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

Hamilton Health Sciences (HHS)

Status and phase: Unknown; Phase 2

Conditions: Atrial Fibrillation

Treatments: Drug: apixaban dose reduction

Study type: Interventional

Funder types: Other

Identifiers

NCT02809469

ADREL

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 1 patient group

Dose reduction

Experimental group

Description:

Eligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction.

Treatment:

Drug: apixaban dose reduction