Antithrombotics' Therapeutic Optimization in Hospitalized Patients Using Physiologically- and Population-based Pharmacokinetic Modeling

Completed

• Conditions: Cardiovascular Diseases

• Registration Number: NCT03477331
• Lead Sponsor: University Hospital, Geneva

Brief Summary

The main goal of the OptimAT study main goal is to validate a PBPK model for 3 direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) and 3 P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel) in hospitalized patients.

Detailed Description

Patients treated with antithrombotics are at risk of both severe ischemic and bleeding events. However, current clinical scores are insufficiently discriminant to predict the most favorable drug and dosing for an improved net clinical benefit. Physiologically and population-based pharmacokinetic models (PBPK and POPPK respectively) incorporate substrate specific properties obtained from experimental in-vitro experiments as well as patients' demographic, genetic and physiological in vivo data in order to characterize the dose-concentration relationships. As such, they can be used to simulate and predict PK profiles accounting for specific patients' characteristics and are the basis of dosing optimization. These models could be a valuable tool to predict antithrombotic blood concentration in a given patient. Our main goal is to elaborate predictive models characterizing the dose-concentration relationship with influencing variables of three direct oral anticoagulants (DOAC) (rivaroxaban, apixaban, dabigatran) and three P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in hospitalized patients, which will serve as basis for drug selection and dosage optimization.

Study Timeline

• Study Start: 2018-01-14
• Study First Submitted: 2018-02-02
• Study First Submitted QC: 2018-03-23
• Study First Posted: 2018-03-26
• Primary Completion: 2024-01-31
• Study Completion: 2024-01-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-08
• Last Update Posted: 2024-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 444

Inclusion Criteria

• Hospitalized patients at any of the Geneva University Hospitals 18 yo and older
• Treated with DOAC (dabigatran, rivaroxaban, apixaban) or/and P2Y12 (clopidogrel, ticragrelor et prasugel) at the time of study blood sampling
• Understanding of French language and able to give an inform consent.

Exclusion Criteria

• Patients with a reduced life span (<6 mois)
• Exclusion criteria during follow up
• Change in dosage or cessation of the DOAC or P2Y12 taken by the participant follow up data will be censored at the time of change.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC)	2 years	Difference between observed and PBPK model-predicted AUC (mean prediction error)

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) (stability of the model over time)	2 years	Difference between observed and model-predicted AUC during patients' rehospitalization (stability of the model over time)
Trough Concentration (Cmin)	2 years	Difference between observed and PBPK model-predicted Cmin (mean prediction error)
Major bleeding event-free survival	2 years	Major bleeding event-free survival according to drug exposure (AUC) during a prospective during a follow-up of two years for DOACs (dabigatran, rivaroxaban, apixaban) and P2Y12 receptor inhibitors (clopidogrel, ticragrelor, prasugel)
Peak concentration (Cmax)	2 years	Difference between observed and PBPK model-predicted Cmax (mean prediction error)
Thrombosis event-free survival	2 years	Thrombosis event-free survival according to drug exposure (AUC) during a prospective during a follow-up of two years for DOACs (dabigatran, rivaroxaban, apixaban) and P2Y12 receptor inhibitors (clopidogrel, ticragrelor, prasugel)

Trial Locations

Locations (1)

Hopitaux universitaires de Genève, 4 rue Gabrielle-Perret-Gentil; 🇨🇭 Genève, GE, Switzerland