Clopidogrel and Response Variability Investigation Study 2 (CLOVIS2)

December 10, 2012 updated by: Assistance Publique - Hôpitaux de Paris

Effect of the Genetic Variant 2C19*2 on Clopidogrel Biological Response in Patients With Premature Coronary Artery Disease

To evaluate the role of the genetic variant 2C19*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Rationale : Clopidogrel is a specific and irreversible of the P2Y12 platelet receptor leading to an inhibition of platelet aggregation. Clopidogrel is a prodrug that must be converted into an active metabolite that selectively and irreversibly binds to the P2Y12 platelet membrane receptor. As a consequence, a loading dose of 300 mg is necessary in percutaneous coronary intervention and in acute coronary syndrome, situations which require a rapid inhibition of platelet aggregation due to the high thrombotic risk.

High platelet reactivity on clopidogrel may be due to various reasons including polymorphism in the gene encoding the cytochrome P-450 2C19 enzyme (CYP2C19) which has been shown to contribute to the variability of platelet response to clopidogrel. CYP2C19 is a key enzyme in this activation process and our group was the first to describe an association between the presence of the loss of function CYP2C19 681G>A polymorphism (also called *2) with lower clopidogrel responsiveness in healthy subjects.

Poor responsiveness to clopidogrel has become a major concern given acute recurrent events following stent placement.

Objective : To evaluate the role of the genetic variant 2C19*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.

Target population :Patients of less than 45 years of age and who survived a MI and enrolled in the AFIJI multicenter registry (Appraisal of risk Factors in young Ischemic patients Justifying aggressive Intervention).

Primary end-point :Comparison of inhibition of the intensity of residual platelet aggregation (IRPA) measured 6 minutes after induction by 20 μmol/L following 300mg or 900 mg of clopidogrel with respect to the presence of the genetic variant CYP2C19*2

  1. Maximum platelet aggregation instead of IRPA
  2. RPA with 5µM and 50 µM of ADP
  3. Measure of clopidogrel and its active metabolites (carboxylated and thiol) at different time points following the loading dose (H0, H1, H2 et H6) with respect to the presence of the genetic variant CYP2C19*2
  4. Relationship between active metabolites concentration and IRPA
  5. Relationship between active metabolites and dose of clopidogrel
  6. Comparison of 300mg vs 900mg on IRPA in the whole population irrespective of the genetic variant

Statistical analysis :Comparison of IRPA with respect to the presence of the genetic variant 2C19*2 by anova Area under the curve of the production of active metabolites with respect to the presence of the genetic variant 2C19*2 Agenda :November 2008 (inclusion of first patient) to december 2009 (analysis of the data)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
109

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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

  • France
      • Paris, France, 75013
        • Hopital la Pitié-Salpétrière Institut de cardiologie

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Age > 18
  • Male gender
  • Included in the AFIJI registry
  • No high bleeding risk profile
  • No recent history of acute coronary syndrome (< 3 months)
  • Written informed consent obtained
  • Genotype CYP2C19 : *1/*1, *1/*2 ou *2/*2
  • Genotype P2Y12 : H1/H1 ou H1/H2

Exclusion Criteria:

  • Female gender
  • Patient with a contraindication to clopidogrel
  • Patient who has received a loading dose of clopidogrel in the past 7 days
  • Patient treated with ticlopidine or GP2B/3A receptor antagonist prior to loading
  • Non compliance
  • Génotype P2Y12 : H2/H2.
  • Patient treated with drugs interacting with platelet aggregation (NSAID, persantine, serotonin inhibitors )
  • Patient treated with drugs interacting 2C19
  • Not affiliated to the national health insurance
  • Patient participating to another randomized study

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

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: 1
patients homozygous for the 2C19*1 genetic variant
Drug: clopidogrel
comparison of two loading strategies of clopidogrel (300mg vs 900mg) in the two genetic profiles
EXPERIMENTAL: 2
carriers of the 2C19*2 genetic variant (homozygous or heterozygous)
Drug: clopidogrel
comparison of two loading strategies of clopidogrel (300mg vs 900mg) in the two genetic profiles

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Inhibition of residual platelet activity 6 hours after a loading dose of clopidogrel
Time Frame: 6 hours
6 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Maximum platelet aggregation instead of IRPA
Time Frame: during the study
during the study
RPA with 5µM and 50 µM of ADP
Time Frame: during the study
during the study
3. Measure of clopidogrel and its active metabolites (carboxylated and thiol) at different time points following the loading dose (H0, H1, H2 ,H6) with respect to the presence of the genetic variant CYP2C19*2
Time Frame: H0, H1, H2, H6
H0, H1, H2, H6
Relationship between active metabolites concentration and IRPA
Time Frame: during the study
during the study
Relationship between active metabolites and dose of clopidogrel
Time Frame: during the study
during the study

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institut National de la Santé Et de la Recherche Médicale, France

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jean-Philippe Collet, MD, Assistance Publique - Hôpitaux de Paris

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2008

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2009

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 13, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 14, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P070117

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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