Atrial FibrillationAWARE-2NCT04823299
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
A study testing PVI-PLUS ARM, INTERVENTIONAL ARM in people with Atrial Fibrillation and Catheter Ablation, run by Ottawa Heart Institute Research Corporation at 2 sites in Canada.
Trial summary
Atrial fibrillation (AF) is a common heart rhythm disorder affecting over a million people in North America and is associated with serious complications including stroke, heart failure, reduced quality of life, and premature death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Catheter Ablation, Radiofrequency Catheter Ablation
- What is being tested?
- PVI-PLUS ARM, INTERVENTIONAL ARM
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 556 participants
- Where
- 2 sitesCanada
- Study dates
- 23 Mar 2026to Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years on the date of consent for the trial.
- 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.
- Subjects must be able to provide informed consent.
Who cannot join
- Persistent and permanent AF.
- History of previous catheter or surgical ablation for AF, AFl, AT, Atrioventricular Nodal Reentrant Tachycardia (AVNRT), Atrioventricular Reentrant Tachycardia (AVRT).
- Documented AVNRT, AVRT, AT or Atrial Flutter prior to enrolment in the trial.
- Previous left atrial (LA) ablation or LA surgery.
- Previous pulmonary vein stenosis or pulmonary vein stent.
- Pre-existing hemi-diaphragmatic paralysis.
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- Active intracardiac thrombus.
- Contraindication to systemic oral anticoagulation therapy
- 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).
- Reversible causes of AF (e.g., uncontrolled hyperthyroidism, within six months of cardiac surgery).
- Left ventricular ejection fraction <35%.
- NYHA Class 4 heart failure.
- Hypertrophic cardiomyopathy
- Significant valve disease (moderate or severe mitral/aortic stenosis or regurgitation).
- Patients with mechanical mitral prosthetic valves
- Known adverse reaction to adenosine.
- Chronic Kidney Disease ≥ Stage 4.
- Significant congenital heart disease (including atrial septal defects or pulmonary vein abnormalities; however, subjects with patent foramen ovale will not be excluded).
- Pregnant subjects.
- Cerebral ischemic event (stroke or transient ischemic attack) in the six months prior to consenting for the trial.
- History of thromboembolic events in the 6 months preceding enrollment.
- Currently participating or anticipated to participate in interventional clinical trials of drug, device or biologic agents that could affect the results of this trial.
- Primary pulmonary hypertension
- Rheumatic heart disease
- Thrombocytosis, thrombocytopenia and other hypercoagulable states
- Active systemic infection
- Patients with life expectancy less than 12 months.
- Unwilling or unable to comply fully with study procedures and follow-up.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Not yet recruiting
McGill University Health Center
Montreal, Quebec, H3G 1A4
Vidal Essebag, MD, vidal.essebag@mcgill.ca
Vidal Essebag, MD
- Recruiting
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Girish Nair, MD, GNair@ottawaheart.ca
Girish Nair, MD
About this study
Official title: 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
Atrial fibrillation (AF) is a common heart rhythm disorder affecting over a million people in North America and is associated with serious complications including stroke, heart failure, reduced quality of life, and premature death. Catheter ablation has been shown to be more effective than medications for controlling symptoms and reducing the risk of these complications; however, recurrence of AF after ablation remains a significant challenge, often due to incomplete or ineffective initial procedures. This clinical trial aims to determine whether a novel, patient-tailored ablation strategy can improve outcomes compared to the current standard-of-care approach. Participants will be randomly assigned to undergo either standard pulmonary vein isolation or a more individualized ablation procedure that identifies and targets patient-specific sources of AF. All participants will undergo the ablation procedure, receive continuous heart rhythm monitoring, and be followed over time to assess recurrence and safety outcomes.
Read the detailed description
This study is a randomized controlled trial evaluating two different catheter ablation strategies for patients with paroxysmal atrial fibrillation (AF). Participants are randomly assigned in a 1:1 ratio to either the control arm or the experimental arm prior to undergoing their ablation procedure. In the control arm, patients receive a pulmonary vein isolation (PVI)-only strategy using pulsed field ablation (PFA). This approach targets only the pulmonary veins, which are the most common source of AF triggers, and does not include additional ablation beyond isolating these veins. In contrast, the experimental arm uses a more comprehensive PVI-PLUS strategy with radiofrequency ablation (RFA). In addition to standard pulmonary vein isolation, this strategy includes patient-specific ablation of non-pulmonary vein triggers and abnormal atrial substrate, such as low-voltage areas identified during electrophysiologic testing. This individualized approach aims to reduce arrhythmia recurrence by addressing additional sources of AF beyond the pulmonary veins.
All participants undergo their assigned catheter ablation procedure as part of routine clinical care, with procedural details tailored according to the randomized strategy. Following the ablation, patients receive an implantable loop recorder (ILR), which is a small device placed under the skin that continuously monitors heart rhythm. The ILR allows for continuous, long-term detection of atrial arrhythmias, including both symptomatic and asymptomatic episodes, ensuring accurate assessment of treatment outcomes throughout the study period.
Participants are followed closely for a total of 24 months after the ablation procedure. During this follow-up period, patients attend scheduled visits at 2, 6, 12, 18, and 24 months, where ILR data are reviewed and clinical assessments are performed. The continuous monitoring provided by the ILR is central to evaluating the study's primary and secondary outcomes, including recurrence of atrial fibrillation, atrial flutter, or atrial tachycardia. In addition to rhythm monitoring, patients complete quality-of-life questionnaires at baseline and at 24 months, and any repeat procedures, hospital visits, or complications are recorded. This structured follow-up ensures comprehensive evaluation of both the effectiveness and safety of the two ablation strategies over time.
- Being tested
- PVI-ONLY, CONTROL ARM, PVI-PLUS ARM, INTERVENTIONAL ARM
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PVI-ONLY, CONTROL ARMProcedure or surgery
PULSED FIELD ABLATION (PFA) PVI-ONLY STRATEGY: CONTROL ARM
PVI-PLUS ARM, INTERVENTIONAL ARMProcedure or surgery
RADIOFREQUENCY CATHETER ABLATION (RFA) PVI-PLUS : INTERVENTION ARM
| Study group | Role | What they receive |
|---|---|---|
| PVI-ONLY ablation | Active comparator | Pulsed Field Ablation (PFA), control arm Receives: Procedure: PVI-ONLY, CONTROL ARM |
| PVI-PLUS ablation | Experimental | RADIOFREQUENCY CATHETER ABLATION (RFA), interventional arm Receives: Procedure: PVI-PLUS ARM, INTERVENTIONAL ARM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Freedom from atrial fibrillation, atrial flutter or atrial tachycardia
AF, AFl or AT, symptomatic or asymptomatic lasting ≥ 30 seconds
Measured: 61 to 730 days after ablation
Secondary outcomes (16)
Atrial fibrillation burden
Total duration of AF recorded on ambulatory monitoring/total duration of monitoring
Measured: 730 days
Long-term rate of documented atrial fibrillation, atrial flutter or atrial tachycardia
Long-term rate of documented AF, AFl or AT lasting ≥ 30 seconds
Measured: 730 days
Incidence of any ECG/ILR documented atrial fibrillation, atrial flutter or atrial tachycardia
Incidence of any ECG/ILR documented AF, AFl or AT (symptomatic or asymptomatic; lasting ≥ 30 seconds
Measured: First 60 days after catheter ablation
Ablation procedure duration
Catheter ablation procedure time
Measured: On day of ablation
Fluoroscopic exposure
Fluoro time in minutes
Measured: On day of ablation
Composite Safety outcomes
Procedure Related Complications at any time including Stroke, PV stenosis, pericarditis, phrenic nerve palsy, cardiac perforation, atrio-esophageal fistula, major bleeding and/or death.
