Laminar LAAX Pivotal IDE Study

• ClinicalTrials.gov Identifier: NCT06168942
• Recruitment Status: Enrolling by invitation
• First Posted: December 13, 2023
• Last Update Posted: April 3, 2024
• Sponsor: Laminar, Inc.
• Collaborator: Cardiovascular Research Foundation, New York
• Information provided by (Responsible Party): Laminar, Inc.

Tracking Information

• First Submitted Date: December 5, 2023
• First Posted Date: December 13, 2023
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: February 22, 2024
• Estimated Primary Completion Date: August 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2023)

• Primary Safety [ Time Frame: 12 months ]
  Composite rate of all-cause mortality, major bleeding (BARC Type 3 or 5), pericardial effusion requiring drainage, device embolization, and device- or procedure-related events requiring open cardiac surgery or major endovascular intervention.
• Primary Efficacy [ Time Frame: 18 months ]
  Composite rate of ischemic stroke or systemic embolism.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 5, 2023)

• Peri-Device Flow [ Time Frame: 18 months ]
  Peri-device flow (defined as ≥ 3mm in width which communicates beyond the device into the body of the left atrial appendage) per TEE evaluated by independent core laboratory.
• Device-Related Thrombosis [ Time Frame: 18 months ]
  Rate of device-related thrombosis per TEE evaluated by independent core laboratory.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Laminar LAAX Pivotal IDE Study
• Official Title: Laminar Left Atrial Appendage Elimination (LAAX) Pivotal IDE Study

Brief Summary

The goal of this clinical trial is to compare the Laminar Left Atrial Appendage Closure System to commercially available left atrial appendage closure devices. This procedure is for patients with non-valvular atrial fibrillation who are at increased risk for stroke, but have a reason to seek an alternative to blood thinning medications. This clinical trial will compare the safety and efficacy of the Laminar Left Atrial Appendage Closure System to commercially available left atrial appendage closure devices.

Participants in this trial will be randomly assigned one-to-one (like flipping a coin) for treatment with either the Laminar Left Atrial Appendage Closure System or a commercially available device (WATCHMAN™ left atrial appendage closure device / Amulet™ left atrial appendage occluder).

Detailed Description

This prospective, randomized, controlled, multicenter, open-label pivotal clinical study will enroll participants with non-valvular atrial fibrillation who are eligible for short-term anticoagulation therapy but have a rationale to seek non-pharmacologic alternative. Participants will be randomized 1:1 to the Laminar Left Atrial Appendage Closure System or commercially available device (WATCHMAN™ left atrial appendage closure device / Amulet™ left atrial appendage occluder). The study will randomize 1,500 eligible participants at up to 100 sites in the United States.

After implantation of left atrial appendage closure device, participants will be continued on appropriate medical therapy per guidelines or best local practices. Participants will be followed for 5 years after device implantation.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomized 1:1 to the Laminar Left Atrial Appendage Closure System or commercially available WATCHMAN and Amulet left atrial appendage closure devices. .

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Non-valvular Atrial Fibrillation
• Stroke

Intervention

• Device: Experimental: Laminar Left Atrial Appendage Closure System
  Participants will be treated with the Laminar Left Atrial Appendage Closure System.
• Device: Active Comparator: WATCHMAN / Amulet
  Participants will be treated with a WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder.

Study Arms

• Experimental: Laminar Device
  Treatment with the Laminar Left Atrial Appendage Closure System.
  Intervention: Device: Experimental: Laminar Left Atrial Appendage Closure System
• Active Comparator: Control LAAC
  Treatment with a commercially-available left atrial appendage closure device.
  Intervention: Device: Active Comparator: WATCHMAN / Amulet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: December 5, 2023): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2032
• Estimated Primary Completion Date: August 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Documented NVAF, defined as AF (paroxysmal, persistent, or permanent) in the absence of moderate-to-severe mitral stenosis or a mechanical heart valve.
2. Subject ≥18 years old.
3. CHA2DS2-VASc score ≥ 2 in men and ≥ 3 in women.
4. Subject deemed appropriate for LAA closure by the Site Investigator and a clinician not a part of the procedural team using an evidenced based decision-making tool.
5. Subject is recommended for chronic oral anticoagulation therapy (OAC) but has an appropriate rationale to seek a non-pharmacologic alternative.
6. Subject eligible for the protocol-specified post-procedural antithrombotic regimen.
7. Subject or Legally Authorized Representative informed of the nature of the study, is willing and able to comply with the protocol, and has provided written informed consent per Institutional Review Board (IRB) requirements.

Exclusion Criteria:

Medical History

1. Single episode, transient, or reversible AF (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures).
2. Stroke or transient ischemic attack within 90 days before the index procedure.
3. Myocardial infarction or unstable angina within 90 days before the index procedure.
4. Prior cardiac surgery or surgery requiring sternotomy
5. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 or patients with end stage renal disease who are dialysis dependent.
6. Active infection undergoing treatment.

7. History of symptomatic pericarditis (acute or chronic).

   Coexisting Cardiovascular Disease

8. Cardiac tumor.
9. History of mitral valve or other severe cardiac valvular disease requiring intervention or presence of prosthetic mechanical valve.
10. Medical condition (other than AF) that mandates chronic oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or mechanical heart valve).
11. Severe heart failure (New York Heart Association Class IV).

12. Symptomatic carotid artery disease (>50% diameter reduction with prior ipsilateral stroke or TIA) or established asymptomatic carotid artery disease (diameter reduction of >70%).

    Previous or Planned Interventions

13. Previous left atrial ablation procedure in the 90 days before the index procedure date or planned left atrial ablation to be performed in less than 90 days after the index procedure.
14. 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, or other electrophysiologic ablation procedure, etc.)
15. Planned (within 60 days after the index procedure) cardiac surgical procedures or any surgeries which require sternotomy.

16. Recent (within 30 days before the index procedure) or planned (within 60 days after the index procedure) noncardiac procedures or surgical interventions.

    Echocardiographic Exclusion Criteria

17. Intracardiac thrombus or persistent dense spontaneous echo contrast visualized by screening TEE or by TEE performed at time of index procedure.
18. Left ventricular ejection fraction (LVEF) <30%.
19. Circumferential pericardial effusion >10 mm, symptomatic pericardial effusion, evidence of tamponade physiology.

20. Complex atheroma with mobile plaque of the aorta.

    Procedural contraindications

21. Pre-procedural interatrial communication, atrial septal defect, or patent foramen ovale that warrants closure.
22. Transfemoral vascular access precluding delivery of implant with catheter-based system.
23. Presence of inferior vena cava (IVC) filter that would interfere with access.
24. Subject unable to undergo general anesthesia.

25. Subject with condition which precludes adequate transesophageal echocardiographic (TEE) assessment.

    Contraindications to Required Medications

26. Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium [i.e. nitinol]).
27. Contrast sensitivity that cannot be adequately pre-medicated.
28. Bleeding diathesis or coagulopathy.

29. Persistent thrombocytopenia (platelet count <75,000 cells/mm3), thrombocytosis (>700,000 cells/mm3), or leukopenia (white blood cell count <3,000 cells/mm3).

    General Exclusions

30. Left atrial appendage anatomy which cannot accommodate both commercially available control device and the Laminar Implant per manufacturer IFU.
31. Pregnant or nursing and those who plan pregnancy in the period up to 1 year following the index procedure. Subjects of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days before index procedure.
32. Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 1 year.
33. Current participation in another investigational drug or device study that in the opinion of the investigator could confound the data interpretation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06168942
• Other Study ID Numbers: CL-0059
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Laminar, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Laminar, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Cardiovascular Research Foundation, New York

Investigators

• Principal Investigator: Saibal Kar, MD; Los Robles Regional Medical Center
• Principal Investigator: Devi Nair, MD; St. Bernards Medical Center

• PRS Account: Laminar, Inc.
• Verification Date: April 2024