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DAPHNE Study: Direct Anticoagulant PHarmacogeNEtic

NCT03112525 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 300

Last updated 2021-09-30

No results posted yet for this study

Summary

New/direct oral anticoagulants (NOAC/DOAC), like apixaban and rivaroxaban, are an interesting alternative to unfractionated or low molecular weight heparin relayed by oral anti-vitamin K anticoagulants (VKA) for the treatment of venous thromboembolism and atrial fibrillation. This new generation of anticoagulants directly inhibit a factor in the blood coagulation pathway and have a wide therapeutic range overcoming several practical issues associated with VKA therapy including the need of routine coagulation monitoring potentially simplifying patient management. However, despite this wide therapeutic range, a large interindividual dose variability related to factors such as age, body surface, smoking, concomitant diseases as well as differences in drug metabolism, could put susceptible patients at risk for uncontrolled bleeding. Both rivaroxaban and apixaban are cleared primarily via cytochrome P450 (CYP) mediated hepatic metabolism, mainly CYP3A, and renal excretion, involving the P-glycoprotein (P-gp). Both CYP3A and P-gp activity show important interindividual variations due to drug interactions and/or genetic polymorphisms in corresponding genes.

The aim of the current study is to evaluate the impact of cytochrome activity and relevant polymorphisms on rivaroxaban/apixaban dosage regimen or treatment efficacy in a hospital setting. The safety issue in this context is particularly relevant, since hospitalisation is linked to a modification of the patient's treatment with often an increase in the number of medications. The resulting changes in metabolism due to modified cytochrome and transporter activities could affect rivaroxaban/apixaban blood concentrations. Our central hypothesis is that genotype and/or phenotype in CYP3A4/5/7 or P-gp may influence the rivaroxaban/apixaban plasma concentration and increase the risk of thrombotic or hemorrhagic events. Thus, investigating how the patient's genotype and/or phenotype for CYP3A4/5/7 and P-gp could potentially alter the bio-disponibility of rivaroxaban and apixaban and therefore the risk to develop adverse events or inefficacy would be of particular interest.

Conditions

  • Anticoagulants and Bleeding Disorders

Interventions

DIAGNOSTIC_TEST

CYP3A4/5 and P-gp phenotyping

Phenotyping using a simplified version of the Geneva cocktail

GENETIC

CYP3A4/5 and P-gp genotyping

Selected CYP3A4, CYP3A5, CYP3A7 and ABCB1 single nucleotide polymorphism (SNP) determination

Sponsors & Collaborators

  • University Hospital, Geneva

    lead OTHER

Principal Investigators

  • Jules Desmeules, Pr. · HUG

  • Victoria Rollason · HUG

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-06-28
Primary Completion
2021-01-07
Completion
2021-01-07

Countries

  • Switzerland

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03112525 on ClinicalTrials.gov