Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF (CORRAL-AF)

Brian O'Neill MD

Status: Withdrawn

Conditions: Atrial Fibrillation; CVA; Left Atrial Appendage Thrombosis

Treatments: Device: LAmbre PlusTM Left Atrial Appendage Closure System; Drug: Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04684212

G-200316

Details and patient eligibility

About

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).

Full 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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 Exclusion Criteria

1. Left atrial appendage anatomy may accommodate implantation of the WATCHMAN device, according to IFU by size.
2. LVEF <25%
3. Intracardiac thrombus or dense spontaneous echo contrast, as visualized by TEE within 2 days prior to implant
4. Presence of a high-risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion >15 mm or length >15 mm) or large shunt (early, within 3 beats and/or substantial passage of bubbles)
5. Moderate or severe mitral valve stenosis (mitral valve area <1.5 cm2)
6. Complex atheroma with mobile plaque of the descending aorta and/or aortic arch (Grade 4 or higher)
7. Presence of an intracardiac tumor

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Device Arm

Experimental group

Description:

The LAmbre PlusTM Left Atrial Appendage Closure System (LAmbre device)

Treatment:

Device: LAmbre PlusTM Left Atrial Appendage Closure System

Control Arm

Active Comparator group

Description:

Market approved oral anticoagulation (OAC)

Treatment:

Drug: Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)

Roll-in Arm

Other group

Description:

225 roll-in subjects

Treatment:

Device: LAmbre PlusTM Left Atrial Appendage Closure System