Atrial Fibrillation
Conditions
Brief summary
This is a prospective randomized comparative evaluation of Edoxaban and Warfarin for safety and efficacy in perioperative use in patients with non-valvular atrial fibrillation (AF) undergoing clinically indicated implantation or replacement of cardiovascular implantable electrical devices.The primary objective is to compare the rates of local and systemic bleeding in subjects randomized to Edoxaban compared to subjects randomized to continuous warfarin in within 30 days of cardiac rhythm device implant with concomitant non-valvular AF.
Detailed description
This is a prospective randomized comparative evaluation of Edoxaban and Warfarin for safety and efficacy in perioperative use in patients with non-valvular atrial fibrillation undergoing clinically indicated implantation or replacement of cardiovascular implantable electrical devices. This study is a randomized, open label, active-controlled trial with an open-label safety extension, designed to compare local and systemic bleeding within 30 days of cardiac rhythm device implant among subjects randomized to continuous Warfarin or interrupted (\<24 hours) Edoxaban. The study will have three phases, a run in phase to establish stable warfarin therapy, an acute open label 30 day phase when subjects will be randomized in a 1:1 ratio to receive interrupted edoxaban or continuous warfarin followed by an open label follow up phase for an additional 5 months for safety monitoring. Drug transitions will be performed according to approved drug labeling.
Interventions
DRUGEdoxaban
DRUGWarfarin
Sponsors
Axio Research Corporation
Electrophysiology Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with established atrial fibrillation (AF) and bradycardia on long term (\>3 weeks) therapeutic oral anticoagulant (OAC) with warfarin or another OAC who are undergoing new pacemaker system implant or existing pacemaker system revision. * Subjects with newly detected bradycardia -tachycardia syndrome and AF who have been recently (less than 3 weeks) started on warfarin, have a therapeutic international normalized ratio (INR) and no thrombus on trans-esophageal echocardiogram (TEE) who are undergoing a new pacemaker system implant or revision. * Subjects with AF and ventricular tachyarrhythmias (VT or VF) or acquired structural heart disease who are candidates for implantable cardioverter-defibrillator (ICD) therapy and are on long term (\>3 weeks) therapeutic OAC with warfarin or another OAC who are undergoing new ICD system implant or existing ICD system revision. * Subjects with newly detected AF with VT or VF who have been recently (less than 3 weeks) started on warfarin, have a therapeutic INR and no thrombus on TEE who are undergoing ICD system implant or revision
Exclusion criteria
* Clinically significant valvular heart disease * Subjects requiring cardiovascular implantable electrical device (CIED) lead extraction e.g. for device site infection, endocarditis, leads under advisory or other conditions warranting lead(s) system extraction. * Recent (\<1 month) myocardial infarction * Documented left atrial (LA) thrombus on TEE * Contraindications to anticoagulant therapy or adverse event with prior warfarin or edoxaban therapy * Creatinine clearance \<30ml/min or \>95 ml/min * Hepatic disease, advanced * Recent stroke (\<3 months) or thromboembolic event * Recent (\<3months) intracranial or other major bleeding event * Use of concomitant dual antiplatelet therapy or other oral, subcutaneous or parenteral anticoagulant therapy * Subjects on warfarin without therapeutic INR levels before study entry * Subjects with other clinically significant medical condition * Subjects with life expectancy \< 1 year * Lead extraction procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding | Within 30 days of procedure | Major local or systemic bleeding as defined in the protocol at 30 days after implant procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thromboembolic and Cardiovascular Events | Within 6 months of procedure | Thrombotic events (embolism or stroke) through 6 months following the procedure in the Edoxaban and Warfarin groups and the rates of MACE events through 6 months following the procedure in the Edoxaban and Warfarin groups |
Countries
United States
Participant flow
Recruitment details
Recruitment period 2015-2017 Recruited in hospital and medical clinic
Participants by arm
| Arm | Count |
|---|---|
| Edoxaban Edoxaban 30 or 60 mg
Edoxaban | 2 |
| Warfarin Warfarin 1 -1 0 mg
Warfarin | 3 |
| Total | 5 |
Baseline characteristics
| Characteristic | Warfarin | Total | Edoxaban |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Continuous | 72.0 years STANDARD_DEVIATION 12.5 | 69.4 years STANDARD_DEVIATION 13 | 60.5 years STANDARD_DEVIATION 13.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment United States | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 2 / 3 | 0 / 2 |
Outcome results
Primary
Major Bleeding
Major local or systemic bleeding as defined in the protocol at 30 days after implant procedure
Time frame: Within 30 days of procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Warfarin | Major Bleeding | 1 Participants |
| Edoxaban | Major Bleeding | 0 Participants |
Secondary
Thromboembolic and Cardiovascular Events
Thrombotic events (embolism or stroke) through 6 months following the procedure in the Edoxaban and Warfarin groups and the rates of MACE events through 6 months following the procedure in the Edoxaban and Warfarin groups
Time frame: Within 6 months of procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Warfarin | Thromboembolic and Cardiovascular Events | 0 Participants |
| Edoxaban | Thromboembolic and Cardiovascular Events | 0 Participants |