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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03477331

Acronym

OptimAT

Enrollment

444

Registered

2018-03-26

Start date

2018-01-14

Completion date

2024-01-31

Last updated

2024-04-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Diseases

Keywords

Direct oral anticoagulant, P2Y12 inhibitors, Physiologically-based pharmacokinetic model (PBPK), Population-based pharmacokinetic model (POPPK)

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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) *

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Trough Concentration (Cmin)	2 years	Difference between observed and PBPK model-predicted Cmin (mean prediction error)
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)
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)

Countries

Switzerland

Outcome results