Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism (ACCEL2C19)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by Gyeongsang National University Hospital.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Gyeongsang National University Hospital
ClinicalTrials.gov Identifier:
NCT00891670
First received: April 30, 2009
Last updated: NA
Last verified: April 2009
History: No changes posted
  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 3

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:


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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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):
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
Bronchodilator Agents

ClinicalTrials.gov processed this record on August 18, 2014