Uninterrupted Dabigatran Etexilate in Comparison to Uninterrupted Warfarin in Pulmonary Vein Ablation (RE-CIRCUIT)
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: Warfarin; Dabigatran Etexilate 150mg
Intervention description: Patients receiving Warfarin to keep International Normalized Ratio (INR)between 2.0 - 3.0; Patients receiving Dabigatran Etexilate 150mg twice daily dosing (BID)
Intervention MeSH terms: Warfarin; Dabigatran
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 678.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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).