Clinical trial NCT03445949: Optimal Antiplatelet Therapy Following Left Atrial Appendage Closure
Official title: Optimal Antiplatelet Treatment to Achieve Stroke Avoidance and Fall in Bleeding Events Following Left Atrial Appendage Closure (SAFE-LAAC). Comparative Health Effectiveness Randomized Trial - PILOT Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: atrial fibrillation, stroke, bleeding, left atrial appendage
Lead sponsor: National Institute of Cardiology, Warsaw, Poland
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2018-02-26
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: SAFE-LAAC Trial has been designed to gather data on the most optimal strategy of antiplatelet therapy after transcatheter left atrial appendage occlusion with Amplatzer or WATCHMAN device

Detailed description: Background:

Transcatheter left atrial appendage closure (LAAC) has been shown to be non-inferior to oral anticoagulation in preventing cardioembolic strokes associated with atrial fibrillation. However, an optimal antithrombotic treatment regimen following successful LAAC remains an unresolved issue. The scope and duration of antiplatelet treatment following LAAC are of paramount importance as they may significantly contribute to post-procedural as well as long-term procedural safety and efficacy.

Objective:

SAFE-LAAC Trial has been designed as a comparative health effectiveness study with the following aims:

1. compare the safety and efficacy of 30 days vs. 6 months of dual antiplatelet therapy following LAAC with Amplatzer or WATCHMAN device (randomized comparison)
2. compare safety and efficacy of stopping all antithrombotic and antiplatelet agents 6 months after LAAC vs. long-term treatment with a single antiplatelet agent (nonrandomized comparison)

Patient population:

Patients (n=200) after successful LAAC with Amplatzer or WATCHMAN device.

Perspective:

Results of this pilot trial will provide: 1. data to aid practitioners and guideline writers recommend the most optimal antithrombotic treatment after LAAC, and 2. data to support power calculations for designing future randomized trials.

Methodology:

SAFE LAAC has been designed as a multicenter (planned contribution of 7 centers in Poland), open-label, comparative health effectiveness trial with central, independent adjudication of events comprising the primary end-point. The first part of the trial is randomized and after 6 months of follow-up continues for another 12 months as a non-randomized study.

Timeline:

The duration of the trial has been planned for 5 years. The enrollment phase has been planned for 3 years.

Eligibility criteria: Inclusion Criteria:

* Successful left atrial appendage occlusion with Amplatzer or WATCHMAN device within 37 days before randomization
* Treatment with dual antiplatelet therapy (clopidogrel and acetylsalicylic acid) between left atrial appendage closure and randomization
* Participant's age 18 years or older at the time of signing the informed consent form
* Participant is willing to follow all study procedures; especially the randomized antiplatelet treatment regimen
* Participant is willing to sign the study informed consent form

Exclusion Criteria:

* Indications to dual antiplatelet therapy other than atrial fibrillation and/or left atrial appendage occlusion at the time of enrollment or predicted appearance of such indications within the duration of the trial (e.g. planned coronary revascularization)
* Indications to anticoagulation at the time of enrollment and/or predicted appearance of such indications within the duration of the trial (e.g. pulmonary embolism)
* Known allergy to clopidogrel and/or acetylsalicylic acid precluding its administration as specified by the protocol
* Any known inborn or acquired coagulation disorders
* Peridevice leak \>5mm on imaging study preceding enrollment
* Left atrial thrombus on an imaging study performed after successful left atrial appendage closure but before enrollment
* Life expectancy of fewer than 18 months
* Participation in other clinical studies with experimental therapies at the time of enrollment and preceding 3 months
* Chronic kidney disease stage IV and V
* Women who are pregnant or breastfeeding; women of childbearing potential who do not consent to apply at least two methods of contraception. This criterion does not apply to women 2 years post menopause (with negative pregnancy test 24 hours prior to randomization if \<55 years old) or after surgical sterilization

Primary outcomes:
measure: Efficacy (a composite of ischemic stroke, transient ischaemic attack, peripheral embolism, nonfatal myocardial infarction, cardiovascular mortality, all-cause mortality, left atrial appendage thrombus)
timeFrame: 17 months
measure: Safety (moderate and/or severe bleeding (BARC type 2, 3, and 5)
timeFrame: 17 months
Secondary outcomes:
measure: Ischemic stroke
timeFrame: 17 months
measure: Transient ischaemic attack
timeFrame: 17 months
measure: Peripheral embolism
timeFrame: 17 months
measure: Nonfatal myocardial infarction
timeFrame: 17 months
measure: Cardiovascular mortality
timeFrame: 17 months
measure: All-cause mortality
timeFrame: 17 months
measure: Moderate and/or severe bleeding (BARC type 2,3, and 5)
timeFrame: 17 months
measure: Left atrial appendage thrombus
timeFrame: 17 months
measure: Any bleeding
timeFrame: 17 months
measure: New moderate or major (≥4 mm) ischemic brain lesions on magnetic resonance imaging
timeFrame: 17 months
measure: Change in cognition score as detected by the Addenbrooke's cognitive examination (ACE-III)
timeFrame: 17 months
Other outcomes:
measure: Number of new ischemic brain lesions on magnetic resonance imaging
timeFrame: 17 months
measure: Volume of new ischemic brain lesions on magnetic resonance imaging
timeFrame: 17 months
Locations:
city: Warsaw
country: Poland
facility: National Institute of Cardiology
state: Mazowieckie
Study officials:
affiliation: Coronary and Structural Heart Diseases Department, National Institute of Cardiology, Warsaw, Poland
name: Radoslaw Pracon, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Coronary and Structural Heart Diseases Department, National Institute of Cardiology, Warsaw, Poland
name: Marcin Demkow, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: