Clinical trial NCT03399851: Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure. (SWISS-APERO)
Official title: Comparison of Amplatzer Amulet vs Watchman Device in Patients Undergoing Left Atrial Appendage Closure: the SWISS-APERO Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Left Atrial Appendage Closure
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2018-01-16
Enrollment: 200
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: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 45 days
Secondary outcomes:
measure: All cause of death, stroke, systemic or pulmonary embolism and spontaneous myocardial infarction
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: LAA patency at 45-day and 13-month CCTA in the per protocol and as treated populations
timeFrame: 45 days and 13 months
measure: Cardiovascular death
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: Ischemic stroke
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: Haemorrhagic stroke
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: Bleeding events according to the BARC classification at each follow up
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: Procedure-related complications
timeFrame: 48 hours, 45 days, 1 year, 2 years, 3 years, 4 years and 5 years
measure: Rate of patients on (N)OAC at 45 days and 6 months
timeFrame: 45 days and 6 months
measure: Device thrombosis
timeFrame: 45 days and 13 months
measure: Number of device implantation attempts
timeFrame: end of procedure
measure: Total time procedure
timeFrame: end of procedure
measure: x-ray dose
timeFrame: end of procedure
measure: fluoroscopy duration
timeFrame: end of procedure
measure: amount of contrast used during the procedure
timeFrame: end of procedure
measure: LAA patency
timeFrame: 45 days
Other outcomes:
Locations:
city: Charleroi
country: Belgium
facility: Centre Hospitalier Universitaire de Charleroi
city: Besançon
country: France
facility: Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Hopital cardiologique Haut Lévêque CHU de Bordeaux
city: Créteil
country: France
facility: Hôpital Hôpitaux Universitaires Henri-Mondor
city: Rouen
country: France
facility: Centre Hospitalier Universitaire Hôpitaux De Rouen
city: Milano
country: Italy
facility: IRCCS Policlinico S.Donato
city: Bern
country: Switzerland
facility: Bern University Hospital
state: Switzerland/Bern
city: Lugano
country: Switzerland
facility: Department of Cardiology, Cardiocentro Ticino
Study officials:
affiliation: Fondazione Cardiocentro Ticino
name: Marco Valgimigli, Prof
role: STUDY_CHAIR
affiliation: Hôpital Hôpitaux Universitaires Henri-Mondor
name: Emmanuel Teiger, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz
name: Nicolas Meneveau, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Hôpitaux De Rouen
name: Frederic Anselme, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Inselspital, Bern University Hospital
name: Lorenz Räber, Prof
role: STUDY_CHAIR
References:
citation: Galea R, De Marco F, Aminian A, Meneveau N, Anselme F, Grani C, Huber AT, Teiger E, Iriart X, Angelillis M, Brugger N, Spirito A, Corpataux N, Franzone A, Vranckx P, Fischer U, Pedrazzini G, Bedogni F, Windecker S, Raber L, Valgimigli M. Design and Rationale of the Swiss-Apero Randomized Clinical Trial: Comparison of Amplatzer Amulet vs Watchman Device in Patients Undergoing Left Atrial Appendage Closure. J Cardiovasc Transl Res. 2021 Oct;14(5):930-940. doi: 10.1007/s12265-020-10095-4. Epub 2021 Apr 21.
citation: Galea R, De Marco F, Meneveau N, Aminian A, Anselme F, Grani C, Huber AT, Teiger E, Iriart X, Babongo Bosombo F, Heg D, Franzone A, Vranckx P, Fischer U, Pedrazzini G, Bedogni F, Raber L, Valgimigli M. Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial. Circulation. 2022 Mar 8;145(10):724-738. doi: 10.1161/CIRCULATIONAHA.121.057859. Epub 2021 Nov 6.