Clinical trial NCT02067182: Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation
Official title: Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Cardioembolic Events
Oral Anticoagulation
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2014-02-20
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion criteria:

1. Written informed consent
2. Patients undergoing circumferential antral PV ablation for non-valvular (mitral regurgitation less than moderate- severe insufficiency; no relevant mitral stenosis with a mean pressure gradient \>5mmHg) symptomatic, paroxysmal AF or persistent AF (duration \< 12 months) with risk factors resulting in a CHA2DS2VASc score ≥2, using a cooled tip RF-, laser- or cryo-balloon-catheter.
3. CHA2DS2VASc score ≥2

Randomization criteria:

1. Sinus rhythm (as assessed by 72h Holter ECG) following the 3 months blanking and 3 months observation period after first or second pulmo-nary vein ablation procedure
2. No clinical evidence of recurrent AF after completing 3 months blanking and 3 months observation period as assessed by symptoms
3. No other relevant contraindication for OAC assessed by randomization MRI of the brain

Exclusion criteria:

1. Severe mental retardation or psychiatrical disorder resulting in incapabil-ity to adequately understand nature, significance, implications and risks of study parcipitation (i.e. bipolar disorders, severe depression, suicidal tendencies, among others) as judged by the local physician, ongoing drug or alcohol addiction (\> 8 drinks/week)
2. Pregnancy /breast feeding
3. Severely impaired renal function, GFR \< 30 ml/min
4. Impaired liver function (ALT/AST transaminase count 3fold higher than normal values) or liver disease with reduced life expectancy \<1 year
5. Valvular AF (moderate- severe mitral insufficiency; relevant mitral steno-sis with a mean pressure gradient \>5mmHg)
6. Long standing persistent (\>12 months) and permanent AF
7. NSTEMI/STEMI/implantated drug eluting stent with indication for dual antiplatelet therapy within 12 months before enrolment
8. History of complex left atrial ablation procedures. One previous PVI al-lowed.
9. Clinical indication for extended left atrial ablation procedures (CFAE-, rotor-ablation)
10. History or presence of left atrial or ventricular thrombus
11. History of stroke / TIA independent from etiology
12. Acute major bleedings
13. Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
14. Need for concomitant anitcoagulation in addition to dabigatran
15. History of previous surgery resulting in contraindication for OAC
16. History of malignoma resulting in contraindication for OAC
17. Mechanical prosthetic heart valve or other indication for permanent OAC
18. Contraindication for MRI (i.e. metal implants unsuitable for MRI, wearing of magnetic or metallic objects that cannot be removed from the body (such as body piercing, implanted electrodes, contraceptive coil), inabil-ity to lie on the back for an extended period of time, uncontrollable claustrophobia, hypersensitivity to noise etc.). Pacemaker and ICD-patients may be included at the discretion of the local investigators/radiologists if MRI is warranted
19. Hypersensitivity against dabigatran or other ingredients of the medical product
20. Concomitant medication with dronedarone, ketoconazole, itraconazole, cyclosporine, tacrolimus or other interacting drugs as specified in the drug information
21. Simultaneous participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
22. 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 / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases
23. Conditions which interfere with the study treatment at the discretion of the investigator

Primary outcomes:
measure: 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)
timeFrame: 12 months
Secondary outcomes:
measure: Location, size and number of new micro- and macro-embolic lesions on cerebral MRI
timeFrame: 12 months
measure: Incidence of clinically evident cardio-embolic events (stroke, TIA, systemic embolism)
timeFrame: 12 months
measure: Severity of neurological deficits assessed by Modified Rankin Scale
timeFrame: 12 months
measure: Incidence of other thrombotic or thrombo-embolic events (myocardial in-farction, deep vein thrombosis, pulmonary embolism)
timeFrame: 12 months
measure: Life-threatening / major / minor bleedings
timeFrame: 12 months
measure: Hemorrhagic cerebral infarction
timeFrame: 12 months
measure: All-cause mortality / Cardiovascular mortality
timeFrame: 12 months
measure: Correlation of cardio-embolic events to method used for PVI (cryo-balloon versus RF)
timeFrame: 12 months
measure: Correlation of cardio-embolic events with arrhythmia recurrence (atrial fi-brillation or atrial flutter post ablationem with ECG documentation or symp-toms)
timeFrame: 12 months
measure: Quality of life questionnaire (AF-specific symptoms, SF36)
timeFrame: 12 months
measure: Neuropsychological questionnaire (RBANS A&B)
timeFrame: 12 months
measure: Assessment of neurocognitive deficits: Minimental Test
timeFrame: 12 months
Other outcomes:
measure: Major / minor bleeding events
timeFrame: 12 months
measure: Clinically evident cardio-embolic events
timeFrame: 12 months
measure: Serious Adverse Events
timeFrame: 12 months
Locations:
city: Bad Krozingen
country: Germany
facility: Heart Center Freiburg University Bad Krozingen
city: Bad Neustadt An Der Saale
country: Germany
facility: Heart Center Bad Neustadt-Saale
city: Bielefeld
country: Germany
facility: Bielefeld Clinical Centre
city: Bonn
country: Germany
facility: Dept. of Medicine-Cardiology University Clinic Bonn
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Gießen
country: Germany
facility: University Hospital Gießen
city: Gottingen
country: Germany
facility: University Hospital Göttingen
city: Hannover
country: Germany
facility: Hannover Medical School
city: Kaiserslautern
country: Germany
facility: Westpfalz-Clinic GmbH Kaiserslautern
city: Karlsruhe
country: Germany
facility: Municipal Clinical Center Karlsruhe
city: Karlsruhe
country: Germany
facility: St. Vincentius Hospital
city: Leipzig
country: Germany
facility: Heart Center Leipzig
city: Ludwigshafen
country: Germany
facility: Ludwigshafen Hospital
city: Lüdenscheid
country: Germany
facility: Hospital Lüdenscheid
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Munich
country: Germany
facility: Peter Osypka Heart Center
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Villingen Schwenningen
country: Germany
facility: Schwarzwald-Baar Hospital Villingen Schwenningen
city: Wuppertal
country: Germany
facility: Helios Hospital
Study officials:
References:
citation: Schrickel JW, Linhart M, Bansch D, Thomas D, Nickenig G. Rationale and design of the ODIn-AF Trial: randomized evaluation of the prevention of silent cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation. Clin Res Cardiol. 2016 Feb;105(2):95-105. doi: 10.1007/s00392-015-0933-1. Epub 2015 Oct 29.