Apixaban in Hemodialysis

End-stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02672709
• Other study ID #: #15-128
• Status: Completed
• Phase: Phase 4
• First received: January 12, 2016
• Last updated: August 29, 2016
• Start date: April 2016
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 79 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• End-stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Drug:
• apixaban

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal

Sponsors (1)

Lead Sponsor	Collaborator
Jewish General Hospital

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View 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. Erratum in: Can J Cardiol. 2014 Dec;30(12):1495. Can J Cardiol. 2015 Oct;31(10):1302. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apixaban concentration	Examine whether apixaban accumulates after an 8-day administration	Day 8	No
Secondary	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	No
Secondary	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	Yes