Evaluation of TAVR Using the NAVITOR Valve in a Global Investigation (VANTAGE)

VANTAGE Clinical Trial Evaluation of TAVR Using the NAVITOR Valve in a Global Investigation

Evaluation of TAVR using the NAVITOR valve in a Global Investigation.

Study Overview

• Status: Recruiting
• Conditions: Symptomatic Severe Aortic Stenosis
• Intervention / Treatment: Device: Navitor Transcatheter Aortic Valve and FlexNav Delivery System

Detailed Description

The VANTAGE clinical trial will evaluate the safety and effectiveness of the Navitor valve in patients with severe, symptomatic aortic stenosis who are at intermediate or low risk of surgical mortality. This trial will also evaluate the safety and effectiveness of the Navitor valve in a valve-in-valve application.

• Study Type: Interventional
• Enrollment (Estimated): 590
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadia Bouhdi; Phone Number: +32 479 94 10 37; Email: nadia.bouhdi@abbott.com
• Study Contact Backup: Name: Li Lihua; Phone Number: +1 612-413-0527; Email: lihua.li1@abbott.com

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • St. Andrew's Hospital
    • Contact: Joseph Montarello
    • Sub-Investigator: Joseph Montarello
  • Melbourne, Australia
    • Recruiting
    • The Alfred Hospital
    • Principal Investigator: Tony Walton
  • Murdoch, Australia, WA 6150
    • Recruiting
    • Fiona Stanley Hospital
    • Contact: Gerald Yong
    • Principal Investigator: Gerald Yong
  • Ryde, Australia
    • Recruiting
    • Macquirie University Hopsital
    • Contact: Stephen Worthley
    • Principal Investigator: Stephen Worthley
  • Sydney, Australia, NSW 2031
    • Recruiting
    • Prince of Wales Hospital
    • Contact: Nigel Jepson
    • Principal Investigator: Nigel Jepson
  • Woolloongabba, Australia, QLD 4102,
    • Recruiting
    • Princess Alexandra Hospital
    • Contact: Anthony Camuglia
    • Principal Investigator: Anthony Camuglia
• Austria
  • Graz, Austria
    • Recruiting
    • Universitätsklinik Graz
    • Contact: Albrecht Schmidt
    • Principal Investigator: Albrecht Schmidt
  • Linz, Austria
    • Not yet recruiting
    • Kepler Universitätsklinikum GmbH
    • Contact: Clemens Steinwender
    • Principal Investigator: Clemens Steinwender
  • Vienna, Austria
    • Recruiting
    • Akh Wien
    • Contact: Martin Andreas
    • Principal Investigator: Martin Andreas
• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Principal Investigator: Ole De Backer
• France
  • Clermont-Ferrand, France
    • Recruiting
    • Chu Gabriel Montpied
    • Contact: Souteyrand Géraud
    • Principal Investigator: Souteyrand Géraud
  • Pessac, France
    • Recruiting
    • Hôpital Haut Lévêque
    • Contact: Lionel Leroux
    • Principal Investigator: Lionel Leroux
  • Toulouse, France
    • Recruiting
    • Clinique Pasteur Toulouse
    • Contact: DIDIER TCHETCHE
    • Principal Investigator: Didier Tchétché
• Germany
  • Bad Nauheim, Germany
    • Recruiting
    • Kerckhoff-Klinik gGmbH
    • Contact: Won-Keun Kim
    • Principal Investigator: Won-Keun Kim
  • Berlin, Germany
    • Recruiting
    • Universitätsmedizin Berlin - Charité Campus Mitte (CCM)
    • Principal Investigator: Henryk Dreger
    • Contact: Henryk Dreger
  • Dortmund, Germany
    • Recruiting
    • St. Johannes-Hospital
    • Principal Investigator: Helge Möllmann
    • Contact: Helge Möllmann
  • Dresden, Germany
    • Recruiting
    • Herzzentrum Dresden
    • Contact: Axel Linke
    • Principal Investigator: Axel Linke
  • Frankfurt, Germany
    • Recruiting
    • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
    • Contact: Philipp Seppelt
    • Principal Investigator: Philipp Seppelt
  • Hamburg, Germany
    • Not yet recruiting
    • UKE Hamburg (Universitatsklinik Eppendorf)
    • Contact: Lenard Conradi
    • Principal Investigator: Lenard Conradi
  • Leipzig, Germany
    • Recruiting
    • Herzzentrum Leipzig GmbH
    • Contact: Mohamed Abdel-Wahab
    • Principal Investigator: Mohamed Abdel-Wahab
  • Mainz, Germany
    • Withdrawn
    • Universität Mainz (Johannes Gutenberg-Universität Mainz)
  • München, Germany
    • Recruiting
    • DHZ München
    • Principal Investigator: Hendrik Ruge
    • Contact: Hendrik Ruge
• Italy
  • Milan, Italy
    • Recruiting
    • Centro Cardiologico Monzino
    • Contact: Federico De Marco
    • Principal Investigator: Federico De Marco
  • Milan, Italy, 20097
    • Recruiting
    • Policlínico San Donato
    • Contact: Francesco Bedogni
    • Principal Investigator: Francesco Bedogni
  • Milan, Italy
    • Recruiting
    • Ospedale San Raffaele - Cardiac
    • Contact: Francesco Maisano
    • Principal Investigator: Francesco Maisano
  • Caserta
    • Castel Volturno, Caserta, Italy, 81030
      • Recruiting
      • Pineta Grande Hospital
      • Contact: Arturo Giordano
      • Principal Investigator: Arturo Giordano
  • Padua
    • Padova, Padua, Italy, 35128
      • Recruiting
      • Azienda Ospedale Universita Padova
      • Contact: Giuseppe Tarantini
      • Principal Investigator: Giuseppe Tarantini
• Netherlands
  • Rotterdam, Netherlands, 3015
    • Recruiting
    • Erasmus MC - Thoraxcenter
    • Contact: Nicolas Van Mieghem
    • Principal Investigator: Nicolas Van Mieghem
• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital General Universitario Dr. Balmis
    • Contact: Juan Ruiz-Nodar
    • Principal Investigator: Juan Ruiz-Nodar
  • Barcelona, Spain
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Ander Regueiro
    • Principal Investigator: Ander Regueiro
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal
    • Contact: Jose Luis Zamorano
    • Principal Investigator: Jose Luis Zamorano
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico Universitario San Carlos
    • Principal Investigator: Luis Nombela
    • Contact: Luis Nombela
  • Sevilla, Spain
    • Recruiting
    • Hospital Virgen de Rocio
    • Principal Investigator: José Diaz
    • Contact: José Diaz
• Switzerland
  • Zürich, Switzerland
    • Not yet recruiting
    • HerzZentrum Hirslanden
    • Contact: Maurizio Taramasso
    • Principal Investigator: Maurizio Taramasso
• United Kingdom
  • Belfast, United Kingdom
    • Recruiting
    • Royal Victoria Hospital
    • Contact: Ganesh Manoharan
    • Principal Investigator: Ganesh Manoharan
  • Leeds, United Kingdom
    • Recruiting
    • Leeds General Infirmary
    • Contact: Michael Cunnington
    • Principal Investigator: Michael Cunnington
  • London, United Kingdom
    • Not yet recruiting
    • Kings College Hospital
    • Contact: Phillip MacCarthy
    • Principal Investigator: Phillip MacCarthy
  • Swansea, United Kingdom, SA6 6NL
    • Recruiting
    • Morriston Hospital
    • Contact: Dave Smith
    • Principal Investigator: Dave Smith

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject who is judged by a Heart Team, including a cardiac surgeon, to be appropriate for transcatheter heart valve intervention therapy, and is deemed to be at intermediate or low risk for open surgical aortic valve replacement (i.e., heart team estimates risk of surgical mortality < 7% at 30 days, considering the Society of Thoracic Surgeons (STS) risk score, overall clinical status, and other clinical co-morbidities unmeasured by the risk calculator). *
2. New York Heart Association (NYHA) Functional Classification of II, III, or IV *

3. Degenerative aortic valve stenosis with echo-derived criteria, defined as:

   aortic valve area (AVA) of ≤ 1.0 cm2 (or indexed EOA ≤ 0.6 cm2/m2) AND either mean gradient ≥ 40 mmHg or peak jet velocity ≥ 4.0 m/s or doppler velocity index (DVI) ≤ 0.25. The echocardiogram supporting the qualifying AVA baseline measurement must be performed within 90 days prior to informed consent). *

4. Aortic annulus diameter of 19-30 mm and ascending aorta diameter of 26-44 mm for the specified valve size listed in the IFU, as measured by CT (systolic phase) conducted within 12 months prior to informed consent.

Exclusion Criteria:

1. Life expectancy is less than 2 years in the opinion of the Investigator.
2. Evidence of an acute myocardial infarction [defined as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) with acute ischemia symptoms and troponin elevation] within 30 days prior to index procedure.
3. Untreated clinically significant coronary artery disease requiring revascularization.
4. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior (except pacemaker or implantable cardioverter defibrillator (ICD) implant) to index procedure or planned within 30 days following the index procedure.
5. 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
6. Active peptic ulcer or upper GI bleeding within 3 months prior to index procedure that would preclude anticoagulation
7. Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA)
8. Renal insufficiency (creatinine > 3.0 mg/dL or eGFR < 30 ml/min/1.73m2) and/ or end stage renal disease requiring chronic dialysis
9. Hostile chest or conditions or complications from prior surgery that would make the subject be considered high surgical risk (i.e., mediastinitis, radiation damage, abnormal chest wall, porcelain aorta, adhesion of aorta or internal mammary artery to sternum, etc.) *
10. Significant frailty as determined by the heart team (after objective assessment of frailty parameters) that would indicate high or extreme surgical risk *
11. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+) *
12. Aortic valve is a congenital unicuspid or congenital bicuspid valve as verified by echocardiography or CT *
13. Severe ventricular dysfunction with LVEF < 30% as measured by resting echocardiogram
14. Pre-existing prosthetic heart valve or other implant (such as prosthetic ring or transcatheter edge-to-edge repair (TEER) clip) in any valve position * (Note: Subjects with a bioprosthetic aortic valve may be included in the ViV cohort.)
15. Severe circumferential mitral annular calcification (MAC) which is continuous with calcium in the left ventricular outflow tract (LVOT) *
16. Severe (greater than or equal to 3+) mitral regurgitation or severe mitral stenosis with pulmonary compromise
17. Minimum access vessel diameter of < 5.0 mm for small FlexNav Delivery System and < 5.5 mm for large FlexNav Delivery System

18. Eccentricity ratio of the annulus < 0.73

    • Criterion not applicable for valve-in-valve application

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: Navitor Transcatheter Aortic Valve, FlexNav Delivery System; Navitor Transcatheter Aortic Valve System Navitor valves (23mm, 25mm, 27mm, 29mm, and 35mm Titan valve), FlexNav Delivery system (small and large) and and Navitor Loading System (small, large, and LG+)

Device: Navitor Transcatheter Aortic Valve and FlexNav Delivery System; For traditional application, the Navitor valve is indicated for transcatheter delivery in patients with symptomatic severe native aortic stenosis who are intermediate or low surgical risk. For the valve-in-valve application, the Navitor valve is indicated for use in patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve. Subjects will undergo transcatheter aortic valve replacement (TAVR) with the Navitor valve and FlexNav Delivery system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of a composite of all-cause mortality or fatal stroke/stroke with disability at 12 months (Primary Safety Endpoint)	A composite of all-cause mortality or fatal stroke/stroke with disability at 12 months post index Navitor implantation procedure per the Valve Academic Research Consortium (VARC) 3 event definitions	12 months post index procedure
The proportion of subjects who have moderate or greater paravalvular leak at 30 days (Primary Effectiveness Endpoint)	Moderate or greater paravalvular leak at 30 days	30 days post index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transvalvular gradient	Mean change in mean transvalvular gradient between baseline and 12 months	12 months post index procedure
Effective orifice area	Mean change in effective orifice area between baseline and 12 months	12 months post index procedure
KCCQ quality of life score	Mean change in KCCQ quality of life score between baseline and 12 months	12 months post index procedure

Other Outcome Measures

Outcome Measure	Time Frame
Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding, acute kidney injury (stage 3), or major vascular complications	30 days
Non-hierarchical composite of all-cause mortality or stroke	12 months
Procedural success defined as successful vascular access, delivery and deployment of the Navitor valve; retrieval with the delivery system and correct positioning of a single Navitor valve in the proper anatomical location and no procedural mortality	Procedure
Mortality (all-cause and cardiovascular-related)	30 days and 12 months
Stroke (All stroke, disabling, and non-disabling)	30 days and 12 months
Transient ischemic attack (TIA)	30 days and 12 months
Bleeding (life threatening, disabling, and major)	30 days
Major vascular complications at 30 days	30 days
Acute kidney injury (Stage 3 requiring dialysis, Stage 3, and Stage 2)	30 days
Permanent pacemaker insertion	30 days and 12 months
Myocardial infarction	30 days and 12 months
Coronary obstruction requiring intervention	30 days and 12 months
Changes in functional status from baseline to follow-up assessments (e.g., NYHA classification, six-minute walk test, quality of life measures)	30 days and 12 months
Rehospitalization (valve-related, procedure-related, or heart failure)	30 days and 12 months
Paravalvular leak (none/trace, mild, moderate or severe)	Discharge, 30 days, 12 months and annually (when collected) through 10 years
Changes in echocardiographic parameters from baseline to follow-up (e.g., mean effective orifice area, mean transvalvular gradient)	30 days, 12 months and annually (when collected) through 10 years
Aortic valve reintervention	at 30 days, 12 months, and annually through 10 years
Prosthetic valve endocarditis	12 months and annually through 10 years
Structural valve deterioration	12 months and annually through 10 years
Successful coronary access as needed	12 months and annually through 10 years
Symptomatic prosthetic valve thrombosis	12 months and annually through 10 years

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Study Director: Vinny Podichetty, Abbott; Principal Investigator: Stephen Worthley, M.D., Ph. D., Macquarie University Hospital; Principal Investigator: Nicolas van Mieghem, M.D., Ph. D., Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2021
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): February 28, 2036

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Transcatheter aortic valve implantation (TAVI); NAVITOR Heart disease; Aortic stenosis Cardiovascular disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: ABT-CIP-10342

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes