Drug ResistanceCEPAGENCT04990596
Mechanisms fo Clopidogrel Resistance in Older Adults (CEPAGE)
An observational study of Drug Resistance, run by Rennes University Hospital at 4 sites in France.
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. Read more about this study
- Who is it for?
- Ages 50 to 100 years
- Conditions the study is for
- Drug Resistance
- What is being tested?
- additional blood sample
- How many people
- 37 participants
- Where
- 4 sitesFrance
- Study dates
- 12 Jul 2021to 28 Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
France4 sites
Hôpital Charles Foix
Paris
Hôpital Européen Georges Pompidou,
Paris
Hôpital Lariboisière
Paris
CHU de RENNES
Rennes
About this study
Official title: 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.
Read the 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.
- Conditions
- Drug Resistance
- Being tested
- additional blood sample
- Keywords
- clopidogrel, primary or secondary prevention of cardiovascular events, older adults, clopidogrel resistance, Drug resistance, Antiplatelet resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: additional blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 0
Secondary outcomes (6)
Correlation of prodrug/active metabolite concentrations
Ratio of prodrug/active metabolite concentrations as a function of age
Measured: Day 0
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
Measured: Day 0
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
Measured: Day 0
Determination of factors influencing PK/PD response
clinical data: gender
Measured: Day 0
Determination of factors influencing PK/PD response
clinical data: body mass index in kg/m^2
Measured: Day 0
Determination of factors influencing PK/PD response
clinical data: Cumulative Illness Rating Scale-Geriatric
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2021
- Study start12 Jul 2021
- Primary completion27 Mar 2024
- Study completion28 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug ResistanceStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominique SOMME, MD, Pr, Principal investigator, CHU de Rennes - Service de GériatrieIsabelle GOUIN-THIBAULT, MD, PhD, Principal investigator, CHU de Rennes - Service d'Hématologie BiologiqueEric PAUTAS, MD, Pr, Principal investigator, Hôpital Charles Foix - Court séjour GériatriqueCorinne FRERE, MD, Principal investigator, CHU Pitié-Salpêtrière - Hématologie BiologiqueElena PAILLAUD, MD, Principal investigator, Hôpital Européen Georges Pompidou, Service de Gériatrie Aiguë,Pascale GAUSSEM, MD, Pr, Principal investigator, Hôpital Européen Georges Pompidou - Service d'Hématologie Biologique,Jean-Guillaume DILLINGER, MD, Principal investigator, Hôpital Lariboisière - Service de CardiologieVirginie SIGURET, MD, Pr, Principal investigator, Hôpital Lariboisière - Hématologie Biologique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04990596
- Sponsor's protocol ID
- 35RC19_9831_CEPAGE
- Acronym
- CEPAGE
- Status last verified
- Mar 2026
- First submitted
- 6 May 2021
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms fo Clopidogrel Resistance in Older Adults
- ClinicalTrials.gov ID
- NCT04990596
- Acronym / sponsor ID
- CEPAGE / 35RC19_9831_CEPAGE
- Conditions
- Drug Resistance
- Keywords
- clopidogrel, primary or secondary prevention of cardiovascular events, older adults, clopidogrel resistance, Drug resistance, Antiplatelet resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 27 Mar 2024 (actual)
- Study completion
- 28 Jan 2025 (actual)
- First posted
- 4 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Age Group 50 to 59 | – | Biological: additional blood sampleInclusion 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. |
| Age Group 60 to 69 | – | Biological: additional blood sampleInclusion 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. |
| Age Group 70 to 79 | – | Biological: additional blood sampleInclusion 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. |
| Age Group 80 to 89 | – | Biological: additional blood sampleInclusion 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. |
| Age Group 90 to 100 | – | Biological: additional blood sampleInclusion 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. |
Who may qualify
- Ages
- 50 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| additional blood sampleOne 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. | Biological | Age Group 50 to 59, Age Group 60 to 69, Age Group 70 to 79, Age Group 80 to 89, Age Group 90 to 100 |
Primary outcome
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
6 secondary outcomes
Correlation of prodrug/active metabolite concentrations
Time frame: 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 Platelet Reactivity Index of VASPphosphorylation and the concentration of the active metabolite of clopidogrel
Time frame: Day 0
Determination of factors influencing PK/PD response
Time frame: Day 0
Determination of factors influencing PK/PD response
Time frame: Day 0
Determination of factors influencing PK/PD response
Time frame: Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique SOMME, MD, Pr principal investigator
CHU de Rennes - Service de Gériatrie
Isabelle GOUIN-THIBAULT, MD, PhD principal investigator
CHU de Rennes - Service d'Hématologie Biologique
Eric PAUTAS, MD, Pr principal investigator
Hôpital Charles Foix - Court séjour Gériatrique
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Resistance, run by Rennes University Hospital at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK/PD correlation - clopidogrel active metabolite concentration (pharmacokinetics PK in ) / platelet response phenotype(pharmacodynamics, PD) (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.