Trial Summary
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.
Do I have to stop taking my current medications for the trial?No, you must continue taking your oral anticoagulants during the trial.
Is the WATCHMAN Device a promising treatment for atrial fibrillation?Yes, the WATCHMAN Device is a promising treatment for atrial fibrillation. It helps reduce the risk of stroke in patients who can't take blood thinners. The newer version, Watchman FLX, is designed to work better in different heart shapes and has shown good results in real-world use.12679
What safety data exists for the WATCHMAN device for atrial fibrillation?The WATCHMAN device has undergone several evaluations for safety. Initial concerns were raised in the PROTECT AF study, leading to a 'not approvable' decision by the FDA in 2009. The PREVAIL trial was later conducted to address these concerns, and a 2013 FDA panel voted favorably on the device's benefits outweighing risks. However, updated data showed more ischemic strokes in the WATCHMAN group, prompting further review. Post-approval data from the MAUDE database (2015-2019) showed a 7.3% adverse event rate and a 0.4% mortality rate, with most events occurring intraoperatively or within a day. The Watchman FLX, a newer version, has shown improved safety in small studies, but larger registries are needed for confirmation.13469
What data supports the idea that WATCHMAN Device for Atrial Fibrillation is an effective treatment?The available research shows that the WATCHMAN Device has been reviewed multiple times by experts. Initially, there were safety concerns, but later studies, like the PREVAIL trial, showed that the benefits of the WATCHMAN Device outweigh the risks for certain patients. Although there were more strokes in the WATCHMAN group in one study, the overall expert opinion was positive. Additionally, newer versions of the device, like the WATCHMAN FLX, have been designed to improve safety and effectiveness, with studies showing good success rates in real-world settings.15689
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
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.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: WATCHMAN deviceExperimental Treatment1 Intervention
Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
Group II: Standard CareActive Control1 Intervention
Participants will receive local, standard medical care
Find a clinic near you
Research locations nearbySelect from list below to view details:
Aultman HospitalCanton, OH
Texas Cardiac Arrhythmia Research FoundationAustin, TX
University of CalgaryCalgary, Canada
Circulate Cardiac & Vascular Centre (CCVC)Burlington, Canada
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Who is running the clinical trial?
Hamilton Health Sciences CorporationLead Sponsor
McMaster UniversityCollaborator
Population Health Research InstituteCollaborator
Boston Scientific CorporationIndustry Sponsor
References
Overview of the Food and Drug Administration circulatory system devices panel meetings on WATCHMAN left atrial appendage closure therapy. [2015]The WATCHMAN left atrial appendage closure (LAAC) technology is a percutaneously delivered permanent cardiac implant placed in the LAA. This device is designed to reduce the risk of stroke and systemic embolism in warfarin-eligible patients with nonvalvular atrial fibrillation. The first circulatory system device panel reviewed the Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) study in 2009, and a "not approvable" letter was issued by the US Food and Drug Administration (FDA) based on safety concerns. Subsequently, the FDA, collaboratively with the sponsor, designed a new Prospective Randomized Evaluation of the WATCHMAN LAAC Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL) trial to address the earlier study limitations. A second panel was convened in December 2013 to review the results of PREVAIL and additional long-term follow-up data from PROTECT AF. The second panel voted favorably 13 to 1 that the benefits of the WATCHMAN LAAC therapy do outweigh the risks for use in patients who meet the criteria specified in the proposed indication. Subsequently, and during the premarket approval review, updated data from the PREVIAL study revealed more ischemic strokes in the WATCHMAN group, corresponding to a total of 13 ischemic strokes in the WATCHMAN group versus 1 in the control group. As a result of these strokes, the FDA called for a third panel to assess the benefit-risk profile of the WATCHMAN device. This summary aims to describe the discussions and recommendations made during the panel meetings.
Watchman Device: Left Atrial Appendage Closure For Stroke Prophylaxis In Atrial Fibrillation. [2020]A concerning proportion of patients with atrial fibrillation (AF) with indications for oral anticoagulation (OAC) discontinue OAC or are never prescribed OAC therapy and many AF patients with the highest risk for embolic events off OAC also have the greatest risk for hemorrhagic complications on OACs. Medium-term efficacy and safety data provide evidence that the WATCHMAN device, the most studied device and the only one with randomized and medium-term follow-up data, may be a viable alternative to chronic warfarin therapy in nonvalvular AF patients. In addition to presenting key data pertaining to LAA closure techniques including the WATCHMAN device, this review will discuss crucial WATCHMAN implantation technical points.
Intracardiac echocardiography-guided implantation of the Watchman FLX left atrial appendage closure device. [2021]The next-generation Watchman FLX left atrial appendage closure (LAAC) device has: (1) an atraumatic closed distal end, (2) reduced height, (3) a recessed screw hub to decrease device-related thrombus (DRT), (4) two rows of J-shape anchors so redeployment is possible after full recapture, and (5) ability to treat a greater size range of LAA ostia.
MAUDE Database Analysis of Post-Approval Outcomes following Left Atrial Appendage Closure with the Watchman Device. [2021]Left atrial appendage closure (LAAC) is an important strategy to reduce stroke risk in patients with non-valvular atrial fibrillation (AF) who are at high risk of bleeding on long-term anticoagulation. Real-world assessments of the safety of the Watchman LAAC device remain limited. The objective of this study was to determine the frequency and timing of adverse events associated with Watchman LAAC device implants performed after FDA approval. Adverse events associated with Watchman LAAC implants performed between March 2015 and March 2019 were identified through a search of the FDA Manufacturer and User Facility Device Experience (MAUDE) database. During the study period, 3,652 unique adverse events were identified. An estimated 43,802 Watchman implants were performed in the United States during the study period. The overall adverse event rate was 7.3% and the mortality rate was 0.4%. Of the 159 unique types of adverse events identified, pericardial effusion was most common (1.4%). Most adverse events (73%) occurred intraoperatively (59%) or within 1 day of the procedure (15%). However, 19% of deaths, 24% of strokes and 27% of device embolizations occurred >1 month after implantation. The rates of most Watchman-related adverse events reported in the MAUDE database were comparable to those observed in clinical trials. A majority of adverse events occurred within 1 day of implant. In conclusion, while the absolute event rates were low, a significant proportion of device embolizations, strokes, and deaths occurred >1 month after Watchman implant.
Impact of operatoŕs experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX.
Real-world experience with the new Watchman FLX device: Data from two high-volume Sicilian centers. The FLX-iEST registry. [2022]The Watchman-FLX left atrial appendage closure (LAAC) device presents innovative features: higher conformability, reduced length, closed distal "flex-ball" during deployment, and flattened surface. We report our real-world experience with the Watchman-FLX device in two centers with consolidated LAAC expertise.
Watchman FLX Implantation for Challenging Left Atrial Appendage Anatomy: Case-Based Discussion. [2022]Left atrial appendage (LAA) occlusion devices provided an acceptable and valid alternative to anticoagulation among patients with atrial fibrillation who carry high bleeding risk. Watchman device is non-inferior to oral anticoagulation to prevent cerebrovascular accidents. The presence of a longer distal portion of the older generation Watchman led to exclusion of patients with prohibitive anatomy of the LAA such as chicken-wing morphology or shallow LAA. Watchman FLX provides a wider range of sizes and can be implanted with complex anatomy or shallow LAA. In the case series, we discuss 3 patients with challenging LAA anatomy that underwent successful Watchman FLX implantation.
Transition from WATCHMAN V.2.5 to WATCHMAN FLX for closure of the left atrial appendage: echocardiographic and clinical findings. [2023]Interventional closure of the left atrial appendage (LAAC) has been established as an alternative treatment for patients with atrial fibrillation (AF) and an elevated risk of stroke. The WATCHMAN FLX (WM FLX) as the newest WATCHMAN LAAC device differs in several technical characteristics from its precursor, the WATCHMAN V.2.5 (WM V.2.5).
Periprocedural outcome in patients undergoing left atrial appendage occlusion with the Watchman FLX device: The ITALIAN-FLX registry. [2023]The Watchman FLX is a novel device for transcatheter left atrial appendage occlusion (LAAO) specifically designed to improve procedural performance in more complex anatomies with a better safety profile. Recently, small prospective non-randomized studies have shown good procedural success and safety compared with previous experiences. Results from large multicenter registries are needed to confirm the safety and efficacy of the Watchman FLX device in a real-world setting.