Measured: 730 days
Emergency room visits or hospitalization due to recurrent atrial fibrillation, atrial flutter or atrial tachycardia
Emergency room visits or hospitalization due to recurrent atrial fibrillation, atrial flutter or atrial tachycardia
Measured: 730 days
Repeat catheter ablation for atrial fibrillation, atrial flutter or atrial tachycardia
Repeat catheter ablation for atrial fibrillation, atrial flutter or atrial tachycardia
Measured: 730 days
Quality of life scale
EuroQol 5-Dimension questionnaire (EQ-5D), scale of 0-100, higher is better perceived health.
Measured: 12 and 24 months
Health Economic analyses
Health Economic analyses
Measured: 730 days
Cumulative duration of Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia (atrial burden)
Cumulative duration of AF, AFL or AT (atrial burden) from day 61 after interventions to end of follow-up
Measured: Day 61- Day 730
Comparison of primary outcome events between patients undergoing PVI-ONLY and PVI-PLUS
Comparison of primary outcome events (freedom from atrial fibrillation, atrial flutter or atrial tachycardia) between patients undergoing PVI only (due to lack of additional triggers/substrate) in the PVI-PLUS strategy and those in the PVI-ONLY group.
Measured: 730 days
Fluoroscopic exposure
Total Air Kerma
Measured: On day of ablation
Fluoroscopic exposure
Dose Area Protocol.
Measured: On day of ablation
Quality of life scale
Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT), 0-100 score range, 100 - no impairment, and 0-very poor quality of life.
Measured: 12 and 24 months
Quality of life scale
Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF), score range 0-4, higher score being worse symptoms, or greater impairment.
Measured: 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start23 Mar 2026
- Primary completionMar 2029 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-blind, prospective, randomized
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 556 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Abbott
- Responsible party
- Sponsor
- Investigators
- Girish Nair, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823299
- Sponsor's protocol ID
- v21022021
- Acronym
- AWARE-2
- Status last verified
- Aug 2026
- First submitted
- 23 Mar 2021
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04823299
- Acronym / sponsor ID
- AWARE-2 / v21022021
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 556 participants (estimated)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Abbott
- Study start
- 23 Mar 2026 (actual)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 30 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Atrial fibrillation (AF) is a common heart rhythm disorder affecting over a million people in North America and is associated with serious complications including stroke, heart failure, reduced quality of life, and premature death. Catheter ablation has been shown to be more effective than medications for controlling symptoms and reducing the risk of these complications; however, recurrence of AF after ablation remains a significant challenge, often due to incomplete or ineffective initial procedures. This clinical trial aims to determine whether a novel, patient-tailored ablation strategy can improve outcomes compared to the current standard-of-care approach. Participants will be randomly assigned to undergo either standard pulmonary vein isolation or a more individualized ablation procedure that identifies and targets patient-specific sources of AF. All participants will undergo the ablation procedure, receive continuous heart rhythm monitoring, and be followed over time to assess recurrence and safety outcomes.
Detailed description
This study is a randomized controlled trial evaluating two different catheter ablation strategies for patients with paroxysmal atrial fibrillation (AF). Participants are randomly assigned in a 1:1 ratio to either the control arm or the experimental arm prior to undergoing their ablation procedure. In the control arm, patients receive a pulmonary vein isolation (PVI)-only strategy using pulsed field ablation (PFA). This approach targets only the pulmonary veins, which are the most common source of AF triggers, and does not include additional ablation beyond isolating these veins. In contrast, the experimental arm uses a more comprehensive PVI-PLUS strategy with radiofrequency ablation (RFA). In addition to standard pulmonary vein isolation, this strategy includes patient-specific ablation of non-pulmonary vein triggers and abnormal atrial substrate, such as low-voltage areas identified during electrophysiologic testing. This individualized approach aims to reduce arrhythmia recurrence by addressing additional sources of AF beyond the pulmonary veins.
All participants undergo their assigned catheter ablation procedure as part of routine clinical care, with procedural details tailored according to the randomized strategy. Following the ablation, patients receive an implantable loop recorder (ILR), which is a small device placed under the skin that continuously monitors heart rhythm. The ILR allows for continuous, long-term detection of atrial arrhythmias, including both symptomatic and asymptomatic episodes, ensuring accurate assessment of treatment outcomes throughout the study period.
Participants are followed closely for a total of 24 months after the ablation procedure. During this follow-up period, patients attend scheduled visits at 2, 6, 12, 18, and 24 months, where ILR data are reviewed and clinical assessments are performed. The continuous monitoring provided by the ILR is central to evaluating the study's primary and secondary outcomes, including recurrence of atrial fibrillation, atrial flutter, or atrial tachycardia. In addition to rhythm monitoring, patients complete quality-of-life questionnaires at baseline and at 24 months, and any repeat procedures, hospital visits, or complications are recorded. This structured follow-up ensures comprehensive evaluation of both the effectiveness and safety of the two ablation strategies over time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Single-blind, prospective, randomized
| Arm | Type | Receives |
|---|---|---|
| PVI-ONLY ablation | Active comparator | Procedure: PVI-ONLY, CONTROL ARMPulsed Field Ablation (PFA), control arm |
| PVI-PLUS ablation | Experimental | Procedure: PVI-PLUS ARM, INTERVENTIONAL ARMRADIOFREQUENCY CATHETER ABLATION (RFA), interventional arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years on the date of consent for the trial.
- 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.
- Subjects must be able to provide informed consent.
Key exclusion criteria (28 listed)
- Persistent and permanent AF.
- History of previous catheter or surgical ablation for AF, AFl, AT, Atrioventricular Nodal Reentrant Tachycardia (AVNRT), Atrioventricular Reentrant Tachycardia (AVRT).
- Documented AVNRT, AVRT, AT or Atrial Flutter prior to enrolment in the trial.
- Previous left atrial (LA) ablation or LA surgery.
- Previous pulmonary vein stenosis or pulmonary vein stent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PVI-ONLY, CONTROL ARMPULSED FIELD ABLATION (PFA) PVI-ONLY STRATEGY: CONTROL ARM | Procedure or surgery | PVI-ONLY ablation |
| PVI-PLUS ARM, INTERVENTIONAL ARMRADIOFREQUENCY CATHETER ABLATION (RFA) PVI-PLUS : INTERVENTION ARM | Procedure or surgery | PVI-PLUS ablation |
Primary outcome
Freedom from atrial fibrillation, atrial flutter or atrial tachycardia
Time frame: 61 to 730 days after ablation
AF, AFl or AT, symptomatic or asymptomatic lasting ≥ 30 seconds
16 secondary outcomes
Atrial fibrillation burden
Time frame: 730 days
Long-term rate of documented atrial fibrillation, atrial flutter or atrial tachycardia
Time frame: 730 days
Incidence of any ECG/ILR documented atrial fibrillation, atrial flutter or atrial tachycardia
Time frame: First 60 days after catheter ablation
Ablation procedure duration
Time frame: On day of ablation
Fluoroscopic exposure
Time frame: On day of ablation
Composite Safety outcomes
Time frame: 730 days
Emergency room visits or hospitalization due to recurrent atrial fibrillation, atrial flutter or atrial tachycardia
Time frame: 730 days
Repeat catheter ablation for atrial fibrillation, atrial flutter or atrial tachycardia
Time frame: 730 days
Quality of life scale
Time frame: 12 and 24 months
Health Economic analyses
Time frame: 730 days
Cumulative duration of Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia (atrial burden)
Time frame: Day 61- Day 730
Comparison of primary outcome events between patients undergoing PVI-ONLY and PVI-PLUS
Time frame: 730 days
Fluoroscopic exposure
Time frame: On day of ablation
Fluoroscopic exposure
Time frame: On day of ablation
Quality of life scale
Time frame: 12 and 24 months
Quality of life scale
Time frame: 12 and 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Girish Nair, MD principal investigator
Ottawa Heart Institute Research Corporation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PVI-PLUS ARM, INTERVENTIONAL ARM in people with Atrial Fibrillation and Catheter Ablation, run by Ottawa Heart Institute Research Corporation at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Girish Nair, MD (613-696-7272, GNair@ottawaheart.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Freedom from atrial fibrillation, atrial flutter or atrial tachycardia (time frame: 61 to 730 days after ablation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026; AzTrials last refreshed its copy on 31 Oct 2026.