Optimal Antiplatelet Therapy Following Left Atrial Appendage Closure in Dialyzed Patients (SAFE LAAC CKD)

Optimal Antiplatelet Treatment to Achieve Stroke Avoidance and Fall in Bleeding Events Following Left Atrial Appendage Closure - Chronic Kidney Disease (SAFE LAAC CKD). Comparative Health Effectiveness Ancillary Study - PILOT

SAFE-LAAC CKD 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 in patients with the end-stage renal disease treated with chronic haemodialysis or peritoneal dialysis

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: long-term treatment with a single antiplatelet agent; Drug: 6 months treatment with a single antiplatelet agent; Drug: short postimplantation dual antiplatelet therapy; Drug: extended postimplantation dual antiplatelet therapy

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 and may significantly contribute to long-term safety and efficacy. Nowadays LAAC is mainly performed in patients with contraindications for oral anticoagulation due to high bleeding risk. Dialyzed patients with end-stage renal disease and atrial fibrillation have simultaneously high thromboembolic and bleeding risk. Such patients were excluded from randomized trials and data on the LAAC efficacy in this population is limited thus prospective studies are warranted.

Objective:

SAFE-LAAC CKD 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 the 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=80) with the end-stage renal disease treated with chronic haemodialysis or peritoneal dialysis, 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, 2. data on the safety and efficacy of LAAC in dialyzed patients, and 3. data to support power calculations for designing future randomized trials.

Methodology:

SAFE LAAC CKD 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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Radoslaw Pracon, MD PhD; Phone Number: +48 22 343 43 42; Email: rpracon@ikard.pl
• Study Contact Backup: Name: Marcin Demkow, MD PhD; Phone Number: +48 22 343 43 42; Email: mdemkow@ikard.pl

Study Locations

• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 04-628
      • Recruiting
      • National Institute of Cardiology
      • Contact: Radoslaw Pracon, MD PhD; Phone Number: +48 22 343 43 42; Email: rpracon@ikard.pl
      • Contact: Marcin Demkow, MD PhD; Phone Number: +48 22 343 43 42; Email: mdemkow@ikard.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Successful left atrial appendage occlusion with Amplatzer or WATCHMAN device within 37 days prior to randomization
• End-stage renal disease treated with chronic haemodialysis or peritoneal dialysis
• 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 left atrial appendage occlusion at the time of enrollment and/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). Does not apply to anticoagulation used during dialysis
• Known allergy to clopidogrel and/or acetylsalicylic acid precluding its administration as specified by the protocol
• 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/or preceding 3 months
• 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 a negative pregnancy test 24 hours before randomization if <55 years old) or after surgical sterilization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 30 days DAPT and long-term treatment with a single antiplatelet agent; short postimplantation dual antiplatelet therapy and long-term treatment with a single antiplatelet agent	Drug: long-term treatment with a single antiplatelet agent; continuing long-term treatment with single antiplatelet agent; Drug: short postimplantation dual antiplatelet therapy; continuing dual antiplatelet therapy up until 6 months after left atrial appendage occlusion with Amplatzer Amulet
Other: 6 months DAPT and long-term treatment with a single antiplatelet agent; extended postimplantation dual antiplatelet therapy and long-term treatment with a single antiplatelet agent	Drug: long-term treatment with a single antiplatelet agent; continuing long-term treatment with single antiplatelet agent; Drug: extended postimplantation dual antiplatelet therapy; stopping dual antiplatelet therapy after 30 days after left atrial appendage occlusion with Amplatzer Amulet and continuing single antiplatelet agent up until 6 months
Other: 30 days DAPT and 6 months treatment with a single antiplatelet agent; short postimplantation dual antiplatelet therapy and 6 months treatment with a single antiplatelet agent	Drug: 6 months treatment with a single antiplatelet agent; continuing single antiplatelet agent up until 6 months; Drug: short postimplantation dual antiplatelet therapy; continuing dual antiplatelet therapy up until 6 months after left atrial appendage occlusion with Amplatzer Amulet
Other: 6 months DAPT and 6 months treatment with a single antiplatelet agent; extended postimplantation dual antiplatelet therapy and 6 months treatment with a single antiplatelet agent	Drug: 6 months treatment with a single antiplatelet agent; continuing single antiplatelet agent up until 6 months; Drug: extended postimplantation dual antiplatelet therapy; stopping dual antiplatelet therapy after 30 days after left atrial appendage occlusion with Amplatzer Amulet and continuing single antiplatelet agent up until 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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*Number of Participants with events/Total patient-years);	17 months
Safety (moderate and/or severe bleeding (BARC type 2, 3, and 5)	Event rates reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic stroke	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Transient ischaemic attack	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Peripheral embolism	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Nonfatal myocardial infarction	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Cardiovascular mortality	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
All-cause mortality	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Moderate and/or severe bleeding (BARC type 2,3, and 5)	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Left atrial appendage thrombus	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Any bleeding	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
New moderate or major (≥4 mm) ischemic brain lesions on magnetic resonance imaging	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
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
Dialysis access thrombosis	Event rate reported per 100 patient-years (calculated as 100*Number of Participants with events/Total patient-years);	17 months
Safety and efficacy of the procedure in the periprocedural period and 1-month follow-up based on registry data	1-month event rate of: cardiac arrest, device embolism, tamponade, pericardial effusion, stroke/TIA/myocardial infarction/peripheral embolus, access site bleeding/vascular complications, bleeding complications unrelated to access site (Number of Participants with event/Total patient number)	1-month

Other Outcome Measures

Outcome Measure	Time Frame
Number of new ischemic brain lesions on magnetic resonance imaging	17 months
Volume of new ischemic brain lesions on magnetic resonance imaging	17 months
The change from baseline in the cumulative dose of heparin anticoagulation used during haemodialysis	17 months
The change from baseline in the dose of erythropoietin used	17 months

Collaborators and Investigators

• Sponsor: Institute of Cardiology, Warsaw, Poland
• Collaborators: Medical Research Agency, Poland
• Investigators: Principal Investigator: Radoslaw Pracon, MD PhD, Coronary and Structural Heart Diseases Department, National Institute of Cardiology, Warsaw, Poland

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: stroke; atrial fibrillation; bleeding; dialysis; left atrial appendage
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Platelet Aggregation Inhibitors
• Other Study ID Numbers: CKD/1458/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No