Atrial FibrillationSAFENCT05434819
Surgical Ablation of AF Efficacy Trial
A study testing Surgical Atrial Fibrillation Ablation in people with Atrial Fibrillation and Heart Failure, run by Population Health Research Institute at 1 site in Canada.
Trial summary
SAFE is an international multicentre RCT of concomitant surgical atrial fibrillation (AF) ablation in patients with paroxysmal or persistent AF undergoing cardiac surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Heart Failure
- What is being tested?
- Surgical Atrial Fibrillation Ablation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jun 2023to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years;
- Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof;
- Documented history of paroxysmal or persistent AF
- Provide informed consent
Who cannot join
- Dominant atrial arrhythmia is atrial flutter;
- Documented left atrial diameter ≥ 6 cm;
- Previous cardiac surgery requiring opening of the pericardium;
- Patients undergoing any of the following procedures:
- Heart transplant
- Complex congenital heart surgery
Show all 10Show fewer
- Sole indication for surgery is ventricular assist device insertion
- Mitral valve repair or replacement
- Tricuspid valve repair or replacement
- Patient resides in a long-term care facility
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
SAFE Coordinators contact
Canada1 site, 1 recruiting
- Recruiting
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
Richard Whitlock, MD PhD FRCSC, 905-527-4322 ext. 40306, richard.whitlock@phri.ca
Richard Whitlock, MD MSc FRCSC
About this study
SAFE is an international multicentre RCT of concomitant surgical atrial fibrillation (AF) ablation in patients with paroxysmal or persistent AF undergoing cardiac surgery.
Read the 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 concomitant surgical AF ablation which is compared to no surgical AF ablation. The primary outcome is hospital readmissions with heart failure during 4 years of follow-up. 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.
- Conditions
- Atrial Fibrillation, Heart Failure
- Being tested
- Surgical Atrial Fibrillation Ablation
- Keywords
- Surgical Ablation, Cardiac Surgery
- Medical subject headings
- Atrial Fibrillation, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical Atrial Fibrillation AblationProcedure or surgery
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 and mitral lines will be allowed.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Atrial Fibrillation Ablation Group | Experimental | Surgeon will perform left atrial ablation during patient's cardiac surgery procedure. Receives: Procedure: Surgical Atrial Fibrillation Ablation |
| No Surgical Atrial Fibrillation Ablation Group | No intervention | Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of hospital readmissions for heart failure over duration of follow-up
Total number of hospital readmissions for heart failure.
Measured: Common termination point for trial (median follow-up of 4 years)
Secondary outcomes (12)
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
Measured: Common termination point for trial (median follow-up of 4 years)
Length of ICU stay
Length of ICU stay, including readmissions, from study intervention surgery to hospital discharge, including readmissions
Measured: 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)
Length of hospital stay
Length of hospital stay
Measured: 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)
Freedom from recurrence of atrial tachyarrhythmia
Freedom from recurrence of atrial tachyarrhythmia
Measured: 1 year post-operatively
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
Measured: Common termination point for trial (median follow-up of 4 years)
All-cause mortality
All-cause mortality
Measured: Common termination point for trial (median follow-up of 4 years)
Cardiovascular mortality
Cardiovascular mortality
Measured: Common termination point for trial (median follow-up of 4 years)
Antiarrhythmic drug use
Antiarrhythmic drug use
Measured: Beyond 6 weeks until common termination point for trial (median follow-up of 4 years)
Number of patients undergoing atrial fibrillation ablation
Number of patients undergoing atrial fibrillation ablation
Measured: 90 days post- study surgery until common termination point for trial (median follow-up of 4 years)
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.
Measured: At 1 year, and at common termination point for trial (median follow-up of 4 years)
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.
Measured: At 1 year, and at common termination point for trial (median follow-up of 4 years)
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.
Measured: At 1 year, and at common termination point for trial (median follow-up of 4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2022
- Study start1 Jun 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation
- Responsible party
- Principal investigator, Richard Whitlock, Population Health Research Institute
- Investigators
- Richard Whitlock, Principal investigator, Population Health Research InstituteEmilie Belley-Côté, Principal investigator, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05434819
- Sponsor's protocol ID
- SAFEV1.0
- Acronym
- SAFE
- Status last verified
- Oct 2026
- First submitted
- 4 May 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgical Ablation of AF Efficacy Trial
- ClinicalTrials.gov ID
- NCT05434819
- Acronym / sponsor ID
- SAFE / SAFEV1.0
- Conditions
- Atrial Fibrillation, Heart Failure
- Keywords
- Surgical Ablation, Cardiac Surgery
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 concomitant surgical AF ablation which is compared to no surgical AF ablation. The primary outcome is hospital readmissions with heart failure during 4 years of follow-up. 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Surgical Atrial Fibrillation Ablation Group | Experimental | Procedure: Surgical Atrial Fibrillation AblationSurgeon will perform left atrial ablation during patient's cardiac surgery procedure. |
| No Surgical Atrial Fibrillation Ablation Group | No intervention | –Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years;
- Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof;
- Documented history of paroxysmal or persistent AF
- Provide informed consent
Key exclusion criteria (10 listed)
- Dominant atrial arrhythmia is atrial flutter;
- Documented left atrial diameter ≥ 6 cm;
- Previous cardiac surgery requiring opening of the pericardium;
- Patients undergoing any of the following procedures:
- Patient resides in a long-term care facility
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgical Atrial Fibrillation AblationSurgeon 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 and mitral lines will be allowed. | Procedure or surgery | Surgical Atrial Fibrillation Ablation Group |
Primary outcome
Number of hospital readmissions for heart failure over duration of follow-up
Time frame: Common termination point for trial (median follow-up of 4 years)
Total number of hospital readmissions for heart failure.
12 secondary outcomes
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)
Length of ICU 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)
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)
Freedom from recurrence of atrial tachyarrhythmia
Time frame: 1 year post-operatively
Number of days free from 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)
All-cause mortality
Time frame: Common termination point for trial (median follow-up of 4 years)
Cardiovascular mortality
Time frame: Common termination point for trial (median follow-up of 4 years)
Antiarrhythmic drug use
Time frame: Beyond 6 weeks until common termination point for trial (median follow-up of 4 years)
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)
Quality of Life - atrial fibrillation specific
Time frame: At 1 year, and at common termination point for trial (median follow-up of 4 years)
Quality of Life - heart failure specific
Time frame: At 1 year, and at common termination point for trial (median follow-up of 4 years)
Quality of Life - General
Time frame: At 1 year, and at common termination point for trial (median follow-up of 4 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
SAFE Coordinators contact
Richard Whitlock principal investigator
Population Health Research Institute
Emilie Belley-Côté principal investigator
Population Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Surgical Atrial Fibrillation Ablation in people with Atrial Fibrillation and Heart Failure, run by Population Health Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Richard Whitlock (905-521-2100, Richard.Whitlock@phri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of hospital readmissions for heart failure over duration of follow-up (time frame: Common termination point for trial (median follow-up of 4 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.