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Atrial FibrillationPhase 4NCT02348723

Uninterrupted Dabigatran Etexilate in Comparison to Uninterrupted Warfarin in Pulmonary Vein Ablation (RE-CIRCUIT)

A Phase 4 study testing Warfarin and Dabigatran Etexilate 150mg in people with Atrial Fibrillation, run by Boehringer Ingelheim at 87 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Warfarin and Dabigatran Etexilate 150mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
678 participants
Where
87 sitesin 11 countries
Study dates
28 Apr 2015to 14 Nov 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 25Show fewer
  • 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
  • Recent malignancy or radiation therapy (<=6 months prior to screening) unless, in the opinion of the Investigator, the estimated life expectancy is greater than 36 months
  • Active liver disease as indicated by at least one of the following:
  • -- Prior and persistent alanine aminotransferase or Aspartate transaminase or alkaline phosphatase >3x upper limit of normal and/or -- Known active hepatitis C and/or -- Known active hepatitis B and/or -- Known active hepatitis A
  • Need for continued treatment with systemic ketoconazole, itraconazole, posaconazole, cyclosporine, tacrolimus, dronedarone, rifampicin, phenytoin, carbamazepine, St. John's Wort or any cytotoxic/myelosuppressive therapy.
  • Pre-menopausal (last menstruation <=1 year prior to screening) who:
  • Are pregnant or breast-feeding or plan to become pregnant during study or
  • Are not surgically sterile or
  • Are of child bearing potential and not practising two acceptable method of birth control, or do not plan to continue practising an acceptable method of birth control throughout the trial
  • Patients who have participated in another trial with an investigational drug or device within the past 30 days preceding the screening visit or are participating in another trial (patients participating in an observational study only will not be excluded)
  • Patients not willing or able to comply with the protocol requirements or considered unreliable by the Investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, who have a life expectancy less than the expected duration of the trial due to concomitant disease and/or subjects who are institutionalised due to official or court orders and/or vulnerable subjects who are dependent on the Sponsor or the Investigator or the site, or patients who have any condition which in the opinion of the Investigator, would not allow safe participation in the study (e.g. drug addiction, alcohol abuse).

Trial locations and contacts

87 sites in 11 countries.

87 sites in 11 countries

United States21 sites

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • New York Methodist Hospital

    Brooklyn, New York, 11215

  • University at Buffalo, The State University of New York

    Buffalo, New York, 14203

  • North Texas Heart Center

    Dallas, Texas, 75231

  • Elkhart General Healthcare System

    Elkhart, Indiana, 46514

  • Providence Regional Medical Center

    Everett, Washington, 98201

  • Mission Cardiovascular Research Institute

    Fremont, California, 94538

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • St Luke's Health Baylor College of Medicine Med Center

    Houston, Texas, 77030

  • Arkansas Cardiology, PA

    Little Rock, Arkansas, 72205

  • University of Tennessee Methodist Physicians

    Memphis, Tennessee, 38104

  • Southwest Florida Research, LLC

    Naples, Florida, 34102

  • Tulane University Hospital and Clinic

    New Orleans, Louisiana, 70112

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104-5068

  • University of California

    Sacramento, California, 95817

  • Mercy Medical Group, a service of Dignity Health Medical Foundation

    Sacramento, California, 95819

  • University of Utah Health Sciences Center

    Salt Lake City, Utah, 84132

  • University of California

    San Francisco, California, 94143

  • St. Louis Heart and Vascular, P.C.

    St Louis, Missouri, 63136

  • Staten Island University Hospital

    Staten Island, New York, 10305

  • University of South Florida

    Tampa, Florida, 33606

Other trials in United States

Japan10 sites

  • Anjo-kosei Hospital

    Aichi, Anjo, 446-8602

  • Nagoya City East Medical Center

    Aichi, Nagoya, 464-8547

  • Nagoya University Hospital

    Aichi, Nagoya, 466-8560

  • Japanese Red Cross Nagoya Daini Hospital

    Aichi, Nagoya, 466-8650

  • Hirosaki University Hospital

    Aomori, Hirosaki, 036-8563

  • New Tokyo Heart Clinic

    Chiba, Matsudo, 271-0077

  • Shonan Kamakura General Hospital

    Kanagawa, Kamakura, 247-8533

  • Sakurabashi Watanabe Hospital

    Osaka, Osaka, 530-0001

  • Nippon Medical School Hospital

    Tokyo, Bunkyo-Ku, 113-8603

  • Tokyo Medical University Hachioji Medical Center

    Tokyo, Hachioji, 193-0998

Other trials in Japan

United Kingdom9 sites

  • Royal Bournemouth and Christchurch Hospital

    Bournemouth, BH7 7DW

  • Royal Sussex County Hospital

    Brighton, BN2 5BE

  • Papworth Hospital

    Cambridge, CB23 3RE

  • Golden Jubilee National Hospital, Clydebank

    Clydebank, G81 4DY

  • Castle Hill Hopsital

    Cottingham, HU16 5JQ

  • Leeds General Infirmary

    Leeds, LS1 3EX

  • St Bartholomew's Hospital

    London, EC1A 4NP

  • James Cook University Hospital

    Middlesbrough, TS4 3BW

  • John Radcliffe Hospital

    Oxford, OX3 9DU

Other trials in United Kingdom

France7 sites

  • HOP Nord Michallon

    La Tronche, 38700

  • HOP Timone

    Marseille, 13005

  • CLI Nouvelles Cliniques Nantaises,Cardio,Nantes Cedex 2

    Nantes, 44000

  • HOP Salpêtrière, Cardio, Paris

    Paris, 75013

  • HOP Européen G. Pompidou

    Paris, 75015

  • HOP Haut-Lévêque

    Pessac, 33604

  • HOP CHU Nancy Brabois, Cardiologie

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Germany7 sites

  • Vivantes Netzwerk für Gesundheit GmbH

    Berlin, 10967

  • Universitätsklinikum Köln (AöR)

    Cologne, 50937

  • Universitätsmedizin Göttingen, Georg-August-Universität

    Göttingen, 37075

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitätsklinikum Schleswig-Holstein, Campus Kiel

    Kiel, 24105

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Belgium6 sites

  • Bonheiden - HOSP Imelda

    Bonheiden, 2820

  • Brussels - UNIV UZ Brussel

    Brussels, 1090

  • UNIV UZ Gent

    Ghent, 9000

  • Centre Hospitalier Universitaire de Liège

    Liège, 4000

  • Antwerpen - HOSP ZNA Middelheim - Pneumo

    Middelheim, 2020

  • Brussels - HOSP Europe (Ste-Elisabeth)

    Uccle, 1180

Other trials in Belgium

Canada6 sites

  • Royal Alexandra Hospital

    Edmonton, Alberta, T5H 3V9

  • Kingston General Hospital

    Kingston, Ontario, K7L 2V7

  • Southlake Regional Health Centre

    Newmarket, Ontario, L3Y 2P9

  • IUCPQ (Laval University)

    Québec, G1V 4G5

  • CHUS Fleurimont

    Sherbrooke, Quebec, J1H 5N4

  • Victoria Cardiac Arrhythmia Trials Inc.

    Victoria, British Columbia, V8T 1Z4

Other trials in Canada

Italy6 sites

  • Ospedale Generale Regionale "Miulli"

    Acquaviva Delle Fonti (BA), 70021

  • A.S.O.S. Croce e Carle

    Cuneo, 12100

  • Osp.dell'Angelo

    Mestre-Venezia, 30174

  • Fondazione Centro San Raffaele del Monte Tabor

    Milan, 20132

  • Centro Cardiologico Monzino-IRCCS

    Milan, 20138

  • Policlinico Casilino U.O. Cardiologia

    Roma, 00169

Other trials in Italy

Russia6 sites

  • Heart&Vessels Diseases,Cardiol&Cardiovas.SurgeryDep,Kamerovo

    Kemerovo, 650002

  • Instit.of Surgery na Vishnevskiy,Treatm.of comp.arrhythm.dep

    Moscow, 117997

  • North-Westrn Fed.med.res.cntr,Almazov Interven.arrhythmo.dep

    Saint Petersburg, 197341

  • City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg

    Saint Petersburg, 199 106

  • Tyumen Cardiology Center, Dept.of Cardiac Arrhythmia

    Tyumen, 625026

  • Yaroslavl Regional Clin. Hospital, Dept. Endocrinology

    Yaroslavl, 150062

Other trials in Russia

Netherlands5 sites

  • VU Medisch Centrum

    Amsterdam, 1081 HV

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam, 1091AC

  • Catharina Ziekenhuis

    Eindhoven, 5623 EJ

  • Medisch Centrum Leeuwarden

    Leeuwarden, 8934 AD

  • Radboud Universitair Medisch Centrum

    Nijmegen, 6525 GA

Other trials in Netherlands

Spain4 sites

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital La Paz

    Madrid, 28046

  • Hospital Virgen del Rocío

    Seville, 41013

  • Hospital Álvaro Cunqueiro

    Vigo (Pontevedra), 36312

Other trials in Spain

About this study

Official title: Randomized Evaluation of Dabigatran Etexilate Compared to warfarIn in pulmonaRy Vein Ablation: Assessment of an Uninterrupted periproCedUral alntIcoagulation sTrategy (The RE-CIRCUIT Trial)

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.

Being tested
Warfarin, Dabigatran Etexilate 150mg
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • WarfarinDrug

    Patients receiving Warfarin to keep International Normalized Ratio (INR)between 2.0 - 3.0

  • Dabigatran Etexilate 150mgDrug

    Patients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)

Study groups in NCT02348723
Study groupRoleWhat they receive
Dabigatran Etexilate 150mgExperimentalPatients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)
Receives: Drug: Dabigatran Etexilate 150mg
WarfarinActive comparatorPatients receiving Warfarin to keep International Normalized Ratio (INR) between 2.0 - 3.0
Receives: Drug: Warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: during and up to 2 months post-ablation

Secondary outcomes (3)

  1. Incidence of the Composite of Stroke, Systemic Embolism, or Transient Ischemic Attack (TIA)

    Stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of haemorrhage or infarction.

    Systemic embolism was defined as an acute vascular occlusion of the extremities or any organ (kidneys, mesenteric arteries, spleen, retina or grafts) and was to be documented by angiography, surgery, scintigraphy or autopsy.

    Transient ischemic attack was defined as a transient episode of focal neurological dysfunction caused by brain, spinal cord, or retinal ischemia, without acute infarction.

    These are based on adjudicated data (blinded evaluation).

    Percentage of patients with composite of stroke, systemic embolism, or transient ischemic attack (TIA) is presented

    Measured: during and up to 2 months post-ablation

  2. Incidence of Minor Bleeding Events

    Minor bleeds were clinical bleeds that did not fulfil the criteria for major bleeds. Percentage of patients with Minor bleeding events are presented.

    These are based on adjudicated data (blinded evaluation)

    Measured: during and up to 2 months post-ablation

  3. Incidence of ISTH MBE, Stroke, Systemic Embolism, or TIA (Composite Endpoint Combining Safety and Efficacy

    Percentage of patients with ISTH MBE, stroke, systemic embolism, or TIA (composite endpoint combining safety and efficacy) are presented.

    These are based on adjudicated data (blinded evaluation)

    Measured: during and up to 2 months post-ablation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2015 (estimated)
  2. Study start28 Apr 2015
  3. Primary completion11 Nov 2016
  4. Study completion14 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
678 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02348723
Sponsor's protocol ID
1160.204
Other IDs
2014-003890-40, 2014
Status last verified
Jan 2018
First submitted
27 Jan 2015
Last updated
29 Jan 2018

Publications

  • 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.

    PubMed 33509678

  • Hohnloser 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.

    PubMed 30758702

  • Calkins 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.

    PubMed 28317415

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Warfarin and Dabigatran Etexilate 150mg in people with Atrial Fibrillation, run by Boehringer Ingelheim at 87 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 87 sites in United States, Japan, United Kingdom, France, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Major Bleeding Events (MBEs), as Defined by the International Society on Thrombosis and Haemostasis (ISTH) (time frame: during and up to 2 months post-ablation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02348723, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2018.

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