Atrial Fibrillation, CVA, Left Atrial Appendage Thrombosis
Conditions
Keywords
LAMBRE device, Left Atrial Appendage Occlusion device, CVA prevention, Atrial Fibrillation, Cardiovascular angiography, Anti-coagulation management, Thromboembolism, nonvalvular atrial fibrillation, non-pharmacological alternative, Thrombosis
Brief summary
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).
Detailed description
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
Interventions
DEVICELAmbre PlusTM Left Atrial Appendage Closure System
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.
DRUGMarket approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)
Continuation of market approved OAC drug.
Sponsors
Lifetech Scientific (Shenzhen) Co., Ltd.
Brian O'Neill MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Potential subjects must meet ALL of the following criteria to be eligible for inclusion in the study: Inclusion Criteria: 1. The patient is a male or non-pregnant female ≥18 years of age 2. The patient has documented paroxysmal, persistent, or permanent non-valvular atrial fibrillation or flutter 3. The patient has a CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3, and is recommended for oral anticoagulation therapy 4. The patient is deemed by their physician to be suitable for short-term OAC, but there is an appropriate rationale for seeking a non-pharmacologic alternative to oral anticoagulation 5. The patient is deemed suitable for LAA closure in a shared decision model with a non-implanting physician 6. The patient is willing and able to comply with protocol-specified treatment and follow-up evaluations 7. The patient (or his or her legally authorized representative) has been informed of the nature of the study, agrees to its provisions, and has been provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC) Potential subjects will be excluded if ANY of the following conditions apply:
Exclusion criteria
1. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following index procedure. Female patients of childbearing potential must have a negative pregnancy test done within 7 days prior to index procedure per site standard test 2. Patients with atrial fibrillation that is defined by a single occurrence, or that is transient or reversible (e.g., secondary to CABG, an interventional procedure, pneumonia, or hyperthyroidism) 3. Patients who require long-term anticoagulation/DAPT for a condition other than atrial fibrillation 4. Patients not suitable for short term oral anti-coagulation (including due to bleeding diathesis or coagulopathy or absolute contraindication to OAC or DAPT ) or who will refuse transfusion 5. Patients with rheumatic mitral valve disease, known severe aortic stenosis requiring surgical or percutaneous valve replacement, or existing mechanical valve prosthesis 6. Active infection with bacteremia 7. Known hypersensitivity or contraindication to aspirin, clopidogrel, heparin/bivalirudin, any device material or component (nitinol, nickel, titanium, PET), and/or contrast sensitivity that cannot be adequately pre-medicated 8. Anatomic conditions that would prevent performance of the LAA occlusion procedure (e.g., prior atrial septal defect \[ASD\] or patient foramen ovale \[PFO\] surgical repair or implanted closure device, or obliterated left atrial appendage) 9. Recent (within 30 days pre-procedure) or planned (within 60 days post procedure) cardiac or non-cardiac interventional or surgical procedure (e.g., cardioversion, ablation, percutaneous coronary intervention, cataract surgery, etc.) 10. Recent (within 90 days pre-procedure) stroke, transient ischemic attack, or myocardial infarction 11. Severe heart failure (New York Heart Association Class IV) 12. Known asymptomatic carotid artery disease with\>70% diameter stenosis OR symptomatic carotid disease (\>50% diameter stenosis with ipsilateral stroke or TIA). Subjects with prior carotid endarterectomy or carotid stent placement may be enrolled, provided that known diameter stenosis is \<50%. 13. Past or pending heart or any other organ transplant, or on the waiting list for any organ transplant 14. Current participation in another investigational drug or device study 15. Size of the left atrial appendage at the LAmbre Plus defined landing zone within outside the manufactures recommendations (Table 2.) 16. Patients with an indication for chronic P2Y12 platelet inhibition therapy 17. Patients who are unable to undergo CT scan Echocardiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of time to first occurrence of stroke, cardiovascular death, or clinically relevant major or non-major bleeding events | through study completion, up to 5 years | 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 |
| Composite of time to first occurrence of ischemic stroke or systemic embolism | through study completion, up to of 5 years | 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. |
| Overall safety | 12 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Complications | 45 days, 6 months, 12 months, 5 years | Occurrence of bleeding complications evaluated as major bleeding (BARC Type ≥3); major and minor bleeding (BARC ≥2) and its components by BARC Type |
| Major Procedure-Related Complications | 45 days | 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 |
| Vascular Complications | 45 days, 6 months, 12 months, 5 years | Occurrence of Vascular complications (VARC 3 defined) |
| Embolic events | 45 days, 6 months, 12 months, 5 years | Occurrence of embolic events, defined as the composite of ischemic stroke (NeuroARC defined) and systemic embolization |
| Ischemic Stroke | 45 days, 6 months, 12 months, 5 years | Occurrence of ischemic stroke (NeuroARC defined) |
| Systemic embolization | 45 days, 6 months, 12 months, 5 years | 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. |
| Mortality | 45 days, 6 months, 12 months, 5 years | Death classified as cardiovascular or non-cardiovascular and reported cumulatively and individually |
| Technical success | within 24 hours Post-procedure | Technical success is defined as successful implantation (acceptable device position, stability, and LAA seal) with the assigned device |
| Closure success | 45 days | 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) |
| Procedural Success | 7 days Post-procedure | Procedural success is defined as technical success without major procedure-related complications |
| Total Procedural Time | within 24 hours Post-procedure | Total procedural time is defined as time elapsed between first venous access and removal of the last catheter from the venous access sheath |
| Device Thrombosis | 45 days, 6 months, 12 months, 5 years | Occurrence of device thrombosis |
| All CNS injury and dysfunction | 45 days, 6 months, 12 months, 5 years | Occurrence of all CNS injury and dysfunction (NeuroARC defined) |
| Myocardial Infarction | 45 days, 6 months, 12 months, 5 years | Occurrence of MI defined by modified Third Universal Definition, which will be adjudicated and classified by an independent Clinical Events Committee (CEC) |
| Peri-Procedural Stroke | 30 days | Occurrence of peri-procedural stroke defined as Overt CNS Injury (NeuroARC defined) |
Countries
United States
Outcome results
None listed