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

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

This is a prospective, single arm, multicenter study in an expanding cohort of 150 symptomatic patients with severe aortic stenosis who will be followed up for up to 5 years.

Study Overview

• Status: Recruiting
• Conditions: Symptomatic Aortic Stenosis
• Intervention / Treatment: Device: Vienna Aortic Valve SE System

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The clinical trial is completed after all 150 patients (including 10 patients from FIH study), that are not prematurely withdrawn, have completed their 5-year follow-up visit involving all specified assessments.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katharina Kiss, Dr; Phone Number: +4369913289414; Email: kkiss@productsandfeatures.com
• Study Contact Backup: Name: Monica Tocchi, MD, PhD; Phone Number: 9176841700; Email: m.tocchi@meditrial.net

Study Locations

• Argentina
  • Bahia Blanca, Argentina, B8000
    • Not yet recruiting
    • Hospital Privado Sur (FUMEBA)
    • Contact: Alejandro Alvarez Iorio, MD; Email: alexalv1970@gmail.com
    • Principal Investigator: Alejandro Alvarez Iorio, MD
  • Buenos Aires, Argentina, C1199ABB
    • Not yet recruiting
    • Hospital Italiano de Buenos Aires
    • Contact: Carla Agatiello, MD; Email: carla.agatiello@hospitalitaliano.org.ar
    • Principal Investigator: Carla Agatiello, MD
  • Buenos Aires, Argentina, C1093
    • Not yet recruiting
    • Fundacion Favaloro
    • Contact: Oscar Mendiz, MD; Email: omendiz@ffavaloro.org
    • Principal Investigator: Oscar Mendiz, MD
  • Buenos Aires, Argentina, C1221
    • Not yet recruiting
    • Hospital César Milstein
    • Contact: Miguel Payaslian, MD; Email: mopian@yahoo.com.ar
    • Principal Investigator: Miguel Payaslian, MD
  • Buenos Aires, Argentina, C1425AGP
    • Not yet recruiting
    • Hospital Dr. Fernandez
    • Contact: Miguel Payaslian, MD; Email: mopian@yahoo.com.ar
    • Principal Investigator: Miguel Payaslian, MD
• Brazil
  • Rio de Janeiro, Brazil, 22261-010
    • Not yet recruiting
    • Instituto Estadual De Cardiologia Aloysio De Castro
    • Contact: Marcio Jose Montenegro Da Costa, MD; Email: marciojmontenegro@gmail.com
    • Principal Investigator: Marcio Jose Montenegro Da Costa, MD
  • São Paulo, Brazil, 04012-909
    • Not yet recruiting
    • Instituto Dante Pazzanese de Cardiologia
    • Contact: Dimytri Siqueira, MD; Email: dimytrisiqueira@gmail.com
    • Principal Investigator: Dimytri Siqueira, MD
  • São Paulo, Brazil, 05403-900
    • Not yet recruiting
    • Instituto Do Coração (InCor) De São Paulo
    • Contact: Alexandre Abizaid, MD; Email: aabizaid@uol.com.br
    • Principal Investigator: Alexandre Abizaid, MD
• Chile
  • Santiago, Chile, 7500691
    • Not yet recruiting
    • Hospital Del Torax De Santiago
    • Principal Investigator: Christian Dauvergne, MD
    • Contact: Christian Dauvergne; Email: cdauvergnem@yahoo.com
  • Santiago, Chile, 8150215
    • Not yet recruiting
    • Hospital Dr Sotero Del Rio De Santiago
    • Contact: Martín Valdebenito, MD; Email: mvaldet@gmail.com
    • Principal Investigator: Martín Valdebenito, MD
  • Talcahuano, Chile, 4270940
    • Not yet recruiting
    • Hospital Las Higueras - Talcahuano
    • Contact: Osvaldo Perez, MD; Email: osperez2000@gmail.com
    • Principal Investigator: Osvaldo Perez, MD
• Lithuania
  • Kaunas, Lithuania, 50161
    • Recruiting
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
    • Contact: Kasparas Briedis, Dr
    • Principal Investigator: Rimantas Benetis, Prof
• Portugal
  • Lisboa, Portugal
    • Not yet recruiting
    • Hospital Santa Marta
    • Contact: Duarte Cacela, Dr.
  • Vila Nova De Gaia, Portugal
    • Not yet recruiting
    • Centro Hospitalar de Vila Nova de Gaia
    • Contact: Bruno Melica, Dr.
• Spain
  • Barcellona, Spain
    • Not yet recruiting
    • Hospital Universitario Bellvtige
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08041
    • Not yet recruiting
    • Hospital de la Santa Creu i Sant Pau
    • Contact: Lluis Asmarats Serra, Dr
  • Madrid, Spain, 28034
    • Not yet recruiting
    • Hospital Universitario Ramon Y Cajal
    • Contact: Ángel Sánchez Recalde, Dr.; Email: asrecalde@hotmail.com
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Hospital Torrejon
    • Contact: Eduardo Alegria, MD; Email: ealegria@torrejonsalud.com
    • Principal Investigator: Eduardo Alegria, MD
  • Málaga, Spain
    • Not yet recruiting
    • Hospital Virgen de la Victoria
  • Valladolid, Spain
    • Not yet recruiting
    • University Clinical Hospital of Valladolid
  • Madrid
    • Majadahonda, Madrid, Spain
      • Not yet recruiting
      • Hospital Puerta de Hierro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Male and Female
2. Age ≥ 65 years at time of consent
3. Women of non-childbearing potential

4. Severe degenerative calcific native aortic valve stenosis with the following criteria assessed either by resting or dobutamine stress TTE:

   1. Aortic valve area (AVA) < 1.0 cm2 or AVA index ≤ 0.6 cm2/m2 and
   2. Jet velocity > 4.0 m/s or mean gradient > 40 mmHg

5. Symptomatic aortic stenosis (AS), defined as a history of at least one of the following:

   1. Dyspnea that qualifies at NYHA class II or greater
   2. Angina pectoris
   3. Cardiac syncope

6. Subject is considered at intermediate or high risk for surgical valve replacement based on at least one of the following:

   1. EuroSCORE II ≥ 4%
   2. Agreement by the Heart Team that subject is at high operative risk of serious morbidity or mortality with surgical valve replacement
   3. The local Heart Team, including at least 1 cardiothoracic surgeon and 1 interventional cardiologist, deems the patient to be eligible for transfemoral TAVI.
7. Perimeter-based aortic annulus diameter between ≥ 18 and ≤ 29 mm measured by computed tomography (CT) performed within 90 days prior to planned implantation
8. Adequate iliofemoral access with minimum average vessel diameter of ≥ 6.0mm and acceptable level of vessel calcification and tortuosity for safe placement of the introducer sheath
9. The distance from coronary ostia to aortic anulus > 12 mm
10. Patient (or legal representative) understands the study requirements and the treatment procedures and provides written informed consent.
11. The patient and the treating physician agree that the patient will return for all required post-procedure follow-up visits.

Exclusion Criteria:

Cardiovascular System:

1. Patient has a congenital unicuspid or bicuspid aortic valve or non-calcified valves.
2. Evidence of an acute myocardial infarction (MI) ≤ 30 days before the 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).
3. Patient has had a cerebrovascular stroke or TIA within the past 90 days before IMD implantation.
4. Patient has a hypertrophic obstructive cardiomyopathy.
5. History of any therapeutic invasive cardiac procedure (including balloon aortic valvuloplasty) within 30 days prior to the planned IMD implantation (except for pacemaker implantation which is allowed).
6. Distance between the aortic ascending and descending is less than 60 mm.
7. Untreated clinically significant coronary artery disease requiring revascularization at the screening visit.
8. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography within 90 days prior.
9. Patient with cardiogenic shock manifested by low cardiac output and hemodynamic instability and vasopressor dependence, or mechanical hemodynamic support
10. 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 valve implantation.

11. Patient has severe peripheral vascular disease:

    1. 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
    2. symptomatic carotid or vertebral disease or successful treatment of carotid stenosis within 30 days before IMD implantation.
12. Patient with iliofemoral vessel characteristics that would preclude safe passage of the introducer [severe calcification, tortuosity (> two 90-degree bends), diameter < 6mm, or subject has had an aorto-femoral bypass]
13. Patient with active bacterial endocarditis within 6 months of planned IMD
14. Patient has (echocardiographic/ CT and/or MRI) evidence of intra-cardiac mass, thrombus or vegetation.
15. Patient has a pre-existing prosthetic heart valve in any position (Note: mitral ring is not an exclusion).
16. Patient has severe mitral regurgitation, severe aortic regurgitation or severe tricuspid regurgitation, moderate or severe mitral stenosis (Baumgartner et al. 2017).

