Clinical trial NCT02809469: Apixaban Dose Reduction in Patients With Elevated Drug Levels
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Atrial Fibrillation
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
First posted: 2016-06-22
Enrollment: 120
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients who achieve target range
timeFrame: 1 week after dose reduction
Secondary outcomes:
measure: Proportion of patients with persistently elevated levels
timeFrame: 2 weeks after initial blood work
measure: Proportion of patients who spontaneously develop levels below the median of the observed on-therapy range
timeFrame: 2 weeks after initial blood work
measure: Proportion of patients who develop low levels after dose reduction
timeFrame: 1 week after dose reduction
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Vinai C. Bhagirath, MD MSc.
role: PRINCIPAL_INVESTIGATOR
References: