Uninterrupted Dabigatran Etexilate in Comparison to Uninterrupted Warfarin in Pulmonary Vein Ablation (RE-CIRCUIT)
Randomized Evaluation of Dabigatran Etexilate Compared to warfarIn in pulmonaRy Vein Ablation: Assessment of an Uninterrupted periproCedUral alntIcoagulation sTrategy (The RE-CIRCUIT Trial)
2 other identifiers
interventional
678
11 countries
87
Brief Summary
The primary objective of this trial is to assess the safety of an uninterrupted dabigatran etexilate periprocedural anticoagulant regimen compared to an uninterrupted warfarin regimen in Non-Valvular Atrial Fibrillation (NVAF) patients undergoing Atrial Fibrillation (AF) ablation in a PROBE (Prospective, randomized, open label, blinded end point) active controlled study. Secondary objectives are to assess additional safety endpoints and efficacy in this clinical setting. It is not intended to assess confirmatory hypothesis, this is an exploratory study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 atrial-fibrillation
Started Apr 2015
Shorter than P25 for phase_4 atrial-fibrillation
87 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 27, 2015
CompletedFirst Posted
Study publicly available on registry
January 28, 2015
CompletedStudy Start
First participant enrolled
April 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 14, 2016
CompletedResults Posted
Study results publicly available
November 14, 2017
CompletedJanuary 29, 2018
January 1, 2018
1.5 years
January 27, 2015
October 16, 2017
January 4, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of Major Bleeding Events (MBEs), as Defined by the International Society on Thrombosis and Haemostasis (ISTH)
Major bleeds were defined according to the ISTH definition of a major bleed, as follows * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or * Bleeding associated with a reduction in haemoglobin of at least 2 g/dL (1.24 mmol/L), or leading to transfusion of 2 or more units of blood or packed cells. and/or * Fatal bleed These are based on adjudicated data (blinded evaluation) Point estimates for the incidence of ISTH MBEs and their 2-sided 95% confidence intervals (CI), based on the normal approximation of independent binomial distribution without stratification, are presented.
during and up to 2 months post-ablation
Secondary Outcomes (3)
Incidence of the Composite of Stroke, Systemic Embolism, or Transient Ischemic Attack (TIA)
during and up to 2 months post-ablation
Incidence of Minor Bleeding Events
during and up to 2 months post-ablation
Incidence of ISTH MBE, Stroke, Systemic Embolism, or TIA (Composite Endpoint Combining Safety and Efficacy
during and up to 2 months post-ablation
Study Arms (2)
Dabigatran Etexilate 150mg
EXPERIMENTALPatients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)
Warfarin
ACTIVE COMPARATORPatients receiving Warfarin to keep International Normalized Ratio (INR) between 2.0 - 3.0
Interventions
Patients receiving Warfarin to keep International Normalized Ratio (INR)between 2.0 - 3.0
Patients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)
Eligibility Criteria
You may qualify if:
- Male or female patients aged \>= 18 years.
- Patients eligible for treatment with dabigatran etexilate 150 mg b.i.d. according to local label.
- Treatment naïve patients or patients on oral anticoagulant treatment with a Vitamin K Antagonist (VKA), dabigatran etexilate, rivaroxaban, apixaban or edoxaban.
- Patient with paroxysmal or persistent NVAF with a planned catheter ablation for AF unless it is performed an investigational ablation technique.
- AF must have been documented at least once either by ECG, Holter monitoring, loop recorder, telemetry, trans-telephonic monitoring, pacemaker or cardiac defibrillator read outs within 24 months prior to screening (Visit 1).
- The patient must be able to give informed consent in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations.
You may not qualify if:
- Patients with permanent AF.
- Patients with AF felt to be secondary to an obvious reversible cause such as, but not limited to, an acute myocardial infarction, pulmonary embolism, recent surgery, pericarditis or thyrotoxicosis.
- Patients with Left Atrium (LA) size \>= 60 mm
- Patients with contraindications to systemic anticoagulation with heparin, warfarin or dabigatran etexilate
- Patients with a known allergy to warfarin tablets and it excipients or to dabigatran etexilate or its excipients
- Mechanical or biological heart valve prosthesis
- Severe renal impairment (estimated Creatinine Clearance (CrCl) calculated by Cockcroft-Gault equation) \<30mL/min at screening
- Stroke within 1 month prior to screening visit
- Major surgery per investigator judgement within the previous month prior to screening.
