Surgical Ablation for Atrial Fibrillation

(SAFE Trial)

Overseen By SAFE Coordinators

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Population Health Research Institute

Disqualifiers: Atrial flutter, Left atrial diameter, Previous cardiac surgery, Heart transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

2000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a procedure called surgical atrial fibrillation ablation for patients already undergoing heart surgery. It focuses on those with atrial fibrillation (an irregular and often rapid heart rate) who are having other heart surgeries, such as bypass or valve replacements. Some participants will receive the ablation during their surgery, while others will not, enabling researchers to assess its effectiveness. Suitable candidates have a history of atrial fibrillation and are already scheduled for specific types of heart surgery. As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance surgical outcomes for future heart surgery patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that surgical atrial fibrillation ablation is safe?

Research shows that surgical procedures for treating atrial fibrillation, such as the Cox-Maze procedure, are generally safe for patients. Studies have found that this procedure significantly improves the chances of maintaining a normal heart rhythm in people with atrial fibrillation (AF). Specifically, five years after the procedure, patients maintain normal heart rhythms 80% of the time, and 65% of the time after ten years.

The Cox-Maze procedure is considered a top choice for treating AF, indicating long-term safety. While success rates can vary, they are usually high, often exceeding 70%. This suggests the procedure is effective and well-tolerated by many patients.

Overall, these findings indicate that surgical atrial fibrillation ablation is generally safe, based on evidence from various studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the surgical ablation for atrial fibrillation because it offers a targeted approach during cardiac surgery. Unlike standard treatments like medication or non-surgical catheter ablation, this method involves directly ablating the left atrium while the patient is already undergoing surgery for another heart condition. This integrated approach could improve the precision and effectiveness of the treatment, potentially reducing the recurrence of atrial fibrillation. By incorporating the ablation into existing surgical procedures, it might also streamline patient care and recovery time.

What evidence suggests that surgical atrial fibrillation ablation is effective for atrial fibrillation?

This trial will compare outcomes for patients undergoing cardiac surgery with and without the addition of surgical atrial fibrillation ablation. Studies have shown that atrial fibrillation ablation effectively maintains a normal heartbeat. Specifically, the Cox-Maze IV procedure has been very successful, with over 70% of patients maintaining a normal heartbeat long-term. Research indicates that this procedure helps 80% of patients avoid irregular heartbeats for five years and 65% for ten years. Adding this procedure during heart surgery significantly increases the chances of maintaining a regular heartbeat compared to not having it. These findings suggest that surgical ablation is a promising option for patients with atrial fibrillation undergoing heart surgery. ^{1 2 3 4 6}

Who Is on the Research Team?

Richard Whitlock

Principal Investigator

Population Health Research Institute

Emilie Belley-Côté

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a history of paroxysmal or persistent atrial fibrillation who are already scheduled for certain heart surgeries like bypass grafting or aortic valve replacement. It's not open to those in long-term care, with very large left atria, primary atrial flutter, previous similar heart surgery, or needing complex procedures like transplants.

Inclusion Criteria

I am scheduled for heart surgery, such as bypass or valve replacement.

Provide informed consent

I have a history of irregular heartbeats.

Exclusion Criteria

My main heart rhythm problem is atrial flutter.

Your left atrial diameter is 6 centimeters or larger, as shown in medical records.

I have had heart surgery that involved opening the protective covering of the heart.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Hospitalization

Participants undergo cardiac surgery with or without surgical AF ablation and are monitored until hospital discharge

Up to hospital discharge

Inpatient stay

Post-operative Follow-up

Participants are followed at hospital discharge, 4 to 6 weeks after surgery, 6 months after surgery, and then at 6-month intervals

4 years

Multiple visits at specified intervals

Long-term Follow-up

Participants are monitored for hospital readmissions with heart failure and other outcomes

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Surgical Atrial Fibrillation Ablation

Trial Overview

The SAFE trial is testing the effectiveness of adding surgical ablation—a procedure that creates scars in the heart to prevent abnormal electrical signals—for treating atrial fibrillation during planned cardiac surgeries. This international study randomly assigns participants to receive this additional treatment.

How Is the Trial Designed?

