Portico NG Approval Study

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the acute safety and effectiveness of the next-generation Navitor (Portico™ NG) Transcatheter Aortic Heart Valve as assessed by the rate of all-cause mortality at 30 days and the rate of moderate or greater paravalvular leak at 30 days in a high or extreme surgical risk patient population to support CE (Conformité Européenne) Mark and FDA approval.

Detailed Description
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The Portico NG Approval study will be conducted as a prospective, multi-center, international, single-arm investigational study. Up to 399 (includes up to 20 roll-ins) high or extreme risk patients with symptomatic, severe native aortic stenosis who are determined by an independent subject selection committee to meet eligibility criteria for Navitor Transcatheter Aortic Heart Valve implantation will undergo Navitor Valve implantation via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR (transcatheter aortic valve replacement) procedure. Subjects participating in the clinical study will be followed for a total of 12 months with data collected at screening, baseline, procedure, prior to hospital discharge, and follow-up at 30 days, 12 months and annually at 2, 3, 4 and 5 years. This study will also include a product size extension, Navitor Titan™ valve, which includes up to 90 subjects (Titan cohort) who will undergo an implant attempt with the Navitor Titan valve. Subjects enrolled in the Titan cohort will undergo the same screening, baseline, procedure and follow-up assessments as the Portico NG cohort.

Official Title
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Evaluation of the Portico™ NG (Next Generation) Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis

Conditions
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Symptomatic Severe Aortic Stenosis

Intervention / Treatment
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* Device: Portico™ NG (Navitor) Valve and FlexNav™ Delivery System
* Device: Navitor Titan Valve (35mm) Valve and Large FlexNav™ Delivery System


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects must have a Society of Thoracic Surgeons (STS) score of ≥7% OR documented heart team agreement of high or extreme risk for surgical aortic valve replacement due to frailty or co-morbidities not captured by the STS score. Subject has symptomatic aortic stenosis as demonstrated by NYHA (New York Heart Association) Functional Classification of II, III, or IV. Subject has senile degenerative aortic valve stenosis with echo-derived criteria, defined as: aortic valve area (AVA) of ≤ 1.0 cm2 (or indexed EOA (effective orifice area) ≤ 0.6 cm2/m2) AND mean gradient ≥40 mmHg or peak jet velocity ≥ 4.0 m/s or doppler velocity index (DVI) ≤0.25. (Qualifying AVA baseline measurement must be within 90 days prior to informed consent). Aortic annulus diameter of 19-30mm and ascending aorta diameter for the specified valve size listed in the IFU (Instructions For Use), as measured by CT (Computed Tomography) Key Exclusion Criteria: Evidence of an acute myocardial infarction (defined as: ST Segment Elevation as evidenced on 12 Lead ECG) within 30 days prior to index procedure. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to index procedure. Blood dyscrasias as defined: leukopenia (WBC<3000 mm3), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count <50,000 cells/mm³). History of bleeding diathesis or coagulopathy Active peptic ulcer or upper GI bleeding within 3 months prior to index procedure that would preclude anticoagulation Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA). Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+). Pre-existing prosthetic heart valve or other implant in any valve position, prosthetic ring, severe circumferential mitral annular calcification (MAC) which is continuous with calcium in the left ventricular outflow tract (LVOT), severe (greater than or equal to 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise. Minimum access vessel diameter of <5.0mm for small FlexNav™ Delivery System and <5.5 mm for large FlexNav™ Delivery System

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Devices under investigation in this clinical study include the Portico™ (Navitor) Valve (23mm, 25mm, 27mm and 29mm sizes), Navitor Titan Valve (35 mm), FlexNav™ Delivery System (small and large) and Portico™ NG (Navitor) Loading System(s) (small and large), and Navitor Loading System - LG+, all of which are currently approved for investigational use only.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Portico™ NG (Navitor) valve, FlexNav™ Delivery System<br>Portico ™ NG (Navitor) valve implantation with the new generation Portico NG (Navitor) valve (23mm, 25mm, 27mm and 29mm sizes), and the second-generation FlexNav Delivery system (small and large), Portico™ NG (Navitor) Loading System(s) (small and large). | Device: Portico™ NG (Navitor) Valve and FlexNav™ Delivery System<br>* Subjects will undergo transcatheter aortic valve implantation (TAVI) with the new generation Portico NG (Navitor) valve and second-generation FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures.<br>|
| Experimental: Navitor Titan Valve<br>Navitor Titan Valve (35mm) implantation with the large FlexNav Delivery system and Navitor Loading System - LG+. | Device: Navitor Titan Valve (35mm) Valve and Large FlexNav™ Delivery System<br>* Subjects will undergo transcatheter aortic valve implantation (TAVI) with the Navitor Titan valve and large FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary safety endpoint is all-cause mortality |  | at 30 days | 
| Primary effectiveness endpoint is moderate or greater paravalvular leak |  | at 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding, acute kidney injury (stage 3), or major vascular complications |  | at 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Stenosis, Transcatheter Aortic Valve Implantation, Heart Valve Disease, High Surgical Risk, Portico NG (Navitor) Valve, Extreme Surgical Risk, Navitor Titan Valve