Condition category
Circulatory System
Date applied
16/06/2014
Date assigned
20/06/2014
Last edited
11/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Atrial fibrillation (AF) is a common heart condition which causes an irregular and rapid heartbeat. People with AF can be of much greater risk of having a stroke than the general population, depending on the presence of additional risk factors (high blood pressure, for example). Reducing this risk has traditionally been via the use of vitamin K antagonists, anticoagulation drugs that reduce blood clotting and thrombosis (blood clots within a blood vessel). Factor Xa inhibitors and direct thrombin inhibitors are new, novel fixed dose oral anticoagulants (NOACS). These NOACS - apixaban, rivaroxaban and dabigatron – have all been shown to prevent stroke in patients with AF and have now been approved for use in the USA, Canada and Europe. The use of NOACS are also recommended in the current guidelines for AF treatment. Between 5-15% of AF patients undergo a procedure to treat their condition called catheter ablation, where radiofrequency energy is used to destroy the area inside the heart that is causing the abnormal beating. While some of these patients are on long-term anticoagulation therapy due to their risk of stroke, all patients undergoing this procedure have to take them in a period just before and after the operation to reduce the risk of a stroke associated with the actual procedure. Some small observational studies have highlighted concerns with using NOACS in patients undergoing catheter ablation. One study investigating the use of dabigatran showed that 4.4% of patients treated with this drug during catheter ablation suffered severe complications such as fluid developing around the heart (pericardial tamponade), stroke and, in some cases, the patients died. This was compared with only 2.1% of patients suffering similar events when VKAs was used. Although it is likely that the results of this study occurred by chance (as since demonstrated by other observational studies), it does mean that the present data suggests that VKAs should be the treatment of choice during catheter ablation. The international consensus statement on AF catheter ablation was published before these reports on dabigatran. It suggests to perform AF catheter ablation on continuous anticoagulation using either a VKA or a NOAC. The focussed update of the European Society of Cardiology (ESC) guidelines on AF, however, published after these reports on dabigatran became available, only mentions using a VKA. The aim of this study is to test whether NOACs can be safely and effectively used for catheter ablation of AF.

Who can participate?
Patients who have AF, are going to undergo catheter ablation and are at an increased risk of stroke (have, for example, had a previous stroke, are aged at least 75 years, have high blood pressure, diabetes mellitus or symptomatic heart failure)

What does the study involve?
Comparison of two therapies: NOACs and VKAs during the atrial fibrillation ablation procedure

What are the possible benefits and risks of participating?
The patient will receive a particularly thorough medical examination as part of the participation in the study. Beyond that, no further personal health benefits, besides the usual standard of care, are expected for the patient. In the AXAFA study, no investigational drugs or interventions not yet approved by health authorities will be applied. All study drugs are market approved and will be used within the approved indications, for AF only. All concomitant study procedures and therapies, e. g. the catheter ablation for AF, are standard care procedures according to applicable medical guidelines.

Where is the study run from?
7 EU countries: Germany, Italy, Spain, Belgium, Netherlands, UK, Denmark, USA

When is the study starting and how long is it expected to run for?
January 2015 – July 2017

Who is funding the study?
German Atrial Fibrillation Network (Germany) – AFNET e.V.

Who is the main contact?
Bianca-Maria Klein
b.klein@cri-muc.eu

Trial website

Contact information

Type

Scientific

Primary contact

Prof Paulus Kirchhof

ORCID ID

Contact details

c/o Bianca-Maria Klein
Projektmanagement
CRI - The Clinical Research Institute GmbH
Arnulfstraße 19
München
80335
Germany

Additional identifiers

EudraCT number

2014-002442-45

ClinicalTrials.gov number

NCT02227550

Protocol/serial number

N/A

Study information

Scientific title

Anticoagulation using the direct factor Xa inhibitor apixaban during atrial fibrillation catheter ablation and comparison to vitamin K antagonist therapy: A investigator-initiated, prospective, parallel-group, randomised, open, blinded outcome assessment (PROBE) interventional multi-centre trial.

