Apixaban Dose Reduction in Patients With Elevated Drug Levels

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: apixaban dose reduction


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose reduction<br>Eligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction. | Drug: apixaban dose reduction<br>* 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).<br>* Other names: Eliquis dose reduction;|

What is the study measuring?
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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 |