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

Atrial Fibrillation Clinical Trial

— ODIn-AF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02067182
• Other study ID #: MED2-201301
• Secondary ID: 2013-003492-35
• Status: Completed
• Phase: Phase 4
• Start date: August 2015
• Est. completion date: September 15, 2020

Study information

• Verified date: November 2022
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: September 15, 2020
• Est. primary completion date: September 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cardioembolic Events
• Oral Anticoagulation
• Thromboembolism

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Germany	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	Gottingen
Germany	Hannover Medical School	Hannover
Germany	Westpfalz-Clinic GmbH Kaiserslautern	Kaiserslautern
Germany	Municipal Clinical Center Karlsruhe	Karlsruhe
Germany	St. Vincentius Hospital	Karlsruhe
Germany	Heart Center Leipzig	Leipzig
Germany	Hospital Lüdenscheid	Lüdenscheid
Germany	Ludwigshafen Hospital	Ludwigshafen
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

Sponsors (2)

Lead Sponsor	Collaborator
Georg Nickenig	Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Major / minor bleeding events		12 months
Other	Clinically evident cardio-embolic events		12 months
Other	Serious Adverse Events		12 months
Primary	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	Location, size and number of new micro- and macro-embolic lesions on cerebral MRI		12 months
Secondary	Incidence of clinically evident cardio-embolic events (stroke, TIA, systemic embolism)		12 months
Secondary	Severity of neurological deficits assessed by Modified Rankin Scale		12 months
Secondary	Incidence of other thrombotic or thrombo-embolic events (myocardial in-farction, deep vein thrombosis, pulmonary embolism)		12 months
Secondary	Life-threatening / major / minor bleedings		12 months
Secondary	Hemorrhagic cerebral infarction		12 months
Secondary	All-cause mortality / Cardiovascular mortality		12 months
Secondary	Correlation of cardio-embolic events to method used for PVI (cryo-balloon versus RF)		12 months
Secondary	Correlation of cardio-embolic events with arrhythmia recurrence (atrial fi-brillation or atrial flutter post ablationem with ECG documentation or symp-toms)		12 months
Secondary	Quality of life questionnaire (AF-specific symptoms, SF36)		12 months
Secondary	Neuropsychological questionnaire (RBANS A&B)		12 months
Secondary	Assessment of neurocognitive deficits: Minimental Test		12 months