EdoxabaN or Warfarin Therapy In Device Procedures in Patients With Non-Valvular Atrial Fibrillation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Edoxaban or Warfarin Therapy In Cardiovascular Implantable Electrical Device Procedures in Patients With Non-valvular Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Edoxaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edoxaban<br>Edoxaban 30 or 60 mg | Drug: Edoxaban<br> <br> * Other names: Savaysa;|
| Active Comparator: Warfarin<br>Warfarin 1 -1 0 mg | Drug: Warfarin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Bleeding | Major local or systemic bleeding as defined in the protocol at 30 days after implant procedure | Within 30 days of procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Within 6 months of procedure |