Reversal of Atrial Substrate to Prevent Atrial
- Conditions
- Atrial Fibrillation
- Interventions
- Other: Aggressive Risk Factor ControlOther: Standard of Care
- Registration Number
- NCT03682991
- Lead Sponsor
- Nova Scotia Health Authority
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 670
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aggressive Risk Factor Control Aggressive Risk Factor Control Multifaceted risk factor management relating to BP, exercise, sleep apnea, alcohol intake and diabetes management Standard of Care Standard of Care 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.
- Primary Outcome Measures
Name Time Method Number of AF related hospitalizations post ablation up to 72 months AF-related hospitalizations (lasting more than 24 hours) from 2-months post ablation to end of follow up.
Number of AF related Emergency Department (ED) visits post ablation up to 72 months AF-related emergency department visits from 2-months post ablation to end of follow up.
Number of clinically significant AF events post ablation up to 72 months 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.
- Secondary Outcome Measures
Name Time Method Number of AF-related hospitalizations up to 72 months AF-related hospitalizations (lasting more than 24 hours) from randomization to end of follow up.
Number of AF-related emergency department (ED) visits up to 72 months AF-related emergency department visits from randomization to end of follow up.
Number of Clinically significant AF events up to 72 months 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.
Mean AF burden up to 72 months Average percentage of time in AF during follow up, as measured by insertable cardiac monitor.
Stroke or systemic embolism events up to 72 months Total number of stoke or systemic embolism events.
Quality of Life - CCS-SAF Up to 24 months 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.
Quality of Life - AFEQT Up to 24 months 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.
Number of recurrent AF-ablations up to 72 months Number of re-ablations required.
Cardioversions up to 72 months Number of cardioversions required.
All-cause mortality up to 72 months Any deaths occurring at any time during the study.
AF at any time Up to 72 months post randomization Atrial fibrillation (confirmed by ICM, 12-lead ECG or telemetry)
Health Outcomes Up to 24 months Measured by the Euroqol-5D-5L questionnaire
Association between gender, AF risk factors and aggressive risk factor management UP to 24 months This will be determined by the use of the GENESIS Praxy Gender questionnaire
Major Bleeding Up to 72 months Any event which includes the following criteria: fall in Hgb of ≥2 g/dL, transfusion of ≥2 units PRBC or whole blood, in a critical location (e.g., intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial), causes death
Trial Locations
- Locations (17)
Foothills Hospital
🇨🇦Calgary, Alberta, Canada
Mazankowski Alberta Heart Institute
🇨🇦Edmonton, Alberta, Canada
Kelowna General Health
🇨🇦Kelowna, British Columbia, Canada
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Saint John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
QE II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Hamilton Health Sciences Center
🇨🇦Hamilton, Ontario, Canada
St. Mary's General Hospital
🇨🇦Kitchener, Ontario, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Laval Hospital
🇨🇦Laval, Quebec, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Sacre Coeur Hospital
🇨🇦Montreal, Quebec, Canada
Regina General Hospital
🇨🇦Regina, Saskatchewan, Canada