Apixaban Dose Reduction in Patients With Elevated Drug Levels (ADREL)

Optimal Dosing of Apixaban in Patients at Risk of Elevated Drug Levels: A Study Evaluating a Strategy of Apixaban Drug Level Measurement and Dose Reduction in Patients With Atrial Fibrillation Who Are at Risk of Elevated Drug Levels

Apixaban is an anticoagulant which is increasingly being used to prevent stroke in atrial fibrillation (AF). Phase III clinical trials have demonstrated that apixaban is efficacious and safe for the overall AF population; however, patients older than age 85, with creatinine clearance <40mL/min, or who weighed <50kg were poorly represented in these trials, yet they are commonly seen in real-world clinical scenarios. Advanced age, poor renal function, and low body weight are all associated with elevated drug levels, and elevated drug levels are associated with an increased risk of bleeding. Therefore, clinicians are concerned about the risk of bleeding and are unsure of how best to treat this patient population. Although other anticoagulants are available, apixaban is attractive because it has a low rate of bleeding, low dependence on the kidneys for clearance, and does not require frequent ongoing monitoring and dose adjustment. This study will include patients taking apixaban who were not well-represented in phase III trials - those with age >85, creatinine clearance <40mL/min, or weight <50kg - who are also at increased risk of having elevated drug levels due to these clinical characteristics. Participants will have apixaban levels measured, and those with persistently elevated levels will have their dose reduced. Drug levels will be measured again after dose reduction to determine if the levels are reduced without becoming dangerously low.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: apixaban dose reduction

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with non-valvular atrial fibrillation (permanent, paroxysmal, or persistent) receiving apixaban with any of the following characteristics: age>85; creatinine clearance <40mL/min; or body weight <50kg.

Exclusion Criteria:

• Inability to visit Hamilton General Hospital;
• Inability or unwillingness to provide written informed consent.
• Stroke or thromboembolic event in the past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose reduction; Eligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction.	Drug: apixaban dose reduction; Participants taking apixaban 5mg BID will have their dose reduced to 2.5mg BID, and those taking 2.5mg BID will have their dose reduced to 2.5mg once daily (in the morning).; Other Names: Eliquis dose reduction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who achieve target range	Patients who undergo dose reduction will have their apixaban drug level measured one week later. The proportion who develop levels between 50-170ng/mL after dose reduction will be determined.	1 week after dose reduction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with persistently elevated levels	Patients meeting inclusion criteria will have apixaban drug levels measured. Those with levels above 170ng/mL will have levels repeated 2 weeks later. The proportion of eligible patients with levels above 170ng/mL on both occasions will be determined.	2 weeks after initial blood work
Proportion of patients who spontaneously develop levels below the median of the observed on-therapy range	Patients meeting inclusion criteria will have apixaban drug levels measured. Those with levels above 170ng/mL will have levels repeated 2 weeks later. The proportion of patients with levels above 170ng/mL on the first measurement who spontaneously develop levels below 122ng/mL on the second measurement will be determined.	2 weeks after initial blood work
Proportion of patients who develop low levels after dose reduction	Patients who undergo dose reduction will have apixaban drug levels measured 7-10 days after dose reduction. The proportion of patients with drug levels below 50ng/mL after dose reduction will be determined.	1 week after dose reduction

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Population Health Research Institute
• Investigators: Principal Investigator: Vinai C. Bhagirath, MD MSc., McMaster University

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ANTICIPATED): August 1, 2018
• Study Completion (ANTICIPATED): August 1, 2018

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 21, 2016
• First Posted (ESTIMATE): June 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): June 22, 2016
• Last Update Submitted That Met QC Criteria: June 21, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: ADREL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO