Stroke
Conditions
Keywords
Non-valvular atrial fibrillation, Left Atrial Appendage
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.
Interventions
DEVICEAmulet Left Atrial Appendage Occluder
Transcatheter left atrial appendage closure
Transcatheter left atrial appendage closure
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | At 12-months | 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 |
| Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis) | At 18-months | 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. |
| Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis) | At 45-days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism | At 18-months | 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. |
| Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis) | At 18-months | 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 |
| Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab | At 45-days | 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. |
| Rate of Major Bleeding (Superiority Analysis) | At 18-months | 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 |
| 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) | At 12-months | 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 |
Countries
Australia, Canada, Czechia, Denmark, Germany, Italy, Netherlands, Portugal, Spain, Switzerland, United States
Participant flow
Recruitment details
A total of 2079 subjects were enrolled at 115 investigational centers and Amulet IDE trial included 2079 subjects with 1878 Randomized subjects (934 in the Amulet group and 944 in the Watchman group) and 201 roll-in subjects.
Pre-assignment details
Of the 2592 subjects who consented initially, 513 subjects did not enroll in the Amulet IDE trial due to screen failures, withdrawal of consent, and other reasons. Hence, the actual enrollment was 1878 Randomized subjects and 201 roll-in subjects.
Participants by arm
| Arm | Count |
|---|---|
| Amulet Amulet left atrial appendage occluder
Amulet Left Atrial Appendage Occluder: Transcatheter left atrial appendage closure | 934 |
| WATCHMAN (Control) WATCHMAN left atrial appendage closure device
WATCHMAN Left Atrial Appendage Closure: Transcatheter left atrial appendage closure | 944 |
| Total | 1,878 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 251 | 263 |
| Overall Study | Lost to Follow-up | 23 | 28 |
| Overall Study | Other Reasons | 8 | 12 |
| Overall Study | Withdrawal by Subject | 42 | 79 |
Baseline characteristics
| Characteristic | Amulet | WATCHMAN (Control) | Total |
|---|---|---|---|
| Age, Continuous | 75.0 years STANDARD_DEVIATION 7.6 | 75.1 years STANDARD_DEVIATION 7.6 | 75.0 years STANDARD_DEVIATION 7.6 |
| History of major or minor bleeding | 515 Participants | 503 Participants | 1018 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 21 Participants | 20 Participants | 41 Participants |
| Race/Ethnicity, Customized Declined or Unable to Disclose Due to Local Regulation | 57 Participants | 52 Participants | 109 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 26 Participants | 35 Participants | 61 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 9 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 838 Participants | 851 Participants | 1689 Participants |
| Region of Enrollment Australia | 36 participants | 34 participants | 70 participants |
| Region of Enrollment Canada | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Europe | 102 participants | 101 participants | 203 participants |
| Region of Enrollment United States | 792 participants | 806 participants | 1598 participants |
| Sex: Female, Male Female | 385 Participants | 365 Participants | 750 Participants |
| Sex: Female, Male Male | 549 Participants | 579 Participants | 1128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 251 / 934 | 263 / 944 |
| other Total, other adverse events | 293 / 934 | 266 / 944 |
| serious Total, serious adverse events | 542 / 934 | 535 / 944 |
Outcome results
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.
Time frame: At 45-days
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis) | 98.9 Percentage of participants |
| WATCHMAN (Control) | Mechanism of Action Primary Endpoint: Rate of Device Closure, by the Echocardiography Core Lab (Non-inferiority Analysis) | 96.8 Percentage of participants |
Comparison: The following hypothesis was tested:~H0: p3(Amulet) - p3(Watchman) ≤ -Δ3~H1: p3(Amulet) - p3(Watchman) \> -Δ3;~where Δ3 is the absolute value of the non-inferiority margin and p3 is the 45-day closure probability.p-value: <0.0001Farrington Manning test
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.
Time frame: At 18-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis) | 2.8 Percentage of participants |
| WATCHMAN (Control) | Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism (Non-inferiority Analysis) | 2.8 Percentage of participants |
Comparison: The following hypothesis was tested:~H0: p2(Amulet) - p2(Watchman) ≥ Δ2~H1: p2(Amulet) - p2(Watchman) \< Δ2;~where Δ2 is the absolute value of the non-inferiority margin for the effectiveness endpoint and p2 is the probability of a subject experiencing a primary effectiveness endpoint event.p-value: <0.0001Kaplan-Meier estimate
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
Time frame: At 12-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | 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) | 14.5 Percentage of participants |
| WATCHMAN (Control) | 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) | 14.7 Percentage of participants |
Comparison: The following hypothesis was tested:~H0: p1(Amulet) - p1 (Watchman) ≥ Δ1~H1: p1(Amulet) - p1(Watchman) \< Δ1;~where Δ1 is the absolute value of the non-inferiority margin for the safety endpoint and p1 is the probability of a primary safety endpoint event.p-value: 0.0002Kaplan-Meier estimate
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
Time frame: At 18-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis) | 5.6 Percentage of participants |
| WATCHMAN (Control) | Composite Rate of All Stroke, Systemic Embolism, or Cardiovascular/Unexplained Death (Non-inferiority Analysis) | 7.7 Percentage of participants |
p-value: <0.0001Kaplan-Meier estimate
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
Time frame: At 18-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Rate of Major Bleeding (Superiority Analysis) | 11.6 Percentage of participants |
| WATCHMAN (Control) | Rate of Major Bleeding (Superiority Analysis) | 12.3 Percentage of participants |
p-value: 0.3229Kaplan-Meier estimate
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.
Time frame: At 18-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism | 2.8 Percentage of participants |
| WATCHMAN (Control) | Superiority Test of Primary Effectiveness Endpoint: Composite Rate of Ischemic Stroke or Systemic Embolism | 2.8 Percentage of participants |
p-value: 0.5017Kaplan-Meier estimate
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.
Time frame: At 45-days
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab | 98.9 Percentage of participants |
| WATCHMAN (Control) | Superiority Test of Primary Mechanism of Action Endpoint: Rate of Device Closure, by the Echocardiography Core Lab | 96.8 Percentage of participants |
p-value: 0.0025Farrington Manning test
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
Time frame: At 12-months
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | 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) | 14.5 percentage of participants |
| WATCHMAN (Control) | 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) | 14.7 percentage of participants |
p-value: 0.466Kaplan-Meier estimate
Post Hoc
Composite Rate of Ischemic Stroke and Systemic Embolism
Ischemic Stroke is defined as an acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue and Systemic Embolism is define 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.
Time frame: 5 Years
Population: Analysis included subjects who underwent an implant attempt regardless of the device attempted or implanted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Composite Rate of Ischemic Stroke and Systemic Embolism | 7.4 percentage of participants |
| WATCHMAN (Control) | Composite Rate of Ischemic Stroke and Systemic Embolism | 7.1 percentage of participants |
Post Hoc
Composite Rate of Stroke, Systemic Embolism, or CV/Unexplained Death
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
Time frame: 5 Years
Population: Analysis included subjects who underwent an implant attempt regardless of the device attempted or implanted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Composite Rate of Stroke, Systemic Embolism, or CV/Unexplained Death | 20.3 percentage of participants |
| WATCHMAN (Control) | Composite Rate of Stroke, Systemic Embolism, or CV/Unexplained Death | 20.7 percentage of participants |
Post Hoc
Rate of Major Bleeding
Major bleeding: Type 3a: Any transfusion with overt bleeding. Overt bleeding plus a hemoglobin drop of ≥ 3 to \< 5 g/dL. Type 3b: Overt bleeding plus hemoglobin drop ≥ 5 g/dL. Cardiac tamponade. Bleeding requiring surgical intervention for Watchman (excluding dental/nasal/skin/ hemorrhoid). Bleeding requiring intravenous vasoactive drugs. Type 3c:Intracranial hemorrhage including subdural hemorrhages (does not include microbleeds or hemorrhagic transformation, does include intraspinal). Subcategories confirmed by autopsy or imaging or 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 (by either clinical specimen) or confirmed on autopsy.
Time frame: 5 Years
Population: Analysis included subjects who underwent an implant attempt regardless of the device attempted or implanted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amulet | Rate of Major Bleeding | 20.1 percentage of participants |
| WATCHMAN (Control) | Rate of Major Bleeding | 20.0 percentage of participants |