Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism

NCT ID: NCT00891670

Last Updated: 2009-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2009-07-31

Brief 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.

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.

Conditions

Coronary Artery Stenosis; Maximal Platelet Aggregation; Late Platelet Aggregation; High Post-Treatment Platelet Reactivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

triple group

received cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily

Group Type: ACTIVE_COMPARATOR

cilostazol

Intervention Type: DRUG

100mg twice daily for at least 1 month

aspirin

Intervention Type: DRUG

aspirin 100mg

high maintenance dose group

received clopidogrel 150 mg/day with aspirin 100mg once daily

Group Type: ACTIVE_COMPARATOR

clopidogrel

Intervention Type: DRUG

75mg once daily (triple group arm)

150mg once daily (high maintenance dose group arm)

aspirin

Intervention Type: DRUG

aspirin 100mg

Interventions

cilostazol

100mg twice daily for at least 1 month

Intervention Type: DRUG

clopidogrel

75mg once daily (triple group arm)

150mg once daily (high maintenance dose group arm)

Intervention Type: DRUG

aspirin

aspirin 100mg

Intervention Type: DRUG

Other Intervention Names

pletaal; plavix

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gyeongsang National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gyeongsang National University Hospital

Principal Investigators

Young-Hoon Jeong, MD, phD

Role: PRINCIPAL_INVESTIGATOR

Gyeong-Sang Natinal University Hospital

Locations

Gyeong-Sang National University Hospital

Jinju, Gyeong-Nam, South Korea

Countries

South Korea

Central Contacts

Young-Hoon Jeong, MD, phD

Role: CONTACT

goodoctor@naver.com

82-55-750-8065

References

Jeong YH, Abadilla KA, Tantry US, Park Y, Koh JS, Kwak CH, Hwang JY, Gurbel PA. Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study. J Thromb Haemost. 2013 Jun;11(6):1194-7. doi: 10.1111/jth.12200. No abstract available.

Reference Type: DERIVED

PMID: 23517020 (View on PubMed)

Jeong YH, Kim IS, Park Y, Kang MK, Koh JS, Hwang SJ, Kwak CH, Hwang JY. Carriage of cytochrome 2C19 polymorphism is associated with risk of high post-treatment platelet reactivity on high maintenance-dose clopidogrel of 150 mg/day: results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) study. JACC Cardiovasc Interv. 2010 Jul;3(7):731-41. doi: 10.1016/j.jcin.2010.05.007.

Reference Type: DERIVED

PMID: 20650435 (View on PubMed)

Other Identifiers

GCS-0901-D

Identifier Type: -

Identifier Source: org_study_id