Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: Comparison to vitamin K antagonist therapy
| ISRCTN | ISRCTN87711003 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN87711003 |
| EudraCT/CTIS number | 2014-002442-45 |
| ClinicalTrials.gov number | NCT02227550 |
| Secondary identifying numbers | N/A |
- Submission date
- 16/06/2014
- Registration date
- 20/06/2014
- Last edited
- 13/05/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
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?
8 EU countries: Austria, Germany, Italy, Spain, Belgium, Netherlands, UK, Denmark, USA
When is the study starting and how long is it expected to run for?
January 2015 – September 2017
Who is funding the study?
Kompetenznetz Vorhofflimmern e.V. (AFNET)
[Atrial Fibrillation NETwork] (Germany)
Who is the main contact?
Elisabeth Freund
e.freund@cri-muc.eu
Contact information
Scientific
c/o Elisabeth Freund
Head of Clinical Operations
CRI - The Clinical Research Institute GmbH
Arnulfstraße 19
München
80335
Germany
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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. |
| Study 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(s) | 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 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Test IMP: Apixaban, comparator IMP: locally used VKA |
| Primary outcome measure | 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 Updated 18/10/2017: 16. MRI sub-study, only: Prevalence of clinically “silent” MRI-detected brain lesions within 48 hours after the ablation procedure 17. MRI sub-study, only: Impact of ablation-associated clinically overt strokes or MRI-detected but clinically “silent” acute brain lesions on cognitive function after ablation |
| Overall study start date | 01/01/2015 |
| Overall study end date | 12/09/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 630 |
| Total final enrolment | 674 |
| 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 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 Added 18/10/2017: 7. Any stroke within 14 days before randomisation 8. 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 9. 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. 10. Any previous ablation or surgical therapy for AF 11. Cardiac ablation therapy for any indication (catheter-based or surgical) within 3 months prior to randomisation 12. Clinical need for triple therapy (combination therapy of clopidogrel, acetylsalicylic acid, and oral anticoagulation) 13. Other contraindications for use of VKA or apixaban Exclusion criteria based on laboratory abnormalities 14. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) <15 ml/min Added 18/10/2017: 15. Documented atrial thrombi less than 3 months prior to randomisation |
| Recruitment start date | 01/01/2015 |
| Recruitment end date | 10/04/2017 |
Locations
Countries of recruitment
- Austria
- Belgium
- Denmark
- Germany
- Italy
- Netherlands
- Spain
- United Kingdom
- United States of America
Study participating centre
80335
Germany
Sponsor information
Research organisation
Mendelstr. 11
Münster
48149
Germany
| Website | http://www.kompetenznetz-vorhofflimmern.de |
|---|---|
"ROR" |
https://ror.org/01spm3d88 |
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 18/03/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/01/2017 | Yes | No | |
| Results article | results | 21/08/2018 | 13/05/2019 | Yes | No |
Editorial Notes
13/05/2019: Publication reference and total final enrolment added.
18/10/2017: The study contact has been updated from Bianca-Maria Klein (b.klein@cri-muc.eu) to Elisabeth Freund. The sponsor name has been updated from "German Atrial Fibrillation Network - AFNET e.V. (Germany)" to Kompetenznetz Vorhofflimmern e.V. (AFNET) [Atrial Fibrillation NETwork]". Austria has been added to the countries of recruitment. The overall trial end date has been updated from 01/07/2017 to 12/09/2017. The recruitment end date have been updated from 01/07/2017 to 10/04/2017. The Plain English summary has been updated accordingly. Publication and dissemination plans and individual participant data sharing statement has been added.
11/05/2016: Ethics approval information added.
