An observational study in Anticoagulants and Bleeding Disorders, sponsored by University Hospital, Geneva. Completed at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-30.
Sponsored by University Hospital, Geneva · Observational
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.
503 studies on the registry are indexed under Hemostatic Disorders; 71 are open to participants now.
This study's enrollment of 300 is above the median of 100 across 229 observational studies indexed under Hemostatic Disorders.
Browse Hemostatic Disorders studies →University Hospital, Geneva is the lead sponsor of 372 studies on the registry; 68 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with atrial fibrillation, pulmonary embolism or deep-vein thrombosis, treated or on long-term prophylaxis with rivaroxaban or apixaban in a real-life clinical setting. All patients will be recruited at the Geneva University Hospitals
Exclusion Criteria:
Diagnostic Test: CYP3A4/5 and P-gp phenotyping · Genetic: CYP3A4/5 and P-gp genotyping
Diagnostic Test: CYP3A4/5 and P-gp phenotyping · Genetic: CYP3A4/5 and P-gp genotyping
Phenotyping using a simplified version of the Geneva cocktail
Selected CYP3A4, CYP3A5, CYP3A7 and ABCB1 single nucleotide polymorphism (SNP) determination
Comparison Apixaban Area Under the Curve (AUC) according to patient CYP3A phenotype
Time frame: 6 weeks
Comparison Rivaroxaban AUC according to patient P-gp phenotype
Time frame: 6 weeks
Comparison Apixaban AUC according to patient CYP3A genotype
Time frame: 6 weeks
Comparison Rivaroxaban AUC according to patient P-gp genotype
Time frame: 6 weeks
Comparison Apixaban AUC according to patient hepatic function
Time frame: 6 weeks
Comparison Rivaroxaban AUC according to patient hepatic function
Time frame: 6 weeks
Comparison Apixaban AUC according to patient renal function
Time frame: 6 weeks
Comparison Rivaroxaban AUC according to patient renal function
Time frame: 6 weeks
Comparison adverse event (bleeding) occurrence according to patient CYP3A phenotype
Time frame: 6 weeks
Comparison adverse event (bleeding) occurrence according to patient P-gp phenotype
Time frame: 6 weeks
Comparison bleeding management outcomes
Recording of all interventions, procedures and outcomes related to any reported bleeding
Time frame: 6 weeks
Plan to share: No
No publications or documents are linked to this record.
This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University Hospital, Geneva