Apixaban in Hemodialysis

Study Overview
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Brief Summary
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This study aims to determine the effects of end-stage renal disease on the pharmacokinetics, pharmacodynamics, safety, and tolerability of apixaban. This is a single-center open-label pharmacological study. Apixaban will be prescribed at the dose of 2.5 mg twice per day for nine days. The concentration of the drug will be measured with repetitive blood tests the first and the eighth day of administration (non-dialysis days). The same blood tests will be repeated before, during, and after dialysis on dialysis days. If the study shows inadequate or suboptimal efficacy with the 2.5 mg dose, it will be repeated with the 5 mg twice-daily dose.

Official Title
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Pharmacokinetics and Pharmacodynamics of Apixaban in End-stage Renal Disease Patients on Hemodialysis

Conditions
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End-stage Renal Disease

Intervention / Treatment
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* Drug: apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age>18 years end-stage renal disease on stable hemodialysis treatment (3 weekly sessions of 4 hours) for at least 6 months no residual kidney function non-valvular atrial fibrillation Exclusion Criteria: age ≥80 years Body mass index (BMI)<21 or BMI>40 active bleeding high bleeding risk (HAS BLED score >3) active malignancy psychiatric disorders decompensated thyroid disorders decompensated heart failure acute myocardial infarction-cerebrovascular accident-head trauma in the last 3 months previous history of venous thromboembolic disease in the last 6 months previous history of coagulopathy already treated by vitamin K antagonists (VKAs) or novel oral anticoagulants uncorrected rhythm or conduction disturbances dual antiplatelet therapy known liver disease or elevated transaminases > 2x upper limit of normal Hemoglobin < 90 g/l platelets < 100,000 /ml known hypersensitivity to apixaban treatment with a potent inhibitor or inducer of the cytochrome P450 3A4 and/or P-glycoprotein absence of effective contraception where applicable drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anticoagulation<br>Apixaban will be prescribed at the dose of 2.5 mg twice per day for nine days. | Drug: apixaban<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apixaban concentration | Examine whether apixaban accumulates after an 8-day administration | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apixaban concentration before, during, and after hemodialysis | Apixaban levels to be measured before dialysis, then every hour until the end of dialysis on day 2 and day 9 | Before dialysis, then every hour until the end of dialysis on day 2 and day 9 | 
| Number of participants with treatment related adverse effects | Short-term treatment related adverse effects: bleeding events, allergic reactions, any other symptom reported by the patient that could be attributed to the drug | Day 1 to 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor Xa Inhibitors, Renal Dialysis