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).
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).
Brief Title
Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Atrial Fibrillation
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
Atrilal fibrillation
anticoagulation
prevention of peri-procedural complication
catheter ablation
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02227550
Org Class
Other
Org Full Name
Atrial Fibrillation Network
Org Study Id
AFNET 5 AXAFA
Overall Status
Completed
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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
Outcome Measure
death and serious cardiovascular events
Outcome Time Frame
appr. 4 months
Secondary Ids
Secondary Id
2014-002442-45
Secondary Outcomes
Outcome Description
number
Outcome Time Frame
appr. 4 months
Outcome Measure
any bleeding event
Outcome Description
number
Outcome Time Frame
appr. 4 months
Outcome Measure
major bleeding events acc. to the ISTH and TIMI definitions
Outcome Description
number
Outcome Time Frame
appr. 4 month
Outcome Measure
strokes, other systemic embolic events and all-cause death
Outcome Description
number of days
Outcome Time Frame
appr. 4 months
Outcome Measure
time from randomisation to ablation
Outcome Description
number
Outcome Time Frame
appr. 4 months
Outcome Measure
nights spent in hospital after ablation
Outcome Time Frame
appr. 4 months
Outcome Measure
health-care related cost calculation
Outcome Description
number
Outcome Time Frame
appr. 4 months
Outcome Measure
hospitalizations for cardiovascular reasons
Outcome Description
number of days
Outcome Time Frame
appr. 4 months
Outcome Measure
Treatment duration prior to ablation and total time on oral anticoagulation
Outcome Description
number of patients
Outcome Time Frame
appr. 4 months
Outcome Measure
patients with clinically indicated TEE
Outcome Description
Active clotting measurements
Outcome Time Frame
during ablation
Outcome Measure
ACT during ablation
Outcome Description
time to recurrent AF
Outcome Time Frame
appr. 4 months
Outcome Measure
recurrent Atrial Fibrillation (AF)
Outcome Description
rythm status documented by 24 hour Holter ECG
Outcome Time Frame
end of follow-up
Outcome Measure
rhythm status at the end of follow-up
Outcome Description
number of events
Outcome Time Frame
appr. 4 months
Outcome Measure
vascular access complications leading to prolongation of in-hospital stay or specific therapy
Outcome Description
questionaire
Outcome Time Frame
baseline to 3 month follow-up
Outcome Measure
Quality-of-life changes
Outcome Description
questionaire
Outcome Time Frame
baseline to 3 month follow-up
Outcome Measure
cognitive function change
Outcome Description
prevalence (MRI-substudy)
Outcome Time Frame
within 48 hours after ablation procedures
Outcome Measure
clinically "silent" MRI-detected brain lesions
Outcome Description
MRI-substudy
Outcome Time Frame
appr. 4 months
Outcome Measure
Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Luigi Dibiase
Investigator Email
ldibiase@montefiore.org
Investigator Phone
347-271-1637
Categories Mesh Debug
Heart/Cardiovascular --- ATRIAL FIBRILLATION
Heart/Cardiovascular --- ARRHYTHMIAS, CARDIAC
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
MeSH Terms
ATRIAL FIBRILLATION
ARRHYTHMIAS, CARDIAC
HEART DISEASES
CARDIOVASCULAR DISEASES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
ACARBOXYPROTHROMBIN
WARFARIN
PHENPROCOUMON
FLUINDIONE
APIXABAN
4-HYDROXYCOUMARINS
COUMARINS
BENZOPYRANS
PYRANS
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING