Left Atrial Appendage Occlusion Study III (LAAOS III)

• ClinicalTrials.gov Identifier: NCT01561651
• Recruitment Status: Completed
• First Posted: March 23, 2012
• Last Update Posted: January 13, 2022
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Richard Whitlock, McMaster University

Study Description

Brief Summary:

Atrial fibrillation (AF) is a common heart rhythm disorder that leads to one-sixth of all strokes. Prevention of strokes in AF is achieved through the use of blood thinners such as coumadin. Although these blood thinners are effective, they are limited by the risk of serious bleeding, by physician and patient reluctance to use, and by noncompliance and discontinuation. The left atrial appendage is a structure on the upper chamber of the heart that is the most common source of stroke in patients with AF. This structure is easily accessible during open heart surgery for removal, and has been an area of interest for stroke prevention. However, there is currently no strong evidence that removing it works.

The LAAOS III trial will randomly (like the flip of a coin) assign patients with AF undergoing heart surgery for other reasons to have the left atrial appendage removed or not. These patients, other than this small procedure which has been shown to be quite safe, will be treated in the usual manner. The full study of 4700 patients, followed for an average of 4 years, will determine if removing the left atrial appendage can reduce stroke and other complications on top of usual therapy. A positive study will change the way heart surgery is performed on AF patients and results in a large reduction in the number of strokes in a large population. Further, it will promote further research into this approach that could be applied beyond AF patients undergoing heart surgery.

Condition or disease	Intervention/treatment	Phase
Cardiac Surgery With Cardiopulmonary Bypass; Atrial Fibrillation	Other: Left Atrial Appendage Occlusion	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4812 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Left Atrial Appendage Occlusion Study III
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: April 2021
• Actual Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Left Atrial Appendage Occlusion Group; Surgeon will close the left atrial appendage using a suture and/or a surgical stapler or a regulatory approved atrial appendage closure device during the patient's cardiac surgery procedure.	Other: Left Atrial Appendage Occlusion; Surgeon will occlude the left atrial appendage using a suture and/or a surgical stapler or a regulatory approved atrial appendage closure during the patient's cardiac surgery procedure.
No Intervention: No Left Atrial Appendage Occlusion Group; Surgeon will not close the left atrial appendage during the patient's cardiac surgery procedure. Patient will be treated as per best medical practice for stroke prevention in atrial fibrillation. Treatment will be decided by the patient's primary care physician.

Outcome Measures

Primary Outcome Measures :

1. Stroke or systemic arterial embolism [ Time Frame: Common termination point (median follow-up of 4 years) ]
   First occurrence of ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism

Secondary Outcome Measures :

1. All cause stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism [ Time Frame: Common termination point (median follow-up of 4 years) ]
   All cause stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism
2. Ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism or death [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Ischemic stroke* or transient ischemic attack with positive neuroimaging or systemic arterial embolism or death
3. Ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism > 30 days after surgery [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism > 30 days after surgery
4. Total mortality [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Total mortality

Other Outcome Measures:

1. Readmission for heart failure [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Readmission for heart failure
2. Post-operative safety outcomes [ Time Frame: 30 days post-surgery ]
   Operative safety outcomes (30-day mortality, chest tube output in the first post-operative 24 hours, rate of post-operative re-exploration for bleeding)
3. Major bleeding [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Major bleeding
4. Myocardial infarction [ Time Frame: Common termination point (median follow-up of 4 years) ]
   Myocardial infarction

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Greater than 18 years of age
2. Undergoing a clinically indicated cardiac surgical procedure with the use of cardiopulmonary bypass
3. Have a documented history of atrial fibrillation or atrial flutter
4. CHA2DS2-VASc score ≥ 2
5. Have provided informed consent

Exclusion Criteria:

1. Patients undergoing off-pump cardiac surgery

2. Patients undergoing any of the following procedures:

   • heart transplant
   • complex congenital heart surgery
   • sole indication for surgery is ventricular assist device insertion
   • previous cardiac surgery requiring opening of the pericardium
   • mechanical valve implant
3. Patients who have had a previous placement of a percutaneous left atrial appendage closure device

Contacts and Locations

Locations

Canada, Ontario

Hamilton General Hospital

Hamilton, Ontario, Canada, L8L 2X2

Sponsors and Collaborators

Population Health Research Institute

Investigators

• Principal Investigator: Richard Whitlock, MD; Population Health Research Institute/McMaster University
• Study Chair: Stuart Connolly, MD, PhD; Population Health Research Institute/McMaster University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, Reents W, Budera P, Baddour AJ, Fila P, Devereaux PJ, Bogachev-Prokophiev A, Boening A, Teoh KHT, Tagarakis GI, Slaughter MS, Royse AG, McGuinness S, Alings M, Punjabi PP, Mazer CD, Folkeringa RJ, Colli A, Avezum A, Nakamya J, Balasubramanian K, Vincent J, Voisine P, Lamy A, Yusuf S, Connolly SJ; LAAOS III Investigators. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. N Engl J Med. 2021 Jun 3;384(22):2081-2091. doi: 10.1056/NEJMoa2101897. Epub 2021 May 15.

• Responsible Party: Richard Whitlock, Assistant Professor, McMaster University
• ClinicalTrials.gov Identifier: NCT01561651
• Other Study ID Numbers: LAAOSIII-2012
• First Posted: March 23, 2012
• Last Update Posted: January 13, 2022
• Last Verified: January 2022

Keywords provided by Richard Whitlock, McMaster University:

cardiac surgery; left atrial appendage; atrial fibrillation; stroke; non-CNS systemic embolism

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes