MedDataX Logo

Mechanisms fo Clopidogrel Resistance in Older Adults (CEPAGE)

NCT ID: NCT04990596

Last Updated: 2023-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-12

Study Completion Date

2026-01-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Drug Resistance

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

additional blood sample

Intervention Type BIOLOGICAL

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.

additional blood sample

Intervention Type BIOLOGICAL

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.

additional blood sample

Intervention Type BIOLOGICAL

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.

additional blood sample

Intervention Type BIOLOGICAL

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.

additional blood sample

Intervention Type BIOLOGICAL

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

50 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Dominique SOMME, MD, Pr

Role: PRINCIPAL_INVESTIGATOR

CHU de Rennes - Service de Gériatrie

Isabelle GOUIN-THIBAULT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU de Rennes - Service d'Hématologie Biologique

Eric PAUTAS, MD, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Charles Foix - Court séjour Gériatrique

Corinne FRERE, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Pitié-Salpêtrière - Hématologie Biologique

Elena PAILLAUD, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges Pompidou, Service de Gériatrie Aiguë,

Pascale GAUSSEM, MD, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges Pompidou - Service d'Hématologie Biologique,

Jean-Guillaume DILLINGER, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Lariboisière - Service de Cardiologie

Virginie SIGURET, MD, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Lariboisière - Hématologie Biologique

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hôpital Charles Foix

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Européen Georges Pompidou,

Paris, , France

Site Status RECRUITING

Hôpital Lariboisière

Paris, , France

Site Status RECRUITING

CHU de RENNES

Rennes, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Joaquim PRUD'HOMM, MD

Role: CONTACT

joaquim.prud'[email protected]
2 99 28 41 10 ext. +33

Isabelle GOUIN-THIBAULT, MD, PhD

Role: CONTACT

[email protected]
2 99 28 95 63 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Eric PAUTAS, Pr

Role: primary

Elena PAILLAUD, MD

Role: primary

Jean-Guillaume DILLINGER, MD

Role: primary

Dominique SOMME, PhD

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

35RC19_9831_CEPAGE

Identifier Type: -

Identifier Source: org_study_id