Mechanisms fo Clopidogrel Resistance in Older Adults (CEPAGE) (CEPAGE)

March 30, 2026 updated by: Rennes University Hospital

Mechanisms fo Clopidogrel Resistance in Older Adults

A clopidogrel resistance rate of 40-50% has been found in the population over 70 years of age, whereas biological resistance, associated with an increased risk of cardiovascular events, is observed in about 20-30% of younger patients. One hypothesis is that the active metabolite is less available in resistant patients. Indeed, 85% of the absorbed clopidogrel undergoes inactivation by esterases. Then the remaining fraction undergoes two steps of metabolisation to the active thiol metabolite by CYP450, essentially the isoform 2C19. In older adults, increased esterase activity and/or decreased CYP450 2C19 activity may lead to a decreased concentration of the active metabolite. Multiple chronic conditions and polypharmacy encountered in older individuals are associated with basal platelet hyperactivity, and may also contribute to a poor response to clopidogrel. No data on the relationship between platelet response and circulating metabolite levels, or on the determinants of response to clopidogrel, are currently available in the geriatric population. Therefore, we propose to analyse the relationship between age and platelet and extra-platelet mechanisms potentially involved in the variability of response to clopidogrel.

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

This study is a prospective observational multi-centre study. The main objective is assessing the pharmacokinetics (PK) and pharmacodynamics (PD) correlation of clopidogrel action in older adults, i.e. correlation between clopidogrel active metabolite concentration (PK) and platelet response phenotype (PD). The primary outcome is the correlation between the concentration of active metabolite of clopidogrel (PK) over the percentage of maximum aggregation at 10 μM ADP (PD) as a function of age. Inclusion criteria are: age 50-100 years old, hospitalization in one of the 4 participating centres, treatment with clopidogrel 75 milligrammes per day, for at least 10 days. The statistical analysis is a multiple linear regression model with the introduction of an interaction term. The first variable of interest (explanatory) is the concentration of the metabolite. A linear regression model will be used to estimate the proportion of variance explained. The analyses will be conducted with SAS version 9.4 (SAS Institute Inc., Cary, N.C., USA). Results will be published in an international scientific review.

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.
Observational

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.
37

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Paris, France
        • Hôpital Lariboisière
      • Paris, France
        • Hôpital Charles Foix
      • Paris, France
        • Hôpital Européen Georges Pompidou,
      • Rennes, France
        • CHU de Rennes

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

50 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

patients from 50 to 100 years treated with clopidogrel 75 mg/d for at least 10 days for primary or secondary prevention of cardiovascular events

Description

Inclusion Criteria:

Consecutive patients per 10-year age range, (20 patients per age range from 50 to 100 years included) :

  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 mg/d for at least 10 days for primary or secondary prevention of cardiovascular events.
  • who have received the information and have not expressed their opposition to participate in the study and who have given their written consent for the performance of genetic examinations and the realization of a biocollection
  • affiliated to French social security system

Exclusion criteria :

  • treatment with another antithrombotic agent,
  • myeloproliferative syndrome,
  • platelet count < 100 G/L,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • under dialysis,
  • no participation in another clinical study,
  • deprived of liberty

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.
Age Group 50 to 59

Inclusion criteria :

  • age 50-100 years old,
  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 milligrammes per day, for at least 10 days, for primary or secondary prevention of cardiovascular events.

Non-inclusion criteria :

  • treatment with another antithrombotic drug,
  • myeloproliferative syndrome,
  • platelet count < 100 gigas/liter,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • dialysis.
Biological: additional blood sample
One sample per patient will be taken 1 to 3 hours after clopidogrel administration. Four additional tubes of 3 mL each will be collected for the study, for a total volume of 12 mL.
Age Group 60 to 69

Inclusion criteria :

  • age 50-100 years old,
  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 milligrammes per day, for at least 10 days, for primary or secondary prevention of cardiovascular events.

Non-inclusion criteria :

  • treatment with another antithrombotic drug,
  • myeloproliferative syndrome,
  • platelet count < 100 gigas/liter,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • dialysis.
Biological: additional blood sample
One sample per patient will be taken 1 to 3 hours after clopidogrel administration. Four additional tubes of 3 mL each will be collected for the study, for a total volume of 12 mL.
Age Group 70 to 79

Inclusion criteria :

  • age 50-100 years old,
  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 milligrammes per day, for at least 10 days, for primary or secondary prevention of cardiovascular events.

