Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy

Study Overview
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Brief Summary
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Study objective is to demonstrate that anticoagulation with the direct factor Xa inhibitor apixaban is not less safe than Vitamin-K-antagonists (VKA) therapy in patients undergoing catheter ablation of non-valvular AF in the prevention of peri-procedural complications. The AXAFA trial will compare peri-ablational treatment with apixaban to peri-ablational treatment wit VKA in a randomized trial of patients undergoing catheter ablation of atrial fibrillation (AF).

Detailed Description
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AXAFA is an open-label trial designed to evaluate the safety and efficacy of two types of anticoagulant therapy, VKA therapy and therapy with the direct factor Xa inhibitor apixaban, in patients undergoing scheduled catheter ablation for AF. All patients will undergo the ablation procedure after pre-treatment with an anticoagulant (either apixaban in the Xa group or a vitamin K antagonist in the VKA group). Patients can undergo catheter ablation within the trial after at least 30 days of continuous effective anticoagulation. Ablation can be performed earlier when or timely after exclusion of atrial thrombi have been excluded by a clinically indicated by transthoracic echocardioggram (TEE). After TEE continuous effective anticoagulation must be ensured until the end of the trial. In the MRI-substudy will be explored wether novel oral anticoagulants (NOAC) have the potential to reduce clinically silent brain lesions after catheter ablation of AF.

Official Title
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An Investigator-driven, Prospective, Parallel-group, Randomised, Open, Blinded Outcome Assessment (PROBE), Multi-centre Trial to Determine the Optimal Anticoagulation Therapy for Patients Untergoing Catheter Ablation of Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Vitamin K antagonist
* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I1. Non-valvular AF (ECG-documented) with a clinical indication for catheter ablation I2. Clinical indication to undergo catheter ablation on continuous anticoagulant therapy I3. Presence of at least one of the CHADS2 stroke risk factors Stroke or TIA age ≥ 75 years, hypertension, defined as chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure > 145/90 mm Hg, diabetes mellitus, symptomatic heart failure (NYHA ≥ II). I4. Age ≥ 18 years I5. Provision of signed informed consent Exclusion Criteria: General exclusion criteria E1. Any disease that limits life expectancy to less than 1 year E2. Participation in another clinical trial, either within the past two months or still ongoing E3. Previous participation in AXAFA E4. Pregnant women or women of childbearing potential not on adequate birth control: only women with a highly effective method of contraception (oral contraception or intra-uterine device) or sterile women can be randomised. E5. Breastfeeding women E6. Drug abuse or clinically manifest alcohol abuse E7. Any stroke within 14 days before randomisation E8. Coadministration with drugs that are strong dual inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) or strong dual inducers of CYP3A4 and P-gp (Appendix VIII). Exclusion criteria related to a cardiac condition E9. Valvular AF (as defined by the focussed update of the ESC guidelines on AF, i.e. severe mitral valve stenosis, mechanical heart valve). Furthermore, patients who underwent mitral valve repair are not eligible for AXAFA. E10. Any previous ablation or surgical therapy for AF E11. Cardiac ablation therapy for any indication (catheter-based or surgical) within 3 months prior to randomisation E12. Clinical need for triple therapy (combination therapy of clopidogrel, acetylsalicylic acid, and oral anticoagulation) E13. Other contraindications for use of VKA or apixaban E14. Documented atrial thrombi less than 3 months prior to randomisation. Exclusion criteria based on laboratory abnormalities E15. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) < 15 ml/min

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban<br>Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose) | Drug: Apixaban<br>* factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose) dose reduction Apixaban 2,5 mg twice daily in patients who fulfill tow of the following criteria at the time of randomisation: chronic kidney disease (serum creatine >= 1.5 mg/dl (133mM), <= 60 kg body weight or age >= 80 years.<br>* Other names: BMS-562247;|
| Active Comparator: Vitamin K antagonist<br>VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine | Drug: Vitamin K antagonist<br>* any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin<br>* Other names: fluindione;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death and serious cardiovascular events | A composite of all-cause death, stroke (ischemic stroke, subarachnoid haemorrhage and haemorrhagic stroke), and major bleeding events, def.as BARC 2 or higher | appr. 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| any bleeding event | number | appr. 4 months | 
| major bleeding events acc. to the ISTH and TIMI definitions | number | appr. 4 months | 
| strokes, other systemic embolic events and all-cause death | number | appr. 4 month | 
| time from randomisation to ablation | number of days | appr. 4 months | 
| nights spent in hospital after ablation | number | appr. 4 months | 
| health-care related cost calculation |  | appr. 4 months | 
| hospitalizations for cardiovascular reasons | number | appr. 4 months | 
| Treatment duration prior to ablation and total time on oral anticoagulation | number of days | appr. 4 months | 
| patients with clinically indicated TEE | number of patients | appr. 4 months | 
| ACT during ablation | Active clotting measurements | during ablation | 
| recurrent Atrial Fibrillation (AF) | time to recurrent AF | appr. 4 months | 
| rhythm status at the end of follow-up | rythm status documented by 24 hour Holter ECG | end of follow-up | 
| vascular access complications leading to prolongation of in-hospital stay or specific therapy | number of events | appr. 4 months | 
| Quality-of-life changes | questionaire | baseline to 3 month follow-up | 
| cognitive function change | questionaire | baseline to 3 month follow-up | 
| clinically silent MRI-detected brain lesions | prevalence (MRI-substudy) | within 48 hours after ablation procedures | 
| Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally silent acute brain lesions on cognitive function after ablation | MRI-substudy | appr. 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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catheter ablation, Atrilal fibrillation, anticoagulation, prevention of peri-procedural complication