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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by German Atrial Fibrillation Network
Sponsor:
Collaborators:
Bristol-Myers Squibb
Pfizer
Information provided by (Responsible Party):
German Atrial Fibrillation Network
ClinicalTrials.gov Identifier:
NCT02227550
First received: June 27, 2014
Last updated: August 27, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Atrial Fibrillation
Drug: Vitamin K antagonist
Drug: Apixaban
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by German Atrial Fibrillation Network:

Primary Outcome Measures:
  • death and serious cardiovascular events [ Time Frame: appr. 4 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: appr. 4 months ] [ Designated as safety issue: Yes ]
    number

  • major bleeding events acc. to the ISTH and TIMI definitions [ Time Frame: appr. 4 months ] [ Designated as safety issue: Yes ]
    number

  • strokes, other systemic embolic events and all-cause death [ Time Frame: appr. 4 month ] [ Designated as safety issue: Yes ]
    number

  • time from randomisation to ablation [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
    number of days

  • nights spent in hospital after ablation [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
    number

  • health-care related cost calculation [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
  • hospitalizations for cardiovascular reasons [ Time Frame: appr. 4 months ] [ Designated as safety issue: Yes ]
    number

  • Treatment duration prior to ablation and total time on oral anticoagulation [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
    number of days

  • patients with clinically indicated TEE [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
    number of patients

  • ACT during ablation [ Time Frame: during ablation ] [ Designated as safety issue: No ]
    Active clotting measurements

  • recurrent Atrial Fibrillation (AF) [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]
    time to recurrent AF

  • rhythm status at the end of follow-up [ Time Frame: end of follow-up ] [ Designated as safety issue: No ]
    rythm status documented by 12-lead ECG and 24 hour Holter ECG

  • vascular access complications leading to prolongation of in-hospital stay or specific therapy [ Time Frame: appr. 4 months ] [ Designated as safety issue: Yes ]
    number of events

  • Quality-of-life changes [ Time Frame: baseline to 3 month follow-up ] [ Designated as safety issue: No ]
    questionaire

  • cognitive function change [ Time Frame: baseline to 3 month follow-up ] [ Designated as safety issue: No ]
    questionaire

  • clinically "silent" MRI-detected brain lesions [ Time Frame: within 48 hours after ablation procedures ] [ Designated as safety issue: No ]
    prevalence (MRI-substudy)

  • Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation [ Time Frame: appr. 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 650
Study Start Date: December 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apixaban
Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)
Drug: Vitamin K antagonist
any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin
Other Names:
  • warfarin
  • phenprocoumon
  • acecoumaril
  • fluindione
Active Comparator: Vitamin K antagonist
VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine
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.
Other Name: BMS-562247

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Exclusion criteria related to a cardiac condition

E8. 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.

E9. Any previous ablation or surgical therapy for AF

E10. Cardiac ablation therapy for any indication (catheter-based or surgical) within 3 months prior to randomisation

E11. Clinical need for "triple therapy" (combination therapy of clopidogrel, acetylsalicylic acid, and oral anticoagulation)

E12. Other contraindications for use of VKA or apixaban

Exclusion criteria based on laboratory abnormalities

E13. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) < 15 ml/min

-

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02227550

Contacts
Contact: Hotline Hotline: +49-89-990 1649-810 axafa@cri-muc.eu

Sponsors and Collaborators
German Atrial Fibrillation Network
Bristol-Myers Squibb
Pfizer
Investigators
Principal Investigator: Paulus Kirchhof, Professor University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany
  More Information

No publications provided

Responsible Party: German Atrial Fibrillation Network
ClinicalTrials.gov Identifier: NCT02227550     History of Changes
Other Study ID Numbers: AXAFA - AFNET 5, 2014-002442-45
Study First Received: June 27, 2014
Last Updated: August 27, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Atrial Fibrillation Network:
Atrilal fibrillation
anticoagulation
prevention of peri-procedural complication
catheter ablation

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Vitamins
Vitamin K
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014