DOAC in Patients with Child a or B Liver Cirrhosis

NCT05869591 | Recruiting Phase 2

• 1 other identifier: CER-VD 2022-01395
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate pharmacokinetics and pharmacodynamics of direct oral anticoagulant drugs (DOAC), specifically apixaban and edoxaban, in patients with Child A or B liver cirrhosis (LC). The primary objective of this study is to verify the ability of apixaban and edoxaban to decrease in vivo thrombin generation in LC patients. Participants will be randomly assigned to either apixaban (Eliquis®) or edoxaban (Lixiana®) at a therapeutic dosage for 7 consecutive days. The results of this investigation will contribute to designing a prospective multicentre interventional study to investigate the efficacy of DOAC to improve clinical outcomes in patients with LC

Conditions

Liver Cirrhosis

Keywords

Cirrhosis; DOAC; Thrombin generation; Anticoagulation

Outcome Measures

Primary Outcomes (4)

• Changes from thrombin generation parameters before and after apixaban (Eliquis®) intake

  Global thrombin generation assay will be performed using ST Genesia (Stago, Asnière-sur-Seine, France) with Drugscreen reagents (high tissue factor concentration) will be used and all thrombin generation parameters will be retrieved.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last pill intake.

• Changes from thrombin generation parameters before and after edoxaban (Lixiana®) intake

  Global thrombin generation assay will be performed using ST Genesia (Stago, Asnière-sur-Seine, France) with Drugscreen reagents (high tissue factor concentration) will be used and all thrombin generation parameters will be retrieved.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last pill intake.

• Changes from peak and trough levels of apixaban (Eliquis ®)

  Concentration of DOAC will be assessed with specific anti-Xa assays using Sysmex CS5100 coagulation analyser (Siemens Healthcare, Erlangen, Germany) and reagents: Hyphen Biophen® Heparin (Hyphen BioMed, Neuville-sur-Oise, France).

  At day 1, at peak level (2 hours after intake). At day 3, at steady state (before intake) and at peak level (2 hours after intake). A day 8 at residual concentration (24 hours after last pill intake). At day 9, 48 hours after last intake.

• Changes from peak and trough levels of edoxaban (Lixiana ®)

  Concentration of DOAC will be assessed with specific anti-Xa assays using Sysmex CS5100 coagulation analyser (Siemens Healthcare, Erlangen, Germany) and reagents: Hyphen Biophen® Heparin (Hyphen BioMed, Neuville-sur-Oise, France).

  At day 1, at peak level (2 hours after intake). At day 3, at steady state (before intake) and at peak level (2 hours after intake). A day 8 at residual concentration (24 hours after last pill intake). At day 9, 48 hours after last intake.

Secondary Outcomes (7)

• Changes from Thrombin-antithrombin complex (TAT) concentration before and after intake of apixaban (Eliquis®) for one week in patients with Child A or B liver cirrhosis.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.

• Changes from Thrombin-antithrombin complex (TAT) concentration before and after intake of edoxaban (Lixiana ®) for one week in patients with Child A or B liver cirrhosis.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.

• Changes from prothrombin activation fragments 1+2 (F1+2) concentration before and after intake of apixaban (Eliquis®) for one week in patients with Child A or B liver cirrhosis.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.

• Changes from prothrombin activation fragments 1+2 (F1+2) concentration before and after intake of edoxaban (Lixiana®) for one week in patients with Child A or B liver cirrhosis.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.

• Changes from D-dimers concentration before and after intake of apixaban (Eliquis®) for one week in patients with Child A or B liver cirrhosis.

  At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.

Study Arms (2)

Cirrhotic patients with Child A or B under apixaban

EXPERIMENTAL

Twenty non-anticoagulated patients with Child A or B liver cirrhosis will receive a therapeutic dose of apixaban (Eliquis®) for 7 consecutive days. Blood samples will be collected just before and after apixban intake at day 1 and 3. Another blood samples are collected at day 8 and at day 9. In vivo thrombin generation parameters (F1+2, TAT, fibrin monomers, D-dimers), ex vivo thrombin generation parameters \[ST Genesia (Drugscreen)\], as well as peak and trough apixaban levels will be measured.

Drug: Apixaban 5 MG [Eliquis]

Cirrrhotic patients with Child A or B under edoxaban

EXPERIMENTAL

Twenty non-anticoagulated patients with Child A or B liver cirrhosis will receive a therapeutic dose of edoxaban (Lixiana®) for 7 consecutive days. Blood samples will be collected just before and after edoxaban intake at day 1 and 3. Another blood samples are collected at day 8 and at day 9. In vivo thrombin generation parameters (F1+2, TAT, fibrin monomers, D-dimers), ex vivo thrombin generation parameters \[ST Genesia (Drugscreen)\], as well as peak and trough edoxaban levels will be measured.

Drug: Edoxaban 60 MG [Lixiana]

Interventions

Apixaban 5 MG [Eliquis] DRUG

Pharmacokinetics and pharmacodynamics assessment of apixaban in patients with Child A or B liver cirrhosis

Cirrhotic patients with Child A or B under apixaban

Edoxaban 60 MG [Lixiana] DRUG

Pharmacokinetics and pharmacodynamics assessment of edoxaban in patients with Child A or B liver cirrhosis

Cirrrhotic patients with Child A or B under edoxaban

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 A or B
• Written informed consent

You may not qualify if:

• Pregnancy
• Oesophageal varices with grade superior to 1 or with red signs
• Active ulcer disease of the gastrointestinal tract
• History of haemorrhagic stroke
• Severe uncontrolled hypertension
• Recent brain, spinal or ophthalmic surgery
• Kidney function inadequate for DOAC treatment
• Concomitant treatment with anti-platelet drugs
• Concomitant treatment with anticoagulant drugs (VKA, LMWH, DOAC)
• Any contraindications for DOAC administration
• Inability to give informed consent

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis

Interventions

apixaban; edoxaban

Condition Hierarchy (Ancestors)

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

Study Officials

• Lorenzo Alberio, Prof Dr. med

  CHUV

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Alberio, Prof Dr. med

CONTACT

0041213140171; lorenzo.alberio@chuv.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr. méd

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: May 22, 2023
• Study Start: January 18, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)