Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation

NCT02067182 | Completed Phase 4 DMC

• 2 other identifiers: MED2-2013012013-003492-35
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 19

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.

Conditions

Atrial Fibrillation; Cardioembolic Events; Oral Anticoagulation

Outcome Measures

Primary Outcomes (1)

• 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)

  12 months

Secondary Outcomes (12)

• Location, size and number of new micro- and macro-embolic lesions on cerebral MRI

  12 months

• Incidence of clinically evident cardio-embolic events (stroke, TIA, systemic embolism)

  12 months

• Severity of neurological deficits assessed by Modified Rankin Scale

  12 months

• Incidence of other thrombotic or thrombo-embolic events (myocardial in-farction, deep vein thrombosis, pulmonary embolism)

  12 months

• Life-threatening / major / minor bleedings

  12 months

Other Outcomes (3)

• Major / minor bleeding events

  12 months

• Clinically evident cardio-embolic events

  12 months

• Serious Adverse Events

  12 months

Study Arms (2)

Oral Anticoagulation with Dabigatran

EXPERIMENTAL

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 Oral Anticoagulation

NO INTERVENTION

Interventions

Dabigatran DRUG

* Antral pulmonary vein ablation for patients with AF * left atrial fibrosis/electrical scar assessment by electroanatomical mapping * followed by 6 months OAC (3 months blanking period + 3 months observation period) * in case of AF-recurrence in month 4-6: re- pulmonary vein ablation * followed again by 6 months OAC (3 months blanking period + 3 months observation period) AF-free patients as assessed by 72h Holter ECG and symptoms wil be random-izedals to the following two interventional arms: * Experimental arm (group A): OAC with dabigatran for 12 months * Control arm (group B): No OAC (no placebo medication) for 12 months - Cerebral MRI at randomisation and 12 months later

Oral Anticoagulation with Dabigatran

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• 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.
• CHA2DS2VASc score ≥2
• Randomization criteria:
• 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
• No clinical evidence of recurrent AF after completing 3 months blanking and 3 months observation period as assessed by symptoms
• No other relevant contraindication for OAC assessed by randomization MRI of the brain

You may not qualify if:

• 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)
• Pregnancy /breast feeding
• Severely impaired renal function, GFR \< 30 ml/min
• Impaired liver function (ALT/AST transaminase count 3fold higher than normal values) or liver disease with reduced life expectancy \<1 year
• Valvular AF (moderate- severe mitral insufficiency; relevant mitral steno-sis with a mean pressure gradient \>5mmHg)
• Long standing persistent (\>12 months) and permanent AF
• NSTEMI/STEMI/implantated drug eluting stent with indication for dual antiplatelet therapy within 12 months before enrolment
• History of complex left atrial ablation procedures. One previous PVI al-lowed.
• Clinical indication for extended left atrial ablation procedures (CFAE-, rotor-ablation)
• History or presence of left atrial or ventricular thrombus
• History of stroke / TIA independent from etiology
• Acute major bleedings
• 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
• Need for concomitant anitcoagulation in addition to dabigatran
• History of previous surgery resulting in contraindication for OAC

Sponsors & Collaborators

• Georg Nickenig: lead
• Boehringer Ingelheim: collaborator

Study Sites (19)

Heart Center Freiburg University Bad Krozingen

Bad Krozingen, 79189, Germany

Location

Heart Center Bad Neustadt-Saale

Bad Neustadt an der Saale, 97616, Germany

Location

Bielefeld Clinical Centre

Bielefeld, 33604, Germany

Location

Dept. of Medicine-Cardiology University Clinic Bonn

Bonn, D-53105, Germany

Location

University Hospital Cologne

Cologne, 50937, Germany

Location

University Hospital Gießen

Giessen, 35392, Germany

Location

University Hospital Göttingen

Göttingen, 37075, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

Westpfalz-Clinic GmbH Kaiserslautern

Kaiserslautern, 67655, Germany

Location

Municipal Clinical Center Karlsruhe

Karlsruhe, 76133, Germany

Location

St. Vincentius Hospital

Karlsruhe, 76137, Germany

Location

Heart Center Leipzig

Leipzig, 04289, Germany

Location

Ludwigshafen Hospital

Ludwigshafen, 67063, Germany

Location

Hospital Lüdenscheid

Lüdenscheid, 58515, Germany

Location

University Hospital Mannheim

Mannheim, 68167, Germany

Location

Peter Osypka Heart Center

Munich, 81379, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Schwarzwald-Baar Hospital Villingen Schwenningen

Villingen-Schwenningen, 78050, Germany

Location

Helios Hospital

Wuppertal, 42117, Germany

Location

Related Publications (1)

• 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.

  PMID: 26514352 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: February 20, 2014
• Study Start: August 1, 2015
• Primary Completion: September 15, 2020
• Study Completion: September 15, 2020
• Last Updated: November 7, 2022

Record last verified: 2022-11

Locations

DE (19)