Clinical trial NCT02879448: AMPLATZER™ Amulet™ LAA Occluder Trial
Official title: AMPLATZER™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Keywords: Non-valvular atrial fibrillation
Left Atrial Appendage
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2016-08-25
Enrollment: 1878
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The Amulet™ device will be evaluated for safety and efficacy by demonstrating its performance is non-inferior to the commercially available WATCHMAN® left atrial appendage closure device in patients with non-valvular atrial fibrillation. Patients who are eligible for the trial will be randomized to receive either the Amulet device or the WATCHMAN device and will be followed for 5 years after device implant.

Detailed description: The Amulet IDE trial is a prospective, randomized, multi-center active control worldwide trial, designed to evaluate the safety and effectiveness of the AMPLATZER™ Amulet™ Left Atrial Appendage Occluder. Subjects will be randomized in a 1:1 ratio between the Amulet left atrial appendage (LAA) occlusion device (treatment) or a Boston Scientific WATCHMAN® LAA closure device (Control). The trial will be conducted at up to 150 sites worldwide. All enrolled subjects will follow the protocol-required tests and assessments at each scheduled follow-up visit.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older
2. Documented paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and the patient has not been diagnosed with rheumatic mitral valvular heart disease
3. At high risk of stroke or systemic embolism defined as CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3
4. Has an appropriate rationale to seek an alternative to warfarin or other anticoagulation medication
5. Deemed by investigator to be suitable for short term warfarin therapy but deemed unable to take long term oral anticoagulation, following the conclusion of shared decision making (see inclusion criteria #6)
6. Deemed suitable for LAA closure by a multidisciplinary team of medical professionals (including an independent non-interventional physician) involved in the formal and shared decision- making process, and by use of an evidence-based decision tool on oral anticoagulation (final determination must be documented in the subject's medical record)
7. Able to comply with the required medication regimen post-device implant
8. Able to understand and willing to provide written informed consent to participate in the trial
9. Able and willing to return for required follow-up visits and examinations

Exclusion Criteria:

1. Requires long-term oral anticoagulation therapy for a condition other than atrial fibrillation
2. Contraindicated for or allergic to aspirin, clopidogrel, or warfarin use
3. Indicated for chronic P2Y12 platelet therapy inhibitor
4. Is considered at high risk for general anesthesia, in the opinion of the investigator, and/or based on past adverse reaction(s) requiring medical intervention or which resulted in prolongation of hospital stay (criterion is only applicable where general anesthesia is planned for the study procedure).
5. Has undergone atrial septal defect (ASD) repair or has an ASD closure device present
6. Has undergone patent foramen ovale (PFO) repair or has a PFO closure device implanted
7. Implanted with a mechanical valve prosthesis
8. Has any of the customary contraindications for a percutaneous catheterization procedure (e.g. subject is too small to accommodate the transesophageal echocardiogram (TEE/TOE) probe or required catheters, or subject has active infection or bleeding disorder)
9. Stroke or transient ischemic attack (TIA) within 90 days prior to randomization or implant procedure (as applicable)
10. Underwent any cardiac or non-cardiac intervention or surgery within 30 days prior to randomization, or intervention or surgery is planned within 60 days after implant procedure (e.g. cardioversion, ablation, cataract surgery, etc.)
11. Myocardial infarction (MI) within 90 days prior to randomization
12. New York Heart Association Class IV Congestive Heart Failure
13. Left ventricular ejection Fraction (LVEF) ≤30%
14. Symptomatic carotid artery disease (defined as \>50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is \<50% stenosis
15. Reversible cause of AF (i.e. secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
16. History of idiopathic or recurrent venous thromboembolism
17. Left atrial appendage is obliterated or surgically ligated
18. Thrombocytopenia or anemia requiring transfusions
19. Hypersensitivity to any portion of the device material or individual components of either the Amulet or Boston Scientific LAA closure device (e.g. nickel allergy)
20. Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
21. Subject is pregnant or pregnancy is planned during the course of the investigation
22. Active endocarditis or other infection producing bacteremia
23. Subject has had a transient case of AF (i.e. never previously detected, provoked/induced by surgical or catheter manipulations, etc.)
24. Subjects with severe renal failure (estimated glomerular filtration rate \<30ml/min/1.73m²)
25. Subject whose life expectancy is less than 2 years
26. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical trial or to comply with follow up requirements, or impact the scientific soundness of the clinical trial results.

Echocardiographic Exclusion Criteria:

1. Intracardiac thrombus visualized by echocardiographic imaging
2. Existing circumferential pericardial effusion \>2mm
3. Significant mitral valve stenosis (i.e. mitral valve area \<1.5 cm\^2)
4. High risk PFO, defined as an atrial septal aneurysm (excursion \> 15mm or length ≥ 15mm; excursion defined as maximal protrusion of the atrial septal aneurysm \[ASA\] beyond the plane of the atrial septum) or large shunt (early, within 3 beats and/or substantial passage of bubbles i.e. ≥ 20)
5. Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
6. Cardiac tumor
7. LAA anatomy cannot accommodate either a Boston Scientific LAA closure device or Amulet device, as per manufacturer's Instructions for Use (IFU). (i.e. the LAA anatomy and sizing must be appropriate for both devices in order to be enrolled in the trial. This is applicable to all roll-in and randomized subjects).
8. Placement of the device would interfere with any intracardiac or intravascular structure

