Clinical trial NCT03658005: Effect of Free Ticagrelor Fraction on Platelet Membrane Post MI
Official title: Population-Based Pharmacokinetic / Pharmacodynamic Modeling of the Effect of Free Ticagrelor Fraction on the Platelet Membrane in Post Myocardial Infarction Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Coronary Syndrome
Keywords: Ticagrelor
acute coronary syndrome
anti-platelet drug
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2018-09-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the Cardiology department with a main diagnosis of acute coronary syndrome and treated with a treatment combination including ticagrelor and aspirin.

Brief summary: The purpose of this study is to assess:

* the population pharmacokinetics of unbound ticagrelor and its metabolite in acute coronary syndrome patients treated by ticagrelor
* ticagrelor and its metabolite levels by LC-MS/MS

Detailed description: Ticagrelor is an anti-platelet agent of the cyclopentyltriazolopyrimidine class. It is administered by the oral route, rapidly absorbed (2-3 hours), and has a bio-availability estimated at around 36%. Contrary to other P2Y12 inhibitors, ticagrelor is not a pro-drug and does not need to be metabolized to exert is pharmacodynamic effect. It had been previously showed that stimulation of platelets by ADP or inhibitors of platelets by ticagrelor modified the organisation of the platelet membrane, with a re-distribution of cholesterol and P2Y12 receptors towards the lipid rafts. This suggests that lipid membranes and cholesterol may play an important role in the anti-platelet activity of ticagrelor.

In this context, the aim of the study is to assess:

* the population pharmacokinetics of unbound ticagrelor and its metabolite in acute coronary syndrome patients treated by ticagrelor
* ticagrelor and its metabolite levels by LC-MS/MS.

Eligibility criteria: Inclusion Criteria:

* Patients aged over 18 years and less than 90 years,
* Patients admitted for myocardial infarction treated with ticagrelor in association with aspirin.
* Patients affiliated to a social security system (or be a beneficiary thereof);
* Sign written informed consent indicating that they have understood the study procedures and objectives, and that they accept to participate and adhere to the study requirements.

Exclusion Criteria:

* Patients with limited legal capacity or patients under legal guardianship
* Patients under judicial protection
* Patients not affiliated to any social security system
* Patients taking any antiplatelet agent other than ticagrelor Patients taking ticagrelor for \<48 hours (treatment not stabilised) Patients with hemoglobin concentration \<10 g/dL on the most recent blood test

Primary outcomes:
measure: concentration of unbound ticagrelor and its metabolite
timeFrame: at 3 hours after administration of the first dose of ticagrelor
measure: concentration of unbound ticagrelor and its metabolite
timeFrame: at 6 hours after administration of the first dose of ticagrelor
measure: concentration of unbound ticagrelor and its metabolite
timeFrame: at 12 hours after administration of the first dose of ticagrelor
Secondary outcomes:
measure: Assess the method of determination of ticagrelor concentration
timeFrame: at 3 hours after administration of the first dose of ticagrelor
measure: Assess the method of determination of ticagrelor concentration
timeFrame: at 6 hours after administration of the first dose of ticagrelor
measure: Assess the method of determination of ticagrelor concentration
timeFrame: at 12 hours after administration of the first dose of ticagrelor
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU Besançon
Study officials:
affiliation: Dept of Cardiology, CHU Besancon
name: Nicolas Meneveau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: