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NCT Number: NCT04990596

Mechanisms fo Clopidogrel Resistance in Older Adults (CEPAGE)

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.

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Key information

Conditions

Drug Resistance

Age range

50 year–100 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital Charles Foix, Paris, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Additional blood sample

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.

Primary outcomes

  1. 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

Secondary outcomes

  1. Correlation of prodrug/active metabolite concentrations

    Time frame: Day 0

    Ratio of prodrug/active metabolite concentrations as a function of age

  2. 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

  3. 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

  4. Determination of factors influencing PK/PD response

    Time frame: Day 0

    clinical data: gender

  5. Determination of factors influencing PK/PD response

    Time frame: Day 0

    clinical data: body mass index in kg/m^2

  6. Determination of factors influencing PK/PD response

    Time frame: Day 0

    clinical data: Cumulative Illness Rating Scale-Geriatric

Sponsors and collaborators

Lead sponsor

Rennes University Hospital

Other

Registry information

Official study title

Mechanisms fo Clopidogrel Resistance in Older Adults

Acronym: CEPAGE

Important dates

Study start
2021
Primary completion
2024
Study completion
2025
First posted
Aug 4, 2021
Registry last updated
Mar 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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