NCT04990596

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jul 2021

Typical duration for all trials

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2021

Completed
2 months until next milestone

Study Start

First participant enrolled

July 12, 2021

Completed
23 days until next milestone

First Posted

Study publicly available on registry

August 4, 2021

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 27, 2024

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 28, 2025

Completed
Last Updated

March 31, 2026

Status Verified

March 1, 2026

Enrollment Period

2.7 years

First QC Date

May 6, 2021

Last Update Submit

March 30, 2026

Conditions

Drug Resistance

Keywords

clopidogrelprimary or secondary prevention of cardiovascular eventsolder adultsclopidogrel resistanceDrug resistanceAntiplatelet resistance

Outcome Measures

Primary Outcomes (1)

  • PK/PD correlation - clopidogrel active metabolite concentration (pharmacokinetics PK in ) / platelet response phenotype(pharmacodynamics, PD)

    Correlation PK (concentration of active metabolite of clopidogrel) / PD (%maximum aggregation at 10 μM ADP) as a function of age

    Day 0

Secondary Outcomes (6)

  • Correlation of prodrug/active metabolite concentrations

    Day 0

  • Correlation between the area under the curve of aggregationat 10 μM ADP and the concentration of the active metabolite of clopidogrel

    Day 0

  • Correlation between the Platelet Reactivity Index of VASPphosphorylation and the concentration of the active metabolite of clopidogrel

    Day 0

  • Determination of factors influencing PK/PD response

    Day 0

  • Determination of factors influencing PK/PD response

    Day 0

  • +1 more secondary outcomes

Study Arms (5)

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

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

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

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

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

Interventions

additional blood sampleBIOLOGICAL

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 50 to 59Age Group 60 to 69Age Group 70 to 79Age Group 80 to 89Age Group 90 to 100

Eligibility Criteria

Age50 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Hôpital Charles Foix

Paris, France

Location

Hôpital Européen Georges Pompidou,

Paris, France

Location

Hôpital Lariboisière

Paris, France

Location

CHU de RENNES

Rennes, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Centralized determination of clopidogrel and active metabolite (pharmacology Samples) Centralized determination of plasma markers of platelet activation (hematology Samples) Centralized study of genetic polymorphisms (pharmacology Samples)

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 6, 2021

First Posted

August 4, 2021

Study Start

July 12, 2021

Primary Completion

March 27, 2024

Study Completion

January 28, 2025

Last Updated

March 31, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

FR(4)