Effect of Free Ticagrelor Fraction on Platelet Membrane Post MI

• Conditions: Acute Coronary Syndrome
• Interventions: Other: Blood sample

• Registration Number: NCT03658005
• Lead Sponsor: Centre Hospitalier Universitaire de Besancon

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.

Study Timeline

• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-09-03
• Study First Posted: 2018-09-05
• Study Start: 2019-04-09
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-29
• Last Update Posted: 2021-02-02
• Primary Completion: 2022-04-09
• Study Completion: 2022-04-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Study cohort	Blood sample	Adult (\>18 years, \<90 years) patients admitted and treated for acute myocardial infarction, and whose treatment includes ticagrelor in association with aspirin. Blood samples will be taken at 3 timepoints between two doses of ticagrelor (taken at 12 hours interval).

Primary Outcome Measures

Name	Time	Method
concentration of unbound ticagrelor and its metabolite	at 12 hours after administration of the first dose of ticagrelor	Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin

Secondary Outcome Measures

Name	Time	Method
Assess the method of determination of ticagrelor concentration	at 12 hours after administration of the first dose of ticagrelor	Identify the optimum settings for the measurement of the concentration of ticagrelor (total and free fraction) and its active metabolite in the plasma by LC-MS/MS

Trial Locations

Locations (1)

CHU Besançon; 🇫🇷 Besançon, France