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: Active, not 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 (Actual): 434
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • St. Andrew's Hospital
  • Melbourne, Australia
    • The Alfred Hospital
  • Ryde, Australia
    • Macquirie University Hopsital
  • Murdoch
    • Murdoch, Murdoch, Australia, WA 6150
      • Fiona Stanley Hospital
  • Sydney
    • Sydney, Sydney, Australia, NSW 2031
      • Prince of Wales Hospital
  • Woolloongabba
    • Woolloongabba, Woolloongabba, Australia, QLD 4102,
      • Princess Alexandra Hospital
• Austria
  • Linz, Austria
    • Kepler Universitätsklinikum GmbH
  • Vienna, Austria
    • AKH Wien
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Clermont-Ferrand, France
    • Chu Gabriel Montpied
  • Pessac, France
    • Hopital Haut Lévêque
  • Toulouse, France
    • Clinique Pasteur Toulouse
• Germany
  • Bad Nauheim, Germany
    • Kerckhoff-Klinik gGmbH
  • Berlin, Germany
    • Universitätsmedizin Berlin - Charité Campus Mitte (CCM)
  • Dortmund, Germany
    • St. Johannes-Hospital
  • Dresden, Germany
    • Herzzentrum Dresden
  • Frankfurt, Germany
    • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Hamburg, Germany
    • UKE Hamburg (Universitatsklinik Eppendorf)
  • Leipzig, Germany
    • Herzzentrum Leipzig GmbH
  • München, Germany
    • DHZ München
• Israel
  • Telaviv
    • Jerusalem, Telaviv, Israel, 9103012
      • Shaare Zedek Medical Center
• Italy
  • Milan, Italy
    • Centro Cardiologico Monzino
  • Milan, Italy
    • Ospedale San Raffaele - Cardiac
  • Caserta
    • Castel Volturno, Caserta, Italy, 81030
      • Pineta Grande Hospital
  • Milan
    • Milan, Milan, Italy, 20097
      • Policlinico San Donato
  • Padua
    • Padova, Padua, Italy, 35128
      • Azienda Ospedale Universita Padova
• Netherlands
  • Rotterdam
    • Rotterdam, Rotterdam, Netherlands, 3015
      • Erasmus MC - Thoraxcenter
• Spain
  • Alicante, Spain
    • Hospital General Universitario Dr. Balmis
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Seville, Spain
    • Hospital Virgen de Rocio
  • Madrid
    • Madrid, Madrid, Spain, 28034
      • Hospital Ramón y Cajal
    • Madrid, Madrid, Spain, 28040
      • Hospital Clinico Universitario San Carlos
• Switzerland
  • Zurich, Switzerland
    • HerzZentrum Hirslanden
• United Kingdom
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • Kings College Hospital
  • Swansea
    • Swansea, Swansea, United Kingdom, SA6 6NL
      • Morriston Hospital

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: Primary Analysis Cohort; Navitor Transcatheter Aortic Valve System Navitor valves (23mm, 25mm, 27mm, 29mm, and 35mm Titan valve), FlexNav Delivery system (small and large) and Navitor Loading System (small, large, and LG+)	Device: Navitor Transcatheter Aortic valve and FlexNav Delivery system; Navitor valve is indicated for transcatheter delivery in patients with symptomatic severe native aortic stenosis who are intermediate or low surgical risk. 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
Primary Effectiveness Endpoint: Percentage of Participants With Moderate or Greater Paravalvular Leak (PVL)	The primary effectiveness endpoint is moderate or greater paravalvular leak (PVL) at 30 days, as assessed by the echocardiographic core laboratory. The hypothesis test was performed based on the implanted population in whom a functional Navitor valve remained implanted at 30 days.	at 30 Days
Primary Safety Endpoint: The Rates of All-cause Mortality or Fatal Stroke/Stroke With Disability	The composite of rate of all-cause mortality or fatal stroke/stroke with disability at 12 months post index Navitor implantation procedure as adjudicated by the CEC per Valve Academic Research Consortium (VARC-3) definitions calculated against the performance goal of 11.3%.	at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Mean Transvalvular Gradient	This endpoint was evaluated by comparing the mean paired difference in mean transvalvular gradient from baseline to 12 months against the performance goal of -10mmHg.	Baseline to 12 months
Mean Change in Effective Orifice Area (EOA)	This endpoint was evaluated by comparing the mean paired difference in effective orifice area (EOA) from baseline to 12 months against the performance goal of 0.4 cm².	Baseline to12 months
Mean Change In KCCQ Quality Of Life Score	This endpoint was evaluated by comparing the mean paired difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life (QoL) score from baseline to 12 months against the performance goal of 5 points. Higher KCCQ scores indicate better symptoms and physical functioning. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a tool of heart failure-specific health status questionnaire. Score ranges from 0 to 100, where 0 represents the worst and 100 represents the best quality of life. Higher scores indicate better quality of life and lower symptoms. The mean change from baseline reflects the average improvement (positive values) or worsening (negative values) in patient-reported health status.	Baseline to 12 months

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: Principal Investigator: Stephen Worthley, M.D., Ph. D., Macquarie University Hospital; Principal Investigator: Nicolas van Mieghem, M.D., Ph. D., Erasmus Medical Center; Study Director: Barathi Sethuraman, Abbott

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): January 2, 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 (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Transcatheter aortic valve implantation (TAVI); NAVITOR Heart disease; Aortic stenosis Cardiovascular disease
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; 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