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

This study has been completed.
Sponsor:
Information provided by:
Gyeongsang National University Hospital
ClinicalTrials.gov Identifier:
NCT01012193
First received: November 10, 2009
Last updated: May 15, 2011
Last verified: May 2011
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Gyeongsang National University Hospital:

Primary Outcome Measures:
  • Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism [ Time Frame: 30-day therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 134
Study Start Date: January 2008
Study Completion Date: September 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01012193

Locations
Korea, Republic of
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, Korea, Republic of, 660-702
Sponsors and Collaborators
Gyeongsang National University Hospital
Investigators
Principal Investigator: Young-Hoon Jeong, MD, PhD Gyeongsang National University Hospital
  More Information

Additional Information:
No publications provided by Gyeongsang National University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Young-Hoon Jeong/Assisstant professor, Gyeongsang National University Hospital
ClinicalTrials.gov Identifier: NCT01012193     History of Changes
Other Study ID Numbers: GNUHIRB-2009-24
Study First Received: November 10, 2009
Last Updated: May 15, 2011
Health Authority: Korea: Food and Drug Administration

Keywords provided by Gyeongsang National University Hospital:
adjunctive cilostazol
high-MD clopidogrel
CYP 2C19 polymorphism
high risk patients

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cilostazol
Ticlopidine
Clopidogrel
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Vasodilator Agents
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Phosphodiesterase 3 Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014