Safety and Efficacy of Apixaban in Severe Renal Impairment

Anticoagulant-induced Bleeding Clinical Trial

Official title:

Safety and Efficacy of Apixaban in Severe Renal Impairment

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03399305
• Other study ID #: 2017-7774
• Status: Withdrawn
• Start date: May 10, 2017
• Est. completion date: August 24, 2022

Study information

• Verified date: August 2022
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Despite emergence of new anticoagulants over the last few years, patients with advanced chronic kidney disease still have limited options and are usually managed with warfarin after venous thromboembolism or diagnosis of atrial fibrillation. The use of all direct oral anticoagulants is not recommended in patients with creatinine clearance below 15 mL/min. Apixaban has the lowest fraction of renal excretion (27%) and is sometimes used in patients with CKD V (GFR < 15 mL/min/BSA) and end stage renal disease (ESRD). Until recently, data on apixaban use in this population were limited to pharmacodynamics as patients with severe renal impairment were excluded from clinical trials. In a 2016 study, it was found that ESRD resulted in 36% increase in apixaban AUC but no increase in Cmax, and that hemodialysis had a limited impact on apixaban clearance.1 There are now data available on inpatient use of apixaban vs.coumadin in patients with creatinine clearance below 25 ml/min.2 There was no significant difference in bleeding events between the two groups but the study period was limited to a hospital admission and may not reflect bleeding risk of long-term anticoagulation.

Use of warfarin in patients on hemodialysis entails several disadvantages in this population. The need for INR monitoring adds clinic visits for patients that already spend a great portion of their time in healthcare facilities. Numerous drug interactions, involving warfarin, complicate management of ESRD patients that are often on many medications. The reduced risk of intracranial bleeding on apixaban, compared to warfarin, in the ARISTOTLE study, is an important consideration in patients that may already be at increased risk due other factors such as uremia and concurrent antiplatelet agents.

Description:

This is a retrospective cohort study. The investigators will use Clinical Looking Glass (CLG) to identify all adult patients with creatinine clearance < 15 ml/min who were treated with apixaban or warfarin, for at least 1 month, between 3/1/2013 and 3/1/2017. The investigators will then review electronic charts in Carecast and Epic to gather data about bleeding and thrombotic events.Primary outcome: clinically significant bleeding, per Control of Anticoagulation Subcommittee criteria: 1) fatal bleed; 2) symptomatic bleed at anatomically critical sites such as intracranial, intraspinal, intraocular, or pericardial hemorrhage; 3)symptomatic noncritical bleeds resulting in transfusion of 2 units or more of red blood cells or drop in hemoglobin of at least 2.0 g/dl.4 Secondary outcomes: venous thromboembolism, cerebrovascular accident, intracranial hemorrhage, bleeding related to HD access

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 24, 2022
• Est. primary completion date: July 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with creatinine clearance <15 mL/min who are on anticoagulation with apixaban or warfarin.

Exclusion Criteria:

• Patients without end stage renal disease who are not on anticoagulation with apixaban or warfarin.

Related Conditions & MeSH terms

• Anticoagulant-induced Bleeding
• Kidney Failure, Chronic
• Renal Disease, End Stage

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically significant bleeding	1) fatal bleed; 2) symptomatic bleed at anatomically critical sites such as intracranial, intraspinal, intraocular, or pericardial hemorrhage; 3) symptomatic noncritical bleeds resulting in transfusion of 2 units or more of red blood cells or drop in hemoglobin of at least 2.0 g/dl	4 years