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

Trial Summary

What is the purpose of this trial?

SAFE is an international multicentre RCT of concomitant surgical atrial fibrillation (AF) ablation in patients with paroxysmal or persistent AF undergoing cardiac surgery.

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 data supports the effectiveness of the treatment Surgical Atrial Fibrillation Ablation, Maze Procedure, Cox-Maze IV Procedure, Surgical AF Ablation?

Research shows that the Cox-Maze procedure, including its latest version, the Cox-Maze IV, is effective in treating atrial fibrillation, especially when other treatments have failed. Studies indicate that these procedures help reduce atrial fibrillation after surgery and improve long-term outcomes. ^{1 2 3 4 5}

Is surgical ablation for atrial fibrillation generally safe for humans?

The research articles provided do not contain specific safety data for surgical ablation for atrial fibrillation or related procedures like the Maze Procedure. They focus on adverse event monitoring in general surgical contexts, not specific to this treatment. ^{6 7 8 9 10}

How is the Surgical Atrial Fibrillation Ablation treatment different from other treatments for atrial fibrillation?

The Surgical Atrial Fibrillation Ablation, specifically the Cox-Maze IV Procedure, is unique because it uses a surgical approach to create precise scar patterns in the heart tissue to disrupt abnormal electrical signals causing atrial fibrillation. Unlike other treatments, it often involves using bipolar radiofrequency energy instead of traditional incisions, making it less invasive while maintaining effectiveness. ^{1 2 4 11 12}

Research Team

Richard Whitlock

Principal Investigator

Population Health Research Institute

Emilie Belley-Côté

Principal Investigator

Population Health Research Institute

Eligibility Criteria

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 18 years old or older.

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

Provide informed consent

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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 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 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]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Results of the surgical treatment of chronic atrial fibrillation. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Surgical ablation as treatment for the elimination of atrial fibrillation: a meta-analysis. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

The long-term outcomes and durability of the Cox-Maze IV procedure for atrial fibrillation. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Surgical treatment of atrial fibrillation with bipolar radiofrequency ablation: mid-term results in one hundred consecutive patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of the Cox-maze procedure for atrial fibrillation concomitant to mitral and tricuspid valve surgery. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Detecting adverse events in dermatologic surgery. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Establishing best practices for structured NSQIP review. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Severity Grading Systems for Intraoperative Adverse Events. A Systematic Review of the Literature and Citation Analysis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

The Nature and Severity of Adverse Events in Select Outpatient Surgical Procedures in the Veterans Health Administration. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Recommendations for Intraoperative Adverse Events Data Collection in Clinical Studies and Study Protocols. An ICARUS Global Surgical Collaboration Study. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. Netherlands pubmed.ncbi.nlm.nih.gov

Mechanisms of human atrial fibrillation: Lessons learned from 20 years of atrial fibrillation surgery. [2021]