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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.
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.
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) | Difference between observed and PBPK model-predicted AUC (mean prediction error) | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Trough Concentration (Cmin) | Difference between observed and PBPK model-predicted Cmin (mean prediction error) | 2 years |
| Area Under the Curve (AUC) (stability of the model over time) | Difference between observed and model-predicted AUC during patients' rehospitalization (stability of the model over time) |
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Inclusion Criteria:
Exclusion Criteria:
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Hospitalized patients
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Luc Reny, Prof | University Hospital, Geneva | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopitaux universitaires de Genève, 4 rue Gabrielle-Perret-Gentil | Geneva | Canton of Geneva | 1205 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37794718 | Background | Terrier J, Gaspar F, Gosselin P, Raboud O, Lenoir C, Rollason V, Csajka C, Samer C, Fontana P, Daali Y, Reny JL; OptimAT study group. Apixaban and rivaroxaban's physiologically-based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side. CPT Pharmacometrics Syst Pharmacol. 2023 Dec;12(12):1872-1883. doi: 10.1002/psp4.13036. Epub 2023 Oct 4. | |
| 37723920 |
| Label | URL |
|---|---|
| Liquid Biopsy for Patient Characterization in Cardiovascular Disease: Verification against Markers of Cytochrome P450 and P-Glycoprotein Activities | View source |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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whole blood
| 2 years |
| Major bleeding event-free survival | 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) | 2 years |
| Peak concentration (Cmax) | Difference between observed and PBPK model-predicted Cmax (mean prediction error) | 2 years |
| Thrombosis event-free survival | 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) | 2 years |
| Background |
| Gaspar F, Terrier J, Favre S, Gosselin P, Fontana P, Daali Y, Lenoir C, Samer CF, Rollason V, Reny JL, Csajka C, Guidi M. Population pharmacokinetics of apixaban in a real-life hospitalized population from the OptimAT study. CPT Pharmacometrics Syst Pharmacol. 2023 Oct;12(10):1541-1552. doi: 10.1002/psp4.13032. Epub 2023 Sep 18. |
| 35262906 | Background | Achour B, Gosselin P, Terrier J, Gloor Y, Al-Majdoub ZM, Polasek TM, Daali Y, Rostami-Hodjegan A, Reny JL. Liquid Biopsy for Patient Characterization in Cardiovascular Disease: Verification against Markers of Cytochrome P450 and P-Glycoprotein Activities. Clin Pharmacol Ther. 2022 Jun;111(6):1268-1277. doi: 10.1002/cpt.2576. Epub 2022 Mar 28. |
| 39798016 | Derived | Gaspar F, Jacost-Descombes C, Gosselin P, Reny JL, Guidi M, Csajka C, Samer C, Daali Y, Terrier J. Improving Understanding of Fexofenadine Pharmacokinetics to Assess Pgp Phenotypic Activity in Older Adult Patients Using Population Pharmacokinetic Modeling. Clin Pharmacokinet. 2025 Feb;64(2):275-283. doi: 10.1007/s40262-024-01470-4. Epub 2025 Jan 11. |