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

Sponsor:	Gyeongsang National University Hospital
Information provided by:	Gyeongsang National University Hospital
ClinicalTrials.gov Identifier:	NCT00891670

Purpose

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.

Condition	Intervention	Phase
Coronary Artery Stenosis Maximal Platelet Aggregation Late Platelet Aggregation High Post-Treatment Platelet Reactivity	Drug: cilostazol Drug: clopidogrel Drug: aspirin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Validation of Adjunctive Cilostazol According to CYP2C19 Polymorphism: Prospective, Randomized, Single-Center Trial:

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

Drug Information available for: Acetylsalicylic acid Cilostazol Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by Gyeongsang National University Hospital:

Primary Outcome Measures:

Reduction of maximal platelet aggregation [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of high post-clopidogrel platelet reactivity [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	May 2009
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: triple group received cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily	Drug: cilostazol 100mg twice daily for at least 1 month Other Name: pletaal Drug: aspirin aspirin 100mg
Active Comparator: high maintenance dose group received clopidogrel 150 mg/day with aspirin 100mg once daily	Drug: clopidogrel 75mg once daily (triple group arm) 150mg once daily (high maintenance dose group arm) Other Name: plavix Drug: aspirin aspirin 100mg

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient must be at least 18 years of age
Significant coronary artery stenosis (> 70% by visual estimate)
Elective coronary stent implantation

Exclusion Criteria:

Acute myocardial infarction
Hemodynamic instability active bleeding and bleeding diatheses
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 ≥ 2.5 mg/dL
stroke within 3 months
Noncardiac disease with a life expectancy < 1 year
Inability to follow the protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891670

Contacts

Contact: Young-Hoon Jeong, MD, phD

82-55-750-8065

goodoctor@naver.com

Locations

Korea, Republic of
Gyeong-Sang National University Hospital	Not yet recruiting
Jinju, Gyeong-Nam, Korea, Republic of, 660-702
Principal Investigator: Young-Hoon Jeong, MD, PHD

Sponsors and Collaborators

Gyeongsang National University Hospital

Investigators

Principal Investigator:

Young-Hoon Jeong, MD, phD

Gyeong-Sang Natinal University Hospital

More Information

No publications provided by Gyeongsang National University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Young-Hoon Jeong, Gyeongsang National University Hospital
ClinicalTrials.gov Identifier:	NCT00891670 History of Changes
Other Study ID Numbers:	GCS-0901-D
Study First Received:	April 30, 2009
Last Updated:	April 30, 2009
Health Authority:	Korea: Food and Drug Administration

Keywords provided by Gyeongsang National University Hospital:

CYP2C19 polymorphism
platelet
Adjunctive cilostazol
high maintenance dose clopidogrel
P2Y12 Reaction Unit

Additional relevant MeSH terms:

Coronary Stenosis
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Aspirin
Cilostazol
Clopidogrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on February 09, 2012