Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure. (SWISS-APERO)

Study Overview
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Brief Summary
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Left atrial appendage closure (LAAC) is an emerging therapeutic option in non-valvular atrial fibrillation (NVAF) patients with high thromboembolic and bleeding risks. In Europe the devices most frequently utilized for LAAC are Amplatzer Amulet (St. Jude Medical-Abbott) and Watchman (Boston Scientific) system. However there are currently no randomized controlled trials assessing the degree of LAA closure between the two devices. The main purpose of this trial is to evaluate the feasibility and the efficacy of the devices in terms of LAA complete occlusion with a non-invasive imaging technique such as cardiac computed tomography angiography (CCTA).

Detailed Description
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Non-valvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia and a major cause of morbidity and mortality because of cardioembolic stroke. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) or Non-vitamin K antagonist anticoagulant (NOAC) is the most effective prophylaxis for stroke in NVAF. However (N)OAC therapy is associated with a significant bleeding liability and long-term (N)OAC therapy in patients with NVAF and concomitant high bleeding risk poses safety issues in a sizable and growing population in clinical practice. Thus, a new and emerging therapeutic option in this high-risk patient population is the left atrial appendage closure (LAAC). There are many available systems approved for percutaneous LAAC. One of the most widely used is the Watchman™ system (Boston Scientific), which was tested in the setting of two randomized control trials (RCT), which demonstrated the safety of the procedure and the non-inferiority in terms of stroke reduction compared to OAC. Another device largely used is the Amplatzer Amulet (St. Jude Medical-Abbott). There is no RCT comparing this device with OAC, but many prospective and retrospective studies had shown the same safety profile and the non-inferiority with the OAC. From the very beginning of the LAAC, a crucial assessment is the degree of LAA occlusion granted by the implanted device. Many imaging modalities have been used to assess LAA occlusion, including transesophageal echocardiography (TEE), fluoroscopy or cardiac computed tomography angiography (CCTA). In the setting of available randomized trials, successful closure was defined with the presence of a regurgitant flow ≤ 5 mm assessed with TEE. In the last years several groups assessed the value of CCTA as non-invasive post-procedural surveillance imaging modality after endovascular LAAC to evaluate atrial-side device thrombus, residual leak (and mechanisms thereof), device position, pericardial effusion and most importantly LAA patency. There are currently no randomized controlled trials assessing the degree of LAA occlusion between Amulet and Watchman.

Official Title
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Comparison of Amplatzer Amulet vs Watchman Device in Patients Undergoing Left Atrial Appendage Closure: the SWISS-APERO Randomized Clinical Trial

Conditions
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Left Atrial Appendage Closure

Intervention / Treatment
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* Device: Amplatzer Amulet for left atrial appendage closure
* Device: Watchman/FLX for left atrial appendage closure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Male or female subject aged 18 years or more with no upper age limit and willing to comply with the protocol Indication to a LAAC as indicated in study population (HAS BLEED ≥3 or High bleeding risk as defined by Munich consensus document and CHA2DS2-VASc≥2) Exclusion Criteria: New York Heart Association class IV congestive heart failure Atrial septal defect or atrial septal repair or closure device Single occurrence of atrial fibrillation Cardioversion or ablation procedure planned within 30 days Implanted mechanical valve prosthesis Heart transplantation Enrolled in another IDE or IND investigation of a cardiovascular device or an investigational drug Pregnant or pregnancy is planned during the course of the investigation Active infection of any kind Severe chronic kidney insufficiency (CrCl< 30 ml/min) Terminal illness with life expectancy < 1 yr Echocardiographic exclusion criteria Left ventricular ejection fraction < 20% Intra-cardiac thrombus or dense spontaneous echo contrast as visualized by TEE within 2 days before implant Significant mitral valve stenosis (ie, MV <1.5 cm2) Complex aortic atheroma with mobile plaque of the descending aorta and/or aortic arch Cardiac tumor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amplatzer Amulet<br>Left atrial appendage closure (LAAC) with Amplatzer Amulet implantation will be performed according to device specific instruction for use, based on both TEE guidance and angiography, femoral venous access and inter-atrial septum crossing. | Device: Amplatzer Amulet for left atrial appendage closure<br>* The closure of the left atrial appendage (LAAC) is performed percutaneously. Implantation of the Amplatzer Amulet will be performed according to device specific instruction for use, based on both TEE guidance and angiography, femoral venous access and inter-atrial septum crossing.<br>|
| Active Comparator: Watchman/FLX<br>Left atrial appendage closure (LAAC) with Watchman/FLX implantation will be performed according to device specific instruction for use, based on both TEE guidance and angiography, femoral venous access and inter-atrial septum crossing. | Device: Watchman/FLX for left atrial appendage closure<br>* The closure of the left atrial appendage (LAAC) is performed percutaneously. Implantation of the Watchman/FLX will be performed according to device specific instruction for use, based on both TEE guidance and angiography, femoral venous access and inter-atrial septum crossing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of left atrial appendage (LAA) patency at 45 day evaluated with cardiac computed tomography angiography (CCTA) or the crossover from one device to the other device based on morphological/anatomical considerations during device implantation | Composite endpoint | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause of death, stroke, systemic or pulmonary embolism and spontaneous myocardial infarction | Composite endpoint | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| LAA patency at 45-day and 13-month CCTA in the per protocol and as treated populations | LAA patency (arterial and/or venous phase) at 45-day and 13-month CCTA in the per protocol and as treated populations | 45 days and 13 months | 
| Cardiovascular death | Cardiovascular death | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| Ischemic stroke | Ischemic stroke | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| Haemorrhagic stroke | Haemorrhagic stroke | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| Bleeding events according to the BARC classification at each follow up | Bleeding events according to the BARC classification at each follow up | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| Procedure-related complications | Procedure-related complications | 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years | 
| Rate of patients on (N)OAC at 45 days and 6 months | Rate of patients on (N)OAC at 45 days and 6 months | 45 days and 6 months | 
| Device thrombosis | Device related thrombosis at 45 day TEE/CCTA and 13-month CCTA in the per protocol and as treated populations | 45 days and 13 months | 
| Number of device implantation attempts | Number of device implantation attempts | end of procedure | 
| Total time procedure | Total time procedure (minutes) | end of procedure | 
| x-ray dose | x-ray dose (cGy.cm2) | end of procedure | 
| fluoroscopy duration | fluoroscopy duration (minutes) | end of procedure | 
| amount of contrast used during the procedure | amount of contrast used during the procedure (ml) | end of procedure | 
| LAA patency | LAA patency at 45 day by TEE in the per protocol and as treated populations | 45 days |