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

Primary Purpose

Atrial Fibrillation

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Vitamin K antagonist
Apixaban
Sponsored by
Atrial Fibrillation Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Atrilal fibrillation, anticoagulation, prevention of peri-procedural complication, catheter ablation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Montefiore Medical Center
  • Hospital of the University of Pennsyvlania
  • Vanderbilt University Medical Center
  • Texas Cardiac Arrhythmia Research
  • Sentara Cariovascular Research Insititute
  • 4 Sites
  • 5 Sites
  • 5 Sites
  • 13 Sites
  • 4 Sites
  • 6 Sites
  • 3 Sites
  • 4 Sites

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Apixaban

Vitamin K antagonist

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
June 27, 2014
Last Updated
October 19, 2017
Sponsor
Atrial Fibrillation Network
Collaborators
Bristol-Myers Squibb, Pfizer, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
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1. Study Identification

Unique Protocol Identification Number
NCT02227550
Brief Title
Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Atrial Fibrillation Network
Collaborators
Bristol-Myers Squibb, Pfizer, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
Atrilal fibrillation, anticoagulation, prevention of peri-procedural complication, catheter ablation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
676 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apixaban
Arm Type
Experimental
Arm Description
Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)
Arm Title
Vitamin K antagonist
Arm Type
Active Comparator
Arm Description
VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine
Intervention Type
Drug
Intervention Name(s)
Vitamin K antagonist
Other Intervention Name(s)
warfarin, phenprocoumon, acecoumaril, fluindione
Intervention Description
any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
BMS-562247
Intervention Description
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.
Primary Outcome Measure Information:
Title
death and serious cardiovascular events
Description
A composite of all-cause death, stroke (ischemic stroke, subarachnoid haemorrhage and haemorrhagic stroke), and major bleeding events, def.as BARC 2 or higher
Time Frame
appr. 4 months
Secondary Outcome Measure Information:
Title
any bleeding event
Description
number
Time Frame
appr. 4 months
Title
major bleeding events acc. to the ISTH and TIMI definitions
Description
number
Time Frame
appr. 4 months
Title
strokes, other systemic embolic events and all-cause death
Description
number
Time Frame
appr. 4 month
Title
time from randomisation to ablation
Description
number of days
Time Frame
appr. 4 months
Title
nights spent in hospital after ablation
Description
number
Time Frame
appr. 4 months
Title
health-care related cost calculation
Time Frame
appr. 4 months
Title
hospitalizations for cardiovascular reasons
Description
number
Time Frame
appr. 4 months
Title
Treatment duration prior to ablation and total time on oral anticoagulation
Description
number of days
Time Frame
appr. 4 months
Title
patients with clinically indicated TEE
Description
number of patients
Time Frame
appr. 4 months
Title
ACT during ablation
Description
Active clotting measurements
Time Frame
during ablation
Title
recurrent Atrial Fibrillation (AF)
Description
time to recurrent AF
Time Frame
appr. 4 months
Title
rhythm status at the end of follow-up
Description
rythm status documented by 24 hour Holter ECG
Time Frame
end of follow-up
Title
vascular access complications leading to prolongation of in-hospital stay or specific therapy
Description
number of events
Time Frame
appr. 4 months
Title
Quality-of-life changes
Description
questionaire
Time Frame
baseline to 3 month follow-up
Title
cognitive function change
Description
questionaire
Time Frame
baseline to 3 month follow-up
Title
clinically "silent" MRI-detected brain lesions
Description
prevalence (MRI-substudy)
Time Frame
within 48 hours after ablation procedures
Title
Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation
Description
MRI-substudy
Time Frame
appr. 4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paulus Kirchhof, Professor
Organizational Affiliation
University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center
City
New York
State/Province
New York
Country
United States
Facility Name
Hospital of the University of Pennsyvlania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Texas Cardiac Arrhythmia Research
City
Austin
State/Province
Texas
Country
United States
Facility Name
Sentara Cariovascular Research Insititute
City
Norfolk
State/Province
Virginia
Country
United States
Facility Name
4 Sites
City
Different
Country
Austria
Facility Name
5 Sites
City
Different
Country
Belgium
Facility Name
5 Sites
City
Different
Country
Denmark
Facility Name
13 Sites
City
Different
Country
Germany
Facility Name
4 Sites
City
Different
Country
Italy
Facility Name
6 Sites
City
Different
Country
Netherlands
Facility Name
3 Sites
City
Different
Country
Spain
Facility Name
4 Sites
City
Different
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28130378
Citation
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.
Results Reference
background
PubMed Identifier
35135308
Citation
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.
Results Reference
derived
PubMed Identifier
32725107
Citation
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.
Results Reference
derived

Learn more about this trial

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

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