Clinical trial NCT04226547: Amplatzer Amulet LAAO vs. NOAC
Official title: Clinical Trial of Atrial Fibrillation Patients Comparing Left Atrial Appendage Occlusion Therapy to Non-vitamin K Antagonist Oral Anticoagulants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Stroke
Bleeding
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 2650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to evaluate the safety and effectiveness of the Amulet LAA occluder compared to NOAC therapy in patients with non-valvular AF at increased risk for ischemic stroke and who are recommended for long-term NOAC therapy.

The clinical investigation is a prospective, randomized, multicenter active control worldwide trial. Subjects will be randomized in a 1:1 ratio between the Amulet LAA occlusion device ("Device Group") and a commercially available NOAC medication ("Control Group"). The choice of NOAC in the Control Group will be left to study physician discretion.


Eligibility criteria: Inclusion Criteria:

* Documented paroxysmal, persistent, or permanent non-valvular AF (documentation must include an electrocardiogram, Holter, or event recorder)
* At high risk of stroke or systemic embolism, defined as a CHA2DS2-VASc score of ≥ 2 for men and ≥ 3 for women
* Eligible for long-term NOAC therapy
* Able to comply with the required NOAC medication regimen if randomized to the Control Group
* Able to comply with the required medication regimen post-device implant if subject is randomized to the Device Group or subject is a Roll-in
* Able to understand, and is willing to provide, written informed consent to participate in the trial, prior to any clinical investigation related procedure or assessment
* 18 years of age or older, or the age of legal consent
* Able and willing to return for required follow-up visits and assessments

Exclusion Criteria:

* Requires long-term OAC therapy for a condition other than AF
* Planned cardiac intervention or surgery, which is invasive or requires sedation or anesthesia, within 3 months following randomization, other than study-related procedures such as LAAO and cardiac imaging (if applicable)
* Known contraindication to, or allergic to, aspirin, clopidogrel, or OAC medication use
* Indicated for P2Y12 platelet inhibitor for \>1 year post-randomization
* In the opinion of the investigator, is considered at high risk for general anesthesia and general anesthesia is planned for the study procedure
* Has undergone atrial septal defect (ASD) repair or has an ASD closure device present
* Has undergone patent foramen ovale (PFO) repair or has a PFO closure device implanted
* Is implanted with a mechanical valve prosthesis
* Is implanted with an inferior vena cava filter
* History of rheumatic or congenital mitral valve heart disease
* Has any of the customary contraindications for a percutaneous catheterization procedure (e.g. subject is too small to accommodate the ICE probe (if planned) or required catheters, or subject has active infection or bleeding disorder)
* Customary contraindications for TEE/TOE (e.g., presence of esophageal varices, esophageal stricture, or history of esophageal cancer)
* Experienced stroke or transient ischemic attack (TIA) within 90 days prior to randomization or implant procedure (as applicable)
* Underwent any cardiac or non-cardiac intervention or surgery within 30 days prior to randomization
* Underwent catheter ablation for AF or atrial flutter within 60 days prior to randomization
* Experienced myocardial infarction within 90 days prior to randomization
* New York Heart Association Class IV Congestive Heart Failure
* Left ventricular ejection fraction ≤ 30% (per most recent assessment)
* Symptomatic carotid disease (defined as \> 50% lumen diameter narrowing on CTA, MRA, or TCD 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% lumen diameter narrowing
* Has known intracranial atherosclerosis and/or intracranial small vessel disease (defined as 6 points on the Fazekas Scale)
* Reversible cause of AF (i.e., secondary to thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
* History of idiopathic or recurrent venous thromboembolism
* LAA is obliterated or surgically ligated
* Thrombocytopenia (defined as \< 50,000 platelets per microliter (\<50 x 10\^9 /L)or anemia (defined as hemoglobin \< 10 g/dL) requiring transfusions
* Hypersensitivity to any portion of the device material or individual components of the Amulet LAA occluder device (e.g., nickel allergy)
* Actively enrolled in, or plans to enroll in, a concurrent clinical study in which the active treatment arm may confound the results of this trial
* Is pregnant or breastfeeding, or pregnancy is planned during the course of the investigation
* Active endocarditis or other infection producing bacteremia
* Transient case of AF (i.e., never previously detected, provoked/induced by surgical or catheter manipulations, etc.)
* Severe renal failure (estimated glomerular filtration rate \<30 ml/min/1.73m2), but not on dialysis
* Life expectancy is less than 2 years in the opinion of the Investigator
* 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 investigation or to comply with follow up requirements, or impact the scientific soundness of the clinical investigation results.

Primary outcomes:
measure: Composite of ischemic stroke, systemic embolism, or cardiovascular (CV) mortality
timeFrame: 2 years
measure: Major bleeding or clinically relevant non-major bleeding (CRNMB) events, excluding procedure related events
timeFrame: 2 years
measure: Composite of ischemic stroke or systemic embolism
timeFrame: 3 years
Secondary outcomes:
measure: Major bleeding or CRNMB events
timeFrame: 2 years
measure: Major bleeding or CRNMB events
timeFrame: 2 years
measure: Disabling or fatal strokes
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Hospital - Univ. of Alabama at Birmingham (UAB)
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Jonesboro
country: United States
facility: Arrhythmia Research Group
state: Arkansas
city: Little Rock
country: United States
facility: UAMS Medical Center
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: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Sacramento
country: United States
facility: Mercy Medical Group - Cardiology
state: California
city: San Diego
country: United States
facility: University of California at San Diego (UCSD) Medical Center
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates PC
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Altamonte Springs
country: United States
facility: AdventHealth Florida Cardiology - Altamonte Springs
state: Florida
city: Jacksonville
country: United States
facility: St. Vincent's Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Lake Mary
country: United States
facility: AdventHealth Florida Cardiology - Lake Mary
state: Florida
city: Naples
country: United States
facility: NCH Healthcare System
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Oviedo
country: United States
facility: AdventHealth Florida Cardiology - Oviedo
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Atlanta
country: United States
facility: St. Joseph's Hospital
state: Georgia
city: Lawrenceville
country: United States
facility: Northside Hospital (CardioVascular Group Lawrenceville)
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Lutheran Hospital of Indiana
state: Indiana
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: Overland Park
country: United States
facility: Overland Park Mid America Cardiology
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center - St. Francis Campus
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Physician Group
state: Louisiana
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
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: Jackson
country: United States
facility: Jackson Heart Clinic
state: Mississippi
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Omaha
country: United States
facility: CHI Health Creighton University Medical Center-Bergan Mercy
state: Nebraska
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Bay Shore
country: United States
facility: South Shore University Hospital-Northwell
state: New York
city: Buffalo
country: United States
facility: Buffalo General 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 Hospital/Cornell University
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital Northwell
state: New York
city: Asheville
country: United States
facility: Mission Health & Hospitals
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart & Vascular Research
state: North Carolina
city: Cincinnati
country: United States
facility: TriHealth Bethesda North Hospital
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute at Utica
state: Oklahoma
city: Harrisburg
country: United States
facility: Pinnacle Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health
state: Pennsylvania
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center
state: South Dakota
city: Chattanooga
country: United States
facility: Erlanger Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: Tennova Healthcare-Turkey Creek Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Heart & Vascular Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia
state: Texas
city: Forth Worth
country: United States
facility: Baylor All Saints Medical Center at Fort Worth
state: Texas
city: Houston
country: United States
facility: Park Plaza Hospital
state: Texas
city: Houston
country: United States
facility: CHI St. Luke's Health Baylor College of Medicine Med. Ctr.
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Katy Cardiology Associates
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: San Antonio
country: United States
facility: Methodist Texsan Hospital
state: Texas
city: Shenandoah
country: United States
facility: Heart Rhythm Associates
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Morgantown
country: United States
facility: Monongalia General Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital - City Campus
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montreal (Montreal Heart Inst.)
city: Montréal
country: Canada
facility: CHUM
city: Vancouver
country: Canada
facility: Vancouver General Hospital (U of BC)
city: Prague
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Prague
country: Czechia
facility: Nemocnice Na Homolce
city: Arhus
country: Denmark
facility: Skejby University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Massy
country: France
facility: Institute Cardio. Paris-Sud - Institut Jacques Cartier
city: Paris
country: France
facility: Mutualiste Montsouris
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)
state: Brandenburg
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Lübeck
state: Schleswig-Holstein
city: Bad Segeberg
country: Germany
facility: Segeberger Kliniken GmbH
city: Bonn
country: Germany
facility: St. Marien-Hospital-Bonn
city: Frankfurt
country: Germany
facility: Cardioangiologisches Centrum am Bethanien Krankenhaus
city: Gießen
country: Germany
facility: Klinikum der Justus-Liebig-Universität
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Munich
country: Germany
facility: Internistisches Klinikum München SUD
city: Siegburg
country: Germany
facility: Helios Klinikum Siegburg
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong (Queen Mary Hospital)
city: Massa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Toyohashi
country: Japan
facility: Toyohashi Heart Center
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba University
state: Chiba
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Kurashiki-shi
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center
state: Tokyo
city: Tokyo
country: Japan
facility: Institute of Science Tokyo Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Klinikos
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Zabrze
country: Poland
facility: Slaskie Centrum Chorob Serca
city: Łódź
country: Poland
facility: Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
state: Community of Madrid
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Bern
country: Switzerland
facility: Center Inselspital Bern
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Brighton
country: United Kingdom
facility: The Royal Sussex County Hospital
Study officials:
affiliation: Mt. Sinai Medical Center
name: Vivek Reddy, MD
role: PRINCIPAL_INVESTIGATOR
References: