Reversal of Atrial Substrate to Prevent Atrial (RASTA AF)

Reversal of Atrial Substrate to Prevent Atrial Fibrillation

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

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Other: Aggressive Risk Factor Control; Other: Standard of Care

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 minimum sample size required is 500. Safety outcomes include: AF catheter ablation procedural complications, Anti-arrhythmic medication related adverse events, & Death.

• Study Type: Interventional
• Enrollment (Actual): 509
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Hospital
    • Edmonton, Alberta, Canada
      • Mazankowski Alberta Heart Institute
  • British Columbia
    • Kelowna, British Columbia, Canada
      • Kelowna General Health
    • Vancouver, British Columbia, Canada
      • St. Paul's Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada
      • Saint John Regional Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QE II Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences Center
    • Kitchener, Ontario, Canada
      • St. Mary's General Hospital
    • London, Ontario, Canada
      • London Health Sciences Center
    • Ottawa, Ontario, Canada
      • Ottawa Heart Institute
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Laval, Quebec, Canada
      • Laval Hospital
    • Montreal, Quebec, Canada
      • McGill University Health Centre
    • Montreal, Quebec, Canada
      • Montreal Heart Institute
    • Montreal, Quebec, Canada
      • Sacre Coeur Hospital
  • Saskatchewan
    • Regina, Saskatchewan, Canada
      • Regina General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aggressive Risk Factor Control; Multifaceted risk factor management relating to BP, exercise, sleep apnea, alcohol intake and diabetes management	Other: Aggressive Risk Factor Control; 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
Active Comparator: 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.	Other: Standard of Care; Recommendations based on current guidelines

What is the study measuring?

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 72 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 72 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 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 AF-related hospitalizations	AF-related hospitalizations (lasting more than 24 hours) from randomization to end of follow up.	up to 72 months
Number of AF-related emergency department (ED) visits	AF-related emergency department visits from randomization to end of follow up.	up to 72 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 72 months
Mean AF burden	Average percentage of time in AF during follow up, as measured by insertable cardiac monitor.	up to 72 months
Stroke or systemic embolism events	Total number of stoke or systemic embolism events.	up to 72 months
Number of recurrent AF-ablations	Number of re-ablations required.	up to 72 months
Cardioversions	Number of cardioversions required.	up to 72 months
All-cause mortality	Any deaths occurring at any time during the study.	up to 72 months
AF at any time	Atrial fibrillation (confirmed by ICM, 12-lead ECG or telemetry)	Up to 72 months post randomization
Health Outcomes	Measured by the Euroqol-5D-5L questionnaire	Up to 24 months
Association between gender, AF risk factors and aggressive risk factor management	This will be determined by the use of the GENESIS Praxy Gender questionnaire	UP to 24 months
Major Bleeding	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	Up to 72 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ablation procedural complications [Safety]	Periprocedural complications will be assessed.	up to 72 months
Number of antiarrhythmic drug adverse effects [Safety]	Adverse drug reactions will be assessed.	up to 72 months
Death (Safety)	All cause mortality occurring at any time post randomization	Up to 72 months

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Collaborators: Canadian Institutes of Health Research (CIHR); Abbott; Philips Healthcare; Cardiac Arrhythmia Network of Canada
• Investigators: Principal Investigator: Ratika Parkash, Nova Scotia Health Authority; Study Director: Allan Skanes, London Health Sciences Centre; Study Director: David Birnie, University of Ottawa Heart Institution; Study Director: George Wells, University of Ottawa Heart Institution; Study Director: Isabelle vanGelder, University of Groningen; Study Director: Jeff Healey, Hamilton Health Sciences Centre; Study Director: Jennifer Reed, University of Ottawa Heart Institution; Study Director: Anthony Tang, London Health Sciences Centre; Study Director: John Sapp, Nova Scotia Health Authority; Study Director: Vidal Essebag, McGill University Hospital; Study Director: Chris Blanchard, Nova Scotia Health; Study Director: Michiel Rienstra, University of Groningen

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: RP-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No