NAUTILUS CE-mark Trial of the FLOWer Cerebral Embolic Protection Device (NAUTILUS)

Clinical Study of a Novel Transcatheter Anti-embolic Filter (FLOWer) for Cerebral Protection During Aortic Valve Interventions

The purpose of this clinical study is to assess the safety, performance, and treatment effect of the use of the AorticLab FLOWer System, in preventing cerebral thromboembolic complications in patients with indication for a TAVI (Transcatheter Aortic Valve Implant).

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Intracranial Embolism and Thrombosis
• Intervention / Treatment: Procedure: TAVI (Transcatheter Aortic Valve Implant); Device: FLOWer Embolic Protection System

Detailed Description

A single arm, prospective, multicenter non-randomized clinical study of the AorticLab FLOWer System to prevent embolic complications during transcatheter aortic valve procedures.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • HartCentrum, Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
  • Brussels, Belgium, 1070
    • CUB Hôpital Erasme (ULB)
• Italy
  • Milano, Italy, 20138
    • Centro Cardiologico Monzino IRCCS
  • Novara, Italy, 28100
    • Clinica San Gaudenzio
  • MB
    • Monza, MB, Italy, 20900
      • Casa di Cura Policlinico di Monza
  • MI
    • Milan, MI, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • San Donato Milanese, MI, Italy, 20097
      • IRCCS Policlinico San Donato
  • PZ
    • Potenza, PZ, Italy, 85100
      • San Carlo Azienda Ospedaliera Regionale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects of age ≥ 18 years
2. Subject is scheduled to undergo transfemoral aortic valve implant (TAVI) procedure on a stenotic native aortic valve and is qualified based on pre-operative CT-scan examination (trans-thoracic echocardiogram (TTE) can be used as confirmatory assessment)
3. Subject anatomy with Ilio-femoral artery segment compatible with a 12 F device catheter size
4. The subject and the treating physician agree that the subject will undergo the scheduled pre-procedural testing and return for all required post-procedure follow-up visits
5. The subject, or legally authorized representative, has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the appropriate Medical Ethics Committee (EC) or Institutional Review Board (IRB)

Exclusion Criteria:

Clinical exclusion criteria (preoperative screening)

1. Subjects with hypercoagulable state that cannot be corrected by additional periprocedural heparin
2. Subjects with contraindication to cerebral MRI
3. Subjects with a history of a stroke or transient ischemic attack within the prior 6 months
4. Subjects with known diagnosis of acute myocardial infarction (AMI) within 30 days preceding the index procedure
5. Renal insufficiency (creatinine > 3.0 mg/dL or Glomerular Filtration Rate GFR < 30) and/or renal replacement therapy at the time of screening
6. Subjects with a history of bleeding diathesis or coagulopathy or patients in whom anti-platelet and/or anticoagulant therapy is contraindicated, patients who will refuse transfusion, or patients with an active peptic ulcer or history of upper gastrointestinal (GI) bleeding within the prior 3 months
7. Subjects with known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, clopidogrel/ticlopidine, nitinol, stainless steel alloy, and/or contrast sensitivity that cannot be adequately pre-medicated
8. Subject is currently participating in another drug or device clinical study or has other medical illnesses that may cause the subject to be non-compliant with the protocol or confound the data interpretation
9. Subjects with a previously implanted prosthetic aortic valve (i.e., planned valve-in-valve with a TAVI)
10. Subject requires an emergent procedure
11. Subject has active major psychiatric disease
12. Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
13. Subject has an ejection fraction of 30% or less
14. Subjects with active endocarditis or other systemic infection
15. Subjects undergoing therapeutic thrombolysis
16. Subject is pregnant or lactating. Pregnancy confirmed by positive urine or serum test

Computerized Tomographic exclusion criteria (preoperative screening)

1. Subjects with documented friable or mobile atherosclerotic plaque in the aortic arch
2. Subjects with echocardiographic evidence of aortic mass, thrombus or vegetation
3. Subjects with a diameter of the ascending aorta < 25 and > 39 mm at baseline CT (measured 10 mm upstream of the first vessel of the brachiocephalic trunk)
4. Subjects undergoing transcatheter aortic valve implantation (TAVI) via the trans-axillary, trans-subclavian, or trans-aortic route
5. Subjects with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery of sheath vascular access
6. Subjects in whom the aortic arch is heavily calcified, severely atheromatous, or severely tortuous

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: TAVI + Embolic protection; Subjects with severe native aortic valve stenosis who meet the clinically approved indications for aortic valve interventions such as TAVI	Procedure: TAVI (Transcatheter Aortic Valve Implant); Placement of a filter to capture and remove emboli or debris detached during any transcatheter heart procedures; Device: FLOWer Embolic Protection System; FLOWer Embolic Protection System; Other Names: transcatheter embolic protection for TAVI procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FLOWer Device Safety: Rate of Major Adverse Cardiac and Cerebrovascular Events	Primary Safety Endpoint: FLOWer device Safety, rate of Major Adverse Cardiac and Cerebrovascular Events (MACCEs) related to FLOWer device and procedure as adjudicated by a Clinical Event Committee. MACCEs are based on the Valve Academic Research Consortium (VARC- 3) criteria: all death;; all stroke (disabling and non-disabling);; acute kidney injury (stage 3 at discharge or 72 hours post index procedure, whichever occurs first)	30 days
Reduction in total volume of new cerebral lesions in all territories at serial DWMRI	Primary Clinical Benefit Endpoint: Reduction in total volume of new cerebral lesions in all territories at serial DWMRI, compared to historical data in control arm (unprotected) data from previous randomized studies	Within 2-5 days after procedure vs. baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative occurrence of Serious Clinical Events related to FLOWer device and procedure as adjudicated by a Clinical Event Committee.	Secondary Safety Endpoint: Cumulative occurrence of Serious Clinical Events related to FLOWer device and procedure as adjudicated by a Clinical Event Committee. all-cause mortality including cardiovascular mortality; all stroke (disabling and non-disabling);; bleeding (life-threatening or disabling);; acute kidney injury (stage 3 at discharge or 72 hours post index procedure, whichever occurs first);; major device access related vascular complications;; coronary artery obstruction requiring intervention;; valve-related dysfunction requiring repeat procedure (balloon aortic valvuloplasty, repeat TAVI, or surgical aortic valve replacement).	7 and 30 days
Brain imaging (DW-MRI)	Secondary Clinical Benefit Endpoints: Acute cerebral embolic burden reduction after TAVI, defined as number and volume of new cerebral lesions in all cerebral territories assessed by DW-MRI	Within 2-5 days after procedure vs. baseline
Neurocognitive	Secondary Clinical Benefit Endpoints: Neurocognitive protection assessed by NIHSS, Montreal Cognitive Assessment, and mRS	2-7 days and 30-days vs. baseline
Technical Success	Secondary Performance Endpoints: Technical Success defined as successful placement, insertion and removal of the FLOWer System	Immediately after procedure
Debris capture	Secondary Performance Endpoints: Debris captured by the FLOWer System with gross and histopathological evaluation including particle size and composition	Immediately after procedure
FLOWer System Usability	Secondary Performance Endpoints: FLOWer System Usability graded by the Investigator with a 5-point Likert scale The minimum and the maximum values of the scale are defined as follows: (1) Unacceptable; (2) Poor; (3) Acceptable; (4) Good; (5) Excellent	Immediately after procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive	Neurocognitive protection assessed by NIHSS, Montreal Cognitive Assessment, and mRS	2-7 days and 30-days vs. baseline
Brain imaging (DW-MRI)	Reduction in the total volume of new cerebral lesions in all territories at serial DW-MRI, compared to historical data in the control arm (unprotected)	procedure vs. baseline

Collaborators and Investigators

• Sponsor: AorticLab Srl
• Collaborators: Meditrial Europe Ltd.
• Investigators: Study Chair: Franco Osta, AorticLab Srl

Publications and helpful links

Helpful Links

• Aorticlab Sponsor website
• Meditrial Clinical Research Organization

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): June 6, 2023
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: TAVI; Transcatheter Anti-embolic Filter; Cerebral Embolic Protection; Embolic Protection Device; Debris; Embolic material
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Thromboembolism; Embolism; Aortic Valve Stenosis; Thrombosis; Embolism and Thrombosis; Intracranial Embolism; Intracranial Embolism and Thrombosis
• Other Study ID Numbers: #2020-01 (EU)

Drug and device information, study documents

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