DOAC in Patients with Child a or B Liver Cirrhosis
ConditionLiver Cirrhosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorCentre Hospitalier Universitaire Vaudois
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 years or older
Patient with previously diagnosed liver cirrhosis Child A or B
Written informed consent
Disqualifiers
Pregnancy
Oesophageal varices with grade superior to 1 or with red signs
Active ulcer disease of the gastrointestinal tract
History of haemorrhagic stroke
Trial design
Design model
Parallel
Treatments tested in this trial
Apixaban 5 MG [Eliquis]
DrugPharmacokinetics and pharmacodynamics assessment of apixaban in patients with Child A or B liver cirrhosis
Edoxaban 60 MG [Lixiana]
DrugPharmacokinetics and pharmacodynamics assessment of edoxaban in patients with Child A or B liver cirrhosis
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Cirrhotic patients with Child A or B under apixabanExperimental treatment 1 intervention
Group B: Cirrrhotic patients with Child A or B under edoxabanExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last pill intake.2
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.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last pill intake.3
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).
Time frame
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.4
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).
Time frame
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
1
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.
In vivo markers of coagulation as TAT (in ng/ml) will be measured by a quantitative enzyme immunoassay (ELISA), according to the protocol of the manufactures (Enzygnost® TAT micro Siemens). The absorbance will be measured using a Dynex microplate reader at 450 nm.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.2
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.
In vivo markers of coagulation as TAT (in ng/ml) will be measured by a quantitative enzyme immunoassay (ELISA), according to the protocol of the manufactures (Enzygnost® TAT micro Siemens). The absorbance will be measured using a Dynex microplate reader at 450 nm.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.3
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.
In vivo markers of coagulation as F1+2 (in pmol/l) will be measured by a quantitative enzyme immunoassay (ELISA), according to the protocol of the manufactures (Enzygnost® F1+2 micro Siemens). The absorbance will be measured using a Dynex microplate reader at 492 nm.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.4
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.
In vivo markers of coagulation as F1+2 (in pmol/l) will be measured by a quantitative enzyme immunoassay (ELISA), according to the protocol of the manufactures (Enzygnost® F1+2 micro Siemens). The absorbance will be measured using a Dynex microplate reader at 492 nm.
Time frame
At day 1 and day 3 before DOAC intake and 2 hours after intake. At day 8, 24 hours after last DOAC pill intake.Sponsors and contacts
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Source ClinicalTrials.gov