Acronym

AXAFA-AFNET5

Study hypothesis

Anticoagulation with the direct factor Xa inhibitor apixaban is not less safe than VKA therapy in patients undergoing catheter ablation of non-valvular AF in the prevention of peri-procedural complications.

Ethics approval

Ethics Committee at the Medical Faculty of the University of Leipzig (Ethik-Kommission an der Medizinischen Fakultät der Universität Leipzig), 20/01/2015, ref: 341/14-ff

Study design

Prospective phase IV parallel-group randomised open, blinded outcome assessment (PROBE) interventional multi-centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Non-valvular atrial fibrillation with a clinical indication for catheter ablation/bleeding + stroke risk/cardiology

Intervention

Anticoagulation therapy with new oral anticoagulants and vitamin-k-antagonists during atrial fibrillation ablation

Intervention type

Drug

Phase

Phase IV

Drug names

Apixaban

Primary outcome measures

A composite of
1. All-cause death
2. Stroke (ischemic stroke, subarachnoid hemorrhage and hemorrhagic stroke)
3. Major bleeding events, defined as BARC 2 or higher

Secondary outcome measures

1. Any bleeding event
2. Major bleeding events according to the ISTH and TIMI definitions
3. Number of strokes, other systemic embolic events, and all-cause deaths
4. Time from randomisation to ablation
5. Nights spent in hospital after ablation
6. Health-care related cost calculation
7. Number of hospitalizations for cardiovascular reasons
8. Treatment duration prior to ablation and total time on oral anticoagulation
9. Number of patients with clinically indicated TEE
10. ACT during ablation
11. Time to recurrent AF
12. Rhythm status at the end of follow-up
13. Vascular access complications leading to prolongation of in-hospital stay or specific therapy
14. Quality-of-life changes at month 3 compared to baseline
15. Cognitive function change at month 3 compared to baseline
16. Impact of silent brain lesions on cognitive function (MRI sub-study)
17. Impact of clinically overt strokes and of MRI-detected silent brain lesions on cognitive function (MRI sub-study)

Overall trial start date

01/01/2015

Overall trial end date

01/07/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Non-valvular AF (ECG-documented) with a clinical indication for catheter ablation
2. Clinical indication to undergo catheter ablation on continuous anticoagulant therapy
3. Presence of at least one of the CHADS2 stroke risk factors
3a. Stroke or TIA
3b. Age ≥75 years
3c. Hypertension, defined as chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure >145/90 mm Hg
3d. Diabetes mellitus
3e. Symptomatic heart failure (NYHA ≥II)
4. Age ≥18 years
5. Provision of signed informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

630

Participant exclusion criteria

General exclusion criteria
1. Any disease that limits life expectancy to less than 1 year
2. Participation in another clinical trial, either within the past two months or still ongoing
3. Previous participation in AXAFA
4. 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.
5. Breastfeeding women
6. Drug abuse or clinically manifest alcohol abuse

Exclusion criteria related to a cardiac condition
7. 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.
8. Any previous ablation or surgical therapy for AF
9. Cardiac ablation therapy for any indication (catheter-based or surgical) within 3 months prior to randomisation
10. Clinical need for “triple therapy” (combination therapy of clopidogrel, acetylsalicylic acid, and oral anticoagulation)
11. Other contraindications for use of VKA or apixaban

Exclusion criteria based on laboratory abnormalities
12. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) <15 ml/min

Recruitment start date

01/01/2015

Recruitment end date

01/07/2017

Locations

Countries of recruitment

Belgium, Denmark, Germany, Italy, Netherlands, Spain, United Kingdom, United States of America

Trial participating centre

c/o Bianca-Maria Klein
München
80335
Germany

Sponsor information

Organisation

German Atrial Fibrillation Network - AFNET e.V. (Germany)

Sponsor details

Domagkstr. 11
Münster
48149
Germany

Sponsor type

Research organisation

Website

http://www.kompetenznetz-vorhofflimmern.de

Funders

Funder type

Research organisation

Funder name

German Atrial Fibrillation Network (Germany) - AFNET e.V.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/05/2016: Ethics approval information added.