Surgical Ablation of AF Efficacy Trial (SAFE)
Primary Purpose
Atrial Fibrillation, Heart Failure
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Surgical Atrial Fibrillation Ablation
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation focused on measuring Surgical Ablation, Cardiac Surgery
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years;
- Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof;
- Documented history of paroxysmal (AF episode(s) lasting more that 30 seconds but terminating within 7 days) or persistent AF (AF lasting for more than 7 days but less than one year).
- Provide informed consent
Exclusion Criteria:
- Dominant atrial arrhythmia is atrial flutter;
- Documented left atrial diameter ≥ 5.5 cm or left atrial volume ≥100 mL (absolute);
- Long-standing persistent AF (absence of any sinus rhythm for more than 1 year);
Patients undergoing any of the following procedures:
- Previous cardiac surgery requiring opening of the pericardium
- Heart transplant
- Complex congenital heart surgery
- Sole indication for surgery is ventricular assist device insertion
- Mitral valve repair or replacement
- Tricuspid valve repair or replacement
- Closure of an atrial septal defect (excluding patent foramen ovale) or ventricular septal defect
- Patient resides in a long-term care facility
Sites / Locations
- Hamilton General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Surgical Atrial Fibrillation Ablation Group
No Surgical Atrial Fibrillation Ablation Group
Arm Description
Surgeon will perform left atrial ablation during patient's cardiac surgery procedure.
Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure.
Outcomes
Primary Outcome Measures
Number of hospital readmissions for heart failure over duration of follow-up
Total number of hospital readmissions for heart failure.
Secondary Outcome Measures
Number of Ischemic stroke or systemic arterial embolism events over duration of follow up
Number of Ischemic stroke or systemic arterial embolism events over duration of follow up
Length of ICU stay
Length of ICU stay, including readmissions, from study intervention surgery to hospital discharge, including readmissions
Length of hospital stay
Length of hospital stay
Freedom from recurrence of atrial tachyarrhythmia
Freedom from recurrence of atrial tachyarrhythmia
Number of days free from admission to healthcare facility or presentation to the emergency department for heart failure
Number of days free admission to healthcare facility or presentation to the emergency department for heart failure
All-cause mortality
All-cause mortality
Cardiovascular mortality
Cardiovascular mortality
Antiarrhythmic drug use
Antiarrhythmic drug use
Number of patients undergoing atrial fibrillation ablation
Number of patients undergoing atrial fibrillation ablation
Quality of Life - atrial fibrillation specific
Atrial fibrillation specific quality of life as assessed by the Atrial Fibrillation Effect on QualiTy of Life questionnaire (AFEQT) which is 20 questions using a 7 point Likert scale where a higher score means a worse outcome.
Quality of Life - heart failure specific
Heart failure specific quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) which is a 12 questions using Likert scales where a higher score is a better outcome.
Quality of Life - General
Quality of life- general as assessed by the European quality of life index version 5D (EQ-5D-5L) which consists of a descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
Full Information
NCT ID
NCT05434819
First Posted
May 4, 2022
Last Updated
October 20, 2023
Sponsor
Population Health Research Institute
Collaborators
Hamilton Health Sciences Corporation
1. Study Identification
Unique Protocol Identification Number
NCT05434819
Brief Title
Surgical Ablation of AF Efficacy Trial
Acronym
SAFE
Official Title
Surgical Ablation of AF Efficacy Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Actual)
Primary Completion Date
September 30, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Population Health Research Institute
Collaborators
Hamilton Health Sciences Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
SAFE is an international multicentre RCT of concomitant surgical atrial fibrillation (AF) ablation in patients with paroxysmal or persistent AF undergoing cardiac surgery.
Detailed Description
Atrial fibrillation (AF) affects more than 1% of the general population and is an important risk factor for stroke. AF prevalence increases with age, occurring in 10 to 15% of patients older than 80 years of age, which is important with the aging population. Of patients undergoing cardiac surgery, 10.8% have a history of AF. AF is believed to cause the left atrium to dilate and lose its transport function. AF significantly increases the risk of ischemic stroke of cardioembolic origin, but is also associated with heart failure and impairs quality of life. Although the causal relationship between the 2 clinical entities has not been fully elucidated, AF is believed to cause heart failure via several mechanisms.
Ablation of AF is the application of scars to the atrial tissue to disrupt faulty electrical signals that cause the arrhythmia. If surgical ablation of AF yields a benefit similar to catheter-based AF ablation, thousands of people undergoing cardiac surgery could benefit from this procedure each year. SAFE will be a landmark trial in cardiac surgery, definitely establishing surgical AF ablation's impact on cardiovascular outcomes. Cardiac surgery is the optimal setting to establish whether maintenance of sinus rhythm through AF ablation yields clinical benefit, and is a setting where sham-control is possible. This will not only provide evidence for the cardiac surgical patients but will bolster the evidence for ablation (catheter or stand-alone surgical) in other AF patients.
The intervention under investigation is surgical AF ablation which is compared to no surgical AF ablation. The primary outcome is hospital readmissions for heart failure at 4 years. This study will enroll 2000 patients from 50 centres, globally. Patients will be followed at hospital discharge, 4 to 6 weeks after surgery, 6 months after surgery, and then at 6-month intervals until the final follow-up visit, for a median follow-up for 4 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Heart Failure
Keywords
Surgical Ablation, Cardiac Surgery
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Each patient will be assigned in a blinded fashion to one of two groups (atrial fibrillation ablation or no atrial fibrillation ablation) in a 1:1 ratio.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Blinding to allocation will be maintained for all parties, excluding the operating surgeon and necessary operating room personnel.
Allocation
Randomized
Enrollment
2000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Surgical Atrial Fibrillation Ablation Group
Arm Type
Experimental
Arm Description
Surgeon will perform left atrial ablation during patient's cardiac surgery procedure.
Arm Title
No Surgical Atrial Fibrillation Ablation Group
Arm Type
No Intervention
Arm Description
Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure.
Intervention Type
Procedure
Intervention Name(s)
Surgical Atrial Fibrillation Ablation
Intervention Description
Surgeon will preform surgical atrial fibrillation ablation using either cryoablation or bipolar radiofrequency clamps including 2 layers of atrium or vein, a minimum of 2 burns per clamping with at least 3 lines in the ablation group. Cavo-tricuspid isthmus lines will be allowed.
Primary Outcome Measure Information:
Title
Number of hospital readmissions for heart failure over duration of follow-up
Description
Total number of hospital readmissions for heart failure.
Time Frame
Common termination point for trial (median follow-up of 4 years)
Secondary Outcome Measure Information:
Title
Number of Ischemic stroke or systemic arterial embolism events over duration of follow up
Description
Number of Ischemic stroke or systemic arterial embolism events over duration of follow up
Time Frame
Common termination point for trial (median follow-up of 4 years)
Title
Length of ICU stay
Description
Length of ICU stay, including readmissions, from study intervention surgery to hospital discharge, including readmissions
Time Frame
From the date of study intervention surgery completion to the date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years)
Title
Length of hospital stay
Description
Length of hospital stay
Time Frame
From the date of study intervention surgery completion to the date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years)
Title
Freedom from recurrence of atrial tachyarrhythmia
Description
Freedom from recurrence of atrial tachyarrhythmia
Time Frame
1 year post-operatively
Title
Number of days free from admission to healthcare facility or presentation to the emergency department for heart failure
Description
Number of days free admission to healthcare facility or presentation to the emergency department for heart failure
Time Frame
Common termination point for trial (median follow-up of 4 years)
Title
All-cause mortality
Description
All-cause mortality
Time Frame
Common termination point for trial (median follow-up of 4 years)
Title
Cardiovascular mortality
Description
Cardiovascular mortality
Time Frame
Common termination point for trial (median follow-up of 4 years)
Title
Antiarrhythmic drug use
Description
Antiarrhythmic drug use
Time Frame
Beyond 6 weeks until common termination point for trial (median follow-up of 4 years)
Title
Number of patients undergoing atrial fibrillation ablation
Description
Number of patients undergoing atrial fibrillation ablation
Time Frame
90 days post- study surgery until common termination point for trial (median follow-up of 4 years)
Title
Quality of Life - atrial fibrillation specific
Description
Atrial fibrillation specific quality of life as assessed by the Atrial Fibrillation Effect on QualiTy of Life questionnaire (AFEQT) which is 20 questions using a 7 point Likert scale where a higher score means a worse outcome.
