End-stage Renal Disease
Conditions
Keywords
Factor Xa Inhibitors, Renal Dialysis
Brief summary
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.
Interventions
DRUGapixaban
Sponsors
Jewish General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 79 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apixaban concentration | Day 8 | Examine whether apixaban accumulates after an 8-day administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apixaban concentration before, during, and after hemodialysis | Before dialysis, then every hour until the end of dialysis on day 2 and day 9 | Apixaban levels to be measured before dialysis, then every hour until the end of dialysis on day 2 and day 9 |
| Number of participants with treatment related adverse effects | Day 1 to 9 | Short-term treatment related adverse effects: bleeding events, allergic reactions, any other symptom reported by the patient that could be attributed to the drug |
Countries
Canada
Outcome results
None listed