Adjunctive Cilostazol Versus High Maintenance-dose Clopidogrel According to Cytochrome 2C19 Polymorphism (ACCEL-2C19)

May 15, 2011 updated by: Gyeongsang National University Hospital

CYP 2C19 Polymorphism and Response to Adjunctive Cilostazol and High Maintenance-dose Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention

The purpose of this study is to determine the impact of adjunctive cilostazol versus high maintenance-dose clopidogrel on platelet inhibition in carriers and non-carriers of the loss-of-function CYP2C19 mutant allele.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The additional platelet inhibition with clopidogrel, a thienopyridine inhibitor of the platelet P2Y12 adenosine diphosphate (ADP) receptor, has reduced the risk of ischemic events after coronary stent implantation. Because of inter-individual variability in platelet response to clopidogrel, a significant proportion of suboptimal platelet inhibition has been reported. In addition, persistent residual platelet reactivity measured with platelet function testing has shown the association with the cardiovascular outcomes after percutaneous coronary intervention (PCI).

Various clinical factors and genetic polymorphisms have been studied to predict the degree of antiplatelet response to clopidogrel. Interestingly, recent studies found that carriers of the loss-of-function hepatic cytochrome (CYP) 2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events than did non-carriers, in the setting of PCI and acute coronary syndrome (ACS). These findings raise the need of solutions to overcome enhanced post-clopidogrel platelet reactivity by the influence of the loss-of-function CYP2C19 allele. Increasing the dose of clopidogrel and new potent P2Y12 antagonists (such as prasugrel) may be alternative antiplatelet regimens in patients with the loss-of-function CYP variant.

Cilostazol reversibly induces platelet inhibition via its blockade of phosphodiesterase (PDE) type 3 and is catalysed mainly by CYP3A. A recent study demonstrated that adjunctive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) intensified platelet inhibition as compared with a high maintenance-dose (MD) of 150 mg/day. Therefore, triple antiplatelet therapy could also be an alternative antiplatelet therapy to improve platelet inhibition and clinical outcomes in carriers of CYP2C19 mutant allele.

We compared the enhanced inhibition of platelet aggregation by adjunctive cilostazol 100 mg twice daily versus high-MD clopidogrel 150 mg/day in patients treated with elective coronary stenting, according to the CYP2C19 polymorphism.

Study Type

Interventional

Enrollment (Actual)

134

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
    • Gyeongsangnam-do
      • Jinju, Gyeongsangnam-do, Korea, Republic of, 660-702
        • Gyeongsang National University 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Significant coronary artery stenosis (>70% by visual estimate)
  • Elective coronary stent implantation

Exclusion Criteria:

  • Acute myocardial infarction
  • Active bleeding and bleeding diatheses
  • Hemodynamic instability
  • Oral anticoagulation therapy with warfarin
  • Use of peri-procedural glycoprotein IIb/IIIa inhibitors
  • Contraindication to antiplatelet therapy
  • Left ventricular ejection fraction < 30%
  • Leukocyte count < 3,000/mm3, platelet count < 100,000/mm3, AST or ALT ≥ 3 times upper normal
  • Serum creatinine level ≥ 3 mg/dL
  • Stroke within 3 months
  • Noncardiac disease with a life expectancy < 1 year
  • Inability to follow the protocol

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 Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: adjunctive cilostazol
adjunctive cilostazol 100mg bid to dual antiplatelet therapy
Drug: cilostazol 100mg bid or clopidogrel 150-mg daily
Adjunctive cilostazol: cilostazol 100-mg bid +clopidogrel 75mg daily+aspirin 200mg daily High-MD clopidogrel: clopidogrel 150mg daly +aspirin 200mg daily
Active Comparator: high maintenance-dose clopidogrel
double dose of clopidogrel 150mg/day
Drug: cilostazol 100mg bid or clopidogrel 150-mg daily
Adjunctive cilostazol: cilostazol 100-mg bid +clopidogrel 75mg daily+aspirin 200mg daily High-MD clopidogrel: clopidogrel 150mg daly +aspirin 200mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism
Time Frame: 30-day therapy
30-day therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Reduction of late platelet aggregation, reduction of P2Y12 reaction unit, and the rate of high post-clopidogrel platelet reactivity according to CYP 2C19 polymorphism
Time Frame: 30-day therapy
30-day therapy

Collaborators and Investigators

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

Sponsor

Gyeongsang National University Hospital

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

Helpful Links

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

January 1, 2008

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

November 10, 2009

First Submitted That Met QC Criteria

November 10, 2009

First Posted (Estimate)

November 11, 2009

Study Record Updates

Last Update Posted (Estimate)

May 17, 2011

Last Update Submitted That Met QC Criteria

May 15, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GNUHIRB-2009-24

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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