Apixaban in Hemodialysis

• ClinicalTrials.gov Identifier: NCT02672709
• Recruitment Status: Completed
• First Posted: February 3, 2016
• Last Update Posted: August 30, 2016
• Sponsor: Jewish General Hospital
• Information provided by (Responsible Party): Mark L. Lipman, Jewish General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
End-stage Renal Disease	Drug: apixaban	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Pharmacokinetics and Pharmacodynamics of Apixaban in End-stage Renal Disease Patients on Hemodialysis
• Study Start Date: April 2016
• Actual Primary Completion Date: August 2016
• Actual Study Completion Date: August 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Anticoagulation; Apixaban will be prescribed at the dose of 2.5 mg twice per day for nine days.	Drug: apixaban

Outcome Measures

Primary Outcome Measures :

1. Apixaban concentration [ Time Frame: Day 8 ]
   Examine whether apixaban accumulates after an 8-day administration

Secondary Outcome Measures :

1. Apixaban concentration before, during, and after hemodialysis [ Time Frame: 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
2. Number of participants with treatment related adverse effects [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Canada

Jewish General Hospital

Montreal, Canada

Sponsors and Collaborators

Jewish General Hospital

More Information

Publications:

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. Erratum In: Can J Cardiol. 2014 Dec;30(12):1495. Can J Cardiol. 2015 Oct;31(10):1302.

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.

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.

• Responsible Party: Mark L. Lipman, Associate Professor of Medicine, Jewish General Hospital
• ClinicalTrials.gov Identifier: NCT02672709
• Other Study ID Numbers: #15-128
• First Posted: February 3, 2016
• Last Update Posted: August 30, 2016
• Last Verified: August 2016

Keywords provided by Mark L. Lipman, Jewish General Hospital:

Factor Xa Inhibitors; Renal Dialysis

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants