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

NCT ID: NCT02067182

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2020-09-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Dabigatran

Intervention Type: 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

No Oral Anticoagulation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dabigatran

• 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Georg Nickenig

OTHER

Sponsor Role: lead

Responsible Party

Georg Nickenig

Prof.

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Heart Center Freiburg University Bad Krozingen

Bad Krozingen, , Germany

Heart Center Bad Neustadt-Saale

Bad Neustadt an der Saale, , Germany

Bielefeld Clinical Centre

Bielefeld, , Germany

Dept. of Medicine-Cardiology University Clinic Bonn

Bonn, , Germany

University Hospital Cologne

Cologne, , Germany

University Hospital Gießen

Giessen, , Germany

University Hospital Göttingen

Göttingen, , Germany

Hannover Medical School

Hanover, , Germany

Westpfalz-Clinic GmbH Kaiserslautern

Kaiserslautern, , Germany

Municipal Clinical Center Karlsruhe

Karlsruhe, , Germany

St. Vincentius Hospital

Karlsruhe, , Germany

Heart Center Leipzig

Leipzig, , Germany

Ludwigshafen Hospital

Ludwigshafen, , Germany

Hospital Lüdenscheid

Lüdenscheid, , Germany

University Hospital Mannheim

Mannheim, , Germany

Peter Osypka Heart Center

Munich, , Germany

University Hospital Tübingen

Tübingen, , Germany

Schwarzwald-Baar Hospital Villingen Schwenningen

Villingen-Schwenningen, , Germany

Helios Hospital

Wuppertal, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 26514352 (View on PubMed)

Other Identifiers

2013-003492-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MED2-201301

Identifier Type: -

Identifier Source: org_study_id