Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation (ODIn-AF)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by University Hospital, Bonn
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Georg Nickenig, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT02067182
First received: February 18, 2014
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

Oral anticoagulation treatment (OAC) following clinically successful catheter abla-tion of atrial fibrillation (AF) is controversial. Recent guidelines recommended con-tinuation of OAC in all patients with CHA2DS2VASc score ≥2 even if there is no evidence of recurrent AF (Camm JA et al., Eur Heart J 2012). The net clinical ben-efit of OAC after successful ablation in these patients remains to some extent un-clear. As OAC bears the risk of bleeding events, the ODIn-AF study aims to evalu-ate the positive effect of OAC on the incidence of silent cerebral embolic events in patients with a high risk for embolic events, free from AF after successful pulmo-nary vein ablation. ODIn-AF aims to determine that continued administration of dabigatran is superior in the preven-tion of silent cerebral embolism to discontinuation of OAC after 3 months in pa-tients free from symptomatic AF-episodes with a CHA2DS2VASc score ≥2 after the first pulmonary vein ablation for paroxysmal AF.


Condition Intervention Phase
Atrial Fibrillation
Cardioembolic Events
Oral Anticoagulation
Drug: Dabigatran
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • Incidence of new micro- and macro-embolic lesions on cerebral MRI incl. flare and diffusion weighted imaging 12 months after randomization compared to baseline MRI (3 months after AF catheter ablation) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Location, size and number of new micro- and macro-embolic lesions on cerebral MRI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of clinically evident cardio-embolic events (stroke, TIA, systemic embolism) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Severity of neurological deficits assessed by Modified Rankin Scale [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of other thrombotic or thrombo-embolic events (myocardial in-farction, deep vein thrombosis, pulmonary embolism) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Life-threatening / major / minor bleedings [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Hemorrhagic cerebral infarction [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • All-cause mortality / Cardiovascular mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Correlation of cardio-embolic events to method used for PVI (cryo-balloon versus RF) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Correlation of cardio-embolic events with arrhythmia recurrence (atrial fi-brillation or atrial flutter post ablationem with ECG documentation or symp-toms) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of life questionnaire (AF-specific symptoms, SF36) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Neuropsychological questionnaire (RBANS A&B) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Assessment of neurocognitive deficits: Minimental Test [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Major / minor bleeding events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Clinically evident cardio-embolic events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Serious Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 630
Study Start Date: October 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Anticoagulation with Dabigatran

The recommended daily dose of Pradaxa is 300 mg taken as one 150 mg capsule twice daily.

For the following patients the recommended daily dose of Pradaxa is 220 mg taken as one 110 mg capsule twice daily:

  • Patients aged 75 years or above
  • Cr-Cl 30-50 ml/min
  • Patients who receive concomitant verapamil

For the following groups, the daily dose of Pradaxa of 300 mg or 220 mg should be selected based on an individual assessment of the thromboembolic risk and the risk of bleeding:

  • Patients with moderate renal impairment
  • Patients with gastritis, esophagitis or gastroesophageal reflux
  • Other patients at increased risk of bleeding
Drug: Dabigatran
No Intervention: No Oral Anticoagulation

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Patients scheduled for circumferential antral PV ablation for non-valvular (mitral regurgitation less than moderate- severe; no relevant mitral steno-sis with a mean pressure gradient >5mmHg) symptomatic, paroxysmal AF or persistent AF (duration < 12 months) using a cooled tip RF- or cryobal-loon-catheter
  • CHA2DS2VASc score ≥ 2

Randomization criteria:

  • Sinus rhythm after AF ablation (as assessed by 72h Holter ECG) following the 3 months blanking period
  • No clinical evidence of recurrent AF after completing 3 months blanking period as assessed by symptoms

Exclusion Criteria:

  • Lack of written informed consent
  • Severe mental disorder, drug or alcohol addiction (> 8 drinks/week)
  • Pregnancy/breast feeding
  • Severely impaired renal function, GFR < 30 ml/min
  • Impaired liver function (ALT/AST transaminase count 3fold higher than normal values)
  • Age > 80 years
  • Valvular (less than moderate- severe; no relevant mitral stenosis with a mean pressure gradient >5mmHg) AF
  • Long standing persistent (>12 months) and permanent AF
  • NSTEMI/STEMI/implantated drug eluting stent with indication for dual an-tiplatelet therapy within 12 months before enrolment
  • History of any left atrial ablation procedure
  • Clinical indication for extended left atrial ablation procedures (lines, CFAE-, rotorablation)
  • History or presence of left atrial or ventricular thrombus
  • History of cardioembolic stroke / TIA
  • History of major bleeding or predisposition to bleeding incidences
  • Cerebral lesions or clinical situations of other organ systems with a high risk of severe bleeding
  • History of previous surgery with contraindication for OAC
  • History of malignoma with contraindication for OAC
  • Significant carotid stenosis
  • Mechanical prosthetic heart valve or other indication for permanent OAC
  • Contraindication for MRI
  • Hypersensitivity against dabigatran or other ingredients of the medicinal product
  • Concomitant use of another OAC or heparines
  • Concomitant medication with dronedarone, ketoconazole, itraconazole, cyclosporine, tacrolimus or other interacting drugs as specified in the drug information
  • Simultaneous participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
  • Females of childbearing potential, who are not using or not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterecto-mized or there are any other criteria considered sufficiently reliable by the investigator in individual cases
  • Conditions which interfere with the study treatment at the discretion of the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02067182

Contacts
Contact: Georg Nickenig, Prof. +49-228-287-15217 georg.nickenig@ukb.uni-bonn.de
Contact: Jan W Schrickel, Prof. +49-228-287-15217 jan.schrickel@ukb.uni-bonn.de

Locations
Germany
Dept. of Medicine-Cardiology University Clinic Bonn Not yet recruiting
Bonn, Germany, D-53105
Contact: Jan W Schrickel, Prof.    +49-228-287-15217    jan.schrickel@ukb.uni-bonn.de   
Principal Investigator: Georg Nickenig, Prof.         
Sub-Investigator: Jan W Schrickel, Prof.         
Sub-Investigator: Markus Linhart, Dr.         
Sub-Investigator: Rene Andrié, Ass.-Prof.         
Sponsors and Collaborators
Georg Nickenig
Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Georg Nickenig, Prof., University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT02067182     History of Changes
Other Study ID Numbers: MED2-201301, 2013-003492-35
Study First Received: February 18, 2014
Last Updated: February 20, 2014
Health Authority: Federal Institute for Drugs and Medical Devices, Germany":"

Additional relevant MeSH terms:
Atrial Fibrillation
Thromboembolism
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Thrombosis
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014