Clinical trial NCT05554822: Head-to-head Comparison of Single Versus Dual Antiplatelet Treatment Strategy After Percutaneous Left Atrial Appendage Closure: a Multicenter, Randomized Study
Official title: Head-to-head Comparison of Single Versus Dual Antiplatelet Treatment Strategy After Percutaneous Left Atrial Appendage Closure: a Multicenter, Randomized Study - ARMYDA-AMULET
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Left Atrial Appendage Occlusion
Antiplatelet Therapy
Keywords: left atrial appendage
left atrial appendage occlusion
atrial fibrillation
thromboembolic risk
Lead sponsor: Azienda Ospedaliero Universitaria Maggiore della Carita
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2022-09-26
Enrollment: 574
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization
Primary purpose: TREATMENT

Brief summary: The study will perform a randomized, head-to-head comparison between SAPT (aspirin) and DAPT (aspirin plus clopidogrel) after percutaneous LAA closure with implantation of the Amulet device (AbbottTM, Abbott Park, Illinois, US) in patients with AF. Primary outcome measure will be a net composite endpoint at 6 months including all-cause death, DRT, clinically relevant bleeding complications and ischemic events. The SAPT arm will receive aspirin alone up to 6 months, while the DAPT arm will receive DAPT for 3 months and then aspirin alone. Thus, between 3- and 6-month follow-up both groups will be given aspirin alone.

Detailed description: State of the art There is no clear evidence on optimal antiplatelet therapy after percutaneous left atrial appendage (LAA) closure in patients with atrial fibrillation (AF). There is a consensus supporting dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel (without oral anticoagulation) after non-WATCHMAN device implantation. However, the use of DAPT after LAA closure was initially derived from other interventional settings (e.g. the antithrombotic approach used after coronary stenting) and available data essentially derive from observational (and often retrospective), non-randomized, studies. Due to the lack of robust and consolidated evidence, the type and duration of antiplatelet therapy after LAA closure are variable and often guided by the individual convincement of the treating physicians. Patients undergoing LAA closure are generally older and have multiple co-morbidities; thus, in these patients the risk of bleeding events is a major concern and antithrombotic therapy may strongly contribute to such risk. Single-center, observational data have suggested that a strategy with single antiplatelet therapy (SAPT, essentially aspirin, without P2Y12 inhibitor) is associated with similar risk of ischemic cerebral events and device-related thrombosis (DRT) and with a significant reduction of bleeding complications after the intervention with 68% reduction in risk of major bleeding (from 7.0% to 2.3%). However, a recent, retrospective evidence raised concerns regarding the effectiveness of SAPT in preventing DRT in this setting of patients. To date, no randomized study has evaluated whether an approach with SAPT, compared to DAPT, is associated with adequate protection from DRT/ischemic events and with decreased bleeding risk. We will address such issue in a randomized, prospective, multicenter study.

Aim of the study The study will perform a randomized, head-to-head comparison between SAPT (aspirin) and DAPT (aspirin plus clopidogrel) after percutaneous LAA closure with implantation of the Amulet device (AbbottTM, Abbott Park, Illinois, US) in patients with AF. Primary outcome measure will be a net composite endpoint at 6 months including all-cause death, DRT, clinically relevant bleeding complications and ischemic events. The SAPT arm will receive aspirin alone up to 6 months, while the DAPT arm will receive DAPT for 3 months and then aspirin alone. Thus, between 3- and 6-month follow-up both groups will be given aspirin alone. We consider that a 6-month follow-up would be more than enough to detect any possible difference between the two groups.

Primary objective:

To demonstrate that SAPT is not inferior to the current standard antiplatelet therapy (DAPT) after LAA closure regarding the cumulative incidence of the net composite endpoint, including death, thrombotic complications and bleeding events, at 6 months.

Secondary objectives:

Compared to DAPT, SAPT use is associated with a similar incidence of ischemic events and a significantly lower incidence of bleeding complications at 6 months.

Study design The study will be phase IV, prospective, multicenter, with 1:1 randomization, open-label, with parallel groups. Consecutive patients with AF undergoing percutaneous LAA closure with the Amulet device will be enrolled. Patients will be included regardless of the type of AF and of clinical indication for LAA closure. Approximately 15 centers with a consolidated experience in the procedure of percutaneous LAA closure will be included. Enrollment will be competitive; each center will include a maximum number of patients corresponding to the 20% of the global population. After the protocol approval, the high-volume centers (e.g. top implanting centers in Italy) will be asked to participate the study, in addition to the Coordinating Center.

Eligibility criteria: Inclusion Criteria:

* Men or women aged ≥18 years signing a specific informed consent
* Patients with a planned percutaneous LAA closure;
* Patients with documented non-valvular AF, irrespective of the type (paroxysmal, permanent, persistent), and CHA2DS2-VASc score ≥2
* Patients suitable for treatment with aspirin and clopidogrel according to the Summaries of product characteristics (SmPCs);
* Patients considered unsuitable for long-term oral anticoagulant therapy due to a high bleeding risk. Patients will be judged unsuitable for anticoagulation because of bleeding-prone comorbidities, history of previous bleeding (with or without anticoagulant treatment) or an expected low adherence to therapy.
* Patient's availability to undergo the follow-up visits scheduled for the study
* Negative pregnancy testing (if applicable), performed at the time of enrollment.

Exclusion Criteria:

* CHADS-VAsc score 0-1
* Requirement for on-going therapy with clopidogrel at the time of screening evaluation (e.g. current therapy with clopidogrel at the time of the screening evaluation will be an exclusion criterion)
* Known hypersensitivity to the study drugs (aspirin or clopidogrel)
* Patients deemed to be unsuitable for at least 6 months antiplatelet therapy (SAPT or DAPT) because of a recent (\<1 month) major bleeding event
* Planned oral anticoagulant therapy after the procedure
* Moderate to severe mitral stenosis
* Mechanical heart prosthetic valve
* Active endocarditis
* Active bleeding
* Myocardial infarction or percutaneous coronary intervention \<6 months
* Major surgery within one month
* Intracranial neoplasm, aneurysm or arterio-venous malformation
* Platelet count \<50,000/μL
* Recent stroke (\<1 month)
* Fibrinolytic therapy within 10 days
* Baseline hemoglobin \<9 g/dL
* Pregnant woman
* Breast-feeding
* Women unavailable to use contraception during the study period

Primary outcomes:
measure: Primary endpoint:all-cause death, DRT (at 3- or 6-month TEE), ischemic stroke, systemic embolic events (SEE) or BARC classification bleeding ≥3.
timeFrame: 6 months
Secondary outcomes:
measure: Secondary endpoint: Device-related thrombosis
timeFrame: At 3 months and at 6 months
measure: Secondary endpoint: Any-cause death
timeFrame: 6 months
measure: Secondary endpoint: ischemic stroke or systemic embolic events
timeFrame: At 3 months and at 6 months
measure: Secondary endpoint: Any bleeding
timeFrame: At 3 months and at 6 months
measure: Secondary endpoint: BARC ≥3 bleeding
timeFrame: At 3 months and at 6 months
Other outcomes:
Locations:
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele Presidio Ospedaliero G. Rodolico
city: Ciriè
country: Italy
facility: Presidi Ospedalieri Riuniti ASL 6 Ciriè - Presidio Ospedaliero Riunito Sede di Ciriè
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Centro Cardiologico Fondazione Monzino
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Azienda Ospedaliera dei Colli Monaldi
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Paderno Dugnano
country: Italy
facility: Clinica San Carlo
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pavia
country: Italy
facility: Policlinico San Matteo
city: Pisa
country: Italy
facility: Ospedale del Cuore G. Pasquinucci
city: Rivoli
country: Italy
facility: Ospedale di Rivoli
city: Roma
country: Italy
facility: Ospedale S. Eugenio - ASL Roma 2
city: Sassari
country: Italy
facility: Azienda Ospedaliera Universitaria Sassari
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I
city: Torino
country: Italy
facility: Villa Maria Pia Hospital
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
city: Vercelli
country: Italy
facility: Ospedale Sant'Andrea
Study officials:
affiliation: University of Eastern Piedmont, Novara - Maggiore della Carità Hospital, Novara
name: Giuseppe Patti, MD
role: STUDY_DIRECTOR
affiliation: Fondazione Toscana G. Monasterio, Ospedale del Cuore "G. Pasquinucci"
name: Sergio Berti, MD
role: PRINCIPAL_INVESTIGATOR
References: