Direct Oral Anticoagulants (Rivaroxaban and Apixaban) in Patients With Liver Cirrhosis

Summary

The aim of this study is to investigate the pharmacokinetic and pharmacodynamic parameters of rivaroxaban and apixaban in patients with compensated liver cirrhosis (Child-Pugh class A and B). The enrolled participants receive a prophylactic single oral dose of either rivaroxaban (10 mg) or apixaban (2.5 mg) at around 8 a.m. on the day of the trial. Blood samples are taken 0.5 hours pre-dose and 1, 2, 3, 4, 6, 8, 12 hours post-dose. A follow-up telephone call is performed 5 days after the study intervention to collect safety data.

Eligibility

Inclusion Criteria:

* Age 18 years or older
* Patient with previously diagnosed liver cirrhosis (Child-Pugh score grade A and B).
* Written informed consent

Exclusion Criteria:

* Positive pregnancy test (only for women in childbearing age with intact uterus), pregnancy or nursing women
* Intake of prophylactic or therapeutic oral anticoagulant (phenprocoumon, acenocoumarol, dabigatran etc.) 2 weeks prior to inclusion in the study
* Application of parenteral anticoagulant, e.g. unfractionated heparin, low molecular weight heparins, heparin derivatives (fondaparinux etc.) 1 week prior to inclusion in the study
* Pharmacologic platelet inhibition within 2 weeks prior to inclusion in the study
* Known coagulation disorders (e.g. von Willebrand's disease, hemophilia)
* Active, clinically significant bleeding
* Congenital or acquired bleeding disorder
* High risk of bleeding (e.g. active ulcerative gastrointestinal disease)
* Uncontrolled severe hypertension
* Vascular retinopathy
* Acute infection
* Acute bacterial endocarditis
* Severe anemia (haemoglobin ≤100 g/L)
* Hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
* Severe liver dysfunction (Child-Pugh Score grade C)
* Hepatic encephalopathy ≥ grade 3
* Severe renal impairment with a creatinine clearance (GFR) of \<30 ml/min
* Known intolerance to the study medications rivaroxaban and/or apixaban
* Concomitant treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, lopinavir, ritonavir, indinavir).
* Concomitant treatment with a P-glycoprotein inhibitor and a weak or moderate CYP3A4 inhibitor (e.g., erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine).
* Concomitant treatment with a P-glycoprotein inducer and a strong CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampicin).
* Wash-out period of less than two weeks prior to the application of study drug in case of prior treatment with a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor and weak or moderate CYP3A4 inhibitor or with a P-glycoprotein inducer or strong CYP3A4 inducer.

Conditions2

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