EdoxabaN or Warfarin Therapy In Device Procedures in Patients With Non-Valvular Atrial Fibrillation (ENTICED-AF)

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

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.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Warfarin; Drug: Edoxaban

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Warren, New Jersey, United States, 07059
      • Electrophysiology Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edoxaban; Edoxaban 30 or 60 mg	Drug: Edoxaban; Other Names: Savaysa
Active Comparator: Warfarin; Warfarin 1 -1 0 mg	Drug: Warfarin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Electrophysiology Research Foundation
• Collaborators: Axio Research Corporation
• Investigators: Study Chair: Sanjeev Saksena, MBBS MD, Electrophysiology Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: September 24, 2015
• First Submitted That Met QC Criteria: September 25, 2015
• First Posted (Estimate): September 28, 2015

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban; Warfarin
• Other Study ID Numbers: EPRF2015-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No