Clinical trial NCT02227550: Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: Atrilal fibrillation
anticoagulation
prevention of peri-procedural complication
catheter ablation
Lead sponsor: Atrial Fibrillation Network
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Pfizer
name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
First posted: 2014-08-28
Enrollment: 676
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: death and serious cardiovascular events
timeFrame: appr. 4 months
Secondary outcomes:
measure: any bleeding event
timeFrame: appr. 4 months
measure: major bleeding events acc. to the ISTH and TIMI definitions
timeFrame: appr. 4 months
measure: strokes, other systemic embolic events and all-cause death
timeFrame: appr. 4 month
measure: time from randomisation to ablation
timeFrame: appr. 4 months
measure: nights spent in hospital after ablation
timeFrame: appr. 4 months
measure: health-care related cost calculation
timeFrame: appr. 4 months
measure: hospitalizations for cardiovascular reasons
timeFrame: appr. 4 months
measure: Treatment duration prior to ablation and total time on oral anticoagulation
timeFrame: appr. 4 months
measure: patients with clinically indicated TEE
timeFrame: appr. 4 months
measure: ACT during ablation
timeFrame: during ablation
measure: recurrent Atrial Fibrillation (AF)
timeFrame: appr. 4 months
measure: rhythm status at the end of follow-up
timeFrame: end of follow-up
measure: vascular access complications leading to prolongation of in-hospital stay or specific therapy
timeFrame: appr. 4 months
measure: Quality-of-life changes
timeFrame: baseline to 3 month follow-up
measure: cognitive function change
timeFrame: baseline to 3 month follow-up
measure: clinically "silent" MRI-detected brain lesions
timeFrame: within 48 hours after ablation procedures
measure: Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation
timeFrame: appr. 4 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsyvlania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research
state: Texas
city: Norfolk
country: United States
facility: Sentara Cariovascular Research Insititute
state: Virginia
city: Different
country: Austria
facility: 4 Sites
city: Different
country: Belgium
facility: 5 Sites
city: Different
country: Denmark
facility: 5 Sites
city: Different
country: Germany
facility: 13 Sites
city: Different
country: Italy
facility: 4 Sites
city: Different
country: Netherlands
facility: 6 Sites
city: Different
country: Spain
facility: 3 Sites
city: Different
country: United Kingdom
facility: 4 Sites
Study officials:
affiliation: University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany
name: Paulus Kirchhof, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Biase L, Callans D, Haeusler KG, Hindricks G, Al-Khalidi H, Mont L, Cosedis Nielsen J, Piccini JP, Schotten U, Kirchhof P. Rationale and design of AXAFA-AFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation. Europace. 2017 Jan;19(1):132-138. doi: 10.1093/europace/euw368.
citation: Haeusler KG, Eichner FA, Heuschmann PU, Fiebach JB, Engelhorn T, Blank B, Callans D, Elvan A, Grimaldi M, Hansen J, Hindricks G, Al-Khalidi HR, Mont L, Nielsen JC, Piccini JP, Schotten U, Themistoclakis S, Vijgen J, Di Biase L, Kirchhof P. MRI-Detected Brain Lesions and Cognitive Function in Patients With Atrial Fibrillation Undergoing Left Atrial Catheter Ablation in the Randomized AXAFA-AFNET 5 Trial. Circulation. 2022 Mar 22;145(12):906-915. doi: 10.1161/CIRCULATIONAHA.121.056320. Epub 2022 Feb 9.
citation: Zink MD, Chua W, Zeemering S, di Biase L, Antoni BL, David C, Hindricks G, Haeusler KG, Al-Khalidi HR, Piccini JP, Mont L, Nielsen JC, Escobar LA, de Bono J, Van Gelder IC, de Potter T, Scherr D, Themistoclakis S, Todd D, Kirchhof P, Schotten U. Predictors of recurrence of atrial fibrillation within the first 3 months after ablation. Europace. 2020 Sep 1;22(9):1337-1344. doi: 10.1093/europace/euaa132.