To evaluate the safety and performance of the Lotus Valve system for transcathether aortic valve replacment (TAVR) in symptomatic subjects with severe calcific aortic stenosis who are considered high risk for surgical valve replacement.
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Primary Device Performance Endpoint: mean aortic valve pressure gradient at
30 days post implant procedure as measured by echocardiography and assessed by
an independent core laboratory
- Primary Safety Endpoint: all-cause mortality at 30 days post implant
procedure
Secondary outcome
- Effective orifice area at 30 days as measured by echocardiography and
assessed by an independent core laboratory
- Device performance endpoints peri- and post-procedure:
*successful vascular access, delivery and deployment of the Lotus Valve System,
and successful retrieval of the delivery system
*successful repositioning of the Lotus Valve System if repositioning is
attempted
*successful retrieval of the Lotus Valve System if retrieval is attempted
*grade of aortic valve regurgitation: paravalvular, central and combined
- Device success based on the Valve Academic Research Consortium definitions
(VARC)
- Additional measurements based on the VARC endpoints and definitions will be
collected throughout the study:
*safety endpoints adjudicated by an independent Clinical Events Committee:
mortality, stroke, myocardial infarction, bleeding, etc.
*proesthetic aortic valve performance as measured by transthoracic
echocardiography (TTE) and assessed by an independent core laboratory
*functional status
*neurological status
*health status
Background summary
Justification for the use of the investigational device in human subjects
The incidence of aortic stenosis (AS) is increasing due to the aging of the
world-wide population and the lack of drug therapies to prevent, halt, or
effectively slow the stenotic process. Nearly 5% of individuals >75 years of
age have some degree of AS. Once symptoms manifest, the prognosis is poor,
especially when associated with congestive heart failure. Successful treatment
of aortic valve obstruction can result in the improvement of symptoms,
hemodynamic parameters, systolic function, and cardiac hypertrophy along with
increased survival.
Surgical aortic valve replacement (SAVR) remains the gold standard treatment
for the management of subjects with severe AS. However, the operative risk is
increased in elderly subjects, in subjects with concomitant coronary artery
disease or severely reduced left ventricular (LV) function, and in subjects
with associated comorbidities such as cerebral and peripheral vascular disease,
renal failure, and respiratory dysfunction. Percutaneous transluminal aortic
valvuloplasty, which was introduced as an alternative to SAVR in elderly and/or
high-risk subjects, can provide symptomatic relief and/or temporary improvement
but does not provide definitive treatment in subjects with severe calcified AS.
It is also associated with relatively high mortality and complication rates.
Transcatheter aortic valve replacement has recently emerged as an alternative
to the surgical approach in the treatment of severe AS in subjects who are not
suitable candidates for open-heart surgery. This technology is generally
restricted to subjects considered at prohibitive or high surgical risk.
Evidence of the safety of the procedure using either a balloon expandable or a
self-expanding bioprosthetic heart valve has rapidly accumulated through
observational studies, device-specific registries, national registries, and
randomized controlled trials. Through 2-year follow-up in the PARTNER US IDE
trial there have been significant reductions in mortality and repeat
hospitalization rates compared to standard medical therapy in subjects
unsuitable for SAVR29, and similar mortality rates compared to surgical valve
replacement in high-surgical-risk subjects. An expert consensus document on
TAVR was recently published.
Related literature is referenced in the full-text study protocol.
Table 4.1 1 in the protocol summarizes the peri-operative event rates through
30 days post-procedure from several TAVR studies that enrolled similar subjects
as those planned for this study, as well as the results from the inoperable
(Cohort B) and high risk (Cohort A) subjects with severe aortic stenosis
enrolled in the PARTNER US IDE trial. A more detailed summary of the available
literature is presented in the Investigator Brochure.
REPRISE I Study
The aforementioned results notwithstanding, TAVR with early generation devices
has been associated with increased stroke risk versus surgical valve
replacement. Cerebrovascular accidents and vascular complications associated
with TAVR have been significant predictors of mortality. The paravalvular
regurgitation more commonly seen with TAVR compared to surgery has also been
accompanied by higher early and late mortality. While careful subject selection
may serve to mitigate these risks, device design improvements such as seen with
the Lotus Valve System (Section 5.1) may enable more precise placement,
minimize or eliminate paravalvular regurgitation, and obviate the need for
valve-in-valve repeat intervention.
