The primary objective is to demonstrate the safety and efficacy of the implantation of the LAmbre PlusTM device in patients with large or irregularly shaped appendages with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism compared to oral anticoagulation (OAC).
This prospective, randomized, multicenter study will enroll 2,931 subjects (2706 randomized subjects, 225 roll-in subjects) at up to 75 investigational sites in the United States. Patients presenting with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHA2DS2-VASc scores, and who are recommended for oral anticoagulation therapy but have an appropriate rationale to seek a non-pharmacologic alternative to oral anticoagulation, and who meet all eligibility criteria will be enrolled in the study. Subjects will have clinical follow-up in-hospital and at 45 days, 6 months, 12 months, and annually up to 5-years. CT/Imaging or Transesophageal echocardiographic (TEE) follow-up will occur at 45 days and TEE at 1-year. The LAmbre PlusTM Left Atrial Appendage (LAA) Closure System is intended to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation who: * Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for oral anticoagulation (OAC) therapy; AND * Are deemed by their physician to be suitable for OAC; AND * Have an appropriate rationale to seek a non-pharmacological alternative to OAC, taking into account the safety and effectiveness of the device compared to OAC
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
The LAmbre Plus device is a self-expanding occluder, composed of a distal Umbrella and a proximal Cover laser welded together, delivered percutaneously via femoral venous access and trans-septal puncture. The distal Umbrella consists of an elastic nitinol frame and outer PET membrane, and has circumferential anchors to secure the occluder to the left atrial appendage (LAA) wall. The proximal Cover is a disc of elastic nitinol mesh, which seals the orifice of the LAA and minimizes thrombus formation, and includes a PET membrane to prevent the passage of blood into the LAA after implantation.
Henry Ford Hospital
Detroit, Michigan, United States
Composite of time to first occurrence of stroke, cardiovascular death, or clinically relevant major or non-major bleeding events
Defined as composite of: First occurrence of stroke defined by NeuroARC; Cardiovascular death defined as any death due to proximate cause (e.g., MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure related deaths, including those related to concomitant treatment; Clinically relevant major or non-major bleeding events defined by hemoglobin of ≥2.0 g/dl during a 24-h period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding
Time frame: through study completion, up to 5 years
Composite of time to first occurrence of ischemic stroke or systemic embolism
Defined as composite of: First occurrence of ischemic stroke defined by NeuroARC; Systemic embolization defined as acute vascular insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical/autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation). When there is presence of prior peripheral artery disease, angiographic or surgical or autopsy evidence is required to show abrupt arterial occlusion.
Time frame: through study completion, up to of 5 years
Overall safety
Overall safety is defined as the composite of: Major procedure-related complications, defined as the composite of cardiac perforation, pericardial effusion with tamponade, device embolization, and major vascular complications (adjudicated by the independent Clinical Events Committee as related to the study device or procedure); AND Major adverse events, defined as all death, all stroke and major bleeding as compared to OAC
Time frame: 12 months
Mortality
Death classified as cardiovascular or non-cardiovascular and reported cumulatively and individually
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Time frame: 45 days, 6 months, 12 months, 5 years
Myocardial Infarction
Occurrence of MI defined by modified Third Universal Definition, which will be adjudicated and classified by an independent Clinical Events Committee (CEC)
Time frame: 45 days, 6 months, 12 months, 5 years
Peri-Procedural Stroke
Occurrence of peri-procedural stroke defined as Overt CNS Injury (NeuroARC defined)
Time frame: 30 days
Bleeding Complications
Occurrence of bleeding complications evaluated as major bleeding (BARC Type ≥3); major and minor bleeding (BARC ≥2) and its components by BARC Type
Time frame: 45 days, 6 months, 12 months, 5 years
Major Procedure-Related Complications
Occurrence of major procedure-related complications, defined as the composite of cardiac perforation, pericardial effusion with tamponade, ischemic stroke (NeuroARC defined), device embolization, major vascular complications (VARC 3 defined), and major bleeding
Time frame: 45 days
Vascular Complications
Occurrence of Vascular complications (VARC 3 defined)
Time frame: 45 days, 6 months, 12 months, 5 years
Embolic events
Occurrence of embolic events, defined as the composite of ischemic stroke (NeuroARC defined) and systemic embolization
Time frame: 45 days, 6 months, 12 months, 5 years
Ischemic Stroke
Occurrence of ischemic stroke (NeuroARC defined)
Time frame: 45 days, 6 months, 12 months, 5 years
Systemic embolization
Occurrence of systemic embolization defined by acute vascular insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical/autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation). When there is presence of prior peripheral artery disease, angiographic or surgical or autopsy evidence is required to show abrupt arterial occlusion.
Time frame: 45 days, 6 months, 12 months, 5 years
All CNS injury and dysfunction
Occurrence of all CNS injury and dysfunction (NeuroARC defined)
Time frame: 45 days, 6 months, 12 months, 5 years
Technical success
Technical success is defined as successful implantation (acceptable device position, stability, and LAA seal) with the assigned device
Time frame: within 24 hours Post-procedure
Closure success
Closure success is defined as technical success followed by successful LAA closure (complete LAA closure or peri-device residual jet \<5 mm in width by TEE/Imaging or CT)
Time frame: 45 days
Procedural Success
Procedural success is defined as technical success without major procedure-related complications
Time frame: 7 days Post-procedure
Total Procedural Time
Total procedural time is defined as time elapsed between first venous access and removal of the last catheter from the venous access sheath
Time frame: within 24 hours Post-procedure
Device Thrombosis
Occurrence of device thrombosis
Time frame: 45 days, 6 months, 12 months, 5 years