Reversal of Atrial Substrate to Prevent Atrial

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

Official Title
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Reversal of Atrial Substrate to Prevent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Other: Aggressive Risk Factor Control
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Left atrial size > 5.5 cm, 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a parallel group, open label randomized clinical trial, with blinded endpoint evaluation (PROBE design)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aggressive Risk Factor Control<br>Multifaceted risk factor management relating to BP, exercise, sleep apnea, alcohol intake and diabetes management | Other: Aggressive Risk Factor Control<br>* Sleep apnea screening, therapy is recommended if apopnea-hypopnea (AHI) index is greater than 15, with a target index of less than 5. Counseling regarding alcohol reduction to 2 drinks/day for men, 1 drink/day for women, no binge drinking (>5 drinks at one setting). Participation in a 12 week structured, home-based exercise program and nutritional counseling. Weight reduction will be emphasized through modification of diet and exercise. Blood Pressure management to achieve a target systolic blood pressure (SBP) of <120/80 mm/Hg Smoking cessation facilitated through local resources already established at each site<br>|
| Active Comparator: Standard of Care<br>All patients in the control arm will receive therapies for AF as per the existing guidelines. BP, cholesterol, diabetic management will be administered as per the available guidelines. | Other: Standard of Care<br>* Recommendations based on current guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of AF related hospitalizations post ablation | AF-related hospitalizations (lasting more than 24 hours) from 2-months post ablation to end of follow up. | up to 48 months | 
| Number of AF related Emergency Department (ED) visits post ablation | AF-related emergency department visits from 2-months post ablation to end of follow up. | up to 48 months | 
| Number of clinically significant AF events post ablation | Clinically significant AF events lasting >24 hours (either an irregular R-R interval, or atrial cycle length < 280 ms, as obtained from an insertable cardiac monitor) from 2-months post ablation to end of follow up. | up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of AF-related hospitalizations | AF-related hospitalizations (lasting more than 24 hours) from randomization to end of follow up. | up to 48 months | 
| Number of AF-related emergency department (ED) visits | AF-related emergency department visits from randomization to end of follow up. | up to 48 months | 
| Number of Clinically significant AF events | Clinically significant AF events lasting >24 hours (either an irregular R-R interval, or atrial cycle length < 280 ms, as obtained from an insertable cardiac monitor) from randomization to end of follow up. | up to 48 months | 
| Mean AF burden | Average percentage of time in AF during follow up, as measured by insertable cardiac monitor. | up to 48 months | 
| Stroke or systemic embolism events | Total number of stoke or systemic embolism events. | up to 48 months | 
| Quality of Life - CCS-SAF | Symptom burden as measured by the Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) scale. CCS-SAF scores range from 0 to 4, with higher values representing more severe impact of symptoms on quality of life and activities of daily living. | Up to 24 months | 
| Quality of Life - AFEQT | Quality of life as measured by the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) scale. The scale consists of 21 questions with 7-point Likert scale responses. Questions 1-18 are grouped into three subscales (symptoms, daily activities and treatment concern). Questions 19-21 capture satisfaction with treatment and are not include in the HRQoL score of the questionnaire. Overall and subscale scores range from 0 to 100. Lower scores correspond to higher levels of disability (e.g., 0 corresponds to complete disability or responding extremely limited, difficult or bothersome to all questions answered), while a score of 100 corresponds to no disability (e.g., responding not at all limited, difficult or bothersome to all questions answered). For Satisfaction questions, a score of 100 corresponds to extreme satisfaction with current treatment. | Up to 24 months | 
| Number of recurrent AF-ablations | Number of re-ablations required. | up to 48 months | 
| Cardioversions | Number of cardioversions required. | up to 48 months | 
| All-cause mortality | Any deaths occurring at any time during the study. | up to 48 months |