Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence

Atrial Fibrillation Clinical Trial

— AWARE  

Official title:

AUGMENTED WIDE AREA CIRCUMFERENTIAL CATHETER ABLATION FOR REDUCTION OF ATRIAL FIBRILLATION RECURRENCE - A RANDOMIZED CLINICAL TRIAL (The AWARE Trial)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02150902
• Other study ID #: IRIS 2771
• Secondary ID: 201610PJT-376677
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 2015
• Est. completion date: September 30, 2025

Study information

• Verified date: January 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation (AF) is an abnormal heart rhythm in which the top chambers of the heart beat very fast. AF catheter ablation is a known technique to convert heart rhythm from AF to normal rhythm. The technique sends out electrical energy through a catheter (long thin round solid tubes) to destroy the heart tissues in a focused area where AF is starting. This technique is practiced at many hospitals, including the Heart Institute, and is not experimental.

The AWARE study will compare two techniques of AF catheter ablation:

1. Ablation of tissues in wide circular bands around the opening of the pulmonary veins (bring blood back from lungs) in the left upper chamber of the heart. A medicine called adenosine will be given to unmask any incompletely ablated area. Additional ablations will be given if required. This is standard procedure.

2. Same as above but adenosine will not be used. Instead, additional ablation of a second circular band of tissues around the opening of the pulmonary veins will be given. This additional ablation is not standard procedure and is considered experimental.

The Investigators are testing if adding more ablation sites will help maintain normal heart rhythm and reduce the rate of return to AF. The study will compare the occurrence of medical events and complications between the two groups.

Identical supplies and equipment used in both techniques have been approved by Health Canada. Adenosine is currently approved by Health Canada for the treatment and diagnosis of arrhythmias.

396 participants from study sites across Canada will be randomly assigned "similar to flipping a coin" to treatment group 1 or group 2.

After the ablation, participants will have study follow-up at 3, 6 and 12 months. All participant's will be followed for a minimum of 12 months.

Description:

Clinical relevance:

The problem of PV reconnection and recurrent AF after catheter ablation for paroxysmal AF is one of the important challenges faced by treating physicians.

Rationale:

The understanding of the role contact force plays in adequate lesion formation during catheter ablation and the fact that this may reduce pulmonary vein (PV) reconnection and AF recurrence is an exciting advance in the field of catheter ablation for AF. A few small clinical trials have demonstrated the safety and feasibility of contact force guided catheter ablation in reducing PV reconnection and AF recurrence. There is a clear need for well designed and adequately powered clinical trials to evaluate the effectiveness of this new strategy. The investigators have developed a novel "augmented" CF guided augmented ablation strategy and will test this against the current clinical gold standard ablation technique.

Objective:

Using contact force (CF) technology, our intention is to evaluate an "augmented- wide area circumferential catheter ablation strategy" that could potentially reduce the incidence of pulmonary vein reconnection and AF recurrence after catheter ablation in patients with paroxysmal AF.

Hypothesis:

In patients with symptomatic paroxysmal AF an augmented-wide area circumferential catheter ablation strategy will result in fewer electrocardiographically documented atrial arrhythmias (AF, atrial flutter and atrial tachycardia) recurrences compared to conventional wide-area catheter ablation.

All subjects in the control arm of the trial will undergo wide area circumferential catheter ablation (WACA; lesions delivered 1-2 cm away from the pulmonary vein ostium) around all four pulmonary veins to the endpoint of electrical isolation (demonstrated by entry and exit block using differential pacing). Catheter ablation will be performed using CF and VISITAG guidance (average CF >10g, Force time integral (FTI) > 500 g-sec and minimum ablation duration >10 sec). Dormant PV conduction will be tested using adenosine, after completion of the lesion set, and additional lesions will be delivered to eliminate dormant PV conduction.

In the experimental arm of the trial all subjects will undergo WACA as described above; however without adenosine testing. In addition these subjects will receive "augmented" ablation lesions, guided by CF feedback, on the outer aspect of the first WACA lesion set. Our hypothesis is that this "belts and suspender" strategy of redundant, CF guided antral ablation lesions will result in a wider band of irreversible atrial muscle and cardiac autonomic ganglionated-plexi damage. It is our expectation that the augmented WACA strategy will result in more durable PV isolation and thereby significantly reduce AF recurrence.

