10.1016/s0735-1097(01)01783-1.

    PubMed 11849859
  • Yamashita S, Bujo H, Arai H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa Y. Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb. 2008 Dec;15(6):292-303. doi: 10.5551/jat.e610. Epub 2008 Dec 6.

    PubMed 19060422

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing HMG-CoA Reductase Inhibitor, Probucol and Cilostazol in people with Hyperlipidemias, run by Seoul National University Hospital at 5 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01291641, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2019.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in