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

Atrial Fibrillation Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02348723
• Other study ID #: 1160.204
• Secondary ID: 2014-003890-40
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2015
• Last updated: January 4, 2018
• Start date: April 28, 2015
• Est. completion date: November 14, 2016

Study information

• Verified date: January 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 678
• Est. completion date: November 14, 2016
• Est. primary completion date: November 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Warfarin
Patients receiving Warfarin to keep International Normalized Ratio (INR)between 2.0 - 3.0
• Dabigatran Etexilate 150mg
Patients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)

Locations

Country	Name	City	State
Belgium	Bonheiden - HOSP Imelda	Bonheiden
Belgium	Brussels - UNIV UZ Brussel	Brussel
Belgium	UNIV UZ Gent	Gent
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Antwerpen - HOSP ZNA Middelheim - Pneumo	Middelheim
Belgium	Brussels - HOSP Europe (Ste-Elisabeth)	Ukkel
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	IUCPQ (Laval University)	Quebec
Canada	CHUS Fleurimont	Sherbrooke	Quebec
Canada	Victoria Cardiac Arrhythmia Trials Inc.	Victoria	British Columbia
France	HOP Nord Michallon	La Tronche
France	HOP Timone	Marseille
France	CLI Nouvelles Cliniques Nantaises,Cardio,Nantes Cedex 2	Nantes
France	HOP Européen G. Pompidou	Paris
France	HOP Salpêtrière, Cardio, Paris	Paris cedex 13
France	HOP Haut-Lévêque	Pessac
France	HOP CHU Nancy Brabois, Cardiologie	Vandoeuvre les Nancy
Germany	Vivantes Netzwerk für Gesundheit GmbH	Berlin
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Universitätsklinikum Köln (AöR)	Köln
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Ulm	Ulm
Italy	Ospedale Generale Regionale "Miulli"	Acquaviva Delle Fonti (BA)
Italy	A.S.O.S. Croce e Carle	Cuneo
Italy	Osp.dell'Angelo	Mestre-Venezia
Italy	Centro Cardiologico Monzino-IRCCS	Milano
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milano
Italy	Policlinico Casilino U.O. Cardiologia	Roma
Japan	Anjo-kosei Hospital	Aichi, Anjo
Japan	Japanese Red Cross Nagoya Daini Hospital	Aichi, Nagoya
Japan	Nagoya City East Medical Center	Aichi, Nagoya
Japan	Nagoya University 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
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Russian Federation	Heart&Vessels Diseases,Cardiol&Cardiovas.SurgeryDep,Kamerovo	Kemerovo
Russian Federation	Instit.of Surgery na Vishnevskiy,Treatm.of comp.arrhythm.dep	Moscow
Russian Federation	City Pokrovskiy Hospital, Cardiology Dept., Saint Petersburg	Saint Petersburg
Russian Federation	North-Westrn Fed.med.res.cntr,Almazov Interven.arrhythmo.dep	St. Petersburg
Russian Federation	Tyumen Cardiology Center, Dept.of Cardiac Arrhythmia	Tyumen
Russian Federation	Yaroslavl Regional Clin. Hospital, Dept. Endocrinology	Yaroslavl
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital La Paz	Madrid
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Álvaro Cunqueiro	Vigo (Pontevedra)
United Kingdom	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 States	Johns Hopkins Hospital	Baltimore	Maryland
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	North Texas Heart Center	Dallas	Texas
United States	Elkhart General Healthcare System	Elkhart	Indiana
United States	Providence Regional Medical Center	Everett	Washington
United States	Mission Cardiovascular Research Institute	Fremont	California
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	St Luke's Health Baylor College of Medicine Med Center	Houston	Texas
United States	Arkansas Cardiology, PA	Little Rock	Arkansas
United States	University of Tennessee Methodist Physicians	Memphis	Tennessee
United States	Southwest Florida Research, LLC	Naples	Florida
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Mercy Medical Group, a service of Dignity Health Medical Foundation	Sacramento	California
United States	University of California	Sacramento	California
United States	St. Louis Heart and Vascular, P.C.	Saint Louis	Missouri
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	University of California	San Francisco	California
United States	Staten Island University Hospital	Staten Island	New York
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Japan,  Netherlands,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	during and up to 2 months post-ablation
Secondary	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)	during and up to 2 months post-ablation
Secondary	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)	during and up to 2 months post-ablation

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