Apixaban Dose Reduction in Patients With Elevated Drug Levels

Atrial Fibrillation Clinical Trial

— ADREL  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02809469
• Other study ID #: ADREL
• Status: Not yet recruiting
• Phase: Phase 2
• First received: June 20, 2016
• Last updated: June 21, 2016
• Start date: August 2016
• Est. completion date: August 2018

Study information

• Verified date: June 2016
• Source: Hamilton Health Sciences Corporation
• Contact: Vinai C. Bhagirath, MD MSc.
• Phone: 905 527 1710
• Email: bhagiv[@]mcmaster.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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).

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	Population Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes