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Rationale and design of VENTURE-AF: a randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation

Abstract

Purpose

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.

Methods/design

This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0–3.0) and stabilized on anticoagulation therapy for 1–7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4–5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range = 300–400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30 ± 5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.

Relevance

This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.

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Fig. 1

Abbreviations

AF:

Atrial fibrillation

CEC:

Clinical Endpoint Committee

CNS:

Central nervous system

CrCl:

Creatinine clearance

DVT:

Deep vein thrombosis

FDA:

Food and Drug Administration

FXa:

Factor Xa

GUSTO:

Global Use of Strategies to Open Occluded Coronary Arteries

INR:

International normalized ratio

ISTH:

International Society on Thrombosis and Haemostasis

ITT:

Intention-to-treat

LMWH:

Low molecular weight heparin

NVAF:

Nonvalvular atrial fibrillation

PE:

Pulmonary embolism

PT:

Prothrombin time

PTT:

Partial thromboplastin time

TEE:

Transesophageal echocardiogram

TIA:

Transient ischemic attack

TIMI:

Thrombolysis in Myocardial Infarction

US:

United States

VKA:

Vitamin K antagonist

VTE:

Venous thromboembolism

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Acknowledgments

Members of the Steering Committee thank participating patients, VENTURE-AF Investigators, and their teams for patient identification, enrollment, care and reporting, past and present members of the VENTURE-AF Core Integrated Team at Johnson & Johnson and Bayer, and Johnson & Johnson and Bayer for sponsorship of this study. Thanks also to C. V. Damaraju, PhD for initial expert statistical support.

Conflict of interest

All authors received research grant support from the sponsors of the trial (Johnson & Johnson and Bayer). Gerald V. Naccarelli, MD, FACC, FHRS is a consultant for Glaxo-Smith-Kline, Pfizer, Xention, Sanofi, Bristol Myers Squibb, Merck, Biosense-Webster, Janssen, Otsuka, Daiichi-Sankyo, and Boehringer Ingelheim. Riccardo Cappato, MD, FESC: Biosense Webster, St Jude Medical, and Bard. StefanH. Hohnloser, MD, FACC, FESC, FHRS: consulting and lecture fees from Boehringer Ingelheim, BMS, Bayer, Pfizer, and Sanofi-aventis. Francis E. Marchlinski, MD, FACC: no further disclosures. David J. Wilber, MD, FAHA, FACC, FHRS: lectures and consulting fees from Biosense Webster, Medtronic, St Jude, Cardioinsight and research support from Biosense Webster, Medtronic. Changsheng Ma, MD, FHRS: no further disclosures. David Wyn Davies MD, FRCP, FHRS: consultant for Boston Scientific, Janssen, Medtronic and Rhythmia. Andrea Natale MD, FACC, FHRS, FESC: Biosense Webster, Boston Scientific, Janssen, St. Jude Medical, Medtronic and Biotronik. Larry E. Fields, MD, FAHA, FACC: is an employee of Johnson & Johnson at Janssen Scientific Affairs, LLC. Jim Xiang, PhD: is an employee of Johnson & Johnson at Janssen Research & Development, LLC. Susanne Hess, MD: is an employee of Bayer.

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Correspondence to Andrea Natale.

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Naccarelli, G.V., Cappato, R., Hohnloser, S.H. et al. Rationale and design of VENTURE-AF: a randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation. J Interv Card Electrophysiol 41, 107–116 (2014). https://doi.org/10.1007/s10840-014-9924-9

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Keywords

  • Atrial fibrillation
  • Catheter ablation
  • Rivaroxaban
  • Vitamin K antagonist