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

Phase 4
Completed
Conditions
Atrial Fibrillation
Interventions
Registration Number
NCT02227550
Lead Sponsor
Atrial Fibrillation Network
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
676
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vitamin K antagonistVitamin K antagonistVKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine
ApixabanApixabanXa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)
Primary Outcome Measures
NameTimeMethod
death and serious cardiovascular eventsappr. 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
NameTimeMethod
any bleeding eventappr. 4 months

number

major bleeding events acc. to the ISTH and TIMI definitionsappr. 4 months

number

strokes, other systemic embolic events and all-cause deathappr. 4 month

number

hospitalizations for cardiovascular reasonsappr. 4 months

number

Treatment duration prior to ablation and total time on oral anticoagulationappr. 4 months

number of days

patients with clinically indicated TEEappr. 4 months

number of patients

ACT during ablationduring ablation

Active clotting measurements

time from randomisation to ablationappr. 4 months

number of days

nights spent in hospital after ablationappr. 4 months

number

health-care related cost calculationappr. 4 months
recurrent Atrial Fibrillation (AF)appr. 4 months

time to recurrent AF

rhythm status at the end of follow-upend of follow-up

rythm status documented by 24 hour Holter ECG

vascular access complications leading to prolongation of in-hospital stay or specific therapyappr. 4 months

number of events

Quality-of-life changesbaseline to 3 month follow-up

questionaire

cognitive function changebaseline to 3 month follow-up

questionaire

clinically "silent" MRI-detected brain lesionswithin 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 ablationappr. 4 months

MRI-substudy

Trial Locations

Locations (10)

6 Sites

🇳🇱

Different, Netherlands

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Texas Cardiac Arrhythmia Research

🇺🇸

Austin, Texas, United States

Hospital of the University of Pennsyvlania

🇺🇸

Philadelphia, Pennsylvania, United States

Sentara Cariovascular Research Insititute

🇺🇸

Norfolk, Virginia, United States

4 Sites

🇬🇧

Different, United Kingdom

3 Sites

🇪🇸

Different, Spain

13 Sites

🇩🇪

Different, Germany

5 Sites

🇩🇰

Different, Denmark

Montefiore Medical Center

🇺🇸

New York, New York, United States

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