- Patient has received an organ transplant or is on a waiting list for an organ transplant
- History of intracranial haemorrhage, intraocular, spinal, retroperitoneal or non-traumatic intra-articular bleeding
- Gastrointestinal haemorrhage within one month prior to screening, unless, in the opinion of the investigator, the cause has been permanently eliminated (e.g. by surgery).
- Major bleeding episode (ISTH definition) one month prior to the screening visit.
- Haemorrhagic disorder or bleeding diathesis (e.g. von Willebrand disease, haemophilia A or B or other hereditary bleeding disorder, history of spontaneous intra-articular bleeding, history of prolonged bleeding after surgery/intervention)
- Anaemia (haemoglobin \<10g/dL) or thrombocytopenia including heparin-induced thrombocytopenia (platelet count \<100 x 10\^9/L) at screening
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (87)
Arkansas Cardiology, PA
Little Rock, Arkansas, 72205, United States
Mission Cardiovascular Research Institute
Fremont, California, 94538, United States
University of California
Sacramento, California, 95817, United States
Mercy Medical Group, a service of Dignity Health Medical Foundation
Sacramento, California, 95819, United States
University of California
San Francisco, California, 94143, United States
Southwest Florida Research, LLC
Naples, Florida, 34102, United States
University of South Florida
Tampa, Florida, 33606, United States
Elkhart General Healthcare System
Elkhart, Indiana, 46514, United States
Tulane University Hospital and Clinic
New Orleans, Louisiana, 70112, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
St. Louis Heart and Vascular, P.C.
St Louis, Missouri, 63136, United States
New York Methodist Hospital
Brooklyn, New York, 11215, United States
University at Buffalo, The State University of New York
Buffalo, New York, 14203, United States
Staten Island University Hospital
Staten Island, New York, 10305, United States
University of Oklahoma
Oklahoma City, Oklahoma, 73104-5068, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
University of Tennessee Methodist Physicians
Memphis, Tennessee, 38104, United States
North Texas Heart Center
Dallas, Texas, 75231, United States
St Luke's Health Baylor College of Medicine Med Center
Houston, Texas, 77030, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132, United States
Providence Regional Medical Center
Everett, Washington, 98201, United States
Bonheiden - HOSP Imelda
Bonheiden, 2820, Belgium
Brussels - UNIV UZ Brussel
Brussels, 1090, Belgium
UNIV UZ Gent
Ghent, 9000, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
Antwerpen - HOSP ZNA Middelheim - Pneumo
Middelheim, 2020, Belgium
Brussels - HOSP Europe (Ste-Elisabeth)
Uccle, 1180, Belgium
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9, Canada
Victoria Cardiac Arrhythmia Trials Inc.
Victoria, British Columbia, V8T 1Z4, Canada
Kingston General Hospital
Kingston, Ontario, K7L 2V7, Canada
Southlake Regional Health Centre
Newmarket, Ontario, L3Y 2P9, Canada
CHUS Fleurimont
Sherbrooke, Quebec, J1H 5N4, Canada
IUCPQ (Laval University)
Québec, G1V 4G5, Canada
HOP Nord Michallon
La Tronche, 38700, France
HOP Timone
Marseille, 13005, France
CLI Nouvelles Cliniques Nantaises,Cardio,Nantes Cedex 2
Nantes, 44000, France
HOP Salpêtrière, Cardio, Paris
Paris, 75013, France
HOP Européen G. Pompidou
Paris, 75015, France
HOP Haut-Lévêque
Pessac, 33604, France
HOP CHU Nancy Brabois, Cardiologie
Vandœuvre-lès-Nancy, 54511, France
Vivantes Netzwerk für Gesundheit GmbH
Berlin, 10967, Germany
Universitätsklinikum Köln (AöR)
Cologne, 50937, Germany
Universitätsmedizin Göttingen, Georg-August-Universität
Göttingen, 37075, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Kiel, 24105, Germany
Universitätsklinikum Regensburg
Regensburg, 93053, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Ospedale Generale Regionale "Miulli"
Acquaviva Delle Fonti (BA), 70021, Italy
A.S.O.S. Croce e Carle
Cuneo, 12100, Italy
Osp.dell'Angelo
Mestre-Venezia, 30174, Italy
Fondazione Centro San Raffaele del Monte Tabor
Milan, 20132, Italy
Centro Cardiologico Monzino-IRCCS
Milan, 20138, Italy
Policlinico Casilino U.O. Cardiologia
Roma, 00169, Italy
Anjo-kosei Hospital
Aichi, Anjo, 446-8602, Japan
Nagoya City East Medical Center
Aichi, Nagoya, 464-8547, Japan
Nagoya University Hospital
Aichi, Nagoya, 466-8560, Japan
Japanese Red Cross Nagoya Daini Hospital
Aichi, Nagoya, 466-8650, Japan
Hirosaki University Hospital
Aomori, Hirosaki, 036-8563, Japan
New Tokyo Heart Clinic
Chiba, Matsudo, 271-0077, Japan
Shonan Kamakura General Hospital
Kanagawa, Kamakura, 247-8533, Japan
Sakurabashi Watanabe Hospital
Osaka, Osaka, 530-0001, Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-Ku, 113-8603, Japan
Tokyo Medical University Hachioji Medical Center
Tokyo, Hachioji, 193-0998, Japan
VU Medisch Centrum
Amsterdam, 1081 HV, Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, 1091AC, Netherlands
Catharina Ziekenhuis
Eindhoven, 5623 EJ, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, 8934 AD, Netherlands
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA, Netherlands
Heart&Vessels Diseases,Cardiol&Cardiovas.SurgeryDep,Kamerovo
Kemerovo, 650002, Russia
Instit.of Surgery na Vishnevskiy,Treatm.of comp.arrhythm.dep
Moscow, 117997, Russia
North-Westrn Fed.med.res.cntr,Almazov Interven.arrhythmo.dep
Saint Petersburg, 197341, Russia
City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg
Saint Petersburg, 199 106, Russia
Tyumen Cardiology Center, Dept.of Cardiac Arrhythmia
Tyumen, 625026, Russia
Yaroslavl Regional Clin. Hospital, Dept. Endocrinology
Yaroslavl, 150062, Russia
Hospital Clínic de Barcelona
Barcelona, 08036, Spain
Hospital La Paz
Madrid, 28046, Spain
Hospital Virgen del Rocío
Seville, 41013, Spain
Hospital Álvaro Cunqueiro
Vigo (Pontevedra), 36312, Spain
Royal Bournemouth and Christchurch Hospital
Bournemouth, BH7 7DW, United Kingdom
Royal Sussex County Hospital
Brighton, BN2 5BE, United Kingdom
Papworth Hospital
Cambridge, CB23 3RE, United Kingdom
Golden Jubilee National Hospital, Clydebank
Clydebank, G81 4DY, United Kingdom
Castle Hill Hopsital
Cottingham, HU16 5JQ, United Kingdom
Leeds General Infirmary
Leeds, LS1 3EX, United Kingdom
St Bartholomew's Hospital
London, EC1A 4NP, United Kingdom
James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Related Publications (3)
Kimata A, Nogami A, Yamasaki H, Ohigashi T, Gosho M, Igarashi M, Sekiguchi Y, Ieda M, Calkins H, Aonuma K. Optimal interruption time of dabigatran oral administration to ablation (O-A time) in patients with atrial fibrillation: Integrated analysis of 2 randomized controlled clinical trials. J Cardiol. 2021 Jun;77(6):652-659. doi: 10.1016/j.jjcc.2020.12.010. Epub 2021 Jan 25.
PMID: 33509678DERIVEDHohnloser SH, Calkins H, Willems S, Verma A, Schilling R, Okumura K, Nordaby M, Kleine E, Biss B, Gerstenfeld EP; RE-CIRCUIT(R) investigators. Regional differences in patient characteristics and outcomes during uninterrupted anticoagulation with dabigatran versus warfarin in catheter ablation of atrial fibrillation: the RE-CIRCUIT study. J Interv Card Electrophysiol. 2019 Aug;55(2):145-152. doi: 10.1007/s10840-019-00518-x. Epub 2019 Feb 13.
PMID: 30758702DERIVEDCalkins H, Willems S, Gerstenfeld EP, Verma A, Schilling R, Hohnloser SH, Okumura K, Serota H, Nordaby M, Guiver K, Biss B, Brouwer MA, Grimaldi M; RE-CIRCUIT Investigators. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. N Engl J Med. 2017 Apr 27;376(17):1627-1636. doi: 10.1056/NEJMoa1701005. Epub 2017 Mar 19.
PMID: 28317415DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2015
First Posted
January 28, 2015
Study Start
April 28, 2015
Primary Completion
November 11, 2016
Study Completion
November 14, 2016
Last Updated
January 29, 2018
Results First Posted
November 14, 2017
Record last verified: 2018-01