NAUTILUS CE-mark Trial of the FLOWer Cerebral Embolic Protection Device
- Conditions
- Aortic Valve StenosisIntracranial Embolism and Thrombosis
- Interventions
- Procedure: TAVI (Transcatheter Aortic Valve Implant)Device: FLOWer Embolic Protection System
- Registration Number
- NCT04704258
- Lead Sponsor
- AorticLab Srl
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- Subjects of age ≥ 18 years
- 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)
- Subject anatomy with Ilio-femoral artery segment compatible with a 12 F device catheter size
- 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
- 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)
Clinical exclusion criteria (preoperative screening)
- Subjects with hypercoagulable state that cannot be corrected by additional periprocedural heparin
- Subjects with contraindication to cerebral MRI
- Subjects with a history of a stroke or transient ischemic attack within the prior 6 months
- Subjects with known diagnosis of acute myocardial infarction (AMI) within 30 days preceding the index procedure
- Renal insufficiency (creatinine > 3.0 mg/dL or Glomerular Filtration Rate GFR < 30) and/or renal replacement therapy at the time of screening
- 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
- 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
- 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
- Subjects with a previously implanted prosthetic aortic valve (i.e., planned valve-in-valve with a TAVI)
- Subject requires an emergent procedure
- Subject has active major psychiatric disease
- Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- Subject has an ejection fraction of 30% or less
- Subjects with active endocarditis or other systemic infection
- Subjects undergoing therapeutic thrombolysis
- Subject is pregnant or lactating. Pregnancy confirmed by positive urine or serum test
Computerized Tomographic exclusion criteria (preoperative screening)
- Subjects with documented friable or mobile atherosclerotic plaque in the aortic arch
- Subjects with echocardiographic evidence of aortic mass, thrombus or vegetation
- 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)
- Subjects undergoing transcatheter aortic valve implantation (TAVI) via the trans-axillary, trans-subclavian, or trans-aortic route
- Subjects with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery of sheath vascular access
- Subjects in whom the aortic arch is heavily calcified, severely atheromatous, or severely tortuous
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TAVI + Embolic protection FLOWer Embolic Protection System Subjects with severe native aortic valve stenosis who meet the clinically approved indications for aortic valve interventions such as TAVI TAVI + Embolic protection TAVI (Transcatheter Aortic Valve Implant) Subjects with severe native aortic valve stenosis who meet the clinically approved indications for aortic valve interventions such as TAVI
- Primary Outcome Measures
Name Time Method Reduction in total volume of new cerebral lesions in all territories at serial DWMRI Within 2-5 days after procedure vs. baseline 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
FLOWer Device Safety: Rate of Major Adverse Cardiac and Cerebrovascular Events 30 days 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)
- Secondary Outcome Measures
Name Time Method Cumulative occurrence of Serious Clinical Events related to FLOWer device and procedure as adjudicated by a Clinical Event Committee. 7 and 30 days 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).Brain imaging (DW-MRI) Within 2-5 days after procedure vs. baseline 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
Technical Success Immediately after procedure Secondary Performance Endpoints: Technical Success defined as successful placement, insertion and removal of the FLOWer System
Debris capture Immediately after procedure Secondary Performance Endpoints: Debris captured by the FLOWer System with gross and histopathological evaluation including particle size and composition
Neurocognitive 2-7 days and 30-days vs. baseline Secondary Clinical Benefit Endpoints: Neurocognitive protection assessed by NIHSS, Montreal Cognitive Assessment, and mRS
FLOWer System Usability Immediately after procedure 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
Trial Locations
- Locations (8)
CUB Hôpital Erasme (ULB)
🇧🇪Brussels, Belgium
San Carlo Azienda Ospedaliera Regionale
🇮🇹Potenza, PZ, Italy
IRCCS Policlinico San Donato
🇮🇹San Donato Milanese, MI, Italy
Centro Cardiologico Monzino IRCCS
🇮🇹Milano, Italy
Clinica San Gaudenzio
🇮🇹Novara, Italy
Casa di Cura Policlinico di Monza
🇮🇹Monza, MB, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milan, MI, Italy
HartCentrum, Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
🇧🇪Antwerp, Belgium