Edoxaban Treatment Versus Vitamin K Antagonist (VKA) in Patients With Atrial Fibrillation (AF) Undergoing Catheter Ablation - Full Text View

Purpose

There are insufficient data on the safety and efficacy of edoxaban therapy in subjects with AF following catheter ablation. This phase 3b study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a VKA-based antithrombotic regimen in subjects with AF following catheter ablation. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.

Condition	Intervention	Phase
Atrial Fibrillation	Drug: Edoxaban Drug: VKA-Based Regimen	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Prospective, Randomized, Open-Label, Blinded Endpoint Evaluation (PROBE) Parallel Group Study Comparing Edoxaban vs. VKA in Subjects Undergoing Catheter Ablation of Non-valvular Atrial Fibrillation (ELIMINATE-AF)

Resource links provided by NLM:

Genetics Home Reference related topics: familial atrial fibrillation

MedlinePlus related topics: Atrial Fibrillation

Drug Information available for: Edoxaban

Genetic and Rare Diseases Information Center resources: Familial Atrial Fibrillation

U.S. FDA Resources

Further study details as provided by Daiichi Sankyo Inc. ( Daiichi Sankyo Europe, GmbH ):

Primary Outcome Measures:

Number of participants who experienced composite of all-cause death, stroke and major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH) [ Time Frame: Day 1 to Day 90 ]
To compare descriptively the incidence of the composite of all-cause death, stroke (ischemic, hemorrhagic, or undetermined) and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) in the edoxaban group against the vitamin K antagonist (VKA) group in subjects undergoing catheter ablation of atrial fibrillation (AF)
Number of participants who experienced major bleeding according to the ISTH definition [ Time Frame: Day 1 to Day 90 ]

Secondary Outcome Measures:

Number of participants who experienced composite of all-cause death, stroke and major bleeding according to ISTH and alternate definitions [ Time Frame: Day 1 to Day 90 ]
Number of participants who experienced the composite of stroke, systemic embolic events (SEE), and cardiovascular (CV) mortality [ Time Frame: Day 1 to Day 90 ]
Number of participants who experienced the composite of stroke, SEE, and all-cause mortality [ Time Frame: Day 1 to Day 90 ]
Number of participants who experienced the composite of stroke, and transient ischemic attack (TIA) [ Time Frame: Day 1 to Day 90 ]
Number of participants who experienced stroke [ Time Frame: Day 1 to Day 90 ]


Estimated Enrollment:	560
Study Start Date:	March 2017
Estimated Study Completion Date:	November 2018
Estimated Primary Completion Date:	November 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Edoxaban-based regimen Edoxaban-based regimen for 21 days pre- and 90 days post-ablation period.	Drug: Edoxaban Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects. Other Name: Lixiana
Active Comparator: VKA-based regimen VKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)	Drug: VKA-Based Regimen Dosed at International Normalised Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in Canada, Italy, Poland, Hungary, Czech Republic, UK, Taiwan and Korea. Other Name: Warfarin Drug: VKA-Based Regimen Dosed at INR levels. Standard of Care treatment in Germany, Belgium, and the Netherlands. Other Names: Phenprogamma Phenprocoumon Drug: VKA-Based Regimen Dosed at INR levels. Standard of Care treatment in France. Other Names: Previscan Fluindione Drug: VKA-Based Regimen Dosed at INR levels. Standard of Care treatment in Spain. Other Names: Sintrom Acenocoumarol

Arms

Assigned Interventions

Experimental: Edoxaban-based regimen

Edoxaban-based regimen for 21 days pre- and 90 days post-ablation period.

Drug: Edoxaban

Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects.

Other Name: Lixiana

Active Comparator: VKA-based regimen

VKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)

Drug: VKA-Based Regimen

Dosed at International Normalised Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in Canada, Italy, Poland, Hungary, Czech Republic, UK, Taiwan and Korea.

Other Name: Warfarin

Drug: VKA-Based Regimen

Dosed at INR levels. Standard of Care treatment in Germany, Belgium, and the Netherlands.

Other Names:

Phenprogamma
Phenprocoumon

Drug: VKA-Based Regimen

Dosed at INR levels. Standard of Care treatment in France.

Other Names:

Previscan
Fluindione

Drug: VKA-Based Regimen

Dosed at INR levels. Standard of Care treatment in Spain.

