- The objective of the proposed clinical trial is to evaluate the safety and effectiveness of the Navitor Transcatheter Aortic Heart Valve in patients with severe, symptomatic aortic stenosis who are at intermediate or low risk of surgical mortality…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint is a composite of all-cause mortality or disabling
stroke at 12 months.
The primary effectiveness endpoint is moderate or greater paravalvular leak
(PVL) at 30 days post index Navitor implantation procedure.
Secondary outcome
The rate of the following key outcomes will be assessed as descriptive
endpoints for the study:
1. Non-hierarchical composite of all-cause mortality, fatal stroke/stroke with
disability, type 3/type 4 bleeding, stage 3/stage 4 acute kidney injury,
major vascular complications, or major access-related non-vascular
complications at 30 days
2. Non-hierarchical composite of all-cause mortality or all stroke at 12 months
3. Procedural success defined as successful vascular access, delivery and
deployment of the Navitor Valve; retrieval of the delivery system and
correct positioning of a single Navitor Valve in the proper anatomical
location and the absence of procedural mortality
4. Mortality (all-cause, cardiovascular, and valve-related) at 30 days and 12
months
5. Stroke (All stroke, fatal stroke, stroke with disability, and stroke without
disability) at 30 days and 12 months
6. Transient ischemic attack (TIA) at 30 days and 12 months
7. Bleeding (type 4, type 3, and type 2) at 30 days
8. Major vascular complications at 30 days
9. Major access-related non-vascular complications at 30 days
10. Major cardiac structural complications at 30 days
11. Acute kidney injury (stage 4, stage 3, and stage 2) at 30 days
12. Permanent pacemaker insertion at 30 days and 12 months
13. Myocardial infarction at 30 days and 12 months
14. Coronary obstruction requiring intervention at 30 days and 12 months
15. Changes in functional status from baseline to follow-up assessments at 30
days and 12 months (e.g., New York Heart Association (NYHA)
functional classification, six-minute walk test, quality of life
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ))
16. Rehospitalization (procedure-related or valve-related hospitalization, and
other cardiovascular hospitalization) at 30 days and 12 months
17. Paravalvular leak (none/trace, mild, moderate or severe) at discharge, 30
days, 12 months and annually (when collected) through 10 years
18. Changes in echocardiographic parameters from baseline to follow-up at 30
days, 12 months and annually (when collected) through 10 years
(e.g., mean effective orifice area, mean transvalvular gradient)
19. Aortic valve reintervention at 30 days, 12 months, and annually through 10
years
20. Prosthetic valve endocarditis at 12 months and annually through 10 years
21. Structural valve deterioration at 12 months and annually through 10 years
22. Non-structural valve dysfunction at 12 months and annually through 10 years
23. Successful coronary access as needed at 12 months and annually through 10
years
24. Clinically significant prosthetic valve thrombosis at 12 months and
annually through 10 years
Background summary
Aortic stenosis is the most common primary valve disease that can be treated
surgically or through catheter intervention. Once the stenosis gets worse, a
patient may experience chest pain and shortness of breath. Often this is
treated with a replacement of the aortic valve. Since 2002, the replacement of
an aortic valve via a catheter has been possible. Not all patients are eligible
for a heart valve replacement through a catheter.
The primary goals of aortic valve replacement are to reduce the risk of
mortality, which can be as high as 25% per year if left untreated, and to
relieve clinical symptoms such as angina pectoris and dyspnoea.
In 2012, the TAVI technique was recognized in the ESC / EACTS guidelines for
the treatment of valvular heart disease with a class I indication for patients
unsuitable for surgery and a class IIA indication for patients at high surgical
risk. In 2014, comparable Class I indications for TAVI were included in the ACC
/ AHA guidelines for valvular heart disease. In 2017, the AHA / ASC ACC / AHA
guidelines for valvular heart disease were revised to include a Class IIA
indication for TAVI as a reasonable alternative for patients considered
moderate surgical risk.
The devices under investigation in this clinical trial are the Navitor
Transcatheter Aortic Valve and the Navitor Loading System. Both are approved
and marketed for implantation in patients with high surgical risk. The FlexNav*
Delivery System is also used in the study and is approved and commercially
available. The Navitor valve, FlexNav positioning system and Navitor charging
system are used according to the instructions for use.
Since protocol version B, the Navitor Titan valve and the associated loading
system can also be used, both are only available for use in this study and are
not commercially available.
Study objective
- The objective of the proposed clinical trial is to evaluate the safety and
effectiveness of the Navitor Transcatheter Aortic Heart 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.
- Obtain CE mark for the Navitor valve and Navitor loading system for patients
who are considered moderate or low surgical risk.
Study design
The VANTAGE clinical trial is a prospective, single-arm, multi-center,
international, pre-market investigation designed in accordance with ISO
standard 14155:2020.
Intervention
TAVI procedure with implantation of Navitor valve
Study burden and risks
Compared to a standard TAVI implantation, the additional study procedures
involve only low risks.
Follow-up visits also follow the standard of care or will be performed as
replacement of a standard care visit..
A TAVI is less invasive compared to a surgical valve replacement.
Standaardruiter 13
VEENENDAAL 3905 PT
NL
Standaardruiter 13
VEENENDAAL 3905 PT
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Listed location countries
Age
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. #,
F
2. New York Heart Association (NYHA) Functional Classification of II, III, or
IV . #
3. Subject is of legal age for consent in the host country
4. Subject has been informed of the nature of the trial, agrees to its
provisions and has provided written informed consent as approved by the Ethics
Committee (EC) of the respective clinical site.
5. Able and willing to return for required follow-up visits and assessments
6. 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). #
7. 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.
# Eligibility criteria labeled with *#* are not applicable for the ViV cohort.
Sites in Switzerland will not participate in the ViV enrollment.
F: In France and Switzerland, if a subject is deemed low surgical risk, the
subject must be at age 75 or over to be included in this trial.
Exclusion criteria
1. Pregnant or nursing subjects and those who plan pregnancy during the
clinical investigation follow-up period. A pregnancy test is required for all
women of childbearing potential. 2. Need for emergency surgery for any reason
3. Life expectancy is less than 2 years in the opinion of the Investigator 4.
Presence of other anatomic or comorbid conditions, or other medical, social, or
psychological conditions that, in the investigator*s opinion, could limit the
subject*s ability to participate in the clinical trial or to comply with follow
up requirements, or impact the scientific soundness of the clinical trial
results 5. Incapacitated individuals, defined as persons who are mentally ill,
mentally handicapped, individuals with severe dementia or individuals without
legal authority 6. Individuals who are unable to read or write 7. Currently
participating in an investigational drug or device study that has not reached
the primary endpoint or may confound the results of this trial 8. 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 9. Untreated clinically significant coronary artery disease
requiring revascularization 10. 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. 11. 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 12. Refuses blood products 13. Cardiogenic shock
manifested by low cardiac output, vasopressor dependence, or mechanical
hemodynamic support 14. Hemodynamic instability requiring inotropic support or
mechanical heart assistance 15. Hypertrophic cardiomyopathy with obstruction
16. Active peptic ulcer or upper GI bleeding within 3 months prior to index
procedure that would preclude anti-coagulation 17. Known intolerance,
hypersensitivity, or contraindication, including subjects that meet any of the
following conditions: a. Subjects who cannot take any antiplatelets or
anticoagulants #, b. Subjects who have sensitivity to contrast media which
cannot be adequately premedicated, c. Subjects who have known hypersensitivity
to nitinol (nickel or titanium), or d. Subjects who have clinical
contraindication that precludes contrast CT imaging # Note: Subjects who can
take either an antiplatelet or anticoagulant therapy post-procedure will be
eligible. 18. Recent (within 6 months prior to index procedure date)
cerebrovascular accident (CVA) or a transient ischemic attack (TIA) 19. Renal
insufficiency (creatinine > 3.0 mg/dL or eGFR <30 ml/min/1.73m2) and/or end
stage renal disease requiring chronic dialysis 20. Active bacterial
endocarditis within 6 months prior to the index procedure 21. A positive
COVID-19 test within 30 days prior to the index procedure 22. Liver failure
(Child-Pugh class B or C) 23. Subjects with atrial fibrillation who are not on
anticoagulants or who are not implanted with a left atrial appendage occlusion
(LAAO) device 24. Symptomatic carotid or vertebral artery disease, significant
carotid or vertebral artery disease requiring intervention, or successful
treatment of carotid or vertebral stenosis within 30 days prior to index
procedure 25. Severe pulmonary hypertension with pulmonary systolic pressure
greater than two-thirds of systemic pressure 26. Severe lung disease (FEV1 <
50% predicted) or currently on home oxygen 27. 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 (IMA) to sternum,
etc.) * 28. Significant frailty as determined by the heart team (after
objective assessment of frailty parameters) that would indicate high or extreme
surgical risk # 29. Mixed aortic valve disease (aortic stenosis and aortic
regurgitation with predominant aortic regurgitation 3-4+) # 30. Aortic valve is
a congenital unicuspid or congenital bicuspid valve as verified by
echocardiography or CT # 31. Non-calcified aortic valve *# 32. Severe
ventricular dysfunction with LVEF <30% as measured by resting echocardiogram
33. 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 bio-prosthetic aortic valve may be included in the
Valve-in-Valve cohort 34. Severe circumferential mitral annular calcification
(MAC) which is continuous with calcium in the left ventricular outflow tract
(LVOT) # 35. Prohibitive left ventricular outflow tract calcification # 36.
Severe (greater than or equal to 3+) mitral regurgitation or severe mitral
stenosis with pulmonary compromise 37. Severe tricuspid regurgitation or severe
right ventricle dysfunction 38. Echocardiographic or multi-slice computed
tomography (MSCT) evidence of intracardiac mass, thrombus or vegetation 39.
Significant aortic disease, including abdominal aortic or thoracic aneurysm
defined as maximal luminal diameter 5.5cm or greater or ascending aortic
aneurysm defined as maximal luminal diameter 5cm or greater. 40. Marked aortic
tortuosity (hyperacute bend) or severe *unfolding* and tortuosity of the
thoracic aorta (applicable for transfemoral access only) 41. Aortic arch
atheroma (thick [> 5 mm], protruding or ulcerated) 42. Significant narrowing
(calcification and surface irregularities) of the abdominal or thoracic aorta
43. Aortic root angulation > 70° 44. Undue risk of coronary obstruction (e.g.,
low coronary ostia, narrow Sinus of Valsalva anatomy that would prevent
adequate coronary perfusion, or bulky aortic valve leaflets in close proximity
to coronary ostia) 45. Access vessel characteristics that would preclude safe
insertion of the FlexNav Delivery System such as severe obstructive
calcification, protruding thrombus or severe tortuosity 46. Minimum access
vessel diameter of <5.0mm for small FlexNav Delivery System and <5.5 mm for
large FlexNav Delivery System 47. Ascending aorta anatomy that would preclude
safe delivery of the valve to the native aortic annulus 48. Egocentricity ratio
of the annulus <0.73 * Criterion not applicable for ViV cohort
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04788888 |
| CCMO | NL76500.000.21 |