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Title
Quality of Life - heart failure specific
Description
Heart failure specific quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) which is a 12 questions using Likert scales where a higher score is a better outcome.
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Title
Quality of Life - General
Description
Quality of life- general as assessed by the European quality of life index version 5D (EQ-5D-5L) which consists of a descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Other Pre-specified Outcome Measures:
Title
Number of Ischemic stroke and systemic arterial embolism
Description
Safety outcome
Time Frame
Up to 30 days post-operatively
Title
Number of patients requiring permanent pacemaker implantation
Description
Safety outcome
Time Frame
Up to 1 year post-operatively
Title
Volume of chest tube output
Description
Safety outcome - chest tube output measured in mL.
Time Frame
Up to 24 hours post-operatively
Title
Re-operation for bleeding
Description
Safety outcome
Time Frame
From date of study intervention surgery completion to date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years)
Title
All-cause mortality
Description
Safety outcome
Time Frame
Prior to discharge or within 30 days post-operatively (whichever occurs first)
Title
Post-operative major bleeding
Description
Safety outcome
Time Frame
<48 hours after surgery
Title
Number of patients with pulmonary vein stenosis
Description
Safety outcome
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Title
Number of patients with stiff left atrium syndrome
Description
Safety outcome
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Title
Number of patients with esophageal to atrial fistula
Description
Safety outcome
Time Frame
At 1 year, and at common termination point for trial (median follow-up of 4 years)
Title
Health economic analysis of surgical atrial fibrillation
Description
Economic analysis will be assessed via health care utilization by patients
Time Frame
At 1 year, and at common termination point (median follow-up of 4 years)
Title
Health economic analysis of surgical atrial fibrillation
Description
Economic analysis will be assessed via a questionnaire of health care visits and costs incurred by patients.
Time Frame
At 1 year, and at common termination point (median follow-up of 4 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years;
Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof;
Documented history of paroxysmal (AF episode(s) lasting more that 30 seconds but terminating within 7 days) or persistent AF (AF lasting for more than 7 days but less than one year).
Provide informed consent
Exclusion Criteria:
Dominant atrial arrhythmia is atrial flutter;
Documented left atrial diameter ≥ 5.5 cm or left atrial volume ≥100 mL (absolute);
Long-standing persistent AF (absence of any sinus rhythm for more than 1 year);
Patients undergoing any of the following procedures:
Previous cardiac surgery requiring opening of the pericardium
Heart transplant
Complex congenital heart surgery
Sole indication for surgery is ventricular assist device insertion
Mitral valve repair or replacement
Tricuspid valve repair or replacement
Closure of an atrial septal defect (excluding patent foramen ovale) or ventricular septal defect
Patient resides in a long-term care facility
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Whitlock
Phone
905-521-2100
Email
Richard.Whitlock@phri.ca
First Name & Middle Initial & Last Name or Official Title & Degree
SAFE Coordinators
Email
SAFE@phri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Whitlock
Organizational Affiliation
Population Health Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emilie Belley-Côté
Organizational Affiliation
Population Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Whitlock, MD PhD FRCSC
Phone
905-527-4322
Ext
40306
Email
richard.whitlock@phri.ca
First Name & Middle Initial & Last Name & Degree
Richard Whitlock, MD MSc FRCSC
12. IPD Sharing Statement
Learn more about this trial
Surgical Ablation of AF Efficacy Trial
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