The prospective, single arm, multicenter REPRISE I (REpositionable Percutaneous
Replacement of Stenotic Aortic Valve through Implantation of Lotus* Valve
SystEm) feasibility study (N=11) assessed the acute safety and performance of
the Lotus Valve System in symptomatic subjects with calcified stenotic aortic
valves who were considered high risk for surgical valve replacement. The
primary endpoint was clinical procedural success, defined as successful
implantation of a Lotus Valve (per the Valve Academic Research Consortium
[VARC] definitions44) without in-hospital major adverse cardiovascular and
cerebrovascular events (MACCE, defined as all-cause mortality, periprocedural
myocardial infarction <=72 hours after the index procedure, major stroke,
urgent/emergent conversion to surgery or repeat procedure for valve-related
dysfunction) through discharge or 7 days post-procedure, whichever came first.
Clinical follow-up will extend through 5 years.
To date, the study has reached the primary endpoint, which was achieved in 9/11
subjects. The device was successfully implanted in all 11 subjects but there
was a device failure in 1 subject based on not meeting one of four VARC
criteria for device success. The Echocardiography Core Lab concluded that the
device failure (mean aortic valve gradient >20 mmHg) resulted from a
hyperdynamic state in the subject and noted that the prosthetic valve appeared
to be functioning well. Ten (10) of 11 subjects had no in-hospital MACCE; there
were no deaths and 1 major stroke, which was based on preliminary adjudication
by the CEC and is pending full adjudication based on an assessment to be
performed at 90-day follow-up. Paravalvular regurgitation at discharge TTE was
mild in 2 subjects, trivial in 1 subject, and absent in the other 8 subjects;
these outcomes compare favorably with published data16,24,27,28,46.
To date, data are available through 6 months47. There were no additional MACCE
events beyond the primary endpoint. While all REPRISE I subjects were NYHA
Class II (n=6) or Class III (n=5) at baseline, this distribution was
significantly improved at 6 months (6 in Class I, 4 in Class II, 1 in Class
III; P=0.004). The mean aortic valve gradient was 13.9±3.8 mmHg for the cohort
at 6 months, which was below the VARC criterion of 20 mmHg, and there was no
moderate or severe paravalvular aortic regurgitation. The results of the
REPRISE I feasibility study support the acute safety and performance of the
Lotus Valve System.
Justification for the Study Design
As noted above, the Lotus Valve System potentially provides a number of
performance and safety features beyond that of earlier TAVR devices. These
include a pre-loaded delivery system, early leaflet function to maintain
hemodynamic stability during valve deployment, an enhanced ability to place the
valve correctly at the first attempt using the radiopaque marker to aid in
valve positioning, the capacity to reposition the device if the initial
deployment is considered to be suboptimal, the capability of to retrieveing the
device if during the procedure the decision is made not to implant, and the
aforementioned outer seal designed to minimize paravalvular leakage. The
anticipated risks and benefits associated both with the Lotus Valve System and
with participation in this clinical investigation are summarized in the
Investigator Brochure and in Section 19 of this document. The conclusion of
this risk-benefit analysis demonstrates that the known risks associated with
the procedure and the specific use of the Lotus Valve System have been
mitigated to acceptable limits and are comparable to that associated with
existing transcatheter aortic valves. It was also concluded that the
aforementioned design features may improve procedural safety. The available
sponsor-provided training program and proctorship for physicians further
mitigates the risk. The result is a procedure with residual subject risk
comparable to that of currently available transcatheter aortic valves and
significant potential benefit compared with other alternatives.
It is therefore determined that:
• All applicable risks have been addressed through appropriate testing and any
residual risks are acceptable when weighed against the potential benefits to
the subject.
• The potential benefits of the use of the device out-weigh the risks.
Study objective
To evaluate the safety and performance of the Lotus Valve system for
transcathether aortic valve replacment (TAVR) in symptomatic subjects with
severe calcific aortic stenosis who are considered high risk for surgical valve
replacement.
