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

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ClinicalTrials.gov Identifier: NCT03477331
Recruitment Status : Recruiting
First Posted : March 26, 2018
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
Jean-Luc Reny, University Hospital, Geneva

Study Description
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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.

Condition or disease
Cardiovascular Diseases

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 Design
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Study Type : Observational
Estimated Enrollment : 600 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Antithrombotics' Therapeutic Optimization in Hospitalized Patients Using Physiologically- and Population-based Pharmacokinetic Modeling
Actual Study Start Date : January 14, 2018
Estimated Primary Completion Date : January 14, 2022
Estimated Study Completion Date : January 14, 2022
Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Area Under the Curve (AUC) [ Time Frame: 2 years ]
    Difference between observed and PBPK model-predicted AUC (mean prediction error)


Secondary Outcome Measures :
  1. Trough Concentration (Cmin) [ Time Frame: 2 years ]
    Difference between observed and PBPK model-predicted Cmin (mean prediction error)

  2. Area Under the Curve (AUC) (stability of the model over time) [ Time Frame: 2 years ]
    Difference between observed and model-predicted AUC during patients' rehospitalization (stability of the model over time)

  3. Major bleeding event-free survival [ Time Frame: 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)

  4. Peak concentration (Cmax) [ Time Frame: 2 years ]
    Difference between observed and PBPK model-predicted Cmax (mean prediction error)

  5. Thrombosis event-free survival [ Time Frame: 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)


Biospecimen Retention:   Samples With DNA
whole blood

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Hospitalized patients
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03477331


Contacts
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Contact: Jean-Luc Reny, Prof +4122 372 90 59 jean-luc.reny@hcuge.ch
Contact: Jean Terrier, Dr +4122 372 90 59 jean.terrier@hcuge.ch

Locations
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Switzerland
Hopitaux universitaires de Genève, 4 rue Gabrielle-Perret-Gentil Recruiting
Genève, GE, Switzerland, 1205
Sponsors and Collaborators
University Hospital, Geneva
Investigators
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Principal Investigator: Jean-Luc Reny, Prof Hôpitaux universitaires de Genève
More Information
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Responsible Party: Jean-Luc Reny, Prof, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT03477331    
Other Study ID Numbers: 2017-00225
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jean-Luc Reny, University Hospital, Geneva:
Direct oral anticoagulant
P2Y12 inhibitors
Physiologically-based pharmacokinetic model (PBPK)
Population-based pharmacokinetic model (POPPK)
Additional relevant MeSH terms:
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Cardiovascular Diseases