Non-inclusion criteria :

  • treatment with another antithrombotic drug,
  • myeloproliferative syndrome,
  • platelet count < 100 gigas/liter,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • dialysis.
Biological: additional blood sample
One sample per patient will be taken 1 to 3 hours after clopidogrel administration. Four additional tubes of 3 mL each will be collected for the study, for a total volume of 12 mL.
Age Group 80 to 89

Inclusion criteria :

  • age 50-100 years old,
  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 milligrammes per day, for at least 10 days, for primary or secondary prevention of cardiovascular events.

Non-inclusion criteria :

  • treatment with another antithrombotic drug,
  • myeloproliferative syndrome,
  • platelet count < 100 gigas/liter,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • dialysis.
Biological: additional blood sample
One sample per patient will be taken 1 to 3 hours after clopidogrel administration. Four additional tubes of 3 mL each will be collected for the study, for a total volume of 12 mL.
Age Group 90 to 100

Inclusion criteria :

  • age 50-100 years old,
  • in consultation or hospitalization in one of the participating centres,
  • treatment with clopidogrel 75 milligrammes per day, for at least 10 days, for primary or secondary prevention of cardiovascular events.

Non-inclusion criteria :

  • treatment with another antithrombotic drug,
  • myeloproliferative syndrome,
  • platelet count < 100 gigas/liter,
  • acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer,
  • dialysis.
Biological: additional blood sample
One sample per patient will be taken 1 to 3 hours after clopidogrel administration. Four additional tubes of 3 mL each will be collected for the study, for a total volume of 12 mL.

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
Measure Description
Time Frame
PK/PD correlation - clopidogrel active metabolite concentration (pharmacokinetics PK in ) / platelet response phenotype(pharmacodynamics, PD)
Time Frame: Day 0
Correlation PK (concentration of active metabolite of clopidogrel) / PD (%maximum aggregation at 10 μM ADP) as a function of age
Day 0

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
Measure Description
Time Frame
Correlation of prodrug/active metabolite concentrations
Time Frame: Day 0
Ratio of prodrug/active metabolite concentrations as a function of age
Day 0
Correlation between the area under the curve of aggregationat 10 μM ADP and the concentration of the active metabolite of clopidogrel
Time Frame: Day 0
Correlation between the area under the curve of aggregation at 10μM ADP and the concentration of the active metabolite of clopidogrelas a function of age
Day 0
Correlation between the Platelet Reactivity Index of VASPphosphorylation and the concentration of the active metabolite of clopidogrel
Time Frame: Day 0
Correlation between the Platelet Reactivity Index of VASP phosphorylation and the concentration of the active metabolite of clopidogrel in relation to age
Day 0
Determination of factors influencing PK/PD response
Time Frame: Day 0
clinical data: gender
Day 0
Determination of factors influencing PK/PD response
Time Frame: Day 0
clinical data: body mass index in kg/m^2
Day 0
Determination of factors influencing PK/PD response
Time Frame: Day 0
clinical data: Cumulative Illness Rating Scale-Geriatric
Day 0

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.
Rennes University Hospital

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: Dominique SOMME, MD, Pr, CHU de Rennes - Service de Gériatrie
  • Principal Investigator: Isabelle GOUIN-THIBAULT, MD, PhD, CHU de Rennes - Service d'Hématologie Biologique
  • Principal Investigator: Eric PAUTAS, MD, Pr, Hôpital Charles Foix - Court séjour Gériatrique
  • Principal Investigator: Corinne FRERE, MD, CHU Pitié-Salpêtrière - Hématologie Biologique
  • Principal Investigator: Elena PAILLAUD, MD, Hôpital Européen Georges Pompidou, Service de Gériatrie Aiguë,
  • Principal Investigator: Pascale GAUSSEM, MD, Pr, Hôpital Européen Georges Pompidou - Service d'Hématologie Biologique,
  • Principal Investigator: Jean-Guillaume DILLINGER, MD, Hôpital Lariboisière - Service de Cardiologie
  • Principal Investigator: Virginie SIGURET, MD, Pr, Hôpital Lariboisière - Hématologie Biologique

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 (Actual)

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.
July 12, 2021

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.
March 27, 2024

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.
January 28, 2025

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).
May 6, 2021

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.
July 26, 2021

First Posted (Actual)

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.
August 4, 2021

Study Record Updates

Last Update Posted (Actual)

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.
March 31, 2026

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.
March 30, 2026

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.
March 1, 2026

More Information

Terms related to this study

Keywords

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.
  • 35RC19_9831_CEPAGE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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