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

NCT ID: NCT02227550

Last Updated: 2017-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

676 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2017-09-30

Brief Summary

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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

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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.

Conditions

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Atrial Fibrillation

Keywords

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Atrilal fibrillation anticoagulation prevention of peri-procedural complication catheter ablation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Apixaban

Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)

Group Type EXPERIMENTAL

Apixaban

Intervention Type DRUG

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.

Vitamin K antagonist

VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine

Group Type ACTIVE_COMPARATOR

Vitamin K antagonist

Intervention Type DRUG

any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin

Interventions

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Vitamin K antagonist

any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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warfarin phenprocoumon acecoumaril fluindione BMS-562247

Eligibility Criteria

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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

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).


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.


E15. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) \< 15 ml/min
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

OTHER

Sponsor Role collaborator

Atrial Fibrillation Network

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paulus Kirchhof, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany

Locations

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Montefiore Medical Center

New York, New York, United States

Site Status

Hospital of the University of Pennsyvlania

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Cardiac Arrhythmia Research

Austin, Texas, United States

Site Status

Sentara Cariovascular Research Insititute

Norfolk, Virginia, United States

Site Status

4 Sites

Different, , Austria

Site Status

5 Sites

Different, , Belgium

Site Status

5 Sites

Different, , Denmark

Site Status

13 Sites

Different, , Germany

Site Status

4 Sites

Different, , Italy

Site Status

6 Sites

Different, , Netherlands

Site Status

3 Sites

Different, , Spain

Site Status

4 Sites

Different, , United Kingdom

Site Status

Countries

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United States Austria Belgium Denmark Germany Italy Netherlands Spain United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 28130378 (View on PubMed)

Haeusler KG, Eichner FA, Heuschmann PU, Fiebach JB, Engelhorn T, Callans D, De Potter T, Debruyne P, Scherr D, Hindricks G, Al-Khalidi HR, Mont L, Kim WY, Piccini JP, Schotten U, Themistoclakis S, Di Biase L, Kirchhof P. Detection of brain lesions after catheter ablation depends on imaging criteria: insights from AXAFA-AFNET 5 trial. Europace. 2023 Dec 6;25(12):euad323. doi: 10.1093/europace/euad323.

Reference Type DERIVED
PMID: 37897713 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35135308 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32725107 (View on PubMed)

Other Identifiers

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2014-002442-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AFNET 5 AXAFA

Identifier Type: -

Identifier Source: org_study_id