Pivotal Study of the Vienna Transcatheter Self Expandable Aortic Valve SE System

Official title

A Two -Stage First in Human (FIH) Feasibility / Pivotal Study of the Vienna Aortic Valve SE System

Overview

This is a prospective, single arm, multicenter study in an cohort of up to 267 patients (up to 100 Roll-ins and 167 patients implanted per protocol) symptomatic patients with severe aortic stenosis who will be followed up for up to 5 years.

Detailed description

The purpose of this trial is to determine the safety and effectiveness of the Vienna Aortic Valve SE System, a new self-expanding transcatheter heart valve, in patients with symptomatic severe aortic stenosis (SSAS). This is a prospective, single arm, multicenter study in an expanding cohort of symptomatic patients with severe aortic stenosis following the FIH feasibility study. The clinical investigation comprises 11 visits (V1 to V11). After implantation of the IMD at visit 2, safety and effectiveness assessment of the device will be performed at 30 days (V4), 3 months (V5), 6 months (V6), 1 year (V7) and every year thereafter up to 5 years post-implantation (V8 to V11).

In summary, the clinical investigation for the individual patient will end after 5 years with a full clinical evaluation. The primary study endpoints for safety and effectiveness will be reached at 30-day follow-up timepoint.

The clinical trial is completed after all 267 patients, that are not prematurely withdrawn, have completed their 5-year follow-up visit involving all specified assessments.

Interventions

• Device Vienna Aortic Valve SE System
  Vienna Aortic Valve SE system for TAVI.

Primary outcome measures

• All Cause Mortality (30 days) [Time frame: up to 30 days]

Secondary outcome measures (12)

• All-cause, cardiovascular and non-cardiovascular mortality [Time frame: up to 5 years]
• Periprocedural death [Time frame: 72 hours]
• Incidence of TAVI-related complications [Time frame: periprocedural and during index hospitalization]
• Cerebrovascular event [Time frame: Up to 5 years]
• Life-threatening bleeding [Time frame: Up to 1 year]
• Conduction disturbances requiring permanent pacemaker implantation [Time frame: Up to 5 years]
• Rehospitalization [Time frame: Up to 5 years]
• Device Success [Time frame: 72 hours]
• Technical success [Time frame: up to 30 days]
• Clinical Efficacy [Time frame: 1 year]
• Valve-related clinical efficacy [Time frame: Up to 5 years]
• New York Heart Association (NYHA) classification [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Male or Female
• Age ≥ 65 years at time of consent
• Women of non-childbearing potential
• Severe degenerative calcific native aortic valve stenosis with the following criteria assessed either by resting or dobutamine stress TTE:

• Aortic valve area (AVA) < 1.0 cm2 or AVA index ≤ 0.6 cm2/m2 and
• Jet velocity > 4.0 m/s or mean gradient > 40 mmHg
• Symptomatic aortic stenosis (AS), defined as a history of at least one of the following:

• Dyspnea that qualifies at NYHA class II or greater
• Angina pectoris
• Cardiac syncope
• Subject is considered at intermediate or high risk for surgical valve replacement based on at least one of the following:

• EuroSCORE II ≥ 4% along with assessment of frailty, major organ system dysfunction, and procedure-specific impediments, in accordance with scientific guidelines
• Agreement by the Heart Team that subject is at moderate to high operative risk of serious morbidity or mortality with surgical valve replacement.
• The local Heart Team deems the patient to be eligible for transfemoral TAVI.
• Perimeter-based aortic annulus diameter between ≥ 18 and ≤ 29 mm measured by computed tomography (CT) analyzed by a core lab.
• Adequate iliofemoral access with either:

• At least one side with minimum vessel diameter ≥ 6.0 mm and acceptable level of vessel calcification and tortuosity for safe placement of the introducer sheath, as analyzed by a core lab, OR
• At least one side with minimum vessel diameter ≥ 5.5 and no significant calcification or severe tortuosity for safe placement of the introducer sheath, as analyzed by a core lab.
• Patient (or legal representative) understands the study requirements and the treatment procedures and provides written informed consent.
• The patient and the treating physician agree that the patient will return for all required post-procedure follow-up visits.

Exclusion criteria

Cardiovascular System:

• Patient has a congenital unicuspid or bicuspid aortic valve or non-calcified valves.
• Evidence of an acute myocardial infarction (MI) ≤ 30 days prior to screening or IMD implantation (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).
• Patient has had a cerebrovascular stroke or TIA within the past 90 days implantation prior to screening or valve implantation.
• Patient has a hypertrophic obstructive cardiomyopathy.
• History of any therapeutic invasive cardiac procedure (including balloon aortic valvuloplasty) within 30 days prior to screening or IMD implantation (except for pacemaker implantation which is allowed).
• Untreated clinically significant coronary artery disease requiring revascularization at the screening visit.
• Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography.
• Patient with cardiogenic shock manifested by low cardiac output and hemodynamic instability and vasopressor dependence, or mechanical hemodynamic support
• Patients with clinically significant conduction abnormalities (clinically significant sinus bradycardia, sinus block or pauses, clinically significant atrioventricular (AV)-block >I) at screening and at time of IMD implantation.
• Patient has severe peripheral vascular disease:

• including aortic aneurysm defined as maximal luminal diameter > 5 cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick \[> 5 mm\], protruding or ulcerated atheroma in the aortic arch) or
• symptomatic carotid or vertebral disease or successful treatment of carotid stenosis within 30 days prior to screening or IMD implantation.
• Patient with iliofemoral vessel characteristics that would preclude safe passage of the introducer (both sides), as analyzed by a core lab:

• severe calcification,
• severe tortuosity (> two 90-degree bends),
• diameter < 6 mm, in patients with acceptable levels of calcification and acceptable levels of tortuosity
• diameter < 5.5, in patients with no calcification and no significant tortuosity, OR
• subject has had an aorto-femoral bypass
• Patient with active bacterial endocarditis within 6 months prior to screening or IMD implantation.
• Patient has (echocardiographic/ CT and/or MRI) evidence of intra-cardiac mass, thrombus or vegetation.
• Patient has a pre-existing prosthetic heart valve in any position (Note: mitral ring is not an exclusion).
• Patient has severe mitral regurgitation, severe aortic regurgitation or severe tricuspid regurgitation, moderate or severe mitral stenosis.
• Patient has a need for emergency surgery for any reason at time of screening or IMD implantation.

General:

• Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. patient with contraindication to oral antiplatelet therapy)
• Patient with renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/ or renal replacement therapy and/ or has serum creatinine level > 3.0 mg/dL or 265 µmol/L replacement therapy at the time of screening
• Patient with significant pulmonary disease (FEV1 < 30%) or currently on home oxygen
• Severe pulmonary hypertension (e.g., pulmonary artery systolic pressure ≥ 60 mmHg)
• Patients with evidence of an active systemic infection or sepsis.
• Patient has a known hypersensitivity or contraindication to contrast media, bovine tissue, nitinol (titanium or nickel), contraindication to oral antiplatelet therapy (aspirin, ticlopidine or clopidogrel) or heparin.
• Patient has a haemoglobin < 9 g/dL, platelet count < 50,000 cells/mm3 or > 700.000 cells/mm3, or white blood cell count < 1.000 cells/mm3, history of bleeding diathesis or coagulopathy
• Patient has peptic ulcer disease or history of gastrointestinal bleeding within the 3 months prior to screening or IMD implantation.
• Patient refuses blood transfusions.
• Patient has a life expectancy of less than 12 months due to non-cardiac, co-morbid conditions based on the assessment of the investigator at the time of enrolment (i.e. the time of informed consent).
• Patient is pregnant or breast feeding.
• Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
• Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the patient from appropriate consent or adherence to the protocol required follow-up exams.
• Patient is currently participating in another investigational drug or device study that has not reached its primary endpoint (excluding observational studies).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Spain · 8 centers

• Hospital Clinic De Barcelona — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitario Ramón y Cajal — Madrid
• Hospital Clinico San Carlos — Madrid
• University Clinical Hospital of Valladolid — Valladolid
• Hospital Puerta De Hierro — Majadahonda
• Hospital Virgen De La Victoria — Málaga
• Hospital Universitario Central de Asturias — Oviedo

Brazil · 5 centers

• Instituto Nacional de Cardiologia — Rio de Janeiro
• Escola Paulista de Medicina da UNIFESP — São Paulo
• Instituto Estadual De Cardiologia Aloysio De Castro — Rio de Janeiro
• Instituto Dante Pazzanese De Cardiologia — São Paulo
• Instituto Do Coração (InCor) De São Paulo — São Paulo

India · 5 centers

• Narayana Health, Multispeciality Hospital — Bangalore
• Medanta - The Medicity Multi-Speciality Hospital — Gurgaon
• RHL- Rajasthan Hospital — Jaipur
• LISIE Hospital — Kochi
• Christian Medical College Hospital — Vellore

Portugal · 5 centers

• Hospital Santa Marta — Lisbon
• Hospital Santa Maria — Lisbon
• Hospital de Santa Cruz — Carnaxide
• Unidade Local de Saúde de Gaia e Espinho — Vila Nova de Gaia
• Hospital do Espírito Santo de Évora — Evora

Argentina · 3 centers

• Hospital Privado Sur (FUMEBA) — Bahía Blanca
• Fundación Favaloro — Buenos Aires
• Hospital Italiano De Buenos Aires — Buenos Aires

Chile · 3 centers

• Hospital Del Torax De Santiago — Santiago
• Hospital Clínico San Borja Arriarán — Santiago
• Hospital Las Higueras - Talcahuano — Talcahuano

Lithuania · 1 center

• Hospital of Lithuanian University of Health Sciences Kauno klinikos — Kaunas

Turkey (Türkiye) · 1 center

• İ.A.Ü. VM Medical Park Florya Hospital — Istanbul

Publications

• Briedis K, Rumbinaite E, Aldujeli A, Briede K, Jurenas M, Jakuska P, Jankauskas A, Ceponiene I, Lenkutis T, Plisiene J, Benetis R, Zaliunas R. One-year initial efficacy and safety outcomes of the premounted dry-pericardium Vienna self-expandable transcatheter aortic valve system: A first-in-human VIVA feasibility study. Catheter Cardiovasc Interv. 2024 Jun;103(7):1111-1124. doi: 10.1002/ccd.31039. PMID 38591535
• Briedis K, Aldujeli A, Zaliunas R, Benetis R. Early Safety and Performance of the Premounted Dry-Pericardium Vienna Self-Expandable Transcatheter Aortic Valve System: 30-Day Outcomes of the First-in-Human VIVA Feasibility Study. Am J Cardiol. 2023 Oct 1;204:302-311. doi: 10.1016/j.amjcard.2023.07.109. Epub 2023 Aug 9. PMID 37567022
• Briedis K, Mizariene V, Rumbinaite E, Jurenas M, Aldujeli A, Briede K, Jakuska P, Jankauskas A, Ceponiene I, Lenkutis T, Zaliunas R, Benetis R. Safety and performance of the Vienna self-expandable transcatheter aortic valve system: 6-month results of the VIVA first-in-human feasibility study. Front Cardiovasc Med. 2023 Jul 13;10:1199047. doi: 10.3389/fcvm.2023.1199047. eCollection 2023. PMID 37522086

Identifiers

NCT: NCT04861805 · CTP-VIE-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