Transcatheter Mitral Valve Replacement with the Medtronic Intrepid* TMVR Transfemoral System in patients with severe symptomatic mitral regurgitation - APOLLO-EU Trial

Please see section 4.1 of the protocol.

Evaluate the safety and efficacy of Medtronic Intrepid* TMVR TF System in
patients with moderate-to-severe or severe symptomatic mitral regurgitation
who, or moderate symptomatic mitral regurgitation combined with mitral stenosis
in the presence of MAC who, by agreement of the local site multidisciplinary
heart team experienced in mitral valve therapies, are unsuitable for treatment
with approved transcatheter repair or surgical mitral valve intervention.

The trial is designed as a prospective, single-arm, multi-center,
interventional, pre-market trial to evaluate the safety and efficacy of
transcatheter mitral valve replacement in patients with moderate-to-severe or
severe symptomatic mitral regurgitation who, by agreement of the local site
multidisciplinary
heart team experienced in mitral valve therapies, are unsuitable for treatment
with approved transcatheter repair or surgical mitral valve intervention.

All required evaluations, post consent and before the investigation procedure
(screening, baseline, and pre-index follow-up time points), as listed in Table
3 of the CIP, are considered interventional and may be outside the standard of
care for a given subject.

The trial is expected to be conducted at approximately 50 study sites located
in EMEA. Up to 400 subjects will be attempted in the trial to ensure 100
Roll-In subjects and up to 300 analysis subjects.
It is estimated that up to 400 IntrepidTM TMVR TF Systems will be implanted
within this trial.
To ensure a widespread distribution of data and minimize study site bias in
trial results, no site will implant more than 20% of total attempted subjects
at any individual site.
Enrollment will be competitive across study sites; therefore, there is no set
minimum number of subjects to be enrolled per site.
The study methods include the following measures to minimize potential sources
of bias:
• Subjects will be screened to confirm eligibility with pre-defined inclusion
and exclusion criteria prior to enrollment.
• An external, independent Clinical Events Committee (CEC) will review and
adjudicate, at a minimum but not limited to all deaths and endpoint related
adverse events. Safety study endpoint results will be based on CEC
adjudications.
• All sites will follow a standardized protocol for acquisition of
echocardiographic study endpoint data.
• An external, independent echocardiography Core Laboratory will evaluate all
echocardiograms. Echocardiographic study endpoint results will be based on Core
Lab assessments.

The enrollment period is estimated to be approximately 2-3 years, and subjects
will be followed for up to 10 years post-procedure; therefore, the expected
trial duration is approximately 12-13 years.
A schedule of events is outlined in Table 3 of the protocol. Upon completion of
the final protocol visit (discontinuation), subject participation will be
considered complete and the subject should then be followed per the local
standard of care for their condition.

This trial will enroll only subjects with moderate-to-severe or severe
symptomatic mitral regurgitation who by agreement of the local site
multidisciplinary heart team experienced in mitral valve therapies are
unsuitable for treatment with approved transcatheter repair or surgical mitral
valve intervention. This TMVR procedure may provide an alternative mitral valve
replacement for subjects for whom conventional surgery or approved
transcatheter repair is not an option. Transfemoral access may also mitigate
procedural complications compared to transapical access from the TMVR procedure.


The clinical experience, to date, has demonstrated successful implantation of
the Intrepid* TMVR TF System, proper TMVR function, and elimination of mitral
regurgitation, warranting continued study in additional subjects, as proposed
in this trial. The potential benefit of a less invasive transfemoral procedure,
for those that are unsuitable for treatment with approved transcatheter repair,
to reduce their mitral regurgitation is considered to outweigh the risks from
an MVR surgical procedure.

The investigational plan is specifically designed to manage and minimize risks
through careful subject selection, thorough training of investigators,
adherence to the pre-determined time points to assess subject clinical status
and regular clinical monitoring visits by Sponsor appointed monitoring
personnel.

Study subjects will be exposed to the procedural and device risks associated
with TMVR, as well as the study specific risks listed in section 11.1. of the
CIP. However, evidence from the scientific literature indicates subjects with
moderate-to-severe or severe mitral regurgitation who do not receive therapy
are exposed to the serious risks associated with their disease including
worsening heart failure, irreversible ventricular functional impairment, and
death. While most risks are being minimized, there are some residual risks, as
further described in the risk management report. Those residual risks were
considered to have been to an acceptable level for the intended application and
current phase of the device.

While the Intrepid* TMVR TF System is a novel device, based on the results of
the Pilot and Mitral Early Feasibility studies and the benefits observed by
relieving mitral regurgitation in other transcatheter mitral valve repair and
replacement trials, it is expected that these benefits will be conferred to the
study subjects in the APOLLO-EU Trial, and that the benefit of mitral
regurgitation reduction will outweigh the risks of intervention.