Safety and Efficacy of Apixaban in Severe Renal Impairment

NCT03399305 | Withdrawn

• 1 other identifier: 2017-7774
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Disease, End Stage; Anticoagulant-induced Bleeding

Outcome Measures

Primary Outcomes (1)

• 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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henny H Billett, MD

  Albert Einstein College of Medicine and Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Hematology

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 16, 2018
• Study Start: May 10, 2017
• Primary Completion: July 7, 2019
• Study Completion: August 24, 2022
• Last Updated: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)