A Phase 1 interventional study of Rivaroxaban 10 mg Oral Tablet and Apixaban 2.5 mg Oral Tablet in Liver Cirrhosis, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Insel Gruppe AG, University Hospital Bern · Phase 1, Interventional, and Basic science
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.
Background:
Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide but fourth in central Europe. Patients with liver cirrhosis frequently require anticoagulation and the main indication for anticoagulation in cirrhotic patients is portal vein thrombosis.
The most studied and used anticoagulants for patients with liver cirrhosis so far have been low molecular weight heparins (LMWH) and warfarin (vitamin K antagonist, VKA). LMWH are safe and effective in cirrhotic patients, reduce the risk of portal vein thrombosis and liver decompensation and improve liver function and Child-Pugh score as well as overall survival. On the other side, VKA treatment is challenging in patients with liver disease as warfarin has high plasma protein binding (\~99%) and is predominantly eliminated by the liver through a cytochrome P450-dependent metabolism, and INR at baseline is often elevated. Thus, the dose of warfarin and the target International Normalized Ratio (INR) are not well defined in this population. Both of them, LMWH and VKA, have some important drawbacks. On one hand, the LMWH require a daily subcutaneous injection. On the other hand, the orally ingested VKA need monitoring of the INR value. The measurement of the INR value in patients with liver cirrhosis is inadequate to guide anticoagulation as the INR value is altered in association with liver cirrhosis.
Because of the enumerated reasons above, it might be desirable to use direct oral anticoagulants (DOAC) in patients with liver cirrhosis. DOAC do not need routine INR monitoring and can be taken orally at a fixed dose and hence do not need injection. Furthermore, DOAC have a quicker onset of action than Warfarin and show a lower risk of bleeding.
The DOAC rivaroxaban and apixaban are approved for the prevention of venous thromboembolic events in patients who have undergone elective hip or knee replacement surgery, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and to prevent recurrent DVT and PE. Furthermore, they are approved for the prevention of stroke and systemic embolism in case of non-valvular atrial fibrillation. It is important to note that DOAC are already used off label in cirrhotic patients with Child Pugh class A and B. DOAC are not recommended for cirrhotic patients with Child Pugh class C.
However, the scientific evidence for the use of DOAC in cirrhotic patients is scarce as most randomized trials studying DOAC have excluded patients with remarkable liver disease and cirrhosis. Therefore, only limited data exists about the efficacy and safety of DOAC in this specific population. Nevertheless, some studies about the use of DOAC in cirrhotic patients yet exist. As it stands now, studies say it is reasonable to consider DOAC as an alternative in patients with compensated liver cirrhosis. According to them, DOAC appear to be as safe and efficacious as traditional anticoagulants in patients with compensated cirrhosis, provided that liver function is within Child-Pugh stages A or B. However, randomized trials are necessary to investigate the safety and efficacy of DOAC in more detail, especially to establish future guidelines of their use in cirrhosis.
The concerns about the use of DOAC in cirrhotic patients arise due to multiple reasons. One important point is that patients with liver cirrhosis show haemostatic alterations, which affect pro- and anticoagulant state. Affected from the haemostatic alterations are primary haemostasis, coagulation and fibrinolysis. The primary haemostasis undergoes both, prothrombotic (increased von Willebrand factor) and prohaemorrhagic (thrombocytopenia and in vitro thrombocytopathy) changes and possibly results in a rebalanced primary haemostasis. The coagulation shifts to a rather procoagulant state. The reduced activity of coagulation factors is counterbalanced by an increase in factor VIII, decrease of natural anticoagulants, complex changes in circulating microparticles, cell-free DNA and neutrophil extracellular traps. Concerning fibrinolysis, it is not yet clear whether the changes shift fibrinolysis or not. In summary, the changes overall result in a rather prothrombotic state. Another reason for concerns is, that DOAC are metabolized via the liver to various degrees. The two drugs that will be investigated in this trial, rivaroxaban and apixaban, are partially metabolized via cytochrome P450. Considering this, pharmacokinetics and pharmacodynamics of these DOAC can change according to the stage of liver cirrhosis. This could possibly lead to a shift in the risk/benefit ratio of DOAC for cirrhotic patients.
Until now, there exists no randomized trial comparing the safety and efficacy of DOAC versus traditional anticoagulants. Furthermore, as can be seen above, cirrhotic patients were excluded from most randomized trials investigating DOAC. This phase 1 clinical trial offers the opportunity to investigate pharmacokinetics and pharmacodynamics of DOAC in cirrhotic patients. The results of this trial might help to design larger trials in this specific patient population with the final goal of safe and efficient use of rivaroxaban and apixaban in patients with compensated liver cirrhosis.
1,298 studies on the registry are indexed under Liver Cirrhosis; 338 are open to participants now.
This study's planned enrollment of 24 is below the median of 78 across 739 interventional studies indexed under Liver Cirrhosis.
Browse Liver Cirrhosis studies →Insel Gruppe AG, University Hospital Bern is the lead sponsor of 741 studies on the registry; 180 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Pharmacokinetics and pharmacodynamics of rivaroxaban
Drug: Rivaroxaban 10 mg Oral Tablet
Pharmacokinetics and pharmacodynamics of apixaban
Drug: Apixaban 2.5 mg Oral Tablet
Administration of one single dose of rivaroxaban (10 mg) in tablet form.
Also known as: Xarelto
Administration of one single dose of apixaban (2.5 mg) in tablet form.
Also known as: Eliquis
Area under the plasma concentration-time curve (AUC) of rivaroxaban
Time frame: Up to 12 hours
Maximum plasma concentration (Cmax) of rivaroxaban
Time frame: Up to 12 hours
Time to maximum plasma concentration (tmax) of rivaroxaban
Time frame: Up to 12 hours
Terminal half-life (t1/2) of rivaroxaban
Time frame: 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.
Time frame: 0.5 hours pre-dose
AUC of apixaban
Time frame: Up to 12 hours
Cmax of apixaban
Time frame: Up to 12 hours
tmax of apixaban
Time frame: Up to 12 hours
t1/2 of apixaban
Time frame: 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.
Time frame: 0.5 hours pre-dose
Cmax of prothrombin fragment (F1+2) after administration of rivaroxaban
Time frame: Up to 12 hours
tmax of F1+2 after administration of rivaroxaban
Time frame: Up to 12 hours
Cmax of thrombin-antithrombin-complexes (TAT) after administration of rivaroxaban
Time frame: Up to 12 hours
tmax of TAT after administration of rivaroxaban
Time frame: Up to 12 hours
Cmax of D-dimers (DD) after administration of rivaroxaban
Time frame: Up to 12 hours
tmax of DD after administration of rivaroxaban
Time frame: Up to 12 hours
Cmax of F1+2 after administration of apixaban
Time frame: Up to 12 hours
tmax of F1+2 after administration of apixaban
Time frame: Up to 12 hours
Cmax of TAT after administration of apixaban
Time frame: Up to 12 hours
tmax of TAT after administration of apixaban
Time frame: Up to 12 hours
Cmax of DD after administration of apixaban
Time frame: Up to 12 hours
tmax of DD after administration of apixaban
Time frame: Up to 12 hours
Plan to share: No
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Studies of the drugs tested here: Rivaroxaban · Apixaban
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