AMPLATZER™ Amulet™ LAA Occluder Trial

Stroke Clinical Trial

— Amulet IDE  

Official title:

AMPLATZER™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02879448
• Other study ID #: SJM-CIP-10114
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 24, 2016
• Est. completion date: November 1, 2024

Study information

• Verified date: June 2024
• Source: Abbott Medical Devices
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1878
• Est. completion date: November 1, 2024
• Est. primary completion date: December 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stroke

Intervention

Device:
• Amulet Left Atrial Appendage Occluder
Transcatheter left atrial appendage closure
• WATCHMAN Left Atrial Appendage Closure
Transcatheter left atrial appendage closure

Locations

Country	Name	City	State
Australia	St. Andrew's Hospital	Adelaide	South Australia
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	HeartCare St John of God Wexford Medical Centre	Murdoch	Western Australia
Australia	Specialist Cardiology	Wahroonga	New South Wales
Canada	Institut de Cardiologie de Montreal (Montreal Heart Inst.)	Montreal	Quebec
Canada	Vancouver General Hospital (U of BC)	Vancouver	British Columbia
Czechia	Nemocnice Na Homolce	Prague	Central Bohemia
Denmark	Skejby University Hospital	Arhus
Denmark	Rigshospitalet	Copenhagen
Germany	Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)	Berlin
Germany	Evangelisches Krankenhaus Bielefeld	Bielefeld	North Rhine
Germany	Klinikum Coburg GmbH	Coburg	Bavaria
Germany	Medizinische Einrichtungen der Universität Düsseldorf	Dusseldorf	North Rhine
Germany	Elisabeth-Krankenhaus Essen GmbH	Essen	North Rhin
Germany	Cardioangiologisches Centrum am Bethanien Krankenhaus	Frankfurt	Hesse
Germany	CardioVaskuläres Centrum St. Katharinen	Frankfurt	Hesse
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Herzzentrum Leipzig GmbH	Leipzig	Saxony
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz	Mainz	Rhineland
Germany	Internistisches Klinikum München SUD	Munich	Bavaria
Germany	Kliniken Villingen-Schwenningen	Villingen-Schwenningen	Bad-wur
Italy	Ospedale San Raffaele - Aritmologia	Milano	Lombard
Netherlands	St. Antonius Ziekenhuis	Nieuwegein	Utrecht
Portugal	Santa Maria Hospital	Lisboa	Lisbon
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona	Catalonia
Spain	Hospital General Juan Ramon Jimenez	Huelva	Andalu
Spain	Clínica Universidad de Navarra	Pamplona	Navarre
Spain	Hospital Universitario de Salamanca	Salamanca	Castile And Leon
Spain	Hospital Universitario Virgen Macarena	Sevilla	Andalusia
Switzerland	Center Inselspital Bern	Bern
United States	Albany Medical Center	Albany	New York
United States	Mission Health & Hospitals	Asheville	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	Austin Heart	Austin	Texas
United States	Texas Cardiac Arrhythmia	Austin	Texas
United States	Bradenton Cardiology Center	Bradenton	Florida
United States	Lahey Clinic Medical Center	Burlington	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Delray Medical Center	Delray Beach	Florida
United States	Henry Ford Hospital	Detroit	Michigan
United States	Charlton Memorial Hospital	Fall River	Massachusetts
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	The Methodist Hospital	Houston	Texas
United States	Heart Center Research, LLC.	Huntsville	Alabama
United States	St. Vincent Hospital	Indianapolis	Indiana
United States	Baptist Medical Center	Jacksonville	Florida
United States	St. Bernards Medical Center	Jonesboro	Arkansas
United States	Kansas University Medical Center	Kansas City	Kansas
United States	St. Luke's Hospital	Kansas City	Missouri
United States	Scripps Health	La Jolla	California
United States	Watson Clinic Center	Lakeland	Florida
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky	Lexington	Kentucky
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Arkansas Heart Hospital	Little Rock	Arkansas
United States	South Denver Cardiology Associates PC	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	USC University Hospital	Los Angeles	California
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Baptist Hospital of Miami	Miami	Florida
United States	Aurora Medical Group	Milwaukee	Wisconsin
United States	Winthrop-University Hospital	Mineola	New York
United States	VA Medical Center Minneapolis	Minneapolis	Minnesota
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	El Camino Hospital	Mountain View	California
United States	Midwest Cardiovascular Institute	Naperville	Illinois
United States	St. Thomas Hospital	Nashville	Tennessee
United States	Vanderbilt Heart Institute	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Mount Sinai Hospital	New York	New York
United States	New York Presbyterian/Columbia University Medical Center	New York	New York
United States	New York University Hospital	New York	New York
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Advocate Health and Hospitals Corporation	Oakbrook Terrace	Illinois
United States	Kansas City Cardiac Arrhythmia Research Foundation	Overland Park	Kansas
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Cardiovascular Research Center	Phoenix	Arizona
United States	Banner-University Medical Center Phoenix	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	The Heart Hospital Baylor Plano	Plano	Texas
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Beaumont Hospital, Royal Oak	Royal Oak	Michigan
United States	Mercy Medical Group - Cardiology	Sacramento	California
United States	University of California - Davis Medical Center	Sacramento	California
United States	St. Cloud Hospital (Central MN Heart Clinic)	Saint Cloud	Minnesota
United States	St. Joseph's Hospital	Saint Paul	Minnesota
United States	University of Utah Hospital	Salt Lake City	Utah
United States	South Texas Cardiovascular Consultants	San Antonio	Texas
United States	San Diego Cardiac Center	San Diego	California
United States	Pacific Heart Institute	Santa Monica	California
United States	Swedish Medical Center	Seattle	Washington
United States	Tallahassee Research Institute	Tallahassee	Florida
United States	Oklahoma Heart Institute at Utica	Tulsa	Oklahoma
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	Washington Hospital Center	Washington	District of Columbia
United States	Cardiovascular Research Institute of Kansas	Wichita	Kansas
United States	Wake Forest University Medical Center Clinical Sciences	Winston-Salem	North Carolina
United States	Lankenau Institute for Medical Research	Wynnewood	Pennsylvania
United States	WellSpan Health	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abbott Medical Devices

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Denmark,  Germany,  Italy,  Netherlands,  Portugal,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Procedure related complications are adverse events adjudicated by the Clinical Events Committee (CEC), as procedure related and requiring either invasive surgical or percutaneous intervention.; All-cause deaths (cardiovascular or non-cardiovascular) were assessed.; Major Bleeding; Type 3a: Any transfusion with overt bleeding; Overt bleeding+Hb drop of = 3 to < 5 g/dL (provided Hb drop is related to bleed); Type 3b: Overt bleeding+Hb drop = 5 g/dL (provided Hb drop is related to bleed); Cardiac tamponade; Bleeding requiring surgical intervention for (Watchman); Bleeding requiring intravenous vasoactive drugs; Type 3c: Intracranial hemorrhage including subdural hemorrhages; Subcategories confirmed by autopsy/imaging/lumbar puncture; Intraocular bleed compromising vision; Type 5a: Probably fatal bleeding; Type 5b: Definite fatal bleeding	At 12-months
Primary	Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis)	Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.; Systemic Embolism: Acute vascular insufficiency or occlusion of the extremities or any non-central nervous system (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.	At 18-months
Primary	Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis)	Device closure (defined as residual jet around the device = 5 mm) at the 45-day visit documented by transesophageal echocardiogram (TEE/TOE) defined by Doppler flow was assessed.	At 45-days
Secondary	Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis)	Stroke: An acute episode of focal or global neurological dysfunction caused by the brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction.; Systemic Embolism: Acute vascular insufficiency/occlusion of the extremities/any non-CNS organ associated with clinical, imaging, surgical/autopsy evidence of arterial occlusion in the absence of other likely mechanism (trauma/atherosclerosis/instrumentation). When there is presence of prior peripheral artery disease, angiographic/surgical/autopsy evidence is required to show abrupt arterial occlusion.; Cardiovascular/unexplained death includes: Death due to proximate cardiac cause; Death caused by non-coronary/non-CNS vascular conditions; Death from vascular CNS causes; All procedure-related deaths; Sudden/unwitnessed death; Death of unknown cause	At 18-months
Secondary	Rate of Major Bleeding (Superiority Analysis)	Major bleeding rate defined as Type 3 or greater based on the Bleeding Academic Research Consortium (BARC) definition was assessed; Type 3a: Any transfusion with overt bleeding; Overt bleeding+Hb drop of = 3 to < 5 g/dL (provided Hb drop is related to bleed); Type 3b: Overt bleeding+Hb drop = 5 g/dL (provided Hb drop is related to bleed); Cardiac tamponade; Bleeding requiring surgical intervention for (Watchman); Bleeding requiring intravenous vasoactive drugs; Type 3c: Intracranial hemorrhage including subdural hemorrhages; Subcategories confirmed by autopsy/imaging/lumbar puncture; Intraocular bleed compromising vision; Type 5a: Probably fatal bleeding: bleeding that is clinically suspicious as the cause of death, but the bleeding is not directly observed and there is no autopsy or confirmatory imaging; Type 5b: Definite fatal bleeding: bleeding that is directly observed or confirmed on autopsy	At 18-months
Secondary	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)	Procedure related complications are adverse events adjudicated by the Clinical Events Committee (CEC), as procedure related and requiring either invasive surgical or percutaneous intervention.; All-cause deaths (cardiovascular or non-cardiovascular) were assessed.; Major Bleeding; Type 3a: Any transfusion with overt bleeding; Overt bleeding+Hb drop of = 3 to < 5 g/dL (provided Hb drop is related to bleed); Type 3b: Overt bleeding+Hb drop = 5 g/dL (provided Hb drop is related to bleed); Cardiac tamponade; Bleeding requiring surgical intervention for (Watchman); Bleeding requiring intravenous vasoactive drugs; Type 3c: Intracranial hemorrhage including subdural hemorrhages; Subcategories confirmed by autopsy/imaging/lumbar puncture; Intraocular bleed compromising vision; Type 5a: Probably fatal bleeding; Type 5b: Definite fatal bleeding	At 12-months
Secondary	Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism	Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.; Systemic Embolism: Acute vascular insufficiency or occlusion of the extremities or any non-central nervous system (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.	At 18-months
Secondary	Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab	Device closure (defined as residual jet around the device = 5 mm) at the 45-day visit documented by transesophageal echocardiogram (TEE/TOE) defined by Doppler flow was assessed.	At 45-days