Apixaban Dose Reduction in Patients With Elevated Drug Levels (ADREL)
Primary Purpose
Atrial Fibrillation
Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
apixaban dose reduction
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation
Eligibility Criteria
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.
Sites / Locations
- Hamilton General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose reduction
Arm Description
Eligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT02809469
First Posted
June 20, 2016
Last Updated
June 21, 2016
Sponsor
Hamilton Health Sciences Corporation
Collaborators
Population Health Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02809469
Brief Title
Apixaban Dose Reduction in Patients With Elevated Drug Levels
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2016 (undefined)
Primary Completion Date
August 2018 (Anticipated)
Study Completion Date
August 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hamilton Health Sciences Corporation
Collaborators
Population Health Research Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose reduction
Arm Type
Experimental
Arm Description
Eligible patients with apixaban levels persistently above 170ng/mL on two occasions, 2 weeks apart, will undergo apixaban dose reduction.
Intervention Type
Drug
Intervention Name(s)
apixaban dose reduction
Other Intervention Name(s)
Eliquis dose reduction
Intervention Description
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).
Primary Outcome Measure Information:
Title
Proportion of patients who achieve target range
Description
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.
Time Frame
1 week after dose reduction
Secondary Outcome Measure Information:
Title
Proportion of patients with persistently elevated levels
Description
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.
Time Frame
2 weeks after initial blood work
Title
Proportion of patients who spontaneously develop levels below the median of the observed on-therapy range
Description
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.
Time Frame
2 weeks after initial blood work
Title
Proportion of patients who develop low levels after dose reduction
Description
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.
Time Frame
1 week after dose reduction
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vinai C. Bhagirath, MD MSc.
Phone
905 527 1710
Ext
1
Email
bhagiv@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
John Eikelboom, MBBS MSc.
Phone
905 527 4322
Ext
40323
Email
eikelbj@mcmaster.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vinai C. Bhagirath, MD MSc.
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Apixaban Dose Reduction in Patients With Elevated Drug Levels
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