Applause Study I - Append System Early Feasibility Study (Applause)

Early Feasibility Study of the Append System for Left Atrial Appendage (LAA) Elimination by Invagination and Ligation

This early feasibility study is intended to evaluate the safety and feasibility of the Append System for eliminating the left atrial appendage (LAA) through a transcatheter procedure that invaginates and ligates the LAA tissue.

Study Overview

• Status: Recruiting
• Conditions: Non Valvular Atrial Fibrillation
• Intervention / Treatment: Device: Left Atrial Appendage Elimination: Append System

Detailed Description

The objective of this study is to evaluate the safety and performance of the Append System in patients with non-valvular atrial fibrillation who are considered appropriate candidates for LAA closure to reduce the risk of thromboembolism originating from the LAA.

The Append System is designed to eliminate the LAA without the use of a permanent metallic implant. The procedure is performed via a transfemoral, transseptal, transcatheter approach. During the procedure, the LAA is invaginated into the left atrium (LA), and the inverted tissue is ligated using a standard surgical suture, resulting in elimination of the LAA cavity.

Patients will be followed for up to 5 years after the procedure to assess safety, device performance, and long-term outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liz Zinger, MSc; Phone Number: +972-50-2071741; Email: liz.zinger@appendmedical.com

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Recruiting
      • Arrhythmia Research Group
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or non-pregnant female aged ≥18 years
2. Documented non-valvular AF (paroxysmal, persistent, permanent or non-rheumatic valve-related AF)
3. The subject has a calculated CHA2DS2-VASc score of 2 or greater for males or 3 or greater for females.
4. The subject is eligible for the defined protocol medication regimen of anticoagulation and antiplatelet therapy following Append procedure.
5. The patient is deemed appropriate for LAA ligation by the screening committee and the investigator.
6. The patient has been informed of the nature of the study, agrees to its provisions & follow-up evaluations, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

General Exclusion Criteria:

1. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure.
2. Atrial fibrillation that is defined by a single occurrence or that is considered to be reversible (e.g., due to thyroid disorders, acute alcohol intoxication, trauma, or recent major surgical procedures).
3. Patients with an indication for chronic oral anticoagulation other than AF (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or mechanical heart valve)
4. Clinically significant Severe heart failure (New York Heart Association functional class IV)
5. Prior cardiac surgery or surgery requiring sternotomy
6. Recent (within 3 months pre-procedure) stroke or transient ischemic attack.
7. Recent (within 3 months pre-procedure) myocardial infarction
8. Recent (within 30 days before the index procedure) or planned (within 60 days after the index procedure) cardiac interventional procedures (e.g., percutaneous coronary intervention, structural heart valve procedures, etc.)
9. Planned (within 60 days after the index procedure) cardiac surgical procedures or any surgeries which require sternotomy.
10. Recent (within 30 days before the index procedure) or planned (within 60 days after the index procedure) noncardiac procedures or surgical interventions.
11. History of symptomatic pericarditis (acute or chronic).
12. Patient has evidence of cardiac tumor
13. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation), or dialysis at the time of screening
14. Platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <3,000 cells/mm3 or known Bleeding diathesis
15. Active infection with bacteremia
16. Patient has a known allergy, hypersensitivity or contraindication to aspirin, heparin, or that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated
17. Current participation in another investigational drug or device study that would interfere with this study
18. Patient is unable to undergo general anesthesia
19. Patient has a condition which precludes adequate transesophageal echocardiographic (TEE) or computed tomographic (CT) assessment.
20. Known other medical illness or known history of substance abuse that may cause non-compliance with the specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years.

Cardiac Imaging Exclusion Criteria:

1. Intracardiac thrombus observed during screening
2. Left ventricular ejection fraction (LVEF) <30%
3. Circumferential pericardial effusion >5 mm or signs / symptoms of acute or chronic pericarditis, or evidence of tamponade physiology
4. Distance from inter-atrial septum fossa ovalis to LAA ostium is less than 40 mm
5. Any anatomy or prior intervention that would preclude a transseptal approach (including, but not limited to, prior IVC filter placement that cannot be crossed, prior ASD, or prior PFO closure device implantation that precludes transseptal puncture)
6. LAA structure that in the opinion of the screening committee / investigator precludes intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Append System; Elimination of the left atrial appendage (LAA) using the Append System through a transcatheter procedure that invaginates and ligates the LAA tissue.	Device: Left Atrial Appendage Elimination: Append System; Elimination of the left atrial appendage using the Append System through a transcatheter procedure involving invagination and ligation of the LAA tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite major adverse events	Composite rate of major adverse events related to the device or procedure, including all-cause mortality, ischemic stroke, systemic embolism, and cardiac tamponade or pericardial effusion requiring drainage	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure and Technical Success	LAA cavity elimination by LAA invagination and ligation with invagination proximal to the LAA ostium and lack of fluid communication between the LA and LAA- observed by TEE	30 days
Composite major adverse events	Composite rate of major adverse events related to the device or procedure, including all-cause mortality, ischemic stroke, systemic embolism, pericardial effusion requiring drainage, major bleeding (BARC 3/ BARC 5), hemorrhagic stroke, and device or procedure-related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair	6 months

Collaborators and Investigators

• Sponsor: Append Medical Ltd.
• Investigators: Principal Investigator: Vivek Reddy, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2033

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Left Atrial Appendage (LAA)
• Other Study ID Numbers: CLD-000001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. The study is an early feasibility investigation conducted under an FDA IDE, and the data will be retained by the sponsor and reported in aggregate only.

Drug and device information, study documents

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