Study design
The REPRISE II clinical study is a prospective, single-arm, multicenter study
designed to evaluate the safety and performance of the Lotus Valve System for
TAVR in symptomatic subjects who have severe calcific aorta valve stenosis and
who are at high risk for surgical aortic valve replacement (SAVR).
Intervention
The procedure consists of :
- preparation of the subject for the percutaneous procedure following standard
techniques. The commercially approved Lotus Introducer Set will be used as an
accessory to the Lotus Valve System during the procedure.
- a balloon valvuloplasty on the native valve following standard techniques
must be performed with an adequately sized valvuloplasty balloon.
- preparing and using the Lotus Valve System: the implantation procedure
requires 2 operators: first and second operators. Both operators must comply
with the IFU and must be trained and certified by BSC personnel in accordance
with the training plan before performing the procedure.
Study burden and risks
The burden of participating in this trial could be related to the yearly
follow-up visit throughout 5 years after the implantation. On the one hand
these planned follow-up visits are positive for the patients since they will be
followed very closely, on the other hand these yearly follow-up visits can be
experienced as a burden since they are planned up to 5 years after the implant
in a strict timewindow. Patients will also be requested to complete on regular
timepoints (baseline, 30 days, 6 month, 1 year, 3 year and 5 year) Quality of
Life questionnaires. This can also be experienced as a burden for the patients
enrolled in the study. The burden of other planned examinations depends on
routine practice within the hospital. As far as planned examinations per study
protocol are part of the routine examinations in daily practice, they are no
extra burden for the patients enrolled in the trial.
The possible risks and side effects of taking part in this study are listed
above in section E. Patients who take part in this study are subject to similar
risks shared by all patients who receive a similar type of device but are not
in this study. There may also be additional risks or side effects which are
unknown at this time.
As a result of the complications listed above, you may require medical,
percutaneous or surgical intervention, including re-operation and replacement
of the Lotus* Valve. Such complications can be fatal.
As the Lotus* Valve is an investigational device, uncertainty remains over
risks of experiencing some or all of the complications listed above. There may
be risks that are unknown at this time.
rue René Caudron 2
St-Quentin-en-Yvelines CEDEX 78961
FR
rue René Caudron 2
St-Quentin-en-Yvelines CEDEX 78961
FR
Listed location countries
Age
Inclusion criteria
IC1. Subject is >=70 years of age
IC2. Subject has documented calcific native aortic valve stenosis with an initial aortic valve area (AVA) of <1.0 cm2 (or AVA index of <0.6 cm2/m2) and either a mean pressure gradient >40 mm Hg or a jet velocity >4 m/s, as measured by echocardiography
IC3. Subject has a documented aortic annulus size between >=20 and <=27 mm based on pre-procedure diagnostic imaging
IC4. Symptomatic aortic valve stenosis with NYHA Functional Class >= II
IC5. Subject is considered high risk for surgical valve replacement based on at least one of the following:
a. Society of Thoracic Surgeons (STS) score >=8%, AND/OR
b. Agreement by the heart team (which must include an in-person evaluation by an experienced cardiac surgeon) that subject is at high operative risk of serious morbidity or mortality with surgical valve replacement
IC6. Heart team (which must include an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement.
IC7. Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.
IC8. Subject, family member, and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow up visits.
Exclusion criteria
EC1. Subject has a congenital unicuspid or bicuspid aortic valve.
EC2. Subject with an acute myocardial infarction within 30 days of the index procedure (defined as Q-wave MI or non-Q-wave MI with total CK elevation >= twice normal in the presence of CK-MB elevation and/or troponin elevation).
EC3. Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months, or has any permanent neurologic defect prior to study enrollment.
EC4. Subject is on dialysis or has serum creatinine level >3.0 mg/dL or 265 µmol/L.
EC5. Subject has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position.
EC6. Subject has >=3+ mitral regurgitation, >=3+ aortic regurgitation or >=3+ tricuspid regurgitation (i.e., subject cannot have more than moderate mitral, aortic or tricuspid regurgitation).
EC7. Subject has a need for emergency surgery for any reason.
EC8. Subject has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis.
EC9. Subject has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.
EC10. Subject has Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
EC24. Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) that in the opinion of the treating physician is clinically significant and requires a pacemaker implantation.
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 | NCT01627691 |
| CCMO | NL44883.078.13 |