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CompletedNCT03477331OptimATUpdated Apr 10, 2024

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

An observational study in Cardiovascular Diseases, sponsored by University Hospital, Geneva. Completed at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-10.

Sponsored by University Hospital, Geneva · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
444
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cardiovascular Diseases

Keywords

  • Direct oral anticoagulant
  • P2Y12 inhibitors
  • Physiologically-based pharmacokinetic model (PBPK)
  • Population-based pharmacokinetic model (POPPK)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

Hospitalized patients

Eligibility criteria

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.
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
444 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna
05

What researchers measure

Primary outcomes

  1. Area Under the Curve (AUC)

    Difference between observed and PBPK model-predicted AUC (mean prediction error)

    Time frame: 2 years

Secondary outcomes

  1. Trough Concentration (Cmin)

    Difference between observed and PBPK model-predicted Cmin (mean prediction error)

    Time frame: 2 years

  2. 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)

    Time frame: 2 years

  3. 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)

    Time frame: 2 years

  4. Peak concentration (Cmax)

    Difference between observed and PBPK model-predicted Cmax (mean prediction error)

    Time frame: 2 years

  5. 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)

    Time frame: 2 years

06

Study locations

1 site
  • Hopitaux universitaires de Genève, 4 rue Gabrielle-Perret-Gentil
    Genève, GE 1205, Switzerland
07

References and documents

Publications

  • 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. PubMed 37794718 ↗
  • 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. PubMed 37723920 ↗
  • 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. PubMed 35262906 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03477331
Lead sponsor
University Hospital, Geneva
Responsible party
Jean-Luc Reny (Prof, University Hospital, Geneva) — Principal investigator
First posted
Mar 26, 2018
Start date
Jan 14, 2018
Primary completion
Jan 31, 2024
Completion
Jan 31, 2024
Last update
Apr 10, 2024

Study contacts

Jean-Luc Reny, Prof
principal investigator · University Hospital, Geneva

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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