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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01012193
Recruitment Status : Completed
First Posted : November 11, 2009
Last Update Posted : May 17, 2011
Information provided by:
Gyeongsang National University Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Percutaneous Coronary Intervention Drug: cilostazol 100mg bid or clopidogrel 150-mg daily Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: CYP 2C19 Polymorphism and Response to Adjunctive Cilostazol and High Maintenance-dose Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention
Study Start Date : January 2008
Actual Primary Completion Date : July 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism [ Time Frame: 30-day therapy ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01012193

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Korea, Republic of
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, Korea, Republic of, 660-702
Sponsors and Collaborators
Gyeongsang National University Hospital
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Principal Investigator: Young-Hoon Jeong, MD, PhD Gyeongsang National University Hospital
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Young-Hoon Jeong/Assisstant professor, Gyeongsang National University Hospital Identifier: NCT01012193    
Other Study ID Numbers: GNUHIRB-2009-24
First Posted: November 11, 2009    Key Record Dates
Last Update Posted: May 17, 2011
Last Verified: May 2011
Keywords provided by Gyeongsang National University Hospital:
adjunctive cilostazol
high-MD clopidogrel
CYP 2C19 polymorphism
high risk patients
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Vasodilator Agents
Neuroprotective Agents
Protective Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors