WATCHMAN Device for Atrial Fibrillation

(LAAOS-4 Trial)

Recruiting at 55 trial locations

Overseen By Andrea Natale, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hamilton Health Sciences Corporation

Must be taking: Oral anticoagulants

Must not be taking: Direct thrombin inhibitors

Disqualifiers: Age < 18, Thrombus, Prior occlusion, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Procedure duration and immediate recovery

4000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to continue taking their current oral anticoagulant medications (like Vitamin K agonists or factor Xa inhibitors) for the duration of the study.

What data supports the effectiveness of the WATCHMAN device treatment for atrial fibrillation?

The WATCHMAN device is designed to reduce the risk of stroke in patients with atrial fibrillation. The PREVAIL trial showed that the benefits of the WATCHMAN device outweigh the risks for patients who meet specific criteria, despite some concerns about ischemic strokes. The newer WATCHMAN FLX device has shown good procedural success and safety in small studies, with improvements in design to enhance performance and safety. ^{1 2 3 4 5}

Is the WATCHMAN device safe for humans?

The WATCHMAN device has been studied for safety, with an overall adverse event rate of 7.3% and a mortality rate of 0.4% in a large study. Most issues occurred during or shortly after the procedure, but some serious events like strokes and device movement happened more than a month later. The newer WATCHMAN FLX device is designed to improve safety and has shown good results in smaller studies. ^{1 3 4 6 7}

How does the WATCHMAN device treatment for atrial fibrillation differ from other treatments?

The WATCHMAN device is a unique treatment for atrial fibrillation as it is a small implant placed in the heart to prevent strokes by blocking the left atrial appendage, where blood clots often form. Unlike traditional blood-thinning medications, it offers an alternative for patients who are at high risk of bleeding complications from long-term anticoagulant use. ^{1 3 4 8 9}

What is the purpose of this trial?

LAAOS-4 aims to determine if catheter-based endovascular left atrial appendage occlusion prevents ischemic stroke or systemic embolism in participants with atrial fibrillation, who remain at high risk of stroke, despite receiving ongoing treatment with oral anticoagulation.

Research Team

Jeff S Healey, MD

Principal Investigator

Hamilton Health Sciences Corporation

Eligibility Criteria

This trial is for adults with atrial fibrillation who are at high risk of stroke, even while on blood thinners. They should have a CHA2DS2-VASc score of 4 or more, indicating they're more likely to have a stroke. Participants must be willing to continue their current oral anticoagulant therapy throughout the study.

Inclusion Criteria

You have a heightened risk of stroke, determined via the CHA2DS2-VASc score being equal to or greater than four.

I have ongoing or occasional atrial fibrillation and have had a stroke or blood clot.

I have been on blood thinners for at least 3 months and plan to continue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo endovascular left atrial appendage occlusion with the WATCHMAN device or receive standard medical care

Procedure duration and immediate recovery

1 visit (in-person for procedure)

Follow-up

Participants are monitored for safety and effectiveness, including assessment of ischemic stroke or systemic embolism

4 years

Regular follow-up visits (frequency not specified)

Treatment Details

Interventions

• WATCHMAN device

Trial Overview The LAAOS-4 study tests if using the WATCHMAN device can prevent strokes or blood clots in people with atrial fibrillation who still face high stroke risks despite taking blood thinners. The device is implanted through a catheter-based procedure.

Participant Groups

Group I: WATCHMAN device Experimental Treatment 1 Intervention

Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device

Group II: Standard Care Active Control 1 Intervention

Participants will receive local, standard medical care

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Population Health Research Institute

Collaborator

Trials

165

Recruited

717,000+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Findings from Research

The WATCHMAN left atrial appendage closure device is designed to reduce the risk of stroke in patients with nonvalvular atrial fibrillation, but initial studies raised safety concerns leading to a 'not approvable' status from the FDA.

In the subsequent PREVAIL trial, while the device was eventually deemed to have benefits that outweigh risks, updated data indicated a higher incidence of ischemic strokes in the WATCHMAN group (13 strokes) compared to the control group (1 stroke), prompting further review of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the Food and Drug Administration circulatory system devices panel meetings on WATCHMAN left atrial appendage closure therapy. Waksman, R., Pendyala, LK.[2015]

The Watchman FLX device achieved a high procedural success rate of 98.6% for left atrial appendage occlusion (LAAO) in a study involving 359 patients across 26 centers, demonstrating its effectiveness in real-world settings.

The procedure had a low incidence of major peri-procedural complications at only 2.5%, indicating that the Watchman FLX is a safe option for LAAO, regardless of the operator's prior experience with the previous Watchman 2.5 device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of operato&#341;s experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry. Cruz-González, I., Torres Saura, F., Trejo-Velasco, B., et al.[2023]

The Watchman FLX device achieved a remarkable technical success rate of 100% in a study of 772 patients undergoing left atrial appendage occlusion, indicating its effectiveness in real-world settings.

The procedure had a low incidence of major adverse events, with only 2.7% of patients experiencing complications, primarily major extracranial bleeding, showcasing a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periprocedural outcome in patients undergoing left atrial appendage occlusion with the Watchman FLX device: The ITALIAN-FLX registry. Berti, S., De Caterina, AR., Grasso, C., et al.[2023]

The Watchman-FLX left atrial appendage closure device demonstrated a high procedural success rate of 99.5% in a high-risk population of 200 patients, with no reported device embolizations and a low complication rate of 8.5%.

Key advantages of the Watchman-FLX include its ease of implantation and repositioning, effective sealing of the left atrial appendage, and a significantly lower failure rate compared to the first-generation Watchman device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with the new Watchman FLX device: Data from two high-volume Sicilian centers. The FLX-iEST registry. Vizzari, G., Grasso, C., Sardone, A., et al.[2022]

In a study of 169 patients undergoing left atrial appendage closure, the WATCHMAN FLX device showed significant improvements over the WATCHMAN V.2.5, particularly in reducing peridevice leakage and adverse clinical events after 3 months.

The WM FLX device demonstrated continued expansion and reduced device compression over time, which correlated with a lower incidence of complications such as stroke and device-related thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transition from WATCHMAN V.2.5 to WATCHMAN FLX for closure of the left atrial appendage: echocardiographic and clinical findings. Sakriss, C., Roehl, P., Schwenzky, A., et al.[2023]

The Watchman FLX left atrial appendage closure device was successfully implanted in 30 patients using intracardiac echocardiography (ICE), achieving a 100% technical success rate without any procedure-related complications.

Follow-up imaging at about 47 days showed that the device was effective, with no device-related thrombus or significant leaks, indicating its safety and efficacy for patients with atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracardiac echocardiography-guided implantation of the Watchman FLX left atrial appendage closure device. Turagam, MK., Neuzil, P., Petru, J., et al.[2021]

In a study analyzing 43,802 Watchman LAAC device implants from March 2015 to March 2019, the overall adverse event rate was found to be 7.3%, with a low mortality rate of 0.4%.

Most adverse events occurred either during the procedure or within the first day, but a notable percentage of serious complications, including device embolizations and strokes, happened more than a month after implantation, highlighting the need for ongoing monitoring post-procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAUDE Database Analysis of Post-Approval Outcomes following Left Atrial Appendage Closure with the Watchman Device. Ledesma, PA., Uzomah, UA., Yu, X., et al.[2021]

The Watchman FLX device is a safe and effective alternative to anticoagulation for patients with atrial fibrillation at high risk of bleeding, showing non-inferiority in preventing strokes.

Unlike its predecessor, the Watchman FLX can accommodate a wider range of anatomical variations in the left atrial appendage, making it suitable for patients with challenging anatomies, as demonstrated in a case series of three successful implantations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Watchman FLX Implantation for Challenging Left Atrial Appendage Anatomy: Case-Based Discussion. Joury, A., Englert, JAR., Bernard, M., et al.[2022]

The WATCHMAN device offers a promising alternative to long-term warfarin therapy for patients with atrial fibrillation (AF) who are at high risk for embolic events but may face complications from anticoagulants, supported by medium-term efficacy and safety data.

This review highlights important technical aspects of WATCHMAN implantation, emphasizing its role as a well-studied option for nonvalvular AF patients who require oral anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Watchman Device: Left Atrial Appendage Closure For Stroke Prophylaxis In Atrial Fibrillation. N Obeyesekere Mbbs Mrcp Fracp Fhrs, DM.[2020]

References

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

Overview of the Food and Drug Administration circulatory system devices panel meetings on WATCHMAN left atrial appendage closure therapy. [2015]

2. Ireland pubmed.ncbi.nlm.nih.gov

Impact of operato&#341;s experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Periprocedural outcome in patients undergoing left atrial appendage occlusion with the Watchman FLX device: The ITALIAN-FLX registry. [2023]

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

Real-world experience with the new Watchman FLX device: Data from two high-volume Sicilian centers. The FLX-iEST registry. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Transition from WATCHMAN V.2.5 to WATCHMAN FLX for closure of the left atrial appendage: echocardiographic and clinical findings. [2023]

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

Intracardiac echocardiography-guided implantation of the Watchman FLX left atrial appendage closure device. [2021]

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

MAUDE Database Analysis of Post-Approval Outcomes following Left Atrial Appendage Closure with the Watchman Device. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Watchman FLX Implantation for Challenging Left Atrial Appendage Anatomy: Case-Based Discussion. [2022]

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

Watchman Device: Left Atrial Appendage Closure For Stroke Prophylaxis In Atrial Fibrillation. [2020]