Pharmacogenetic and Pharmacokinetic Study of Clopidogrel (PPSC)

October 16, 2017 updated by: Chunjian Li, The First Affiliated Hospital with Nanjing Medical University

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.

Study Overview

Status

Completed

Conditions

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:

  1. 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.
  2. Patient aged >18 years;
  3. Signed inform consent.

Exclusion criteria:

  1. intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
  2. taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
  3. with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
  4. hemoglobin < 90g/L;
  5. with a history of cerebral hemorrhage within 1 year;
  6. in pregnancy.

Clinical data collection:

  1. Patients basic characteristics.
  2. Diagnosis and complicated diseases.
  3. 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:

  1. ADP-induced platelet aggregation: LTA in response to 5μM ADP.
  2. Arachidonic acid (AA)-induced platelet aggregation: LTA in response to 1mM AA.
  3. 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.
  4. 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 Type

Observational

Enrollment (Actual)

1805

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All patients who receive stent implantation and aged >18 years.

Description

Inclusion Criteria:

  1. Successively recruit all patients who receive stent implantation and take aspirin 100 mg and clopidogrel 75 mg daily for more than 5 days.
  2. Patient aged >18 years;
  3. Signed inform consent.

Exclusion Criteria:

  1. intolerant with aspirin or clopidogrel treatment (e.g. allergic reactions or gastrointestinal bleeding);
  2. taking medication that could interfere with the antiplatelet efficacy of clopidogrel (e.g. vitamin K antagonists, direct oral anticoagulants or nonsteroidal anti-inflammatory drugs);
  3. with myelodysplastic syndrome or abnormal baseline platelet counts of < 80 × 10∧9/L or > 450 × 10∧9/L;
  4. hemoglobin < 90g/L;
  5. with a history of cerebral hemorrhage within 1 year;
  6. in pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
All recruited patients
Patients who receive stent implantation and aged >18 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk ratio
Time Frame: 1 year after patients' being recruited
Risk ratio of the genotypes on MACE.
1 year after patients' being recruited
Risk ratio
Time Frame: 1 year after patients' being recruited
Risk ratio of the pharmacokinetic results on MACE.
1 year after patients' being recruited

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk ratio
Time Frame: 1 month after patients' being recruited
Risk ratio of the genotypes on clopidogrel low response.
1 month after patients' being recruited
Risk ratio
Time Frame: 1 month after patients' being recruited
Risk ratio of the pharmacokinetic results on clopidogrel low response.
1 month after patients' being recruited

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk ratio
Time Frame: 1 year after patients' being recruited
Risk ratios of the genotypes and pharmacokinetic results on the minor adverse cardiovascular events.
1 year after patients' being recruited

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

National Natural Science Foundation of China

Investigators

  • Principal Investigator: Chunjian Li, Ph.D, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

October 17, 2017

Study Completion (Actual)

October 17, 2017

Study Registration Dates

First Submitted

October 17, 2013

First Submitted That Met QC Criteria

October 18, 2013

First Posted (Estimate)

October 24, 2013

Study Record Updates

Last Update Posted (Actual)

October 18, 2017

Last Update Submitted That Met QC Criteria

October 16, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 002 (University of CT Health Center)
  • NNSFC/81170181 (Other Grant/Funding Number: NNSFC/81170181)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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