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Apixaban Dose Reduction in Patients With Elevated Drug Levels

Phase 2
Conditions
Atrial Fibrillation
Interventions
Registration Number
NCT02809469
Lead Sponsor
Hamilton Health Sciences Corporation
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dose reductionapixaban dose reductionEligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction.
Primary Outcome Measures
NameTimeMethod
Proportion of patients who achieve target range1 week after dose reduction

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.

Secondary Outcome Measures
NameTimeMethod
Proportion of patients with persistently elevated levels2 weeks after initial blood work

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.

Proportion of patients who spontaneously develop levels below the median of the observed on-therapy range2 weeks after initial blood work

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.

Proportion of patients who develop low levels after dose reduction1 week 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.

Trial Locations

Locations (1)

Hamilton General Hospital

🇨🇦

Hamilton, Ontario, Canada

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