Atrial FibrillationCORRAL-AFNCT04684212
Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF
A study testing LAmbre PlusTM Left Atrial Appendage Closure System and Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa) in people with Atrial Fibrillation and Left Atrial Appendage Thrombosis, run by Brian O'Neill MD at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Left Atrial Appendage Thrombosis, CVA
- What is being tested?
- LAmbre PlusTM Left Atrial Appendage Closure System and Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 11 Jul 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 or flutter
- 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 OAC, but there is an appropriate rationale for seeking a non-pharmacologic alternative to oral anticoagulation
- The patient is deemed suitable for LAA closure in a shared decision model with a non-implanting physician
- 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)
- Potential subjects will be excluded if ANY of the following conditions apply:
Who cannot join
- 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/DAPT for a condition other than atrial fibrillation
- 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
- 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
Show all 25Show fewer
- 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
- Current participation in another investigational drug or device study
- Size of the left atrial appendage at the LAmbre Plus defined landing zone within outside the manufactures recommendations (Table 2.)
- Patients with an indication for chronic P2Y12 platelet inhibition therapy
- Patients who are unable to undergo CT scan
- Echocardiographic Exclusion Criteria
- Left atrial appendage anatomy may accommodate implantation of the WATCHMAN device, according to IFU by size.
- LVEF <25%
- Intracardiac thrombus or dense spontaneous echo contrast, as visualized by TEE within 2 days prior to implant
- 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)
- Presence of an intracardiac tumor
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF: The CORRAL-AF Study
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).
Read the 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
- Conditions
- Atrial Fibrillation, Left Atrial Appendage Thrombosis, CVA
- Being tested
- LAmbre PlusTM Left Atrial Appendage Closure System, Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)
- 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
- Medical subject headings
- Atrial Fibrillation, Thromboembolism, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAmbre PlusTM Left Atrial Appendage Closure SystemDevice
Also called LAmbre device
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.
Market approved oral anticoagulation (OAC), such as warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Savaysa), or betrixaban (Bevyxxa)Drug
Also called OAC
Continuation of market approved OAC drug.
| Study group | Role | What they receive |
|---|---|---|
| Device Arm | Experimental | The LAmbre PlusTM Left Atrial Appendage Closure System (LAmbre device) Receives: Device: LAmbre PlusTM Left Atrial Appendage Closure System |
| Control Arm | Active comparator | Market approved oral anticoagulation (OAC) Receives: 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 | 225 roll-in subjects Receives: Device: LAmbre PlusTM Left Atrial Appendage Closure System |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Measured: 12 months
Secondary outcomes (15)
Mortality
Death classified as cardiovascular or non-cardiovascular and reported cumulatively and individually
Measured: 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)
Measured: 45 days, 6 months, 12 months, 5 years
Peri-Procedural Stroke
Occurrence of peri-procedural stroke defined as Overt CNS Injury (NeuroARC defined)
Measured: 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
Measured: 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
Measured: 45 days
Vascular Complications
Occurrence of Vascular complications (VARC 3 defined)
Measured: 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
Measured: 45 days, 6 months, 12 months, 5 years
Ischemic Stroke
Occurrence of ischemic stroke (NeuroARC defined)
Measured: 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.
Measured: 45 days, 6 months, 12 months, 5 years
All CNS injury and dysfunction
Occurrence of all CNS injury and dysfunction (NeuroARC defined)
Measured: 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
Measured: 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)
Measured: 45 days
Procedural Success
Procedural success is defined as technical success without major procedure-related complications
Measured: 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
Measured: within 24 hours Post-procedure
Device Thrombosis
Occurrence of device thrombosis
Measured: 45 days, 6 months, 12 months, 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start1 Jun 2024 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion11 Jul 2024
Why it stopped: Lack of Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (41)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brian O'Neill MD
- Sponsor type
- University, hospital or other
- Collaborators
- Lifetech Scientific (Shenzhen) Co., Ltd.
- Responsible party
- Sponsor-investigator, Brian O'Neill MD, Henry Ford Health System
- Investigators
- Brian O'Neill, MD, Principal investigator, Henry Ford Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684212
- Sponsor's protocol ID
- G-200316
- Acronym
- CORRAL-AF
- Status last verified
- Oct 2025
- First submitted
- 17 Dec 2020
- Last updated
- 4 Nov 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25842274Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, Stijnen T, Lip GY, Witteman JC. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006 Apr;27(8):949-53. doi: 10.1093/eurheartj/ehi825. Epub 2006 Mar 9.
PubMed 16527828Go 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.
PubMed 11343485Dewland 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.
PubMed 24103419Lau 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.
PubMed 28784826Wolf 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.
PubMed 1866765Stewart 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.
PubMed 12401529Kong B, Liu Y, Huang H, Jiang H, Huang C. Left atrial appendage closure for thromboembolism prevention in patients with atrial fibrillation: advances and perspectives. J Thorac Dis. 2015 Feb;7(2):199-203. doi: 10.3978/j.issn.2072-1439.2015.01.20.
PubMed 25713737Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi: 10.7326/0003-4819-146-12-200706190-00007.
PubMed 17577005January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. No abstract available.
PubMed 24685669Gage BF, van Walraven C, Pearce L, Hart RG, Koudstaal PJ, Boode BS, Petersen P. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004 Oct 19;110(16):2287-92. doi: 10.1161/01.CIR.0000145172.55640.93. Epub 2004 Oct 11.
PubMed 15477396Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263-72. doi: 10.1378/chest.09-1584. Epub 2009 Sep 17.
PubMed 19762550Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov;138(5):1093-100. doi: 10.1378/chest.10-0134. Epub 2010 Mar 18.
PubMed 20299623Brass LM, Krumholz HM, Scinto JM, Radford M. Warfarin use among patients with atrial fibrillation. Stroke. 1997 Dec;28(12):2382-9. doi: 10.1161/01.str.28.12.2382.
PubMed 9412618Chan PS, Maddox TM, Tang F, Spinler S, Spertus JA. Practice-level variation in warfarin use among outpatients with atrial fibrillation (from the NCDR PINNACLE program). Am J Cardiol. 2011 Oct 15;108(8):1136-40. doi: 10.1016/j.amjcard.2011.06.017. Epub 2011 Jul 26.
PubMed 21798501