Symptomatic Severe Aortic Stenosis
Conditions
Keywords
NAVITOR Heart disease, Transcatheter aortic valve implantation (TAVI), Aortic stenosis Cardiovascular disease
Brief summary
Evaluation of TAVR using the NAVITOR valve in a Global Investigation.
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.
Interventions
DEVICENavitor 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.
Sponsors
Abbott Medical Devices
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint: Percentage of Participants With Moderate or Greater Paravalvular Leak (PVL) | at 30 Days | 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. |
| Primary Safety Endpoint: The Rates of All-cause Mortality or Fatal Stroke/Stroke With Disability | at 12 months | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Mean Transvalvular Gradient | Baseline to 12 months | 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. |
| Mean Change in Effective Orifice Area (EOA) | Baseline to12 months | 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. |
| Mean Change In KCCQ Quality Of Life Score | Baseline to 12 months | 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. |
Countries
Australia, Austria, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom
Contacts
PRINCIPAL_INVESTIGATORStephen Worthley, M.D., Ph. D.
Macquarie University Hospital
PRINCIPAL_INVESTIGATORNicolas van Mieghem, M.D., Ph. D.
Erasmus Medical Center
STUDY_DIRECTORBarathi Sethuraman
Abbott
Participant flow
Recruitment details
A total of 434 primary analysis subjects were registered between July 13, 2021 and November 27, 2024.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 77.2 years STANDARD_DEVIATION 4 |
| New York Heart Association functional classification (NYHA Class) Class I | 0 Participants |
| New York Heart Association functional classification (NYHA Class) Class II | 329 Participants |
| New York Heart Association functional classification (NYHA Class) Class III | 105 Participants |
| New York Heart Association functional classification (NYHA Class) Class IV | 0 Participants |
| Region of Enrollment Australia | 70 participants |
| Region of Enrollment Europe | 360 participants |
| Region of Enrollment Israel | 4 participants |
| Sex: Female, Male Female | 217 Participants |
| Sex: Female, Male Male | 217 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 434 |
| other Total, other adverse events | 237 / 434 |
| serious Total, serious adverse events | 166 / 434 |
Outcome results
None listed