Trial Design:

This trial is a multicentre, prospective, randomized, blinded endpoint trial (PROBE) design. Subjects who satisfy the inclusion and exclusion criteria will be enrolled in the clinical trial. Subjects will be randomized (1:1) to either the control arm (WACA only) or the experimental arm (augmented- WACA). Patients randomized to the experimental arm will go on to have augmented-WACA. The first 90 days after catheter ablation will be considered a "blanking-period" and atrial tachyarrhythmias (AF, Atrial Flutter [AFl] or Atrial Tachycardia [AT]) occurring during this period will be documented. However, these will not be considered treatment failures. Patient accrual will occur over a 24-month period and each subject will have a minimum follow-up period of 12 months. The total duration of the trial will be 36-months (24 months for accrual and a minimum of 12 months of follow up for each subject). Patients will be followed at 3, 6, and 12 months, with 14 day continuous ambulatory ECG monitoring done at each follow up visit. A total of three questionnaires will be administered throughout the study, each at a specific time point. The Quality of Life (EQ-5D) and CCS-Severity of AF scale will be completed together, prior to ablation and at the final follow-up visit. The patient satisfaction score will be completed at the final follow-up visit. All participants will be followed for a minimum of 12 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 411
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Subjects must have symptomatic Paroxysmal AF that is refractory to at least one class I or Class III antiarrhythmic medication OR be intolerant of antiarrhythmic medications OR prefer not to trial antiarrhythmic medications

3. At least one episode of AF documented on 12-lead ECG, Holter monitor or Loop recorder.

4. Subjects must be able to provide informed consent

Exclusion Criteria:

1. Subjects with persistent or permanent AF

2. History of previous catheter or surgical ablation for AF

3. Presence of known intracardiac thrombus

4. Subjects with contraindication to systemic oral anticoagulation therapy, including a history of Heparin Induced Thrombocytopenia

5. Subjects with reversible causes of AF

6. Subjects with significant valve disease (moderate or severe mitral/aortic stenosis or regurgitation)

7. Subjects with known adverse reaction to adenosine

8. Subjects with congenital heart disease

9. Subjects that are pregnant

Related Conditions & MeSH terms

• Atrial Fibrillation
• Recurrence

Intervention

Procedure:
• Wide area circumferential catheter ablation
All subjects in the control arm of the trial will undergo wide area circumferential catheter ablation (WACA; lesions delivered 1-2 cm away from the pulmonary vein ostium) around all four pulmonary veins to the endpoint of electrical isolation (demonstrated by entry and exit block using differential pacing). Catheter ablation will be performed using contact force (CF) and electroanatomical mapping system guidance (average CF >10g, FTI > 500 g-sec and minimum ablation duration >10 sec). Dormant pulmonary vein conduction will be tested using adenosine, after completion of the lesion set, and additional lesions will be delivered to eliminate dormant PV conduction.
• Augmented- wide area circumferential ablation procedure
Subjects in this group will have WACA performed as described for WACA. Following completion of the WACA procedure a second set of circumferential ablation lesions will be delivered around the first set of ablation lesions. The ablation catheter tip will be positioned at each of the ablation lesions along the first WACA line and then moved away (from the PV ostia) until healthy, non ablated tissue is recorded from the catheter tip. Energy will be delivered using CF and FTI data as described previously. Once the first WACA ablation line has been completely duplicated the procedure will be deemed complete. In case PV isolation is not achieved after the first WACA lesion set repeat electrophysiologic testing will be performed to determine whether the augmented-WACA procedure was successful in achieving PV isolation.

Locations

Country	Name	City	State
Canada	University of Calgary-Foothills Campus	Calgary	Alberta
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	CIUSSSNIM-Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	McGill University Health Center	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Quebec	Quebec City	Quebec
Canada	Centre hospitalier universitaire de Sherbrooke (CHUS)	Sherbrooke	Quebec
Canada	St. Michael"s Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto General Hospital-University Health Network	Toronto	Ontario
Canada	Victoria Cardiac Arrhythmia Trials Inc.	Victoria	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Recurrence of any ECG documented AF, AFl or AT	Time to first recurrence of any ECG documented AF, AFl or AT (symptomatic or asymptomatic) occurring between days 91 and 364 after catheter ablation in the absence of Class I or III antiarrhythmic drug therapy.	between days 91 and 364 after catheter ablation
Secondary	The need for repeat catheter ablation procedure	The need for repeat catheter ablation procedure because of documented recurrence of symptomatic AF, AFl or AT	days 91 and 364 after catheter ablation
Secondary	ECG documented AF	Incidence of any ECG documented AF (symptomatic or asymptomatic) during the first 90 days after catheter ablation	during the first 90 days after catheter ablation
Secondary	emergency department visits or hospitalizations	The need for emergency department visits or hospitalizations	from randomization to day 364
Secondary	procedure related complications	Composite safety endpoints- procedure related complications (Stroke, PV stenosis, Pericarditis, Cardiac perforation, Atrio-esophageal fistula, Major bleeding) and/or death.	from ablation to day 364
Secondary	Quality of Life measurement using (EQ-5 and Canadian Cardiovascular Society-Severity of AF scales)	Quality of Life (EQ-5 and Canadian Cardiovascular Society-Severity of AF scales)	from randomization to day 364
Secondary	Total procedure duration	total ablation procedure duration in minutes	day of the ablation procedure
Secondary	Total radiation exposure during the procedure	Dose area product in McGy.cm2 and cumulative skin dose in mGv	day of the ablation procedure
Secondary	Health Economic Analysis	Health care related costs	from randomization to day 364