Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04990596
Other study ID # 35RC19_9831_CEPAGE
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date July 12, 2021
Est. completion date January 12, 2026

Study information

Verified date November 2023
Source Rennes University Hospital
Contact Joaquim PRUD'HOMM, MD
Phone 2 99 28 41 10
Email joaquim.prud'homm@chu-rennes.fr
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 100
Est. completion date January 12, 2026
Est. primary completion date July 12, 2025
Accepts healthy volunteers No
Gender All
Age group 50 Years to 100 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
France Hôpital Charles Foix Paris
France Hôpital Européen Georges Pompidou, Paris
France Hôpital Lariboisière Paris
France CHU de RENNES Rennes

Sponsors (1)

Lead Sponsor Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Correlation of prodrug/active metabolite concentrations Ratio of prodrug/active metabolite concentrations as a function of age Day 0
Secondary Correlation between the area under the curve of aggregationat 10 µM ADP and the concentration of the active metabolite of clopidogrel 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
Secondary Correlation between the Platelet Reactivity Index of VASPphosphorylation and the concentration of the active metabolite of clopidogrel Correlation between the Platelet Reactivity Index of VASP phosphorylation and the concentration of the active metabolite of clopidogrel in relation to age Day 0
Secondary Determination of factors influencing PK/PD response clinical data: gender Day 0
Secondary Determination of factors influencing PK/PD response clinical data: body mass index in kg/m^2 Day 0
Secondary Determination of factors influencing PK/PD response clinical data: Cumulative Illness Rating Scale-Geriatric Day 0
See also
  Status Clinical Trial Phase
Not yet recruiting NCT04516395 - Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae N/A
Terminated NCT00319150 - REPEAT Study - Resistance to ErythroPoietin Effectiveness Algorithm Trial Phase 3
Completed NCT00563875 - Laboratory Aspirin Resistance in Diabetics and Non-Diabetics N/A
Completed NCT00389129 - Danish Aspirin Resistance Trial - Pilot Study N/A
Terminated NCT00193947 - An Evaluation of the Development of Nevirapine Induced Mutations in HIV Patients Initiating or Discontinuing Combination Antiretroviral Therapy Phase 4
Enrolling by invitation NCT06037564 - B-free Multistage Trial Phase 4
Completed NCT04326868 - Human Soil Transmitted Helminths (STH) Resistance to Benzimidazole in School Aged Children Living in Gabon Phase 4
Completed NCT01039480 - Aspirin and Clopidogrel Resistance Study N/A
Recruiting NCT05310370 - HRD and Resistance to PAPPi in EOC Patients
Active, not recruiting NCT00457236 - Effect of Clopidogrel Loading and Risk of PCI N/A
Completed NCT02792816 - Molecular Surveillance of Artemisinin Resistance Malaria in Myanmar N/A
Completed NCT01386476 - (18F)FCWAY and the Blood-Brain Barrier
Recruiting NCT03401957 - The Emergence of RAS Mutations in Metastatic Colorectal Cancer Patients Receiving Cetuximab Treatment N/A
Completed NCT04404582 - Clinical Characteristics for the Critical Ill Patients With Klebsiella Pneumoniae Infection
Completed NCT02401204 - Bacterial Transmission Dynamics Study
Completed NCT03114098 - Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs N/A
Recruiting NCT03361267 - Comparison of Bismuth Containing Quadruple Therapy and Based Tailored Therapy for H. Pylori Infection N/A
Completed NCT00302913 - Efficacy of Adjusted Clopidogrel Dose in Patients With Insufficient Platelet Inhibition N/A
Completed NCT04833231 - The Relationship Between Renal Functions and Multi Drug Resistant Organisms
Completed NCT00965042 - Effect of Ceftobiprole on Human Intestinal Microflora Phase 1