Clinical trial NCT03347227: Characterization of Arrhythmia Substrate to Ablate Persistent Atrial Fibrillation
Official title: Characterization of Arrhythmia Substrate to Ablate Persistent Atrial Fibrillation (Coast-AF) Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: AF ablation
Pulmonary vein isolation
Atrial scar ablation
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
First posted: 2017-11-20
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, parallel arm randomized clinical trial
Primary purpose: TREATMENT

Brief summary: A multicentre, parallel group, two arm, single-blinded randomized clinical trial, assessing the efficacy of a patient-tailored catheter ablation (CA) strategy guided by atrial scar mapping in addition to pulmonary vein isolation (PVI) when compared to PVI alone in patients with persistent atrial fibrillation (AF).

Detailed description: The optimal CA strategy for persistent AF remains unknown. Current data highlight the need for a better understanding of the substrate and mechanisms of arrhythmia maintenance in this population. Atrial scar-based catheter ablation has recently emerged as a promising strategy for ablation of AF. However, the available data has limitations that preclude definitive conclusions regarding the utility of this strategy (no data from multicenter, randomized studies available). Further research is needed to assess the role of scar-based ablation for persistent AF.

The Investigators hypothesize that catheter ablation of persistent AF (PeAF) tailored to abolish abnormal atrial substrate identified by intracardiac atrial scar mapping in addition to pulmonary vein isolation (PVI) will result in higher procedural success rates when compared to PVI alone.

The study will recruit 502 patients with PeAF (251 per treatment arm) who are candidates for CA ablation of AF according to the treating physician (and in agreement with current practice guidelines). Subjects will be recruited over a 42 month period. The total duration of the study is 60 months.

Prior to undergoing catheter ablation subjects will be seen by the investigator/ research assistant and the following data will be collected:

i. Age and sex ii. Structural heart disease if present iii. CHADS2VASc score iv. DR-FLASH score v. NYHA class vi. Current medications vii. Duration of uninterrupted AF viii. Height and weight ix. Echocardiogram and other cardiac imaging results (within previous 12 months, including assessment of left ventricular ejection fraction, left atrial volume and valve function) x. ECG, Holter or loop monitor recording (within past 36 months) documenting AF.

Subjects will be randomly assigned in a 1:1 ratio to undergo wide area circumferential ablation for pulmonary vein isolation (PVI- control arm) or wide area circumferential ablation PVI and scar ablation (experimental arm). Randomization will be stratified by centre and by sex. Subjects will be randomized prior to the procedure.

Enrolled subjects will have a clinical follow-up visit at 3, 6, 12 and 18 months after the ablation procedure. A 14-day continuous ambulatory ECG monitor will be completed at each visit. The results of monitoring will be interpreted at a centralized core lab, and the results will be adjudicated by an arrhythmia specialist blinded to treatment group. A total of three questionnaires will be administered throughout the study, each at a specific time point. The Quality of Life (EQ-5D), CCS-Severity of AF scale, and Atrial Fibrillation Effect on Quality of life (AFEQT) will be completed at baseline, and at the 12-month and 18 month visit.

Concomitant medical therapy will be selected according to the treating physician. All subjects will be maintained on systemic oral anticoagulation for at least 2 months following catheter ablation.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years ;
2. Subjects with symptomatic persistent AF AND clinically indicated catheter ablation for AF
3. At least one episode of AF that is sustained beyond 3 months in duration ; documented on 12-lead ECG, Holter monitor, loop monitor or trans-telephonic monitor (TTM) within 36 months of enrollment in the study;
4. Modified DR-FLASH score \>=4

4. Subjects must be able to provide informed consent.

Exclusion Criteria:

1. History of previous catheter ablation for AF or left atrial flutter;
2. History of previous surgical ablation for AF;
3. Known intracardiac thrombus;
4. Contraindication to systemic oral anticoagulation therapy;
5. Reversible causes of AF;
6. Hypertrophic cardiomyopathy;
7. Severe valvular disease (mitral/aortic stenosis or regurgitation);
8. Subjects that are pregnant or breastfeeding;
9. Comorbid condition with life expectancy \< 1 year

Primary outcomes:
measure: Rate of documented (>30s) AF, atrial flutter or atrial tachycardia occuring from day 91 to 18 months post ablation
timeFrame: day 91 post ablation to 18 months
Secondary outcomes:
measure: AF burden
timeFrame: At 12 months and 18 months
measure: Need for repeat ablation procedure for AF, AFl or AT
timeFrame: Up to 18 months
measure: Need for emergency room visits or hospitalization
timeFrame: Up to 18 months
measure: Incidence of any ECG documented AF with 90 days of ablation
timeFrame: up to 90 days
measure: Time to first recurrence at 18 months according to sex and atrial scar extent
timeFrame: 18 months
measure: Composite safety outcome
timeFrame: Up to 18 months
measure: Total ablation delivery time
timeFrame: Day of ablation procedure
measure: Total procedure duration
timeFrame: Day of ablation procedure
measure: Quality of life analyses
timeFrame: 18 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Libin Cardiovascular Institute
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre, Nova Scotia Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
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: Rouge Valley Regional Heart Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Sacre-Coeur Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec City
country: Canada
facility: Institute Universitaire de Cardiologie et Pneumologie du Quebec (IUCPQ)
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de L'Estrie-CHUS-Hopital Fleurimont
state: Quebec
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Pablo Nery, MD
role: PRINCIPAL_INVESTIGATOR
References: