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

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Inselspital, Berne
• Collaborator: Centre Hospitalier Universitaire Vaudois
• Treatments: Apixaban; Rivaroxaban

Criteria

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.