Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction (AMI) Patients According to CYP2C19 Polymorphism (ACCELAMI2C19)

This study has been completed.
Sponsor:
Information provided by:
Gyeongsang National University Hospital
ClinicalTrials.gov Identifier:
NCT00915733
First received: June 5, 2009
Last updated: November 9, 2009
Last verified: November 2009
  Purpose

Percutaneous coronary intervention (PCI) with stent implantation is the preferred reperfusion strategy for treatment of acute myocardial infarction (AMI). Despite advances in both devices and pharmacological support for AMI patients undergoing PCI, the risk of recurrent ischemic events has been higher than that of elective PCI. Among therapeutic options for surmounting clopidogrel hyporesponsiveness, higher loading doses and maintenance doses of clopidogrel achieved significant enhancements in the speed of onset and intensity of inhibition and these approaches have been widely adapted in clinical practice. 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, new potent P2Y12 antagonists (such as prasugrel), or other antiplatelet drugs such as cilostazol may be alternative antiplatelet regimens in patients with the loss-of-function CYP variant. 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.

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. The investigators compared the enhanced inhibition of platelet aggregation by adjunctive cilostazol 100 mg twice daily versus high-MD clopidogrel 150 mg/day in AMI patients treated with emergent coronary stenting, according to the CYP2C19 polymorphism.


Condition Intervention Phase
Myocardial Infarction
Drug: cilostazol
Drug: clopidogrel (Plavix)
Genetic: CYP2C19
Drug: aspirin (Acetylsalicylic acid)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Platelet Inhibitory Effect With Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism

Resource links provided by NLM:


Further study details as provided by Gyeongsang National University Hospital:

Primary Outcome Measures:
  • Absolute reduction of maximal platelet aggregation (Aggmax) by 5 & 20 μM ADP induced LTA [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute reduction of late platelet aggregation (Agglate) by 5 & 20 μM ADP induced LTA [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Absolute reduction of P2Y12 reaction unit (PRU) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • The rate of high post-treatment platelet reactivity [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: May 2009
Study Completion Date: November 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: triple group

Additive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) in patients with acute myocardial infarction (AMI).

Received cilostazol 100 mg twice daily in addition to aspirin 100 mg and clopidogrel 75 mg once daily.

Drug: cilostazol
100 mg twice daily for at least 1 month
Other Name: Otsuka brand of cilostazol
Drug: clopidogrel (Plavix)
150 mg once daily (high maintenance dose group arm), 75 mg once daily (triple group arm)
Other Name: Plavix
Genetic: CYP2C19
CYP2C19 polymorphism study: Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer.
Other Name: Cytochrome 2C19
Drug: aspirin (Acetylsalicylic acid)
aspirin 100 mg qd
Other Name: Acetylsalicylic acid
Active Comparator: high maintenance dose group

High maintenance dose dual antiplatelet therapy in patients with acute myocardial infarction (AMI).

Received clopidogrel 150 mg/day with aspirin 100 mg once daily.

Drug: clopidogrel (Plavix)
150 mg once daily (high maintenance dose group arm), 75 mg once daily (triple group arm)
Other Name: Plavix
Genetic: CYP2C19
CYP2C19 polymorphism study: Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer.
Other Name: Cytochrome 2C19
Drug: aspirin (Acetylsalicylic acid)
aspirin 100 mg qd
Other Name: Acetylsalicylic acid

  Show Detailed Description

  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. clinical symptoms compatible with acute myocardial ischemia within 12 h before admission with a subsequently documented increase in cardiac markers.
  3. Measured pre-discharge platelet reactivity in case of normalized CK-MB value after coronary stenting.

Exclusion Criteria:

  1. A history of active bleeding and bleeding diatheses.
  2. Oral anticoagulation therapy with coumadin.
  3. Contraindication to antiplatelet therapy.
  4. LV ejection fraction < 30% or NYHA 3/4.
  5. Leukocyte count < 3,000/mm3 and/or platelet count < 100,000/mm3.
  6. AST or ALT ≥ 3 times upper normal.
  7. Serum creatinine level ≥ 2.5 mg/dl.
  8. Stroke within 3 months.
  9. Non-cardiac disease with a life expectancy < 1 year.
  10. Inability to follow the protocol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00915733

Locations
Korea, Republic of
Gyeongsang National University Hospital
Jinju, Korea, Republic of, 660-702
Sponsors and Collaborators
Gyeongsang National University Hospital
Investigators
Principal Investigator: In-Suk Kim, MD.PhD. Gyeongsang National University Hospital
  More Information

Publications:

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

Responsible Party: In-Suk Kim, Assistant Professor, Gyeongsang National University Hospital
ClinicalTrials.gov Identifier: NCT00915733     History of Changes
Other Study ID Numbers: ACCEL-AMI-2C19
Study First Received: June 5, 2009
Last Updated: November 9, 2009
Health Authority: South Korea: Institutional Review Board

Keywords provided by Gyeongsang National University Hospital:
acute myocardial infarction
inhibition of platelet aggregation
triple antiplatelet therapy
high maintenance-dose clopidogrel.
CYP2C19 polymorphism
High posttreatment platelet reactivity
Platelet Aggregation Inhibitors
CYP2C19, human

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Aspirin
Cilostazol
Ticlopidine
Clopidogrel
Platelet Aggregation Inhibitors
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
Cyclooxygenase Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014