Left Atrial Appendage Occlusion Study III

NCT01561651 | Completed DMC

• 1 other identifier: LAAOSIII-2012
• Study Type: interventional
• Target: 4,812
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Surgery With Cardiopulmonary Bypass; Atrial Fibrillation

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  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

  Common termination point (median follow-up of 4 years)

• Total mortality

  Common termination point (median follow-up of 4 years)

Other Outcomes (4)

• Readmission for heart failure

  Common termination point (median follow-up of 4 years)

• Post-operative safety outcomes

  30 days post-surgery

• Major bleeding

  Common termination point (median follow-up of 4 years)

Study Arms (2)

Left Atrial Appendage Occlusion Group

EXPERIMENTAL

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

No Left Atrial Appendage Occlusion Group

NO INTERVENTION

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.

Interventions

Left Atrial Appendage Occlusion OTHER

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.

Left Atrial Appendage Occlusion Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients undergoing off-pump cardiac surgery
• 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
• Patients who have had a previous placement of a percutaneous left atrial appendage closure device

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (4)

• Katsanos AH, Whitlock RP, Belley-Cote EP, Brady K, Wang A, Srivastava A, Jacquin G, Weiss V, Volny O, Sramek M, Peeters A, Marto JP, Wrona P, Tsolaki A, Li L, Nucera A, Mikulik R, Perera K, Catanese L, Shoamanesh A, Sharma M. Stroke Mechanism and Severity After Left Atrial Appendage Occlusion: Insights From the LAAOS III Randomized Clinical Trial. JAMA Neurol. 2026 Jan 1;83(1):76-82. doi: 10.1001/jamaneurol.2025.4478.

  PMID: 41247709 DERIVED

• Kim KS, Belley-Cote EP, Walsh M, Wang A, Balasubramanian K, Treleaven N, Garg AX, Guyatt G, Whitlock RP. Left atrial appendage occlusion study III-Kidney substudy. Am Heart J. 2025 Oct;288:90-100. doi: 10.1016/j.ahj.2025.04.018. Epub 2025 Apr 19.

  PMID: 40258408 DERIVED

• Krisai P, Belley-Cote EP, McIntyre WF, Wong J, Tsiplova K, Brady K, Joseph P, Johansson I, Johnson L, Xing LY, Colli A, McGuinness S, Punjabi P, Reents W, Rega F, Budera P, Royse AG, Paparella D, Connolly S, Whitlock RP, Healey JS; on behalf of the LAAOS III Investigators. Heart failure after left atrial appendage occlusion: Insights from the LAAOS III randomized trial. Eur J Heart Fail. 2025 Feb;27(2):285-292. doi: 10.1002/ejhf.3536. Epub 2024 Nov 25.

  PMID: 39586754 DERIVED

• 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.

  PMID: 33999547 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Stroke

Interventions

Left Atrial Appendage Closure

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Catheterization; Catheterization; Therapeutics; Investigative Techniques

Study Officials

• Richard Whitlock, MD

  Population Health Research Institute/McMaster University

  PRINCIPAL INVESTIGATOR

• Stuart Connolly, MD, PhD

  Population Health Research Institute/McMaster University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 20, 2012
• First Posted: March 23, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2021
• Last Updated: January 13, 2022

Record last verified: 2022-01

Locations

CA (1)