Optimal Antiplatelet Therapy Following Left Atrial Appendage Closure

Atrial Fibrillation Clinical Trial

— SAFE-LAAC  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03445949
• Other study ID #: 2.52/IV/16
• Status: Recruiting
• Phase: Phase 4
• Start date: January 23, 2018
• Est. completion date: June 23, 2027

Study information

• Verified date: July 2023
• Source: National Institute of Cardiology, Warsaw, Poland
• Contact: Radoslaw Pracon, MD PhD
• Phone: 22 343 43 42
• Email: rpracon[@]ikard.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 23, 2027
• Est. primary completion date: June 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• short postimplantation dual antiplatelet therapy
continuing dual antiplatelet therapy up until 6 months after left atrial appendage occlusion with Amplatzer or WATCHMAN device
• extended postimplantation dual antiplatelet therapy
stopping dual antiplatelet therapy after 30 days after left atrial appendage occlusion with Amplatzer or WATCHMAN device
• long-term treatment with a single antiplatelet agent
continuing long-term treatment with single antiplatelet agent
• 6 months treatment with a single antiplatelet agent
continuing single antiplatelet agent up until 6 months

Locations

Country	Name	City	State
Poland	National Institute of Cardiology	Warsaw	Mazowieckie

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Cardiology, Warsaw, Poland	Medical Research Agency, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of new ischemic brain lesions on magnetic resonance imaging		17 months
Other	Volume of new ischemic brain lesions on magnetic resonance imaging		17 months
Primary	Efficacy (a composite of ischemic stroke, transient ischaemic attack, peripheral embolism, nonfatal myocardial infarction, cardiovascular mortality, all-cause mortality, left atrial appendage thrombus)	Event rates reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Primary	Safety (moderate and/or severe bleeding (BARC type 2, 3, and 5)	Event rates reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Ischemic stroke	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Transient ischaemic attack	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Peripheral embolism	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Nonfatal myocardial infarction	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Cardiovascular mortality	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	All-cause mortality	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Moderate and/or severe bleeding (BARC type 2,3, and 5)	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Left atrial appendage thrombus	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	Any bleeding	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years);	17 months
Secondary	New moderate or major (=4 mm) ischemic brain lesions on magnetic resonance imaging	Event rate reported per 100 patient-years (calculated as 100*N events/Total patient-years)	17 months
Secondary	Change in cognition score as detected by the Addenbrooke's cognitive examination (ACE-III)	ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual, and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning	17 months