Coronary Artery DiseasePhase 4ACCEL-2C19NCT01012193
Adjunctive Cilostazol Versus High Maintenance-dose Clopidogrel According to Cytochrome 2C19 Polymorphism
A Phase 4 study testing cilostazol 100mg bid or clopidogrel 150-mg daily in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Gyeongsang National University Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Percutaneous Coronary Intervention
- What is being tested?
- cilostazol 100mg bid or clopidogrel 150-mg daily
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jan 2008to Sep 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Significant coronary artery stenosis (>70% by visual estimate)
- Elective coronary stent implantation
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, 660-702
About this study
Official title: CYP 2C19 Polymorphism and Response to Adjunctive Cilostazol and High Maintenance-dose Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention
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.
Read the 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.
- Being tested
- cilostazol 100mg bid or clopidogrel 150-mg daily
- Keywords
- adjunctive cilostazol, high-MD clopidogrel, CYP 2C19 polymorphism, high risk patients
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cilostazol 100mg bid or clopidogrel 150-mg dailyDrug
Adjunctive cilostazol: cilostazol 100-mg bid +clopidogrel 75mg daily+aspirin 200mg daily High-MD clopidogrel: clopidogrel 150mg daly +aspirin 200mg daily
| Study group | Role | What they receive |
|---|---|---|
| adjunctive cilostazol | Active comparator | adjunctive cilostazol 100mg bid to dual antiplatelet therapy Receives: Drug: cilostazol 100mg bid or clopidogrel 150-mg daily |
| high maintenance-dose clopidogrel | Active comparator | double dose of clopidogrel 150mg/day Receives: Drug: cilostazol 100mg bid or clopidogrel 150-mg daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism
Measured: 30-day therapy
Secondary outcomes (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
Measured: 30-day therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2009 (estimated)
- Study startJan 2008
- Primary completionJul 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gyeongsang National University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Young-Hoon Jeong, MD, PhD, Principal investigator, Gyeongsang National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01012193
- Sponsor's protocol ID
- GNUHIRB-2009-24
- Acronym
- ACCEL-2C19
- Status last verified
- May 2011
- First submitted
- 10 Nov 2009
- Last updated
- 17 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jeong YH, Tantry US, Park Y, Kwon TJ, Park JR, Hwang SJ, Bliden KP, Koh EH, Kwak CH, Hwang JY, Kim S, Gurbel PA. Pharmacodynamic effect of cilostazol plus standard clopidogrel versus double-dose clopidogrel in patients with type 2 diabetes undergoing percutaneous coronary intervention. Diabetes Care. 2012 Nov;35(11):2194-7. doi: 10.2337/dc11-2351. Epub 2012 Jul 26.
PubMed 22837373Kim IS, Jeong YH, Park Y, Yoon SE, Kwon TJ, Park JR, Hwang SJ, Koh EH, Kwak CH, Hwang JY, Kim S. Interaction analysis between genetic polymorphisms and pharmacodynamic effect in patients treated with adjunctive cilostazol to dual antiplatelet therapy: results of the ACCEL-TRIPLE (Accelerated Platelet Inhibition by Triple Antiplatelet Therapy According to Gene Polymorphism) study. Br J Clin Pharmacol. 2012 Apr;73(4):629-40. doi: 10.1111/j.1365-2125.2011.04131.x.
PubMed 22007612Hwang SJ, Jeong YH, Kim IS, Park KS, Kang MK, Koh JS, Park JR, Park Y, Koh EH, Kwak CH, Hwang JY, Kim S. Cytochrome 2C19 polymorphism and response to adjunctive cilostazol versus high maintenance-dose clopidogrel in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2010 Oct;3(5):450-9. doi: 10.1161/CIRCINTERVENTIONS.110.949859. Epub 2010 Sep 7.
PubMed 20823393
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CYP 2C19 Polymorphism and Response to Adjunctive Cilostazol and High Maintenance-dose Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention
- ClinicalTrials.gov ID
- NCT01012193
- Acronym / sponsor ID
- ACCEL-2C19 / GNUHIRB-2009-24
- Keywords
- adjunctive cilostazol, high-MD clopidogrel, CYP 2C19 polymorphism, high risk patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Gyeongsang National University HospitalUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Jul 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 11 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| adjunctive cilostazol | Active comparator | Drug: cilostazol 100mg bid or clopidogrel 150-mg dailyadjunctive cilostazol 100mg bid to dual antiplatelet therapy |
| high maintenance-dose clopidogrel | Active comparator | Drug: cilostazol 100mg bid or clopidogrel 150-mg dailydouble dose of clopidogrel 150mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Significant coronary artery stenosis (>70% by visual estimate)
- Elective coronary stent implantation
Key exclusion criteria (12 listed)
- Acute myocardial infarction
- Active bleeding and bleeding diatheses
- Hemodynamic instability
- Oral anticoagulation therapy with warfarin
- Use of peri-procedural glycoprotein IIb/IIIa inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cilostazol 100mg bid or clopidogrel 150-mg dailyAdjunctive cilostazol: cilostazol 100-mg bid +clopidogrel 75mg daily+aspirin 200mg daily High-MD clopidogrel: clopidogrel 150mg daly +aspirin 200mg daily | Drug | adjunctive cilostazol, high maintenance-dose clopidogrel |
Primary outcome
Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism
Time frame: 30-day therapy
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2011.
- Derived from this study: PubMed 22837373Jeong YH, Tantry US, Park Y, Kwon TJ, Park JR, Hwang SJ, Bliden KP, Koh EH, Kwak CH, Hwang JY, Kim S, Gurbel PA. Pharmacodynamic effect of cilostazol plus standard clopidogrel versus double-dose clopidogrel in patients with type 2 diabetes undergoing percutaneous coronary intervention. Diabetes Care. 2012 Nov;35(11):2194-7. doi: 10.2337/dc11-2351. Epub 2012 Jul 26.
- Derived from this study: PubMed 22007612Kim IS, Jeong YH, Park Y, Yoon SE, Kwon TJ, Park JR, Hwang SJ, Koh EH, Kwak CH, Hwang JY, Kim S. Interaction analysis between genetic polymorphisms and pharmacodynamic effect in patients treated with adjunctive cilostazol to dual antiplatelet therapy: results of the ACCEL-TRIPLE (Accelerated Platelet Inhibition by Triple Antiplatelet Therapy According to Gene Polymorphism) study. Br J Clin Pharmacol. 2012 Apr;73(4):629-40. doi: 10.1111/j.1365-2125.2011.04131.x.
- Derived from this study: PubMed 20823393Hwang SJ, Jeong YH, Kim IS, Park KS, Kang MK, Koh JS, Park JR, Park Y, Koh EH, Kwak CH, Hwang JY, Kim S. Cytochrome 2C19 polymorphism and response to adjunctive cilostazol versus high maintenance-dose clopidogrel in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2010 Oct;3(5):450-9. doi: 10.1161/CIRCINTERVENTIONS.110.949859. Epub 2010 Sep 7.
- Pubmed release of ACCEL studyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Young-Hoon Jeong, MD, PhD principal investigator
Gyeongsang National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cilostazol 100mg bid or clopidogrel 150-mg daily in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Gyeongsang National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of maximal platelet aggregation according to CYP 2C19 polymorphism (time frame: 30-day therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01012193, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2011.