Clinical trial NCT02150902: Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence
Official title: AUGMENTED WIDE AREA CIRCUMFERENTIAL CATHETER ABLATION FOR REDUCTION OF ATRIAL FIBRILLATION RECURRENCE - A RANDOMIZED CLINICAL TRIAL (The AWARE Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Catheter ablation for atrial fibrillation
treatment for atrial fibrillation
comparison of catheter ablation techniques for atrial fibrillation
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2014-05-30
Enrollment: 411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to First Recurrence of any ECG documented AF, AFl or AT
timeFrame: between days 91 and 364 after catheter ablation
Secondary outcomes:
measure: The need for repeat catheter ablation procedure
timeFrame: days 91 and 364 after catheter ablation
measure: ECG documented AF
timeFrame: during the first 90 days after catheter ablation
measure: emergency department visits or hospitalizations
timeFrame: from randomization to day 364
measure: procedure related complications
timeFrame: from ablation to day 364
measure: Quality of Life measurement using (EQ-5 and Canadian Cardiovascular Society-Severity of AF scales)
timeFrame: from randomization to day 364
measure: Total procedure duration
timeFrame: day of the ablation procedure
measure: Total radiation exposure during the procedure
timeFrame: day of the ablation procedure
measure: Health Economic Analysis
timeFrame: from randomization to day 364
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary-Foothills Campus
state: Alberta
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials Inc.
state: British Columbia
city: Halifax
country: Canada
facility: QE II Health Sciences Centre
state: Nova Scotia
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael"s Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital-University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: CIUSSSNIM-Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke (CHUS)
state: Quebec
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Girish Nair, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nair GM, Birnie DH, Wells GA, Nery PB, Redpath CJ, Sarrazin JF, Roux JF, Parkash R, Bernier M, Sterns LD, Novak P, Veenhuyzen G, Morillo CA, Singh SM, Sturmer M, Chauhan VS, Angaran P, Essebag V. Augmented wide area circumferential catheter ablation for reduction of atrial fibrillation recurrence (AWARE) trial: Design and rationale. Am Heart J. 2022 Jun;248:1-12. doi: 10.1016/j.ahj.2022.02.009. Epub 2022 Feb 24.