Clinical trial NCT03682991: Reversal of Atrial Substrate to Prevent Atrial
Official title: Reversal of Atrial Substrate to Prevent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Abbott
name: Phillips
name: Cardiac Arrhythmia Network of Canada
First posted: 2018-09-25
Enrollment: 670
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a parallel group, open label randomized clinical trial, with blinded endpoint evaluation (PROBE design)
Primary purpose: TREATMENT

Brief summary: A multi-center, randomized trial to examine the effect of aggressive risk factor control and arrhythmia trigger-based intervention on recurrence of atrial fibrillation.

Detailed description: Atrial fibrillation (AF) is a major health problem, with a prevalence of 0.4-1% of the population. It results in high healthcare costs and significant morbidity, especially for patients with severe symptoms. Exercise and risk factor modification to prevent and modify AF has garnered a significant amount of support in cohort studies that have proven benefit. It is well known that age, body mass index, valvular heart disease, heart failure, hypertension and sleep apnea are risk factors for AF, most of which are modifiable if targeted appropriately. In addition, catheter ablation techniques have evolved and improved to reduce AF recurrence in those who are most symptomatic, and either have heart failure, or are at risk for its development. Despite these advances, the recurrence of AF remains high.

We propose to determine whether early treatment of the arrhythmogenic substrate, with or without aggressive risk factor modification, is most important in prevention of recurrent AF. It is hypothesized that patients with underlying risk factors that promote AF will benefit most from a combined strategy of aggressive risk factor modification in combination with catheter ablation.

The study design will be a two-arm, parallel group, randomized clinical trial comparing catheter ablation versus catheter ablation plus aggressive risk factor therapy, followed by maintenance with blinded endpoint evaluation. Patients with symptomatic AF and two of the following will be included: BP ≥ 140/90 or history of hypertension, BMI≥27, diabetes, prior stroke/TIA, history of heart failure (prior heart failure admission due to AF or LVEF\<40%), age≥65. Patients will be excluded if they are exercising \>150 minutes/week by self-report. Patients will be randomly allocated to one of the following groups: 1) AF ablation within 3 months, 2) AF ablation at 3 months, with a 12 week home-based exercise/risk factor management program, followed by maintenance therapy. A 5-month treatment period will be observed to deliver the interventions and have a 2 month blanking period post ablation. Guideline-directed therapy for risk factors will occur in all groups, including BP, cholesterol, diabetes, alcohol reduction and sleep apnea screening. All patients will undergo implantation of an implantable cardiac monitor (ICM) at baseline. The primary outcome will be a composite of clincally significant AF (AF ≥ 24 hours), AF-related hospitalization/emergency department visits 5 months post randomization. Secondary outcomes will include: Death, Stroke or Systemic embolism, Quality of Life, Health Outcomes, recurrent AF, \& AF burden. The sample size required is 500. Safety outcomes include: AF catheter ablation procedural complications, Anti-arrhythmic medication related adverse events, \& Death.

Eligibility criteria: Inclusion Criteria: Patients with symptomatic (CCS-SAF ≥2) paroxysmal or persistent atrial fibrillation despite rate control, desiring catheter ablation and at least two of the following:

* BMI ≥ 27,
* BP ≥140/90 mmHg or history of hypertension,
* Prior stroke/transient ischemic attack,
* Diabetes,
* Heart failure (prior heart failure admission or left ventricle ejection fraction (LVEF) \<40%),
* Age ≥ 65 years
* Current smoker
* Excessive Alcohol use

Exclusion Criteria:

* Permanent AF (AF lasting \> 3 years)
* Prior catheter ablation for AF
* New York Heart Association (NYHA) Class IV (Severe) heart failure,
* Participation in a cardiac rehabilitation program within the last year,
* Currently performing exercise training \>150 minutes/week of moderate to vigorous physical activity,
* Unable to exercise,
* Unable to give informed consent,
* Other noncardiovascular medical condition making 1 year survival unlikely,
* Less than 18 years of age.

Primary outcomes:
measure: Number of AF related hospitalizations post ablation
timeFrame: up to 72 months
measure: Number of AF related Emergency Department (ED) visits post ablation
timeFrame: up to 72 months
measure: Number of clinically significant AF events post ablation
timeFrame: up to 72 months
Secondary outcomes:
measure: Number of AF-related hospitalizations
timeFrame: up to 72 months
measure: Number of AF-related emergency department (ED) visits
timeFrame: up to 72 months
measure: Number of Clinically significant AF events
timeFrame: up to 72 months
measure: Mean AF burden
timeFrame: up to 72 months
measure: Stroke or systemic embolism events
timeFrame: up to 72 months
measure: Quality of Life - CCS-SAF
timeFrame: Up to 24 months
measure: Quality of Life - AFEQT
timeFrame: Up to 24 months
measure: Number of recurrent AF-ablations
timeFrame: up to 72 months
measure: Cardioversions
timeFrame: up to 72 months
measure: All-cause mortality
timeFrame: up to 72 months
measure: AF at any time
timeFrame: Up to 72 months post randomization
measure: Health Outcomes
timeFrame: Up to 24 months
measure: Association between gender, AF risk factors and aggressive risk factor management
timeFrame: UP to 24 months
measure: Major Bleeding
timeFrame: Up to 72 months
Other outcomes:
measure: Number of ablation procedural complications [Safety]
timeFrame: up to 72 months
measure: Number of antiarrhythmic drug adverse effects [Safety]
timeFrame: up to 72 months
measure: Death (Safety)
timeFrame: Up to 72 months
Locations:
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
city: Kelowna
country: Canada
facility: Kelowna General Health
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Halifax
country: Canada
facility: QE II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Center
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Laval
country: Canada
facility: Laval 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: Montreal
country: Canada
facility: Sacre Coeur Hospital
state: Quebec
city: Regina
country: Canada
facility: Regina General Hospital
state: Saskatchewan
Study officials:
affiliation: Nova Scotia Health Authority
name: Ratika Parkash
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Centre
name: Allan Skanes
role: STUDY_DIRECTOR
affiliation: Nova Scotia Health
name: Chris Blanchard
role: STUDY_DIRECTOR
affiliation: University of Ottawa Heart Institution
name: David Birnie
role: STUDY_DIRECTOR
affiliation: University of Ottawa Heart Institution
name: George Wells
role: STUDY_DIRECTOR
affiliation: University of Groningen
name: Michiel Rienstra
role: STUDY_DIRECTOR
affiliation: Hamilton Health Sciences Centre
name: Jeff Healey
role: STUDY_DIRECTOR
affiliation: University of Ottawa Heart Institution
name: Jennifer Reed
role: STUDY_DIRECTOR
affiliation: London Health Sciences Centre
name: Anthony Tang
role: STUDY_DIRECTOR
affiliation: McGill University Hospital
name: Vidal Essebag
role: STUDY_DIRECTOR
affiliation: University of Groningen
name: Isabelle vanGelder
role: STUDY_DIRECTOR
affiliation: Nova Scotia Health Authority
name: John Sapp
role: STUDY_DIRECTOR
References: