Coronary Artery DiseasePPSCNCT01968499
Pharmacogenetic and Pharmacokinetic Study of Clopidogrel
An observational study of Coronary Artery Disease, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This registration study aims to investigate the associations of the pharmacogenetic and pharmacokinetic factors with clopidogrel low response and clinical outcome in patients with coronary artery disease, and provide new pharmacogenetic and pharmacokinetic targets for the individualized anti-platelet treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- How many people
- 1,805 participants
- Where
- 1 siteChina
- Study dates
- Mar 2011to 17 Oct 2017
- How long will I take part?
- 1 Year
- Phase
- Observational
- 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
Study population: All patients who receive stent implantation and aged >18 years.
Who may be able to join
- Successively recruit all patients who receive stent implantation and take aspirin 100 mg and clopidogrel 75 mg daily for more than 5 days.
- Patient aged >18 years;
- Signed inform consent.
Who cannot join
- intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
- taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
- with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
- hemoglobin < 90g/L;
- with a history of cerebral hemorrhage within 1 year;
- in pregnancy.
Trial locations and contacts
1 site in 1 country.
China1 site
First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210029
About this study
Official title: Associations of the Pharmacogenetic and Pharmacokinetic Factors With Clopidogrel Low Response and Clinical Outcome in Patients With Coronary Stent Implantation: a Registration Study
This registration study aims to investigate the associations of the pharmacogenetic and pharmacokinetic factors with clopidogrel low response and clinical outcome in patients with coronary artery disease, and provide new pharmacogenetic and pharmacokinetic targets for the individualized anti-platelet treatment.
Read the detailed description
Associations of the Pharmacogenetic and Pharmacokinetic Factors With Clopidogrel Low Response and Clinical Outcome in Patients With Coronary Stent Implantation: a Registration Study
Published data linking clopidogrel non-responsiveness to adverse ischaemic events lead to the suggestion that the magnitude of platelet inhibition by clopidogrel can be monitored and individually adjusted. This has been tested in randomised clinical trials (ARCTIC, GRAVITAS and TRIGGER-PCI), but despite reducing platelet reactivity, a strategy of therapy adjustment based on platelet function monitoring did not reduce the incidence of cardiac ischaemic events1, which indicates that most pharmacodynamical tests monitored anti-platelet treatment failed so far.
We accordingly performed this registration study to investigate whether the pharmacogenetic and pharmacokinetic factors are associated with clopidogrel low response as well as clinical outcome, and aimed to provide new targets for the individualized anti-platelet treatment.
Inclusion criteria:
- Successively recruit all patients who receive stent implantation and take aspirin 100 mg and clopidogrel 75 mg once daily (7:00 a.m.) for more than 5 days.
- Patient aged >18 years;
- Signed inform consent.
Exclusion criteria:
- intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
- taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
- with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
- hemoglobin < 90g/L;
- with a history of cerebral hemorrhage within 1 year;
- in pregnancy.
Clinical data collection:
- Patients basic characteristics.
- Diagnosis and complicated diseases.
- Medical treatment and interventional treatment.
Methods:
Blood samples are collected 5 days after the patients' taking clopidogrel to perform the genetic testing and determine the light transmittancy aggregation (LTA) and the serum levels of the parent clopidogrel, intermediate and active metabolites of clopidogrel. LTA is to re-determined 1 month after clopidogrel consumption. Clopidogrel low response is defined as the inhibition of platelet aggregation (IPA) in response to 5μM ADP is more than 40%. Clinical follow-up will be performed 1month, 6month, and 1year after the patients' included. Major adverse cardiovascular events (MACE) is set as death, non-fatal myocardial infarction (MI), ischemic stroke. Associations of the pharmacogenetic and pharmacokinetic factors with clopidogrel low response and clinical outcome will be analyzed.
Tests:
- ADP-induced platelet aggregation: LTA in response to 5μM ADP.
- Arachidonic acid (AA)-induced platelet aggregation: LTA in response to 1mM AA.
- Simultaneous detection of clopidogrel, 2-oxo-clopidogrel and its thiol metabolite in human plasma by the high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.
- GWAS scan or genotyping of ABCB1,CYP2C19, paraoxonase 1 (PON1), CYP3A5, P2RY12.
Sample size: We plan to recruit 1800 patients.
Clinical follow-up: 1 month, 6 month, and 1 year after the patients' included.
Major adverse cardiovascular events (MACE): Death, non-fatal MI, ischemic stroke.
Minor adverse cardiovascular events: Hospitalization, revascularization, stent thrombosis (ARC definition) and minor, moderate, and major bleeding (TIMI definition).
- Conditions
- Coronary Artery Disease
- Keywords
- coronary stent implantation; clopidogrel low response
- 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.
| Study group | Role | What they receive |
|---|---|---|
| All recruited patients | Patients who receive stent implantation and aged >18 years. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Risk ratio
Risk ratio of the genotypes on MACE.
Measured: 1 year after patients' being recruited
Risk ratio
Risk ratio of the pharmacokinetic results on MACE.
Measured: 1 year after patients' being recruited
Secondary outcomes (2)
Risk ratio
Risk ratio of the genotypes on clopidogrel low response.
Measured: 1 month after patients' being recruited
Risk ratio
Risk ratio of the pharmacokinetic results on clopidogrel low response.
Measured: 1 month after patients' being recruited
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2013 (estimated)
- Study startMar 2011
- Primary completion17 Oct 2017
- Study completion17 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,805 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Responsible party
- Principal investigator, Chunjian Li, The First Affiliated Hospital with Nanjing Medical University
- Investigators
- Chunjian Li, Ph.D, Principal investigator, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968499
- Sponsor's protocol ID
- 002
- Other IDs
- NNSFC/81170181
- Acronym
- PPSC
- Status last verified
- Oct 2017
- First submitted
- 17 Oct 2013
- Last updated
- 18 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Siller-Matula JM, Jilma B. Why have studies of tailored anti-platelet therapy failed so far? Thromb Haemost. 2013 Oct;110(4):628-31. doi: 10.1160/TH13-03-0250. Epub 2013 Jul 25.
PubMed 23884166Zong J, Tang Y, Wang T, Ullah I, Xu K, Wang J, Chen P, Chen Z, Zhu T, Chen J, Li J, Wang F, Yang L, Fan Y, Shi L, Gong X, Eikelboom JW, Zhao Y, Li C. Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention. J Am Heart Assoc. 2022 Aug 16;11(16):e025058. doi: 10.1161/JAHA.121.025058. Epub 2022 Aug 5.
PubMed 35929455Wang J, Wang J, Dong Z, Ma J, Teng J, Wang T, Zhang X, Gu Q, Ye Z, Ullah I, Tan C, Abdus S, Shi L, Gong X, Li C. An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention. Thromb J. 2021 Oct 19;19(1):73. doi: 10.1186/s12959-021-00323-5.
PubMed 34666778Xu K, Ye S, Zhang S, Yang M, Zhu T, Kong D, Chen J, Xu L, Li J, Zhu H, Wang F, Yang L, Zhang J, Fan Y, Ying L, Hu X, Zhang X, Chan NC, Li C. Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Platelet Reactivity and Early Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention and Treated With Aspirin and Clopidogrel. Circ Cardiovasc Interv. 2019 May;12(5):e007019. doi: 10.1161/CIRCINTERVENTIONS.118.007019.
PubMed 31018667Ying L, Wang F, Zhang J, Yang L, Gong X, Fan Y, Xu K, Li J, Lu Y, Mei L, Zhou Z, Li C. Impact of hepatitis B virus (HBV) infection on platelet response to clopidogrel in patients undergoing coronary stent implantation. Thromb Res. 2018 Jul;167:119-124. doi: 10.1016/j.thromres.2018.04.017. Epub 2018 Apr 19.
PubMed 29807287
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Associations of the Pharmacogenetic and Pharmacokinetic Factors With Clopidogrel Low Response and Clinical Outcome in Patients With Coronary Stent Implantation: a Registration Study
- ClinicalTrials.gov ID
- NCT01968499
- Acronym / sponsor ID
- PPSC / 002
- Conditions
- Coronary Artery Disease
- Keywords
- coronary stent implantation; clopidogrel low response
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,805 participants (actual)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Study start
- Mar 2011
- Primary completion
- 17 Oct 2017 (actual)
- Study completion
- 17 Oct 2017 (actual)
- First posted
- 24 Oct 2013 (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.
This registration study aims to investigate the associations of the pharmacogenetic and pharmacokinetic factors with clopidogrel low response and clinical outcome in patients with coronary artery disease, and provide new pharmacogenetic and pharmacokinetic targets for the individualized anti-platelet treatment.
Detailed description
Associations of the Pharmacogenetic and Pharmacokinetic Factors With Clopidogrel Low Response and Clinical Outcome in Patients With Coronary Stent Implantation: a Registration Study
Published data linking clopidogrel non-responsiveness to adverse ischaemic events lead to the suggestion that the magnitude of platelet inhibition by clopidogrel can be monitored and individually adjusted. This has been tested in randomised clinical trials (ARCTIC, GRAVITAS and TRIGGER-PCI), but despite reducing platelet reactivity, a strategy of therapy adjustment based on platelet function monitoring did not reduce the incidence of cardiac ischaemic events1, which indicates that most pharmacodynamical tests monitored anti-platelet treatment failed so far.
We accordingly performed this registration study to investigate whether the pharmacogenetic and pharmacokinetic factors are associated with clopidogrel low response as well as clinical outcome, and aimed to provide new targets for the individualized anti-platelet treatment.
Inclusion criteria:
- Successively recruit all patients who receive stent implantation and take aspirin 100 mg and clopidogrel 75 mg once daily (7:00 a.m.) for more than 5 days.
- Patient aged >18 years;
- Signed inform consent.
Exclusion criteria:
- intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
- taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
- with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
- hemoglobin < 90g/L;
- with a history of cerebral hemorrhage within 1 year;
- in pregnancy.
Clinical data collection:
- Patients basic characteristics.
- Diagnosis and complicated diseases.
- Medical treatment and interventional treatment.
Methods:
Blood samples are collected 5 days after the patients' taking clopidogrel to perform the genetic testing and determine the light transmittancy aggregation (LTA) and the serum levels of the parent clopidogrel, intermediate and active metabolites of clopidogrel. LTA is to re-determined 1 month after clopidogrel consumption. Clopidogrel low response is defined as the inhibition of platelet aggregation (IPA) in response to 5μM ADP is more than 40%. Clinical follow-up will be performed 1month, 6month, and 1year after the patients' included. Major adverse cardiovascular events (MACE) is set as death, non-fatal myocardial infarction (MI), ischemic stroke. Associations of the pharmacogenetic and pharmacokinetic factors with clopidogrel low response and clinical outcome will be analyzed.
Tests:
- ADP-induced platelet aggregation: LTA in response to 5μM ADP.
- Arachidonic acid (AA)-induced platelet aggregation: LTA in response to 1mM AA.
- Simultaneous detection of clopidogrel, 2-oxo-clopidogrel and its thiol metabolite in human plasma by the high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.
- GWAS scan or genotyping of ABCB1,CYP2C19, paraoxonase 1 (PON1), CYP3A5, P2RY12.
Sample size: We plan to recruit 1800 patients.
Clinical follow-up: 1 month, 6 month, and 1 year after the patients' included.
Major adverse cardiovascular events (MACE): Death, non-fatal MI, ischemic stroke.
Minor adverse cardiovascular events: Hospitalization, revascularization, stent thrombosis (ARC definition) and minor, moderate, and major bleeding (TIMI definition).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All recruited patients | – | –Patients who receive stent implantation and aged >18 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients who receive stent implantation and aged >18 years.
Key inclusion criteria (3 listed)
- Successively recruit all patients who receive stent implantation and take aspirin 100 mg and clopidogrel 75 mg daily for more than 5 days.
- Patient aged >18 years;
- Signed inform consent.
Key exclusion criteria (6 listed)
- intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
- taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
- with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
- hemoglobin < 90g/L;
- with a history of cerebral hemorrhage within 1 year;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Risk ratio
Time frame: 1 year after patients' being recruited
Risk ratio of the genotypes on MACE.
Risk ratio
Time frame: 1 year after patients' being recruited
Risk ratio of the pharmacokinetic results on MACE.
2 secondary outcomes
Risk ratio
Time frame: 1 month after patients' being recruited
Risk ratio
Time frame: 1 month after patients' being recruited
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 18 Oct 2017.
- Background: PubMed 23884166Siller-Matula JM, Jilma B. Why have studies of tailored anti-platelet therapy failed so far? Thromb Haemost. 2013 Oct;110(4):628-31. doi: 10.1160/TH13-03-0250. Epub 2013 Jul 25.
- Derived from this study: PubMed 35929455Zong J, Tang Y, Wang T, Ullah I, Xu K, Wang J, Chen P, Chen Z, Zhu T, Chen J, Li J, Wang F, Yang L, Fan Y, Shi L, Gong X, Eikelboom JW, Zhao Y, Li C. Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention. J Am Heart Assoc. 2022 Aug 16;11(16):e025058. doi: 10.1161/JAHA.121.025058. Epub 2022 Aug 5.
- Derived from this study: PubMed 34666778Wang J, Wang J, Dong Z, Ma J, Teng J, Wang T, Zhang X, Gu Q, Ye Z, Ullah I, Tan C, Abdus S, Shi L, Gong X, Li C. An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention. Thromb J. 2021 Oct 19;19(1):73. doi: 10.1186/s12959-021-00323-5.
- Derived from this study: PubMed 31018667Xu K, Ye S, Zhang S, Yang M, Zhu T, Kong D, Chen J, Xu L, Li J, Zhu H, Wang F, Yang L, Zhang J, Fan Y, Ying L, Hu X, Zhang X, Chan NC, Li C. Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Platelet Reactivity and Early Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention and Treated With Aspirin and Clopidogrel. Circ Cardiovasc Interv. 2019 May;12(5):e007019. doi: 10.1161/CIRCINTERVENTIONS.118.007019.
- Derived from this study: PubMed 29807287Ying L, Wang F, Zhang J, Yang L, Gong X, Fan Y, Xu K, Li J, Lu Y, Mei L, Zhou Z, Li C. Impact of hepatitis B virus (HBV) infection on platelet response to clopidogrel in patients undergoing coronary stent implantation. Thromb Res. 2018 Jul;167:119-124. doi: 10.1016/j.thromres.2018.04.017. Epub 2018 Apr 19.
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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.
Chunjian Li, Ph.D principal investigator
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
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 6 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 18 Oct 2017. 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 China. 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.
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?
Risk ratio (time frame: 1 year after patients' being recruited). The study lists 2 primary outcomes in all. 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 NCT01968499, which also lists 5 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 18 Oct 2017.