International Multicenter Study of the Navitor/Navitor Vision Transcatheter Aortic Valve Platform

International Multicenter Study of the Navitor/Navitor Vision Transcatheter Aortic Valve Platform (The Intensive Study)

INTENSIVE is a prospective, single-arm, multi-center, international, investigator-initiated study of the Navitor/Navitor Vision Transcatheter Aortic Valve (Navitor/Navitor Vision Valve) in patients with symptomatic, severe native aortic stenosis to monitor the outcomes of this valve in a real-world clinical setting.

This comprehensive data collection across 25 interventional centers, aligned with standard clinical care practices, seeks to provide an objective benchmark for current TAVR practice.

The Navitor System includes the Navitor Transcatheter Aortic Valve (23 mm, 25 mm, 27 mm, 29 mm, and 35 mm), FlexNav Delivery System (small and large), and Navitor Loading System (small, large, and LG+). The FlexNav Delivery System (small and large) is commercially available in Europe. The 23 mm, 25 mm, 27 mm, 29 mm, and 35 mm valves and their loading systems are currently CE marked.

The Navitor Valve maintains several design features of the first-generation Portico Valve including the same valve sizes and range of use (except for the addition of the 35 mm valve to expand the use range), open stent cell design to provide easy coronary access and blood flow, repositionable with the ability to re-sheath and retrieve, leaflets derived from pericardial bovine tissue, and intra-annular placement of leaflets/cuff within the stent frame for early valve function to maintain hemodynamic stability during implantation.

The Study will enroll subjects that, after comprehensive Heart Team evaluation, are scheduled for treatment with the Navitor/Navitor Vision Valve according to the standard of care at up to 25 experienced TAVI implant centers across Europe and the UK. All sites must either have prior Portico or Navitor/Navitor Vision TAVI system experience. Subjects who provide informed consent for the collection of their clinical data in this Study will undergo Navitor/Navitor Vision Valve implantation via a transfemoral or alternative access (subclavian or axillary) approach using the site's anesthesia protocol for TAVI procedures.

In the Study, the point of enrollment is defined as signing of informed consent, whereas the point of registration is defined as the insertion of the FlexNav Delivery System (loaded with a Navitor/Navitor Vision Valve) into the subject's vasculature (the subject is considered to have undergone an attempted Navitor/Navitor Vision Valve implantation at this point). Only registered subjects will be included in the analysis.

The endpoints of interest will be defined according to VARC-3 definitions. Subjects participating in the Study will be followed for a total of 5 years with data collected at baseline, procedure, prior to hospital discharge, and follow-up at 30 days, 12 months and annually thereafter up to 5 years.

The expected duration of enrollment is 12 months, and the total duration of the Study including final data cleaning, reporting, and site close-out is expected to be approximately 6.5 years.

This Study will enroll subjects of all genders who have symptomatic severe AS, either in a native valve or in a surgical bioprosthetic valve, and who have an indication for TAVI. The latter may also be predominantly regurgitant and remain suitable for enrolment. Subjects must meet all general eligibility criteria for the TAVI procedure and provide written informed consent before sites collect any clinical data for this Study.

The operative risk determination of study candidates will be done by the local heart team. The assessment of surgical risk will include the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Risk Calculator score and/or EuroSCORE II, indices of frailty, and comorbidities not captured by risk calculators, as described below, and current TAVI practice guidelines. A member of the site's clinical investigation team previously trained on the protocol must evaluate patients for the general eligibility criteria and, if applicable, enter them into the site-specific Pre-Screening Log. A patient who does not satisfy all general eligibility criteria prior to informed consent is considered a screen failure and should not be enrolled in the Study.

Sites will ask patients meeting all general inclusion criteria and no general exclusion criteria to sign an Informed Consent form following the established Informed Consent process if they wish to participate in the Study.

A patient is considered enrolled in the Intensive Study from the moment the patient provides written informed consent.

Each subject meeting all general eligibility criteria who is enrolled and receives the Navitor valve shall be followed up until completion of the recommended 5-year follow-up period; however, a subject's participation in any clinical study is voluntary and the subject has the right to withdraw at any time without penalty or loss of benefit. Conceivable reasons for discontinuation may include, but are not limited to, the following:

• Subject death
• Subject undergoes the interventional procedure but exits the operating room without an implanted Navitor Valve; in this case, follow-up is limited to 30 days post-procedure for safety assessment
• After Navitor implantation, subject receives another aortic valve intervention during follow-up (e.g., valve-in-valve intervention, surgical AVR, etc.); in this case, follow-up is limited to 30 days after the additional procedure for safety assessment
• Subject voluntary withdrawal
• Subject lost to follow-up as described below
• Subject's follow-up is terminated Sites must collect and document the reason(s) for subject discontinuation. Investigators must also report this to their respective EC as defined by their institution's procedure(s).

No additional follow-up or data collection is required for subjects once withdrawn from the Study, except for the status (deceased/alive).

If a subject withdraws consent, the site should attempt to schedule the subject for a final follow-up visit. At this final follow-up visit, the subject will undergo the following routine assessments, and related data will be collected when available:

• Echocardiography, including a comprehensive transthoracic echocardiogram, including assessment of aortic valve gradients (mean and peak), areas, indices, degree of regurgitation, cardiac output and cardiac index, left ventricular systolic function (global and segmental)
• Adverse event assessment

Inclusion Criteria:

1. Subject is referred to undergo TAVI with a Navitor/Navitor Vision valve according to the local Heart Team. The Heart Team determines the indication for TAVI with Navitor/Navitor Vision before possible enrolment and independently of the study.
2. Subject is of legal age for consent in the host country.
3. Subject has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent as approved by the Ethics Committee (EC) of the respective clinical site.

Exclusion Criteria:

1. Pregnant or nursing subjects

2. Need for emergency surgery for any reason

3. Contraindications to Navitor/Navitor Vision TAVI according to the IFU:

   1. Any sepsis, including active endocarditis
   2. Any evidence of left ventricular or atrial thrombus
   3. Vascular conditions (i.e., stenosis, tortuosity, or severe calcification) that make insertion and endovascular access to the aortic valve impossible
   4. Non-calcified aortic annulus
   5. Any leaflet configuration other than tricuspid
   6. Inability to tolerate antiplatelet/anticoagulant therapy

4. Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, individuals with severe dementia or individuals without legal authority

5. Individuals who are unable to read or write