Group I: Surgical Atrial Fibrillation Ablation Group Experimental Treatment 1 Intervention

Surgeon will perform left atrial ablation during patient's cardiac surgery procedure.

Group II: No Surgical Atrial Fibrillation Ablation Group Active Control 1 Intervention

Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure.

Surgical Atrial Fibrillation Ablation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Surgical AF Ablation for:

• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Approved in United States as Surgical AF Ablation for:

• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation
• Long-standing persistent atrial fibrillation

Approved in Canada as Surgical AF Ablation for:

• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Published Research Related to This Trial

The Cox-maze procedure for treating atrial fibrillation (AF) in 61 patients showed a 4.9% in-hospital mortality rate and a 1.6% late mortality rate, indicating an acceptable surgical risk for this intervention.

Post-surgery, 70.5% of patients achieved stable sinus rhythm at the last evaluation, demonstrating the procedure's efficacy in restoring normal heart rhythm, although some patients experienced arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of the surgical treatment of chronic atrial fibrillation. Kalil, RA., Albrecht, A., Lima, GG., et al.[2019]

Current strategies for monitoring adverse events (AEs) in dermatologic surgery are inconsistent, with morbidity and mortality conferences being the most common reporting method, but more sensitive approaches like retrospective medical record reviews and anonymous electronic systems exist.

There is no standard for AE reporting in dermatologic surgery, highlighting the need for pilot studies to establish effective measures that can enhance AE detection and improve patient safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting adverse events in dermatologic surgery. Pinney, D., Pearce, DJ., Feldman, SR.[2019]

The Cox-Maze IV procedure (CMP-IV) demonstrated excellent long-term efficacy in maintaining sinus rhythm in patients with atrial fibrillation (AF), with freedom from atrial tachyarrhythmia (ATA) rates of 92% at 1 year, 84% at 5 years, and 77% at 10 years based on a study of 853 patients.

Key predictors of ATA recurrence over 10 years included age, left atrial size, and the presence of nonparoxysmal AF, indicating that these factors should be considered when assessing patient outcomes after the CMP-IV procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term outcomes and durability of the Cox-Maze IV procedure for atrial fibrillation. Khiabani, AJ., MacGregor, RM., Bakir, NH., et al.[2023]

The Cox-Maze IV procedure, which uses bipolar radiofrequency ablation, showed a high success rate with 91% of patients free from atrial fibrillation (AF) at 12 months, based on a study of 100 patients with a mean follow-up of 13 months.

This modified procedure significantly reduced operative time compared to the traditional Cox-Maze procedure, making it a more efficient option for treating AF, while maintaining good mid-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical treatment of atrial fibrillation with bipolar radiofrequency ablation: mid-term results in one hundred consecutive patients. Melby, SJ., Kaiser, SP., Bailey, MS., et al.[2022]

The ICARUS Global Surgical Collaboration has developed a comprehensive system for collecting data on intraoperative adverse events (iAEs), addressing the lack of standardized reporting in surgical literature.

This study provides essential tools, including core-set variables and guidelines for reporting iAEs, which are based on globally validated criteria, aiming to improve patient safety and outcomes in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for Intraoperative Adverse Events Data Collection in Clinical Studies and Study Protocols. An ICARUS Global Surgical Collaboration Study. Cacciamani, GE., Eppler, M., Sayegh, AS., et al.[2023]

The Cox-Maze procedure, established 20 years ago, is recognized as the gold standard for surgically treating atrial fibrillation, demonstrating its long-term efficacy and safety.

Recent data from surgeries and catheter ablations indicate that a personalized approach to treating atrial fibrillation may enhance outcomes, suggesting that treatment should be tailored to individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of human atrial fibrillation: Lessons learned from 20 years of atrial fibrillation surgery. Schuessler, RB., Damiano, RJ.[2021]

In a study of 817 patients undergoing mitral valve or mitral valve plus tricuspid valve surgery, the Cox-maze procedure was performed on 236 patients with atrial fibrillation (AF), showing no increase in operative morbidity and a very low thromboembolic rate of 1.7%.

The Cox-maze procedure resulted in high rates of return to sinus rhythm at 6, 12, and 24 months (92%, 91%, and 86%, respectively), indicating its efficacy in managing AF during valve surgery, and suggesting a need for improved education on AF surgical ablation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of the Cox-maze procedure for atrial fibrillation concomitant to mitral and tricuspid valve surgery. Ad, N., Holmes, SD., Massimiano, PS., et al.[2022]

Biatrial surgical ablation procedures are more effective than left atrial-only procedures in achieving freedom from atrial fibrillation, with significantly higher rates of success at all time points measured (3 months, 1, 2, and 3 years).

Survival rates after biatrial and left atrial procedures are comparable, indicating that while biatrial procedures offer better control of atrial fibrillation, they do not compromise patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical ablation as treatment for the elimination of atrial fibrillation: a meta-analysis. Barnett, SD., Ad, N.[2006]

The new multi-purse string technique for the maze IV procedure shows promising results, with 91% of 12 patients remaining free from atrial fibrillation or flutter after an average follow-up of 13 months.

No serious complications, such as mortality or strokes, occurred during the procedure, indicating a high safety profile for this approach in treating atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The multi-purse string maze procedure: a new surgical technique to perform the full maze procedure without atriotomies. Ad, N.[2007]

The INR program significantly improved the review process of adverse events (AEs) in surgical outcomes, reducing the time from occurrence to surgeon recognition from 296 days to just 73 days, which enhances timely intervention and awareness.

Out of 3,026 AEs reviewed, only 1.2% were found inconsistent with NSQIP-defined AEs, indicating that the structured review process increases the accuracy and reliability of surgical outcome data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing best practices for structured NSQIP review. Cunningham, AJ., Howell, B., Polites, S., et al.[2020]

The study reviewed 2957 articles but found only 7 that proposed or validated intraoperative adverse event (iAE) severity grading systems, highlighting a significant gap in standardized assessment methods for surgical complications.

Despite the critical need for grading systems to improve patient safety, only 56.9% of clinical studies that cited these systems actually used them, indicating poor adoption and the necessity for a uniform grading system to enhance data comparability and reduce adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severity Grading Systems for Intraoperative Adverse Events. A Systematic Review of the Literature and Citation Analysis. Sayegh, AS., Eppler, M., Sholklapper, T., et al.[2023]

In a review of outpatient surgeries from 2012 to 2015 involving 2,257 cases, adverse events (AEs) were found in 51% of high-likelihood and 12% of low-likelihood procedures, indicating a significant risk of complications even in outpatient settings.

Among the identified AEs, 10% required repeat surgeries, and 28% led to hospitalization, highlighting the need for quality improvement efforts to address common issues like wound problems and urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Nature and Severity of Adverse Events in Select Outpatient Surgical Procedures in the Veterans Health Administration. Mull, HJ., Itani, KMF., Charns, MP., et al.[2021]

Citations

1.

stopafib.org

stopafib.org/procedures-for-afib/surgery-procedures/maze-procedure/success-rates/

Maze Procedure Success Rates for Atrial Fibrillation

While they generally have high success rates of over 70%, reported success rates can vary for several reasons, including those below.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9810144/

The long-term outcomes and durability of the Cox-Maze IV ...

The CMP-IV had an excellent long-term efficacy at maintaining sinus rhythm. At late follow-up, the results of the CMP-IV remained superior to those reported for ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10949564/

Safety and efficacy of Cox‐Maze procedure for atrial fibrillation ...

Our systematic review suggested that RCTs have demonstrated the addition of the Cox‐Maze procedure for AF leads to a significantly higher rate of sinus rhythm ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0022522325003903

The long-term outcomes of concomitant Cox-Maze IV ...

The concomitant procedure provided good freedom from atrial tachyarrhythmias of 80% and 65% at years 5 and 10, respectively. The freedom from ...

5.

annalscts.com

annalscts.com/article/view/17096/html

Effectiveness of Maze IV procedure versus thoracoscopic ...

This study aims to evaluate and compare the outcomes of TA and CMP-IV in treating AF.

6.

annalscts.com

annalscts.com/article/view/17094/html

Surgical options for atrial fibrillation treatment during ...

A concomitant Cox-Maze procedure resulted in superior freedom from AF rates at every time point (both with and without antiarrhythmic drugs), ...