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

NCT04874428 | Recruiting Phase 1

• 1 other identifier: UVCMHEP001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Liver Cirrhosis

Keywords

Rivaroxaban; Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Pharmacokinetics; Pharmacodynamics; Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Liver Cirrhosis; Liver Diseases

Outcome Measures

Primary Outcomes (10)

• Area under the plasma concentration-time curve (AUC) of rivaroxaban

  Up to 12 hours

• Maximum plasma concentration (Cmax) of rivaroxaban

  Up to 12 hours

• Time to maximum plasma concentration (tmax) of rivaroxaban

  Up to 12 hours

• Terminal half-life (t1/2) of rivaroxaban

  Up to 12 hours

• Trough plasma concentration (Cmin) at 24 hours post application of rivaroxaban (imputed)

  The Cmin value at 24 hours post application is defined to be the same value measured 0.5 hours pre-dose.

  0.5 hours pre-dose

• AUC of apixaban

  Up to 12 hours

• Cmax of apixaban

  Up to 12 hours

• tmax of apixaban

  Up to 12 hours

• t1/2 of apixaban

  Up to 12 hours

• Cmin at 24 hours post application of apixaban (imputed)

  The Cmin value at 24 hours post application is defined to be the same value measured 0.5 hours pre-dose.

  0.5 hours pre-dose

Secondary Outcomes (12)

• Cmax of prothrombin fragment (F1+2) after administration of rivaroxaban

  Up to 12 hours

• tmax of F1+2 after administration of rivaroxaban

  Up to 12 hours

• Cmax of thrombin-antithrombin-complexes (TAT) after administration of rivaroxaban

  Up to 12 hours

• tmax of TAT after administration of rivaroxaban

  Up to 12 hours

• Cmax of D-dimers (DD) after administration of rivaroxaban

  Up to 12 hours

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

Pharmacokinetics and pharmacodynamics of rivaroxaban

Drug: Rivaroxaban 10 mg Oral Tablet

Apixaban

EXPERIMENTAL

Pharmacokinetics and pharmacodynamics of apixaban

Drug: Apixaban 2.5 mg Oral Tablet

Interventions

Rivaroxaban 10 mg Oral Tablet DRUG

Administration of one single dose of rivaroxaban (10 mg) in tablet form.

Also known as: Xarelto

Rivaroxaban

Apixaban 2.5 mg Oral Tablet DRUG

Administration of one single dose of apixaban (2.5 mg) in tablet form.

Also known as: Eliquis

Apixaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Positive pregnancy test (only for women in childbearing age with intact uterus), pregnancy or nursing women
• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

Department of Visceral Surgery and Medicine, University Hospital Inselspital, Berne

Bern, 3010, Switzerland

RECRUITING

Related Publications (7)

• Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014 May 17;383(9930):1749-61. doi: 10.1016/S0140-6736(14)60121-5. Epub 2014 Jan 28.

  PMID: 24480518 BACKGROUND

• Zermatten MG, Fraga M, Moradpour D, Bertaggia Calderara D, Aliotta A, Stirnimann G, De Gottardi A, Alberio L. Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis. Hepatology. 2020 Jun;71(6):2135-2148. doi: 10.1002/hep.31201.

  PMID: 32090357 BACKGROUND

• Weinberg EM, Palecki J, Reddy KR. Direct-Acting Oral Anticoagulants (DOACs) in Cirrhosis and Cirrhosis-Associated Portal Vein Thrombosis. Semin Liver Dis. 2019 May;39(2):195-208. doi: 10.1055/s-0039-1679934. Epub 2019 Apr 12.

  PMID: 30978730 BACKGROUND

• Elhosseiny S, Al Moussawi H, Chalhoub JM, Lafferty J, Deeb L. Direct Oral Anticoagulants in Cirrhotic Patients: Current Evidence and Clinical Observations. Can J Gastroenterol Hepatol. 2019 Jan 8;2019:4383269. doi: 10.1155/2019/4383269. eCollection 2019.

  PMID: 30792971 BACKGROUND

• Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, Tata C, Zecchini R, Gitto S, Petta S, Lei B, Bernabucci V, Vukotic R, De Maria N, Schepis F, Karampatou A, Caporali C, Simoni L, Del Buono M, Zambotto B, Turola E, Fornaciari G, Schianchi S, Ferrari A, Valla D. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012 Nov;143(5):1253-1260.e4. doi: 10.1053/j.gastro.2012.07.018. Epub 2012 Jul 20.

  PMID: 22819864 BACKGROUND

• Turco L, de Raucourt E, Valla DC, Villa E. Anticoagulation in the cirrhotic patient. JHEP Rep. 2019 Jul 16;1(3):227-239. doi: 10.1016/j.jhepr.2019.02.006. eCollection 2019 Sep.

  PMID: 32039373 BACKGROUND

• De Gottardi A, Trebicka J, Klinger C, Plessier A, Seijo S, Terziroli B, Magenta L, Semela D, Buscarini E, Langlet P, Gortzen J, Puente A, Mullhaupt B, Navascues C, Nery F, Deltenre P, Turon F, Engelmann C, Arya R, Caca K, Peck-Radosavljevic M, Leebeek FWG, Valla D, Garcia-Pagan JC; VALDIG Investigators. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int. 2017 May;37(5):694-699. doi: 10.1111/liv.13285. Epub 2016 Nov 19.

  PMID: 27778440 BACKGROUND

Related Links

• Compendium Xarelto
• Compendium Eliquis

MeSH Terms

Conditions

Liver Cirrhosis; Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Liver Diseases

Interventions

Rivaroxaban; Tablets; apixaban

Condition Hierarchy (Ancestors)

Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Dr. med. Guido Stirnimann

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. med. Guido Stirnimann

CONTACT

+41 31 632 47 13; guido.stirnimann@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 5, 2021
• Study Start: May 19, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)