Confirm the technical performance of the new IMPERIA Delivery System and evaluate the safety and efficacy of the entire ALLEGRA THV System.
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Device success at 7 days, defined as
• Absence of procedural mortality AND
• Correct positioning of a single device in the proper anatomical location
(site-reported) AND
• Intended performance of the prosthetic heart valve (as determined by an
independent Echo Core Lab at discharge from index procedure or 7 days post
implant, whichever comes first)
• Indexed Effective Orifice Area (iEOA) > 0.85 cm2/m2 for BMI < 30kg/m2 and
iEOA > 0.70 cm2/m2 for BMI >= 30kg/m2
• Mean aortic valve gradient <20 mmHg or peak velocity <3 m/s
• No moderate or severe prosthetic valve regurgitation
Secondary outcome
1. All-cause mortality (discharge, 30 days, 6 and 12 months)
2. Cardiovascular mortality (discharge, 30 days, 6 and 12 months)
3. All stroke (discharge, 30 days, 6 and 12 months)
4. Transient ischemic attack (TIA)
5. Procedural success, defined as:
• Successful vascular access, delivery and deployment of the ALLEGRA THV
including re-positioning if required and successful retrieval of the
IMPERIA Delivery System (site-reported)
• Correct position of the ALLEGRA THV (site- reported)
• Only one ALLEGRA THV implanted in proper anatomical position (site-reported)
6. Echocardiographic performance assessment of the ALLEGRA THV (discharge, 30
days, and 12 months), as determined by an independent Echo
Core Lab)
• Effective orifice area (EOA)
• Transvalvular mean and peak pressure gradient
• Trans- and paravalvular regurgitation
7. NYHA classification (30 days, 6 months, and 12 months)
8. Safety profile according to VARC-21
• Early safety
• Time-related valve safety
9. Quality of life (KCCQ-12) (30 days, 6 months, and 12 months)
10. New pacemaker implantation (discharge, 30 days, 6 months and 12 months)
11. Delivery System-related AEs (discharge)
Background summary
Degenerative aortic valve stenosis is the most common heart disease in adults
in western industrialized countries and TAVI has emerged as an alternative
treatment for patients with aortic stenosis (AS) who are at high, intermediate
or low risk for surgery with convincing long-term efficacy. In fact, TAVI has
developed as a standardized interventional procedure with a predictable risk
and consequently, the number of implanted TAVI prosthesis has rapidly increased
over the last decade.
After several randomized clinical studies showed non-inferiority or superiority
of TAVI over surgical aortic valve replacement (SAVR), the latest 2020 ACC/AHA
Valvular Heart Disease guidelines recommend TAVI as alternative treatment to
SAVR in patients aged 65 years or older who are candidates for bioprostheses
independent of the surgical risk as assessed by the heart team, but considering
age, clinical and anatomical factors, and patient preferences. In recent years,
the numbers of failing surgical aortic bioprostheses have been increasing and
these high-risk patients also require for minimally invasive treatment options
obvious..
Despite excellent outcomes in most cases, complications such as device
malpositioning, coronary obstruction, para-valvular regurgitation and
conduction system disturbances do occur after TAVI. Iterative design features
in second generation TAVI systems allow more precise valve placement and can
help to address some of these serious complications.
NVT has developed the new IMPERIA Delivery System so that the ALLEGRA THV can
be re-sheathed and re-captured before it is fully released from the delivery
catheter. In this way, the ALLEGRA THV can be repositioned if the initial
position of the THV is not optimal, thus enabling precise final positioning and
reducing the risks associated with suboptimal positioning.
There are additional technical factors making the ALLEGRA THV System especially
suited for this purpose. The IMPERIA Delivery System and the ALLEGRA THV stent
frame incorporate radio-opaque markers. The marker band on the IMPERIA Delivery
System allows an assessment of implantation depth whilst 6 markers placed 12mm
from the inflow on the ALLEGRA THV stent frame delineate the upper margin of
the internal skirt and the level of the new valve closure line as well as
facilitating the achievement of optimal co-axiality of the ALLEGRA THV prior to
implantation.
Study objective
Confirm the technical performance of the new IMPERIA Delivery System and
evaluate the safety and efficacy of the entire ALLEGRA THV System.
Study design
Prospective, multi-center, single-arm, interventional pivotal study with 12
months follow-up.
Intervention
107 symptomatic patients who are candidates for an intervention on severe
calcified and stenotic aortic valves or failing surgical bioprosthetic aortic
valves as assessed by the heart team, the CSC and meeting all eligibility
criteria will be enrolled (ITT-cohort). Each site must treat 3 roll-in patients
with the new ALLEGRA THV System first prior being allowed to recruit patients
in the ITT-cohort of the EMPIRE study. Roll-in patients undergo same procedures
per protocol as patients in the ITT-cohort..
Study burden and risks
The potential anticipated complications, risks and side effects associated with
use of the IMPERIA DS will be similar to those associated with any routine TAVI
procedure. It is not
anticipated that the IMPERIA Delivery System (DS) and Loading System add any
new risks beyond what is currently seen for the first-generation ALLEGRA DS and
Loading System
when implanting the ALLEGRA THV, which include, but may not be limited to:
* Acute coronary closure
* Acute kidney injury
* Acute myocardial infarction
* Acute renal failure
* Allergic reactions/intolerances (e.g. to contrast media)
* Aortic root injury (dissection, perforation)
* Arrhythmias including ventricular tachycardia or fibrillation extending to
cardiac arrest
* Atrioventricular conduction disorders (AV-block, LBBB)
* Bleeding (hemorrhage)
* Cardiac tamponade
* Cardiogenic shock
* Cerebrovascular events such as TIA, Stroke
* Death
* Device embolization / migration
* Emergent cardiac surgery
* Endocarditis
* Exacerbation of heart failure
* Hemolysis
* Hemorrhage requiring transfusion
* Hypertension or hypotension
* Infection
* Mitral valve injury
* Non-structural prosthetic valve dysfunction: paravalvular or/and central
regurgitation
* Prosthetic valve thrombosis
* Structural prosthetic valve damage (e. g. cusps tear, suture line disruption,
stent fracture,
calcification)
* Thromboembolism
* Vascular injury (dissection, perforation)
The risks of long-term anticoagulation and/or antiplatelet therapy should be
considered.
Potential risks related to study participation are expected to be like those
associated with any other routine TAVI procedure. Only patients who were
referred for a transfemoral TAVI procedure may participate in this clinical
study and protocol-required examinations and assessments (outlined in section
10.1) indicate that the EMPIRE TAVI procedure does not differ from routine TAVI
procedure. All patients who are assigned for a transfemoral TAVI procedure
undergo a standard diagnostic program which includes at least a transthoracic
echocardiography, aortic root- / coronary angiogram, angiogram of the
iliofemoral vessels, cardiac CT. Blood samples are taken pre- and
postoperatively for monitoring purpose. A transfemoral TAVI is routinely
performed either in intubation anesthesia or using a local anesthesia in
combination with a mild sedation.
Radiation exposure by fluoroscopic imaging and the burden of applied contrast
media is a side effect of each standard TAVI procedure and may not
significantly differ in the EMPIRE study.
The postoperative care does not differ between TAVI patients and EMPIRE study
participants. Immediately after procedure TAVI patients are routinely monitored
at the intensive care unit for a few days until they are hemodynamically
stable. TTE will be performed at discharge to verify prosthesis function. Blood
samples are controlled to monitor the status and exclude any serious adverse
events.
Patients who will participate in this study will not be exposed to a burden of
any additional invasive examinations. The pre- and postoperative care is
identical with a standard TAVI procedure.
The transfemoral TAVI procedure is associated with risks attributed to the
interventional catheterization. These risks are well known, identified and
elaborated in section 13.7.
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Listed location countries
Age
Inclusion criteria
Inclusion Criteria:
Patients will be included if ALL of the following criteria are met:
1. Symptomatic severe calcific stenosis of a native aortic valve with an AVA
<=1.0 cm2 (or AVA index <=0.6 cm2/m2), AND mean aortic pressure gradient >= 40mmHg
OR maximal transaortic velocity >=4.0m/s OR Doppler velocity index <=0.25 on
site-reported echocardiography OR symptomatic patients with degeneration of a
surgical bioprosthetic valve (stenosis and/or insufficiency) on sitereported
echocardiography
2. Local multi-disciplinary Heart Team and Central Screening Committee (CSC)
agree on indication and eligibility for TAVI
3. Age >=18 years
4. Patient has signed the Patient Informed Consent Form
5. Patient is willing and able to comply with requirements of the study,
including all follow-up visits
Exclusion criteria
Exclusion Criteria
General:
1. Mean aortic annulus diameter as measured by preprocedural CT or internal
diameter of the bioprosthesis is <16.5 mm or >27 mm
2. Echocardiographic evidence of intracardiac thrombus or vegetation
(site-reported)
3. Significant disease of the aorta that would preclude safe advancement of the
ALLEGRA THV System
4. Severe ilio-femoral vessel disease that would preclude safe placement of an
18 Fr introducer sheath or make endovascular access impossible
5. Severe tricuspid regurgitation and/or failing right heart (site-reported)
6. Severe left ventricular dysfunction with ejection fraction (EF) <20%
(site-reported)
7. Evidence of active endocarditis or other acute infections
8. Renal failure requiring continuous renal replacement therapy
9. Untreated clinically significant coronary artery disease requiring
revascularization
10. Any percutaneous interventional procedure (e.g. PCI with stenting) within
14 days prior of the index procedure
11. Acute MI <=30 days prior to the index procedure
12. Symptomatic carotid or vertebral artery disease requiring intervention or
carotid/vertebral intervention within the preceding 45 days
13. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) <=6 months
or prior CVA with moderate or severe disability (e.g. modified Rankin scale
score >2)
14. History of bleeding diathesis or coagulopathy; acute blood dyscrasias as
defined: thrombocytopenia (platelets <80,000/µl), acute anemia (hemoglobin <10
g/dl), leukopenia (WBC <3000/ µl)
15. Active peptic ulcer or gastrointestinal (GI) bleeding <=3 months
16. Severe (greater than 3+) mitral insufficiency (sitereported)
16a. Pre-existing prosthetic heart valve in any position other than aortic
17. Uncontrolled atrial fibrillation
18. Required emergency surgery for any reason
19. Known hypersensitivity to contrast media, which cannot be adequately
pre-medicated or contraindication to anticoagulant or anti-platelet medication
or to nitinol alloy or to bovine tissue
20. Life expectancy <=12 months due to other medical illness
21. Currently participating in another investigational drug or device study
22. Pregnancy or intend to become pregnant during study participation
Specific exclusions in patients with native aortic valve disease
(site-reported):
23. Unicuspid or bicuspid aortic valve
24. Non-calcified aortic stenosis
25. Predominant aortic regurgitation > grade 3
26. Distance between native aortic valve basal plane and the orifice of the
lowest coronary artery <8 mm
Specific exclusions in patients with degenerated surgical bioprosthetic aortic
valves (valve-in-valve) (site-reported):
27. Low position of the coronary ostia, especially in combination with shallow
sinuses (high risk of coronary occlusion)
28. Partially detached leaflets that may obstruct a coronary ostium
29. Para-valvular regurgitation of a surgical bioprosthesis (site-reported)
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 | NCT05478161 |
| CCMO | NL81924.000.22 |