Other Names:

Sintrom
Acenocoumarol

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female at least 18 years of age with documented history of paroxysmal (lasting ≤7 days), persistent (lasting >7 days but ≤12 months) or long-standing [long-lasting] persistent (>12 months) non-valvular AF. Duration of AF can be confirmed by any electrical tracing or a recording in the subject's medical records (e.g., medical chart, hospital discharge summary).
Subject is eligible and is scheduled for either radio frequency (RF) or cryoballoon catheter ablation (both first and repeated procedure included).
Signed informed consent form (ICF).

Exclusion Criteria:

AF considered to be of a transient or reversible nature (such as in myocarditis, post-surgery, ionic disturbances, thyrotoxicosis, pneumonia, severe anemia etc.).
Subject post stroke, or with a systemic thromboembolic event within the past 6 months prior to randomization.
Subject has a thrombus in the left atrial appendage (LAA), left atrium (LA), left ventricle (LV), or aorta, or an intracardial mass.
Subject had a myocardial infarction (MI) within the 2 months prior to randomization or coronary artery bypass graft (CABG) surgery within 3 months prior to the randomization.
Subject has signs of bleeding, history of clinically-relevant bleeding according to ISTH, or conditions associated with high risk of bleeding
Subjects with any contraindication for anticoagulant agents.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02942576

Contacts


Contact: Iris Wittmann	+49 2208 5019 345	Iris.Wittmann@chiltern.com
Contact: Dmytro Kobyshcha	38 067 466 9434	Dmytro.Kobyshcha@chiltern.com

Sponsors and Collaborators

Daiichi Sankyo Europe, GmbH

More Information

Publications:

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016 Nov;18(11):1609-1678. Epub 2016 Aug 27.

Crawford T, Oral H. Current status and outcomes of catheter ablation for atrial fibrillation. Heart Rhythm. 2009 Dec;6(12 Suppl):S12-7. doi: 10.1016/j.hrthm.2009.07.026. Epub 2009 Oct 23. Review.

Hussein AA, Martin DO, Saliba W, Patel D, Karim S, Batal O, Banna M, Williams-Andrews M, Sherman M, Kanj M, Bhargava M, Dresing T, Callahan T, Tchou P, Di Biase L, Beheiry S, Lindsay B, Natale A, Wazni O. Radiofrequency ablation of atrial fibrillation under therapeutic international normalized ratio: a safe and efficacious periprocedural anticoagulation strategy. Heart Rhythm. 2009 Oct;6(10):1425-9. doi: 10.1016/j.hrthm.2009.07.007. Epub 2009 Jul 10.

Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber DJ, Ma CS, Hess S, Wells DS, Juang G, Vijgen J, Hügl BJ, Balasubramaniam R, De Chillou C, Davies DW, Fields LE, Natale A; VENTURE-AF Investigators. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015 Jul 21;36(28):1805-11. doi: 10.1093/eurheartj/ehv177. Epub 2015 May 14.

Chen J, Todd DM, Hocini M, Larsen TB, Bongiorni MG, Blomström-Lundqvist C; Scientific Initiative Committee, European Heart Rhythm Association. Current periprocedural management of ablation for atrial fibrillation in Europe: results of the European Heart Rhythm Association survey. Europace. 2014 Mar;16(3):378-81. doi: 10.1093/europace/euu043.

Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390.

Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, Packer D, Skanes A, Ambrogi F, Biganzoli E. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010 Feb;3(1):32-8. doi: 10.1161/CIRCEP.109.859116. Epub 2009 Dec 7.


Responsible Party:	Daiichi Sankyo Europe, GmbH
ClinicalTrials.gov Identifier:	NCT02942576 History of Changes
Other Study ID Numbers:	DSE-EDO-01-16-EU 2016-002683-14 ( EudraCT Number )
Study First Received:	October 21, 2016
Last Updated:	October 21, 2016
Individual Participant Data
Plan to Share IPD:	Undecided

Additional relevant MeSH terms:


Atrial Fibrillation Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Edoxaban Acenocoumarol Phenprocoumon	Anticoagulants Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017

Edoxaban Treatment Versus Vitamin K Antagonist (VKA) in Patients With Atrial Fibrillation (AF) Undergoing Catheter Ablation (ELIMINATE-AF)