Trial DesignThe PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation) Trial
Section snippets
Study objectives
This primary objective of the trial is to demonstrate the safety and efficacy of the WATCHMAN implant. The primary effectiveness end point is defined as all stroke (including ischemic and hemorrhagic), cardiovascular death (limited to any cardiovascular death or unexplained death), systemic embolism, and documented TIA (defined as an acute focal neurological event lasting at least 5 minutes). The primary safety end point for the study is defined as any life-threatening bleeding as determined by
Patient selection
Patients with paroxysmal, persistent, or permanent nonvalvular AF are candidates if they meet the inclusion and exclusion criteria. The CHADS (Congestive heart failure, Hypertension, Age, Diabetes and Stroke) score has been developed and validated as an instrument to define stroke risk in patients with AF11 and is an integral component for inclusion. To assess the CHADS score, one point is assigned for the presence of each of the four components, and two points are assigned for prior cerebral
Study design
This is a multicenter prospective randomized study comparing the WATCHMAN implant to a control group taking long-term warfarin therapy alone. A 2:1 randomization scheme (two WATCHMAN implants to every control) is used with stratification by center. The trial has been registered by Atritech on the NIH Clinical Trials Web site. The protocol and informed consent have been approved by each investigator's institutional review board before initiation of the study. After informed consent and before
Control patients
The patient's INR is maintained between 2.0 and 3.0 and monitored on a monthly basis, or more frequently if needed. These patients are followed up for any adverse events for the duration of the research study. Follow-up for these patients includes visits at 45 days and 6, 12, 24, 36, 48, and 60 months. Telephone interviews occur at 18, 30, and 42 months post-randomization.
WATCHMAN patients
Preprocedure study requirements for those study patients randomized to the WATCHMAN implant include adjustment of warfarin so that the INR is <2.0 at time of procedure and aspirin 81 mg is begun at least 1 day before procedure. An INR must be drawn within 24 hours of the procedure.
The implant procedure is performed under local or general anesthesia. In addition to fluoroscopic imaging, continuous TEE monitoring and guidance is performed. After standard transseptal puncture, the left atrium is
Statistical analysis: sample size justification
This is a randomized, prospective, multicentered study to determine the safety and effectiveness of the WATCHMAN device. The primary efficacy end point is a composite consisting of the occurrence of all stroke, systemic embolism, cardiovascular death (cardiovascular or unexplainable), or hard TIA. The statistical objective is to determine if the WATCHMAN device is noninferior to the control group with respect to the event rate for the composite end point. Event rate is defined as the expected
Statistical analysis
All statistical analyses will be by intention-to-treat with each patient analyzed as being part of their group regardless of the actual treatment received. All patients not having an event or lost to follow-up will be censored at the time of the last documented follow-up visit.
The primary efficacy end point and each component of the primary end point (all stroke, cardiovascular death (including probable cardiovascular death and unexplained death), systemic embolism, and TIA along with the
Core laboratory requirements
An independent core laboratory will be utilized for this study to interpret all echocardiographic data and chest x-rays gathered on all WATCHMAN study patients. The investigative sites follow a Core Laboratory Imaging Protocol.
Clinical Events Committee
An independent Clinical Events Committee (CEC) is responsible for adjudicating all major adverse events, serious adverse events, and all adverse events that are potentially related to the procedure or device that is reported during the conduct of this clinical trial. The CEC consists of three independent members, including two interventional cardiologists and one neurologist. It is blinded to the patient's treatment arm for the adverse events they are adjudicating. The CEC determines whether
Discussion
Atrial fibrillation exposes large numbers of patients to significant morbidity and mortality, particularly thromboembolic events, with the attendant personal and societal costs and resource utilization issues.
As previously documented, when stroke occurs, it often is the result of thromboembolism from the LAA.
Much has been learned also about the LAA itself. It is the remnant of the original embryonic left atrium that develops during the third week of gestation. In adult life, the LAA has a
Summary
The Protect AF trial is the only randomized trial of a percutaneous LAA isolation device. This trial is focused on evaluation of the relative merits of such a device versus standard therapy with warfarin.
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Cited by (186)
Delayed embolization of next-generation left atrial appendage closure device in an asymptomatic patient
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2023, American Journal of CardiologyCase Report: WATCHMAN Procedure Complicated By Atrial Perforation and Device Dislodgement
2023, Cardiovascular Revascularization MedicineCitation Excerpt :The PROTECT AF trial proposed that LAA with the WATCHMAN device was equivalent to warfarin for preventing stroke in atrial fibrillation with additional reductions in mortality and hemorrhagic stroke [3]. However, the trial reported a high rate of complications in the device group as compared to those treated with warfarin [3]. In general, complications linked to percutaneous LAA closure could be classified as related to one of three things: access, device implantation, or antithrombotic treatment [4].
Long-term outcomes of percutaneous left atrial appendage closure for the prevention of stroke in patients with atrial fibrillation: Asia-Pacific experience
2022, Journal of the Formosan Medical AssociationSafety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device
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