Assessing the Safety and Efficacy of the LAmbre™ Plus Device

Official title

A Prospective, Multicenter, Randomized Controlled Trial Assessing the Safety and Efficacy of the LAmbre™ Plus Left Atrial Appendage Closure System to REDUCE the Risk of Thromboembolism in Patients With Non-Valvular Atrial Fibrillation

Overview

Randomized controlled trial assessing the safety and efficacy of the LAmbre Plus LAA Closure System to rescue the risk of thromboembolism in patients with non-valvular AF.

Detailed description

The goal of this clinical trial is to demonstrate the safety and efficacy of the LAmbre Plus device in patients with non-valvular atrial fibrillation in comparison with the commercially available transcatheter LAAO device(s). The main questions it aims to answer are:

Overall safety of the device that is assessed at the 12 month time period. Overall efficacy, after all subjects have reached the 18 month time period.

Participants will be randomized to either the LAmbre device or other FDA approved LAAO devices.

Interventions

• Device LAmbre investigational device
  Randomized 1:1 to either experimental group or control group.

Primary outcome measures

• Major procedure related complications - cardiac perforation [Time frame: up to 7 days following implant procedure]
• Major procedure related complications - pericardial effusion with tamponade or requiring drainage [Time frame: up to 7 days following implant procedure]
• Major procedure related complications - device embolization [Time frame: up to 7 days following implant procedure]
• Major adverse event - Death [Time frame: up to 7 days following implant procedure]
• Major adverse event - all strokes [Time frame: up to 7 days following implant procedure]
• Major adverse event - systemic embolization [Time frame: up to 7 days following implant procedure]
• Major adverse event - major bleeding [Time frame: up to 7 days following implant procedure]

Secondary outcome measures (7)

• Major adverse event [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• mortality [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• myocardial infarction [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• periprocedural stroke [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• bleeding complications [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• major procedure-related complications [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]
• vascular complications [Time frame: 45 days, 6 months, 12 months, 18 months and 2, 3, 4, and 5 years]

Eligibility criteria

Inclusion criteria

• The patient is a male or non-pregnant female ≥18 years of age
• The patient has documented paroxysmal, persistent, or permanent non- valvular atrial fibrillation
• The patient has a CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3, and is recommended for oral anticoagulation therapy
• The patient is deemed by their physician to be suitable for short-term warfarin therapy, but there is an appropriate rationale for seeking a non-pharmacologic alternative to oral anticoagulation
• The patient is deemed suitable for LAA closure by a multidisciplinary heart team, including at least 1 investigator (e.g. cardiologists) and 1 clinician not involved as part of the procedure team using a shared decision making process, and this determination has been documented in the patient's medical record
• The patient is willing and able to comply with protocol-specified treatment and follow-up evaluations
• 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)

Exclusion criteria

• 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.
• 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)
• Patients who require long-term anticoagulation for a condition other than atrial fibrillation
• Patients with an indication for chronic P2Y12 platelet inhibition therapy
• Patients not suitable for short term warfarin (including due to bleeding diathesis or coagulopathy or absolute contraindication warfarin) or who will refuse transfusion
• Patients with rheumatic mitral valve disease, known severe aortic stenosis requiring surgical or percutaneous valve replacement, or existing mechanical valve prosthesis
• Active infection with bacteremia
• 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
• 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)
• 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.)
• Recent (within 90 days pre-procedure) stroke, transient ischemic attack, or myocardial infarction
• Severe heart failure (New York Heart Association Class IV)
• 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%.
• Past or pending heart or any other organ transplant, or on the waiting list for any organ transplant
• Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol, confound data interpretation, or is associated with a life expectancy of less than 2 years
• Current participation in another investigational drug or device study Echocardiographic Exclusion Criteria
• Left atrial appendage anatomy cannot accommodate either the LAmbre Plus LAAO device or the Control device per manufacturer IFU (e.g., the anatomy and sizing must be for both device to be enrolled in the trial or maximum LAAO length < maximum ostium width by TEE)
• LVEF <30%
• Intracardiac thrombus or dense spontaneous echo contrast, as visualized by TEE within 2 days prior to implant
• Moderate or large circumferential pericardial effusion >10 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology. In the event of a treatable pericardial effusion, the subject may undergo implantation at a later time after it is adequately treated.
• Atrial septal defect that warrants closure.
• 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)
• Moderate or severe mitral valve stenosis (mitral valve area <1.5 cm2)
• Complex atheroma with mobile plaque of the descending aorta and/or aortic arch (Grade 4 or higher)
• Evidence of a Cardiac Tumor

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Lansky AJ, Messe SR, Brickman AM, Dwyer M, van der Worp HB, Lazar RM, Pietras CG, Abrams KJ, McFadden E, Petersen NH, Browndyke J, Prendergast B, Ng VG, Cutlip DE, Kapadia S, Krucoff MW, Linke A, Moy CS, Schofer J, van Es GA, Virmani R, Popma J, Parides MK, Kodali S, Bilello M, Zivadinov R, Akar J, Furie KL, Gress D, Voros S, Moses J, Greer D, Forrest JK, Holmes D, Kappetein AP, Mack M, Baumbach A PMID 28183511
• Mandalenakis Z, Von Koch L, Eriksson H, Dellborg M, Caidahl K, Welin L, Rosengren A, Hansson PO. The risk of atrial fibrillation in the general male population: a lifetime follow-up of 50-year-old men. Europace. 2015 Jul;17(7):1018-22. doi: 10.1093/europace/euv036. Epub 2015 Apr 4. PMID 25842274
• Kalmykov NP, Mashchenko EN. New data on the migration of the family Elephantidae (Mammalia, Proboscidea) in Eurasia. Dokl Biol Sci. 2006 Jan-Feb;406:103-5. doi: 10.1134/s0012496606010303. No abstract available. PMID 16572828
• Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370. PMID 11343485
• Dewland TA, Olgin JE, Vittinghoff E, Marcus GM. Incident atrial fibrillation among Asians, Hispanics, blacks, and whites. Circulation. 2013 Dec 3;128(23):2470-7. doi: 10.1161/CIRCULATIONAHA.113.002449. Epub 2013 Oct 8. PMID 24103419
• Lau DH, Nattel S, Kalman JM, Sanders P. Modifiable Risk Factors and Atrial Fibrillation. Circulation. 2017 Aug 8;136(6):583-596. doi: 10.1161/CIRCULATIONAHA.116.023163. PMID 28784826
• Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22(8):983-8. doi: 10.1161/01.str.22.8.983. PMID 1866765
• Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med. 2002 Oct 1;113(5):359-64. doi: 10.1016/s0002-9343(02)01236-6. PMID 12401529

Identifiers

NCT: NCT06465706 · LA-US-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