Left Atrial Appendage Occlusion Study III (LAAOS III)

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Cardiac Surgery With Cardiopulmonary Bypass
• Intervention / Treatment: Other: Left Atrial Appendage Occlusion

• Study Type: Interventional
• Enrollment (Actual): 4812
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke or systemic arterial embolism	First occurrence of ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism	Common termination point (median follow-up of 4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism	All cause stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism	Common termination point (median follow-up of 4 years)
Ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism or death	Ischemic stroke* or transient ischemic attack with positive neuroimaging or systemic arterial embolism or death	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	Ischemic stroke or transient ischemic attack with positive neuroimaging or systemic arterial embolism > 30 days after surgery	Common termination point (median follow-up of 4 years)
Total mortality	Total mortality	Common termination point (median follow-up of 4 years)

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2012
• Primary Completion (ACTUAL): April 1, 2021
• Study Completion (ACTUAL): May 1, 2021

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (ESTIMATE): March 23, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: cardiac surgery; stroke; atrial fibrillation; left atrial appendage; non-CNS systemic embolism
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: LAAOSIII-2012