The purpose of this clinical investigation is to further assess the performance and safety profile of the commercially available Portico Valve implanted, using the Delivery System and the Loading System, in patients with severe symptomatic aortic…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is all-cause mortality at 1 year post implant (according
to VARC-2)
Secondary outcome
Evaluation of the VARC-2 defined event rates at 30 days, 1 year and annually
through 5 years post implant.
o All-Cause Mortality
o Cardiovascular Mortality
o Myocardial Infarction
o Stroke (disabling and non-disabling)
o New or worsened conduction disturbances and cardiac arrhythmias (including
pacemaker implantation rate at 30 days and new-onset atrial fibrillation (AF)
Evaluation of the VARC-2 defined event rates at 30 days from the index
procedure.
o Vascular access site complication (major and minor)
o Bleeding (life-threatening, major and minor)
o Acute kidney injury
Prosthetic valve function at 30 days, 1 year and annually through 5 years post
implant. (Includes prosthetic valve stenosis and prosthetic valve
regurgitation).
Clinical benefit endpoints at 30 days, 1 year and annually through 5 years post
implant (if available)
o NYHA functional classification
o 6 Minute Walk Test (6MWT)
o Quality of life measured with EQ-5D questionnaire through 1 year post-implant
Evaluation of the TAVI-related resource utilization through hospital discharge
(e.g. index procedural hospital/physician resources)
Interim reporting at 30 days and 1-year all-cause mortality data may be
performed on a subset of patients and compared with an appropriate external
comparator. The results will be presented to appropriate agencies in France and
in other countries where it will be deemed necessary for reimbursement
purposes.
Background summary
Calcific aortic valve stenosis is a common cardiovascular disease, with an
increasing incidence in an aging population. In cases of severe aortic
stenosis, patients develop symptoms and functional limitation unavoidably
followed by physical deterioration, heart failure and poor prognosis.
For many decades, surgical aortic valve replacement has been an effective
treatment improving symptoms and survival, but more than one-third of patients
with symptomatic severe aortic stenosis do not undergo surgery because of a
high surgical risk; these patients are not referred, are refused or are
declined surgery.
Transcatheter aortic valve implantation (TAVI), first performed in 2002, has
permitted the treatment of patients with excessive surgical risk. Since the
first TAVI case in 2002, 50.000 transcatheter aortic valve procedures have been
performed worldwide comparing favorably with surgery in selected cohorts of
patients; TAVI being the only intervention for inoperable aortic stenosis that
demonstrated to prolong life in a randomized study. Several studies have also
reported symptomatic improvement in the short term and midterm after TAVI.
However, nearly 20% of patients experienced no symptomatic improvement
highlighting Aortic Regurgitation (AR) as the most frequent complication and
one of the main factors affecting symptoms and survival. Although significant
transvalvular AR is rare after TAVI, paravalvular regurgitation is more common,
mainly due to incomplete annular sealing. Paravalvular leaks may occur due to
device undersizing, a mismatch between the prosthesis size and the annulus or
incomplete expansion also depending on the anatomical characteristics of the
patient*s annulus and ascending aorta. Paravalvular regurgitation can be caused
also by a non-optimal implantation site where the device is positioned too high
or too low within the valve annulus. While severe paravalvular regurgitation
may result in severe hemodynamic consequences, moderate and even mild leaks are
associated with less favorable late survival rates than no regurgitation.
Although moderate and severe AR after surgical aortic valve replacement or
balloon valvuloplasty has only been reported anecdotally, the prevalence of
moderate and severe AR after TAVI has ranged from 6% to 21%. Recently, the
impact of moderate and severe AR on survival and symptoms after TAVI has been
highlighted. Significant AR is a main contributor to in-hospital death and an
independent predictor of 1-year mortality and poor treatment response. In the
absence of approved therapies, strategies for the prevention of significant AR
seem to be warranted. Prevention and treatment of AR are of particular
importance because there is an increase in the use of TAVI. Moderate AR
ultimately induces a change from Left Ventricle pressure overload to volume
overload in a situation where the backward volume increases the already
elevated end-diastolic pressure resulting in a considerable proportion of
patients having either no symptomatic benefit or dying within the first months.
Regarding valve durability, mid-term reports of commercially available devices
up to 5 years are showing a rare occurrence of leaflet failure and in vitro
accelerated wear testing is comparable with surgical prostheses. However, more
studies and more time will be needed to demonstrate whether transcatheter
bioprosthesis durability will equal that of surgical bioprosthesis.
Another risk of TAVI is related to rhythm disturbances such as partial or
complete heart block due to the position of the atrioventricular conduction
system that passes superficially through the interventricular septum
immediately below the aortic valve. Risk factors are demonstrated to be
advanced age, right bundle branch block, atrioventricular delay, prosthesis
oversizing and ventricular positioning. Published studies report a different
number of new pacemaker implants according to the device used ranging from 4.5%
at 1 year to 3-fold increase with other devices.
The Portico transcatheter aortic valve is indicated for transcatheter delivery
in patients with symptomatic severe native aortic stenosis who are considered
at high surgical risk. It has been designed to minimize the incidence of
paravalvular leakage and damage to the conduction system. Durability is aimed
to be comparable to that of currently available TAVI bioprostheses. The
self-expanding stent is designed to be fully resheathable and repositionable at
the implant site and retrievable if needed. Additionally the low leaflet/cuff
within the stent design allows for sealing without the valve extending deep
into the LVOT, potentially reducing the risk of damage to the AV node or His
bundle and subsequent need for permanent pacemaker implantation. Large stent
cells in the annulus section of the stent allows for tissue to conform around
calcific nodules potentially minimizing paravalvular leaks. Bovine leaflets and
porcine cuff are treated with Linx* Anti-calcification Technology.
The aim of this study is to evaluate the Portico transcatheter aortic Valve up
to five years, according to the VARC 2 criteria.
Study objective
The purpose of this clinical investigation is to further assess the performance
and safety profile of the commercially available Portico Valve implanted, using
the Delivery System and the Loading System, in patients with severe symptomatic
aortic stenosis.
The primary objective of this clinical investigation is to assess the 1 year
all-cause mortality of patients, with severe symptomatic aortic stenosis,
implanted with a Portico Valve as per current guidelines.
The secondary objective of this clinical investigation is to assess the
peri-procedural and long-term performance and safety profile of the Portico
Valve implanted, using Delivery System and the Loading System, in patients with
severe symptomatic aortic stenosis.
Study design
This is an international multicenter, prospective, non-randomized,
interventional clinical investigation without concurrent or matched control,
designed to assess the 1 year all-cause mortality rate of patients implanted
with a Portico Valve. In addition, performance and safety profile data of the
Portico Valve will be evaluated at 30 days, 6 months, 1 year, 2 years, 3 years,
4 years and 5 years.
Intervention
Not applicable, no additional intervention.
Study burden and risks
There is no additional risk voor the patient.
De patient can benefit from the study due to the regular and extensive
follow-up for a period of 5 years.
Standaardruiter 13
VEENENDAAL 3905 PT
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Standaardruiter 13
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Listed location countries
Age
Inclusion criteria
1. Patient has signed the Patient Informed Consent prior to participating in the clinical investigation.
2. Patient has been referred for a Portico Valve implant as per Heart Team decision.
3. Patient has senile degenerative aortic valve stenosis confirmed by echocardiographically derived criteria
4. Patient has a life expectancy of more than (>) 12 months.
Exclusion criteria
1. Any case in which the Portico Valve would not be indicated for the patient as per current IFU (i.e. any *off-label* use).
2. Patient has any other aortic valve than tricuspid one.
3. Patient has a prosthetic valve or ring in the aortic position.
4. Patient needs a concomitant structural heart procedure.
5. Patient is unwilling or unable to comply with all clinical investigation-required follow-up evaluations.
6. Patient is pregnant
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 | NCT01802788 |
| CCMO | NL43748.099.13 |