Effect of Free Ticagrelor Fraction on Platelet Membrane Post MI

Acute Coronary Syndrome Clinical Trial

— PLATIME  

Official title:

Population-Based Pharmacokinetic / Pharmacodynamic Modeling of the Effect of Free Ticagrelor Fraction on the Platelet Membrane in Post Myocardial Infarction Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03658005
• Other study ID #: P/2018/371
• Status: Recruiting
• Start date: April 9, 2019
• Est. completion date: April 9, 2022

Study information

• Verified date: January 2021
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Jennifer Lagoutte-Renosi, MPharm
• Phone: +33370632379
• Email: jlagoutte[@]chu-besancon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 9, 2022
• Est. primary completion date: April 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

Other:
• Blood sample
3 blood samples, for a maximum of 60mL, will be taken at 0-3h, 3-6h and >6h, between two doses of ticagrelor (taken at 0 and 12 hours).

Locations

Country	Name	City	State
France	CHU Besançon	Besançon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	concentration of unbound ticagrelor and its metabolite	Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin	at 3 hours after administration of the first dose of ticagrelor
Primary	concentration of unbound ticagrelor and its metabolite	Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin	at 6 hours after administration of the first dose of ticagrelor
Primary	concentration of unbound ticagrelor and its metabolite	Concentration of unbound ticagrelor and its active metabolite in acute coronary syndrome patients treated by ticagrelor and aspirin	at 12 hours after administration of the first dose of ticagrelor
Secondary	Assess the method of determination of ticagrelor concentration	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	at 3 hours after administration of the first dose of ticagrelor
Secondary	Assess the method of determination of ticagrelor concentration	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	at 6 hours after administration of the first dose of ticagrelor
Secondary	Assess the method of determination of ticagrelor concentration	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	at 12 hours after administration of the first dose of ticagrelor