Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism (ACCEL2C19)
Recruitment status was Not yet recruiting
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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: |
- Reduction of maximal platelet aggregation [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00891670
| Contact: Young-Hoon Jeong, MD, phD | 82-55-750-8065 | goodoctor@naver.com |
| 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 | |
| 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 Cardiovascular Diseases Coronary Disease Heart Diseases Myocardial Ischemia Vascular Diseases Cilostazol Clopidogrel Anti-Asthmatic Agents Autonomic Agents Bronchodilator Agents Cardiovascular Agents Central Nervous System Agents Enzyme Inhibitors Fibrin Modulating Agents |
Fibrinolytic Agents Hematologic Agents Molecular Mechanisms of Pharmacological Action Neuroprotective Agents Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Phosphodiesterase 3 Inhibitors Phosphodiesterase Inhibitors Physiological Effects of Drugs Platelet Aggregation Inhibitors Protective Agents Purinergic Agents Purinergic Antagonists Purinergic P2 Receptor Antagonists |
ClinicalTrials.gov processed this record on March 03, 2015