Apixaban Dose Reduction in Patients With Elevated Drug Levels

NCT02809469 | Unknown Phase 2

• 1 other identifier: ADREL
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Proportion of patients with persistently elevated levels

  2 weeks after initial blood work

• Proportion of patients who spontaneously develop levels below the median of the observed on-therapy range

  2 weeks after initial blood work

• Proportion of patients who develop low levels after dose reduction

  1 week after dose reduction

Study Arms (1)

Dose reduction

EXPERIMENTAL

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

Drug: apixaban dose reduction

Interventions

apixaban dose reduction DRUG

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).

Also known as: Eliquis dose reduction

Dose reduction

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to visit Hamilton General Hospital;
• Inability or unwillingness to provide written informed consent.
• Stroke or thromboembolic event in the past 6 months.

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• Population Health Research Institute: collaborator

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vinai C. Bhagirath, MD MSc.

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vinai C. Bhagirath, MD MSc.

CONTACT

905 527 1710; bhagiv@mcmaster.ca

John Eikelboom, MBBS MSc.

CONTACT

905 527 4322; eikelbj@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: June 22, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: June 22, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)