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

NCT ID: NCT02348723

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 678 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-28
• Study Completion Date: 2016-11-14

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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dabigatran Etexilate 150mg

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

Group Type: EXPERIMENTAL

Dabigatran Etexilate 150mg

Intervention Type: DRUG

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

Warfarin

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

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

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

Interventions

Warfarin

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

Intervention Type: DRUG

Dabigatran Etexilate 150mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Arkansas Cardiology, PA

Little Rock, Arkansas, United States

Mission Cardiovascular Research Institute

Fremont, California, United States

University of California

Sacramento, California, United States

Mercy Medical Group, a service of Dignity Health Medical Foundation

Sacramento, California, United States

University of California

San Francisco, California, United States

Southwest Florida Research, LLC

Naples, Florida, United States

University of South Florida

Tampa, Florida, United States

Elkhart General Healthcare System

Elkhart, Indiana, United States

Tulane University Hospital and Clinic

New Orleans, Louisiana, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

St. Louis Heart and Vascular, P.C.

St Louis, Missouri, United States

New York Methodist Hospital

Brooklyn, New York, United States

University at Buffalo, The State University of New York

Buffalo, New York, United States

Staten Island University Hospital

Staten Island, New York, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Tennessee Methodist Physicians

Memphis, Tennessee, United States

North Texas Heart Center

Dallas, Texas, United States

St Luke's Health Baylor College of Medicine Med Center

Houston, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Providence Regional Medical Center

Everett, Washington, United States

Bonheiden - HOSP Imelda

Bonheiden, , Belgium

Brussels - UNIV UZ Brussel

Brussels, , Belgium

UNIV UZ Gent

Ghent, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Antwerpen - HOSP ZNA Middelheim - Pneumo

Middelheim, , Belgium

Brussels - HOSP Europe (Ste-Elisabeth)

Uccle, , Belgium

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Victoria Cardiac Arrhythmia Trials Inc.

Victoria, British Columbia, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Southlake Regional Health Centre

Newmarket, Ontario, Canada

CHUS Fleurimont

Sherbrooke, Quebec, Canada

IUCPQ (Laval University)

Québec, , Canada

HOP Nord Michallon

La Tronche, , France

HOP Timone

Marseille, , France

CLI Nouvelles Cliniques Nantaises,Cardio,Nantes Cedex 2

Nantes, , France

HOP Salpêtrière, Cardio, Paris

Paris, , France

HOP Européen G. Pompidou

Paris, , France

HOP Haut-Lévêque

Pessac, , France

HOP CHU Nancy Brabois, Cardiologie

Vandœuvre-lès-Nancy, , France

Vivantes Netzwerk für Gesundheit GmbH

Berlin, , Germany

Universitätsklinikum Köln (AöR)

Cologne, , Germany

Universitätsmedizin Göttingen, Georg-August-Universität

Göttingen, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Ospedale Generale Regionale "Miulli"

Acquaviva Delle Fonti (BA), , Italy

A.S.O.S. Croce e Carle

Cuneo, , Italy

Osp.dell'Angelo

Mestre-Venezia, , Italy

Fondazione Centro San Raffaele del Monte Tabor

Milan, , Italy

Centro Cardiologico Monzino-IRCCS

Milan, , Italy

Policlinico Casilino U.O. Cardiologia

Roma, , Italy

Anjo-kosei Hospital

Aichi, Anjo, , Japan

Nagoya City East Medical Center

Aichi, Nagoya, , Japan

Nagoya University Hospital

Aichi, Nagoya, , Japan

Japanese Red Cross Nagoya Daini Hospital

Aichi, Nagoya, , Japan

Hirosaki University Hospital

Aomori, Hirosaki, , Japan

New Tokyo Heart Clinic

Chiba, Matsudo, , Japan

Shonan Kamakura General Hospital

Kanagawa, Kamakura, , Japan

Sakurabashi Watanabe Hospital

Osaka, Osaka, , Japan

Nippon Medical School Hospital

Tokyo, Bunkyo-Ku, , Japan

Tokyo Medical University Hachioji Medical Center

Tokyo, Hachioji, , Japan

VU Medisch Centrum

Amsterdam, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

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

Kemerovo, , Russia

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

Moscow, , Russia

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

Saint Petersburg, , Russia

City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg

Saint Petersburg, , Russia

Tyumen Cardiology Center, Dept.of Cardiac Arrhythmia

Tyumen, , Russia

Yaroslavl Regional Clin. Hospital, Dept. Endocrinology

Yaroslavl, , Russia

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Virgen del Rocío

Seville, , Spain

Hospital Álvaro Cunqueiro

Vigo (Pontevedra), , Spain

Royal Bournemouth and Christchurch Hospital

Bournemouth, , United Kingdom

Royal Sussex County Hospital

Brighton, , United Kingdom

Papworth Hospital

Cambridge, , United Kingdom

Golden Jubilee National Hospital, Clydebank

Clydebank, , United Kingdom

Castle Hill Hopsital

Cottingham, , United Kingdom

Leeds General Infirmary

Leeds, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

James Cook University Hospital

Middlesbrough, , United Kingdom

John Radcliffe Hospital

Oxford, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Italy; Japan; Netherlands; Russia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33509678 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30758702 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28317415 (View on PubMed)

Other Identifiers

2014-003890-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1160.204

Identifier Type: -

Identifier Source: org_study_id