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

Atrial Fibrillation Clinical Trial

— AXAFA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02227550
• Other study ID #: AFNET 5 AXAFA
• Secondary ID: 2014-002442-45
• Status: Completed
• Phase: Phase 4
• First received: June 27, 2014
• Last updated: October 19, 2017
• Start date: December 2014
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: Atrial Fibrillation Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 676
• Est. completion date: September 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Vitamin K antagonist
any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin
• 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.

Locations

Country	Name	City	State
Austria	4 Sites	Different
Belgium	5 Sites	Different
Denmark	5 Sites	Different
Germany	13 Sites	Different
Italy	4 Sites	Different
Netherlands	6 Sites	Different
Spain	3 Sites	Different
United Kingdom	4 Sites	Different
United States	Texas Cardiac Arrhythmia Research	Austin	Texas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Montefiore Medical Center	New York	New York
United States	Sentara Cariovascular Research Insititute	Norfolk	Virginia
United States	Hospital of the University of Pennsyvlania	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
Atrial Fibrillation Network	Bristol-Myers Squibb, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Pfizer

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Denmark,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (1)

Di Biase L, Callans D, Hæusler 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. — View Citation

Outcome

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