AXAFA: Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Apixaban Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose) |
Drug: Apixaban
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.
Other Names:
|
| Active Comparator: Vitamin K antagonist VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine |
Drug: Vitamin K antagonist
any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- death and serious cardiovascular events [appr. 4 months]
A composite of all-cause death, stroke (ischemic stroke, subarachnoid haemorrhage and haemorrhagic stroke), and major bleeding events, def.as BARC 2 or higher
Secondary Outcome Measures
- any bleeding event [appr. 4 months]
number
- major bleeding events acc. to the ISTH and TIMI definitions [appr. 4 months]
number
- strokes, other systemic embolic events and all-cause death [appr. 4 month]
number
- time from randomisation to ablation [appr. 4 months]
number of days
- nights spent in hospital after ablation [appr. 4 months]
number
- health-care related cost calculation [appr. 4 months]
- hospitalizations for cardiovascular reasons [appr. 4 months]
number
- Treatment duration prior to ablation and total time on oral anticoagulation [appr. 4 months]
number of days
- patients with clinically indicated TEE [appr. 4 months]
number of patients
- ACT during ablation [during ablation]
Active clotting measurements
- recurrent Atrial Fibrillation (AF) [appr. 4 months]
time to recurrent AF
- rhythm status at the end of follow-up [end of follow-up]
rythm status documented by 24 hour Holter ECG
- vascular access complications leading to prolongation of in-hospital stay or specific therapy [appr. 4 months]
number of events
- Quality-of-life changes [baseline to 3 month follow-up]
questionaire
- cognitive function change [baseline to 3 month follow-up]
questionaire
- clinically "silent" MRI-detected brain lesions [within 48 hours after ablation procedures]
prevalence (MRI-substudy)
- Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation [appr. 4 months]
MRI-substudy
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center | New York | New York | United States | |
| 2 | Hospital of the University of Pennsyvlania | Philadelphia | Pennsylvania | United States | |
| 3 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | |
| 4 | Texas Cardiac Arrhythmia Research | Austin | Texas | United States | |
| 5 | Sentara Cariovascular Research Insititute | Norfolk | Virginia | United States | |
| 6 | 4 Sites | Different | Austria | ||
| 7 | 5 Sites | Different | Belgium | ||
| 8 | 5 Sites | Different | Denmark | ||
| 9 | 13 Sites | Different | Germany | ||
| 10 | 4 Sites | Different | Italy | ||
| 11 | 6 Sites | Different | Netherlands | ||
| 12 | 3 Sites | Different | Spain | ||
| 13 | 4 Sites | Different | United Kingdom |
Sponsors and Collaborators
- Atrial Fibrillation Network
- Bristol-Myers Squibb
- Pfizer
- Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Investigators
- Principal Investigator: Paulus Kirchhof, Professor, University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
- AFNET 5 AXAFA
- 2014-002442-45