Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism
Information source: Gyeongsang National University Hospital
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Coronary Artery Stenosis; Maximal Platelet Aggregation; Late Platelet Aggregation; High Post-Treatment Platelet Reactivity
Intervention: cilostazol (Drug); clopidogrel (Drug); aspirin (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: Gyeongsang National University Hospital Official(s) and/or principal investigator(s):
Young-Hoon Jeong, MD, phD, Principal Investigator, Affiliation: Gyeong-Sang Natinal University Hospital
Overall contact:
Young-Hoon Jeong, MD, phD, Phone: 82-55-750-8065, Email: goodoctor@naver.com
Summary
The purpose of this study was to determine the impact of adjunctive cilostazol on platelet
inhibition in carriers and non-carriers of the loss-of-function CYP2C19 allele.
Clinical Details
Official title: Validation of Adjunctive Cilostazol According to CYP2C19 Polymorphism: Prospective, Randomized, Single-Center Trial:
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacodynamics Study
Primary outcome: Reduction of maximal platelet aggregation
Secondary outcome: Rate of high post-clopidogrel platelet reactivity
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. The patient must be at least 18 years of age
2. Significant coronary artery stenosis (> 70% by visual estimate)
3. Elective coronary stent implantation
Exclusion Criteria:
1. Acute myocardial infarction
2. Hemodynamic instability active bleeding and bleeding diatheses
3. Oral anticoagulation therapy with warfarin,use of peri-procedural glycoprotein
IIb/IIIa inhibitors
4. Contraindication to antiplatelet therapy
5. Left ventricular ejection fraction < 30%
6. Leukocyte count < 3,000/mm3, platelet count < 100,000/mm3
7. AST or ALT ≥ 3 times upper normal
8. Serum creatinine level ≥ 2. 5 mg/dL
9. stroke within 3 months
10. Noncardiac disease with a life expectancy < 1 year
11. Inability to follow the protocol
Locations and Contacts
Young-Hoon Jeong, MD, phD, Phone: 82-55-750-8065, Email: goodoctor@naver.com
Gyeong-Sang National University Hospital, Jinju, Gyeong-Nam 660-702, Korea, Republic of
Additional Information
Starting date: May 2009
Ending date: July 2009
Last updated: April 30, 2009
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