Primary outcomes:
measure: Primary Safety Endpoint: Composite Endpoint Rate of Procedure-related Complications, or All-cause Death or Major Bleeding (Defined as Type 3 or Greater Based on the Bleeding Academic Research Consortium (BARC) Definition) (Non-inferiority Analysis)
timeFrame: At 12-months
measure: Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis)
timeFrame: At 18-months
measure: Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis)
timeFrame: At 45-days
Secondary outcomes:
measure: Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis)
timeFrame: At 18-months
measure: Rate of Major Bleeding (Superiority Analysis)
timeFrame: At 18-months
measure: Superiority Test of Primary Safety Endpoint: Composite Endpoint Rate of Procedure-related Complications, or All-cause Death or Major Bleeding (Defined as Type 3 or Greater Based on the Bleeding Academic Research Consortium (BARC) Definition)
timeFrame: At 12-months
measure: Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism
timeFrame: At 18-months
measure: Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab
timeFrame: At 45-days
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC.
state: Alabama
city: Phoenix
country: United States
facility: Banner-University Medical Center Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernards Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: USC University Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Sacramento
country: United States
facility: University of California - Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Mercy Medical Group - Cardiology
state: California
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: Santa Monica
country: United States
facility: Pacific Heart Institute
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates PC
state: Colorado
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Bradenton
country: United States
facility: Bradenton Cardiology Center
state: Florida
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic Center
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Advocate Health and Hospitals Corporation
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cardiac Arrhythmia Research Foundation
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Burlington
country: United States
facility: Lahey Clinic Medical Center
state: Massachusetts
city: Fall River
country: United States
facility: Charlton Memorial Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital, Royal Oak
state: Michigan
city: Minneapolis
country: United States
facility: VA Medical Center Minneapolis
state: Minnesota
city: Saint Cloud
country: United States
facility: St. Cloud Hospital (Central MN Heart Clinic)
state: Minnesota
city: Saint Paul
country: United States
facility: St. Joseph's Hospital
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Mineola
country: United States
facility: Winthrop-University Hospital
state: New York
city: New York
country: United States
facility: New York University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian/Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Health & Hospitals
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Medical Center Clinical Sciences
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute at Utica
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health
state: Pennsylvania
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: St. Thomas Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Heart Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: San Antonio
country: United States
facility: South Texas Cardiovascular Consultants
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora Medical Group
state: Wisconsin
city: Wahroonga
country: Australia
facility: Specialist Cardiology
state: New South Wales
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: St. Andrew's Hospital
state: South Australia
city: Murdoch
country: Australia
facility: HeartCare St John of God Wexford Medical Centre
state: Western Australia
city: Vancouver
country: Canada
facility: Vancouver General Hospital (U of BC)
state: British Columbia
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal (Montreal Heart Inst.)
state: Quebec
city: Prague
country: Czechia
facility: Nemocnice Na Homolce
state: Central Bohemia
city: Arhus
country: Denmark
facility: Skejby University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Villingen-Schwenningen
country: Germany
facility: Kliniken Villingen-Schwenningen
state: Bad-wur
city: Coburg
country: Germany
facility: Klinikum Coburg GmbH
state: Bavaria
city: Munich
country: Germany
facility: Internistisches Klinikum München SUD
state: Bavaria
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum am Bethanien Krankenhaus
state: Hesse
city: Frankfurt
country: Germany
facility: CardioVaskuläres Centrum St. Katharinen
state: Hesse
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld
state: North Rhine
city: Dusseldorf
country: Germany
facility: Medizinische Einrichtungen der Universität Düsseldorf
state: North Rhine
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen GmbH
state: North Rhin
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
state: Rhineland
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
state: Saxony
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Milano
country: Italy
facility: Ospedale San Raffaele - Aritmologia
state: Lombard
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
state: Utrecht
city: Lisboa
country: Portugal
facility: Santa Maria Hospital
state: Lisbon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Andalusia
city: Huelva
country: Spain
facility: Hospital General Juan Ramon Jimenez
state: Andalu
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
state: Castile And Leon
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
state: Catalonia
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarre
city: Bern
country: Switzerland
facility: Center Inselspital Bern
Study officials:
affiliation: University of Kansas
name: Dhanunjaya Lakkireddy, MD
role: STUDY_CHAIR
affiliation: The Comprehensive Stroke Center at Tufts Medical Center
name: David Thaler, MD, PhD
role: STUDY_CHAIR
affiliation: Inselspital, University of Bern
name: Stephan Windecker, MD, PhD
role: STUDY_CHAIR
References:
citation: Alkhouli M, Russo AM, Thaler D, Windecker S, Anderson JA, Gage R, Lakkireddy D. Sex Differences in Safety and Effectiveness of LAAO: Insights From the Amulet IDE Trial. JACC Cardiovasc Interv. 2022 Nov 14;15(21):2143-2155. doi: 10.1016/j.jcin.2022.06.037. Epub 2022 Oct 12.
citation: Price MJ, Ellis CR, Nielsen-Kudsk JE, Thaler D, Gupta N, Koulogiannis K, Anderson JA, Gage R, Lakkireddy D. Peridevice Leak After Transcatheter Left Atrial Appendage Occlusion: An Analysis of the Amulet IDE Trial. JACC Cardiovasc Interv. 2022 Nov 14;15(21):2127-2138. doi: 10.1016/j.jcin.2022.09.001.
citation: Lakkireddy D, Thaler D, Ellis CR, Swarup V, Sondergaard L, Carroll J, Gold MR, Hermiller J, Diener HC, Schmidt B, MacDonald L, Mansour M, Maini B, O'Brien L, Windecker S. Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized, Controlled Trial. Circulation. 2021 Nov 9;144(19):1543-1552. doi: 10.1161/CIRCULATIONAHA.121.057063. Epub 2021 Aug 30.