Personalized wide-area radiofrequency ablation plus pulmonary vein isolation versus pulsed-field pulmonary vein isolation for paroxysmal atrial fibrillation

AWARE-2 - Randomized Controlled Trial Ablation Strategy for Paroxysmal Atrial Fibrillation - Trigger and Substrate Guided Wide Area Radiofrequency Ablation Compared to Pulsed Field Ablation Pulmonary Vein Isolation

This trial will test whether a patient-tailored radiofrequency ablation that targets extra atrial sources plus pulmonary vein isolation prevents recurrent atrial fibrillation better than pulsed-field pulmonary vein isolation in adults with paroxysmal AF.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 556 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ottawa Heart Institute Research Corporation (other)
• Locations: 2 sites (Ottawa, Ontario and 1 other locations)
• Trial ID: NCT04823299 on ClinicalTrials.gov

What this trial studies

This randomized 1:1 trial compares two catheter ablation strategies for adults with paroxysmal atrial fibrillation: standard pulmonary vein isolation performed with pulsed field ablation (PFA) versus a patient-tailored wide-area pulmonary vein isolation plus targeted radiofrequency ablation (RFA) of non-pulmonary vein triggers and low-voltage atrial substrate. Participants are randomly assigned before their procedure and undergo the assigned ablation as part of routine clinical care at participating Canadian centers. After ablation all participants receive an implantable loop recorder for continuous long-term rhythm monitoring and are followed over time to compare arrhythmia recurrence and the need for repeat procedures. The trial aims to determine whether the individualized RFA-based approach reduces AF recurrence compared with PFA-only PVI.

Who should consider this trial

Good fit: Adults aged 18 or older with paroxysmal atrial fibrillation and at least one documented episode in the past 12 months who have not had prior left atrial ablation or surgery are ideal candidates.

Not a fit: Patients with persistent or permanent AF, prior left atrial ablation or surgery, documented other arrhythmias (AVNRT/AVRT/AT/Atrial Flutter), or contraindications to anticoagulation or ILR implantation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the individualized ablation approach could reduce recurrent atrial fibrillation, improve symptoms, and decrease the need for repeat procedures.

How similar studies have performed: Pulmonary vein isolation is an established effective treatment and pulsed-field ablation has shown promising safety and efficacy, but direct comparisons with individualized substrate-guided radiofrequency strategies are limited and this head-to-head approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years on the date of consent for the trial.
2. Subjects must have paroxysmal AF with at least one episode of AF over the past 12 months (patients on antiarrhythmic medications do not need to satisfy this criterion).

   At least one episode of AF documented on 12-lead ECG, Holter monitor, Trans-telephonic monitor (TTM) or Loop Recorder.
3. Subjects must be able to provide informed consent.

Exclusion Criteria:

1. Persistent and permanent AF.
2. History of previous catheter or surgical ablation for AF, AFl, AT, Atrioventricular Nodal Reentrant Tachycardia (AVNRT), Atrioventricular Reentrant Tachycardia (AVRT).
3. Documented AVNRT, AVRT, AT or Atrial Flutter prior to enrolment in the trial.
4. Previous left atrial (LA) ablation or LA surgery.
5. Previous pulmonary vein stenosis or pulmonary vein stent.
6. Pre-existing hemi-diaphragmatic paralysis.
7. Active intracardiac thrombus.
8. Contraindication to systemic oral anticoagulation therapy
9. Current immunosuppressant therapy (corticosteroids, biologic immunomodulators; such patients may be considered if they can safely discontinue immunosuppressants for three months prior to and for three months following catheter ablation).
10. Reversible causes of AF (e.g., uncontrolled hyperthyroidism, within six months of cardiac surgery).
11. Left ventricular ejection fraction \<35%.
12. NYHA Class 4 heart failure.
13. Hypertrophic cardiomyopathy
14. Significant valve disease (moderate or severe mitral/aortic stenosis or regurgitation).
15. Patients with mechanical mitral prosthetic valves
16. Known adverse reaction to adenosine.
17. Chronic Kidney Disease ≥ Stage 4.
18. Significant congenital heart disease (including atrial septal defects or pulmonary vein abnormalities; however, subjects with patent foramen ovale will not be excluded).
19. Pregnant subjects.
20. Cerebral ischemic event (stroke or transient ischemic attack) in the six months prior to consenting for the trial.
21. History of thromboembolic events in the 6 months preceding enrollment.
22. Currently participating or anticipated to participate in interventional clinical trials of drug, device or biologic agents that could affect the results of this trial.
23. Primary pulmonary hypertension
24. Rheumatic heart disease
25. Thrombocytosis, thrombocytopenia and other hypercoagulable states
26. Active systemic infection
27. Patients with life expectancy less than 12 months.
28. Unwilling or unable to comply fully with study procedures and follow-up.

Where this trial is running

Ottawa, Ontario and 1 other locations

• University of Ottawa Heart Institute — Ottawa, Ontario, Canada (RECRUITING)
• McGill University Health Center — Montreal, Quebec, Canada (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Girish Nair, MD — Ottawa Heart Institute Research Corporation
• Study coordinator: Girish Nair, MD

Conditions: Atrial Fibrillation, Catheter Ablation, Radiofrequency Catheter Ablation