Demonstrate that the self-expandable Allegra TAVI system provides lower mean gradient assessed by TTE compared to balloon-expandable valve systems in a population of all women patients with symptomatic severe aortic valve stenosis.
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Trans-aortic mean gradient measured by TTE 30 days after the TAVI procedure.
Secondary outcome
Following endpoints will be assessed as defined by VARC-3 Criteria
Technical success (at exit from procedure room)
• Freedom from mortality
• Successful access, delivery of the device, and retrieval of the delivery
system
• Correct positioning of a single prosthetic heart valve into the proper
anatomical location
• Freedom from surgery or intervention related to the device* or to a major
vascular or access-related, or cardiac structural complication
Device success (at 30 days*)
• Technical success
• Freedom from mortality
• Freedom from surgery or intervention related to the device* or to a major
vascular or access-related or cardiac structural complication
• Intended performance of the valve* (mean gradient <20 mmHg, peak velocity <3
m/s, Doppler velocity index >= 0.25, and less than moderate aortic regurgitation)
Early safety (at 30 days)
• Freedom from all-cause mortality
• Freedom from all stroke
• Freedom from VARC type 2-4 bleeding (in trials where control group is
surgery, it is appropriate to include only Type 3 and 4 bleeding)
• Freedom from major vascular, access-related, or cardiac structural
complication
• Freedom from acute kidney injury stage 3 or 4
• Freedom from moderate or severe aortic regurgitation
• Freedom from new permanent pacemaker due to procedure-related conduction
abnormalities
• Freedom from surgery or intervention related to the device
Clinical efficacy (at 1 year)
• Freedom from all-cause mortality
• Freedom from all stroke
• Freedom from hospitalization for procedure- or valve-related causes
• Freedom from KCCQ Overall Summary Score <45 or decline from baseline of >10
point (i.e. Unfavourable Outcome)
* In-hospital may be used if 30-day data are not available.
* Haemodynamic valve performance standards may differ depending on the specific
valve sizes implanted.
Background summary
Degenerative aortic valve stenosis (AS) is the most common heart valve disease
in adults in Western countries and is steadily increasing as the average age of
the population increases. Patients with AS are asymptomatic for a long period
of the disease course. However, once the first symptoms such as angina, syncope
and dyspnea appear, the prognosis is poor. A mortality rate of 25% in the first
year and 50% in the second year after the onset of symptoms is reported,
despite drug treatment.
Treatments such as open surgical aortic valve replacement (SAVR) and
transfemoral transcatheter aortic valve implantation (TAVI), a minimally
invasive procedure, have significantly improved long-term survival rates.
Today, TAVI has been developed as a standardized interventional procedure with
predictable and acceptable risk. Therefore, the number of implanted TAVI
prostheses has increased rapidly over the past decade.
The target population of this study, women, make up less than 50% of patients
undergoing TAVI. Women and men undergoing TAVI have different baseline
characteristics that may impact post-TAVI and long-term events differently.
Compared with men, women have a smaller annulus of the aortic valve, a lower
origin of the coronary arteries, smaller peripheral vessels, as well as a
higher prevalence of osteoporosis and frailty, and a greater risk of bleeding.
Women also have a higher prevalence of coexisting valve disease and heart
failure.
The ALLEGRA TAVI system TF (NVT AG, Morges, Switzerland) was investigated in
NVT's Pilot (NVT01PST) and Pivotal (NVT02PT) studies, respectively. The
combined data set from both studies in a population of 81 patients (76.5%
female and 23.5% male) showed excellent performance and acceptable safety data,
comparable to other self-expanding transcatheter aortic valve prostheses. The
purpose of the study is to test the hypothesis that, in a population of only
women with symptomatic severe AS, the self-expandable ALLEGRA TAVI system TF
provides a superior hemodynamic profile, in terms of a TTE mean gradient,
compared to balloon expandable valves.
Study objective
Demonstrate that the self-expandable Allegra TAVI system provides lower mean
gradient assessed by TTE compared to balloon-expandable valve systems in a
population of all women patients with symptomatic severe aortic valve stenosis.
Study design
Multicenter, randomized versus balloon-expandable valve system, post-market,
superiority clinical trial.
Study burden and risks
Risks of adverse events are those of current care TAVI procedures using
CE-marked devices. These have been demonstrated to be safe by providing
clinical benefit to the patients. Participation in the study does not expose
the patients to any medical risk in addition to the current care practice of
TAVI procedures and related examinations.
Eligible patients will undergo a standard diagnostic program which includes
TTE, cardiac MSCT and coronary angiogram. Pre- and post-procedural blood
samples are taken for monitoring purposes as per hospital standard of care. As
a result of participation in this study, patients won*t undergo any additional
invasive or burdensome examination when compared to a TAVI treatment outside of
this study. For postoperative follow up patients are asked to return to the
hospital after 30 days, and at 1 year. TTE will be performed during these
visits to verify the valve function. TTE is not considered as invasive or to be
burdensome for the patients though.
As the participation in the study does not expose the patients to any medical
risk in addition to the current care practice of TAVI procedures and related
examinations, the research is justified because it contributes to increase the
knowledge on the treatment of female patients with aortic valve stenosis.
Route des Dailles 2 0
Villars-sur-Glâne 1752
CH
Route des Dailles 2 0
Villars-sur-Glâne 1752
CH
Listed location countries
Age
Inclusion criteria
Subjects will be included if all of the following criteria are met:
1. Female sex
2. Age >= 75 years (according to ESC/EACTS, Guidelines for the management of
valvular heart disease)
3. Severe calcific aortic valve stenosis defined as follows: high-gradient
aortic valve stenosis (mean pressure gradient across aortic valve > 40 mmHg or
peak velocity > 4.0 m/s)
4. Symptomatic aortic valve stenosis with New York Heart Association (NYHA)
Class >=II
5. ECG-gated Multi-Slice Computed Tomographic (MSCT) measurements determined an
aortic annulus perimeter-derived average diameter >19 mm and <27.4 mm or
area-derived diameter >18 and <28 mm
6. Anatomy suitable for trans-femoral TAVI for both devices used in the study,
including a minimum femoral diameter of 6 mm.
7. Subject with a documented local Heart Team (HT) indication for TF TAVI
8. Life expectancy longer than 1 year.
9. Willingness to undergo clinical and echocardiographic follow-up after the
procedure.
10. Subject can understand the purpose of the clinical investigation, has
signed voluntarily the informed consent form and is agreeing to the scheduled
follow-up requirements
Exclusion criteria
Subjects will not be included if any of the following criteria are met:
1. Male sex
2. Non-calcific acquired aortic valve stenosis
3. Native unicuspid/bicuspid aortic valve or congenital aortic abnormality
4. Previous implantation of heart valve in any position
5. Severe aortic regurgitation (> 3+)
6. Severe mitral regurgitation (> 3+)
7. Severe tricuspid regurgitation (> 3+)
8. Severe left ventricular dysfunction (Left Ventricular Ejection Fraction
(LVEF) < 30%)
9. Echocardiographic evidence of intracardiac mass, thrombus or vegetation
10. Untreated cardiac conduction disease in need of pacemaker implantation
11. Evidence of acute Myocardial Infarction (MI) less than 30 days before
signing informed consent
12. Any need for emergency surgery
13. Any active bleeding that precludes anticoagulation
14. Liver failure (Child-C)
15. End-stage renal disease requiring chronic dialysis or creatinine clearance
< 30cc/min
16. Pulmonary hypertension (systolic pressure > 80mmHg)
17. A known hypersensitivity or contraindication to all
anticoagulation/antiplatelet regimens (or inability to be anticoagulated for
the index procedure), to cobalt chromium, to bovine and/or collagen,
glutaraldehyde or contrast media
18. Any medical, social or psychological condition that in the opinion of the
investigator precludes the subject from giving appropriate consent or adherence
to the required follow-up procedures
19. Currently participating in another drug or device trial (excluding
observational registries) for which the primary endpoint has not been assessed
20. Subject under judicial protection, tutorship or curatorship (for France
only)
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 | NCT05989074 |
| CCMO | NL85255.100.23 |