Clinical trial NCT02672709: Apixaban in Hemodialysis
Official title: Pharmacokinetics and Pharmacodynamics of Apixaban in End-stage Renal Disease Patients on Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Disease
Keywords: Factor Xa Inhibitors
Renal Dialysis
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
First posted: 2016-02-03
Enrollment: 7
Sex: ALL
Minimum age (years): 19
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.


Eligibility criteria: 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

Primary outcomes:
measure: Apixaban concentration
timeFrame: Day 8
Secondary outcomes:
measure: Apixaban concentration before, during, and after hemodialysis
timeFrame: Before dialysis, then every hour until the end of dialysis on day 2 and day 9
measure: Number of participants with treatment related adverse effects
timeFrame: Day 1 to 9
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Jewish General Hospital
Study officials:
References:
citation: Verma A, Cairns JA, Mitchell LB, Macle L, Stiell IG, Gladstone D, McMurtry MS, Connolly S, Cox JL, Dorian P, Ivers N, Leblanc K, Nattel S, Healey JS; CCS Atrial Fibrillation Guidelines Committee. 2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation. Can J Cardiol. 2014 Oct;30(10):1114-30. doi: 10.1016/j.cjca.2014.08.001. Epub 2014 Aug 13.
citation: Granger CB, Chertow GM. A pint of sweat will save a gallon of blood: a call for randomized trials of anticoagulation in end-stage renal disease. Circulation. 2014 Mar 18;129(11):1190-2. doi: 10.1161/CIRCULATIONAHA.113.007549. Epub 2014 Jan 22. No abstract available.
citation: Wang X, Tirucherai G, Marbury TC, Wang J, Chang M, Zhang D, Song Y, Pursley J, Boyd RA, Frost C. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol. 2016 May;56(5):628-36. doi: 10.1002/jcph.628. Epub 2015 Dec 22.