Coronary Artery StenosisPhase 3ACCEL2C19NCT00891670
Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism
A Phase 3 study testing cilostazol, clopidogrel and aspirin in people with Coronary Artery Stenosis and Maximal Platelet Aggregation, run by Gyeongsang National University Hospital at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Stenosis, Maximal Platelet Aggregation, Late Platelet Aggregation
- What is being tested?
- cilostazol, clopidogrel and aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2009to Jul 2009
- Phase
- Phase 3
- 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
- The patient must be at least 18 years of age
- Significant coronary artery stenosis (> 70% by visual estimate)
- Elective coronary stent implantation
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Gyeong-Sang National University Hospital
Jinju, Gyeong-Nam, 660-702
Young-Hoon Jeong, MD, PHD
About this study
Official title: Validation of Adjunctive Cilostazol According to CYP2C19 Polymorphism: Prospective, Randomized, Single-Center Trial:
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.
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.
- Conditions
- Coronary Artery Stenosis, Maximal Platelet Aggregation, Late Platelet Aggregation, High Post-Treatment Platelet Reactivity
- Being tested
- cilostazol, clopidogrel, aspirin
- Keywords
- CYP2C19 polymorphism, platelet, Adjunctive cilostazol, high maintenance dose clopidogrel, P2Y12 Reaction Unit
- Medical subject headings
- Coronary Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cilostazolDrug
Also called pletaal
100mg twice daily for at least 1 month
clopidogrelDrug
Also called plavix
75mg once daily (triple group arm)
150mg once daily (high maintenance dose group arm)
aspirinDrug
aspirin 100mg
| Study group | Role | What they receive |
|---|---|---|
| triple group | Active comparator | received cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily Receives: Drug: cilostazol; Drug: aspirin |
| high maintenance dose group | Active comparator | received clopidogrel 150 mg/day with aspirin 100mg once daily Receives: Drug: clopidogrel; Drug: aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of maximal platelet aggregation
Measured: 30 days
Secondary outcomes (1)
Rate of high post-clopidogrel platelet reactivity
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2009 (estimated)
- Study startMay 2009
- Primary completionJun 2009 (estimated)
- Study completionJul 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery StenosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gyeongsang National University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Young-Hoon Jeong, MD, phD, Principal investigator, Gyeong-Sang Natinal University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00891670
- Sponsor's protocol ID
- GCS-0901-D
- Acronym
- ACCEL2C19
- Status last verified
- Apr 2009
- First submitted
- 30 Apr 2009
- Last updated
- 1 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jeong YH, Abadilla KA, Tantry US, Park Y, Koh JS, Kwak CH, Hwang JY, Gurbel PA. Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study. J Thromb Haemost. 2013 Jun;11(6):1194-7. doi: 10.1111/jth.12200. No abstract available.
PubMed 23517020Jeong YH, Kim IS, Park Y, Kang MK, Koh JS, Hwang SJ, Kwak CH, Hwang JY. Carriage of cytochrome 2C19 polymorphism is associated with risk of high post-treatment platelet reactivity on high maintenance-dose clopidogrel of 150 mg/day: results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) study. JACC Cardiovasc Interv. 2010 Jul;3(7):731-41. doi: 10.1016/j.jcin.2010.05.007.
PubMed 20650435
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Adjunctive Cilostazol According to CYP2C19 Polymorphism: Prospective, Randomized, Single-Center Trial:
- ClinicalTrials.gov ID
- NCT00891670
- Acronym / sponsor ID
- ACCEL2C19 / GCS-0901-D
- Conditions
- Coronary Artery Stenosis, Maximal Platelet Aggregation, Late Platelet Aggregation, High Post-Treatment Platelet Reactivity
- Keywords
- CYP2C19 polymorphism, platelet, Adjunctive cilostazol, high maintenance dose clopidogrel, P2Y12 Reaction Unit
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Gyeongsang National University HospitalUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- Jun 2009 (estimated)
- Study completion
- Jul 2009 (estimated)
- First posted
- 1 May 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 was to determine the impact of adjunctive cilostazol on platelet inhibition in carriers and non-carriers of the loss-of-function CYP2C19 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| triple group | Active comparator | Drug: cilostazol, Drug: aspirinreceived cilostazol 100 mg twice daily in addition to aspirin 100mg and clopidogrel 75mg once daily |
| high maintenance dose group | Active comparator | Drug: clopidogrel, Drug: aspirinreceived clopidogrel 150 mg/day with aspirin 100mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- The patient must be at least 18 years of age
- Significant coronary artery stenosis (> 70% by visual estimate)
- Elective coronary stent implantation
Key exclusion criteria (11 listed)
- 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%
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 |
|---|---|---|
| cilostazolAlso: pletaal100mg twice daily for at least 1 month | Drug | triple group |
| clopidogrelAlso: plavix75mg once daily (triple group arm) 150mg once daily (high maintenance dose group arm) | Drug | high maintenance dose group |
| aspirinaspirin 100mg | Drug | high maintenance dose group, triple group |
Primary outcome
Reduction of maximal platelet aggregation
Time frame: 30 days
1 secondary outcome
Rate of high post-clopidogrel platelet reactivity
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2009.
- Derived from this study: PubMed 23517020Jeong YH, Abadilla KA, Tantry US, Park Y, Koh JS, Kwak CH, Hwang JY, Gurbel PA. Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study. J Thromb Haemost. 2013 Jun;11(6):1194-7. doi: 10.1111/jth.12200. No abstract available.
- Derived from this study: PubMed 20650435Jeong YH, Kim IS, Park Y, Kang MK, Koh JS, Hwang SJ, Kwak CH, Hwang JY. Carriage of cytochrome 2C19 polymorphism is associated with risk of high post-treatment platelet reactivity on high maintenance-dose clopidogrel of 150 mg/day: results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) study. JACC Cardiovasc Interv. 2010 Jul;3(7):731-41. doi: 10.1016/j.jcin.2010.05.007.
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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
Gyeong-Sang Natinal 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 3 study testing cilostazol, clopidogrel and aspirin in people with Coronary Artery Stenosis and Maximal Platelet Aggregation, 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 3 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 1 May 2009. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Young-Hoon Jeong, MD, phD (82-55-750-8065, goodoctor@naver.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of maximal platelet aggregation (time frame: 30 days). 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 NCT00891670, which also lists 2 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 1 May 2009.