17. Patient has a need for emergency surgery for any reason at time of screening and valve implantation.

    General:

18. Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. patient with contraindication to oral antiplatelet therapy)
19. 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
20. Patient with significant pulmonary disease (FEV1 < 30%) or currently on home oxygen
21. Severe pulmonary hypertension (e.g., pulmonary systolic pressure greater than two- thirds of systemic pressure )
22. Patients with evidence of an active systemic infection or sepsis.
23. 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.
24. 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
25. Patient has peptic ulcer disease or history of gastrointestinal bleeding within the past 3 months.
26. Patient refuses blood transfusions.
27. 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.
28. Patient is pregnant or breast feeding.
29. 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).
30. 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.
31. Patient is currently participating in another investigational drug or device study that has not reached its primary endpoint (excluding observational studies).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Vienna Aortic Valve; transcatheter aortic valve implantation (TAVI)	Device: Vienna Aortic Valve SE System; Vienna Aortic Valve SE system for TAVI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Cause Mortality (30 days)	All-cause mortality at 30 days from the index procedure.	up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause, cardiovascular and non-cardiovascular mortality	All-cause, cardiovascular and non-cardiovascular mortality at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation.	up to 5 years
Periprocedural death	Incidence of peri-procedural death (to capture intra-procedural events that result in immediate or consequent death ≤72 h post-procedure)	72 hours
Incidence of TAVI-related complications	Incidence of TAVI-related complications: Valve-related complication requiring repeat procedure; Vascular complications resulting in interventions; Ventricular septal perforation ≤7 days after IMD implantation; Acute kidney injury-Stage 2 or 3 ≤7 days post IMD implantation; Coronary artery obstruction requiring intervention; Atrio-ventricular block requiring pacemaker implantation; Mitral valve apparatus damage or dysfunction; Evidence of a new pericardial effusion/ tamponade related to the TAVI procedure; Prosthetic valve endocarditis; Prosthetic valve thrombosis; Prosthetic valve mispositioning; Prosthetic valve embolization; Valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, EOA ≤0.9-1.1 cm2 and/or DVI peak velocity >0.35 m/s, AND/OR moderate or severe prosthetic valve regurgitation)	periprocedural and during index hospitalization
Cerebrovascular event	Cerebrovascular event (at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation): Stroke, defined as an acute episode of focal or global neurological dysfunction caused by the brain, spinal cord, or retinal vascular injury as a result of haemorrhage or infarction; Transient ischemic attack (TIA), defined as a transient episode of focal neurological dysfunction caused by the brain, spinal cord, or retinal ischemia, without acute infarction. The difference between TIA and ischemic stroke is the presence of tissue damage on neuro-imaging studies or new sensory-motor deficit persisting >24 h. By definition, a TIA does not produce a lasting disability.	Up to 5 years
Life-threatening bleeding	Life-threatening bleeding (at 30 days, 3 months, 6 months and 1 year post-implantation).	Up to 1 year
Conduction disturbances requiring permanent pacemaker implantation	Conduction disturbances requiring permanent pacemaker implantation (at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation)	Up to 5 years
Rehospitalization	Re-hospitalization for valve-related complications or worsening congestive heart failure (at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation)	Up to 5 years
Device Success	Device success defined as: a. correct positioning of a single prosthetic investigational heart valve in the proper anatomical location AND ability to provide appropriate hemodynamic AND absence of peri-procedural mortality within 72 hours after implantation	72 hours
Technical success	Technical success defined as; successful vascular access, delivery and deployment of the IMD and successful retrieval of the delivery system; and; correct positioning of a single prosthetic investigational heart valve in the proper anatomical location; in patients alive at 30 days with implanted Vienna valve:Total aortic regurgitation of none/trace/mild/mild-moderatePatient prosthesis mismatch (PPM) insignificant*Mean gradient < 20 mmHg	up to 30 days
Clinical Efficacy	Clinical efficacy (at 1 year and thereafter); 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)	1 year
Valve-related clinical efficacy	Valve-related clinical efficacy; Freedom from bioprosthetic Valve Failure (defined as: Valve-related mortality OR Aortic valve re-operation/re-intervention OR Stage 3 haemodynamic valve deterioration); Freedom from stroke or peripheral embolism (presumably valve-related, after ruling out other non-valve aetiologies); Freedom from VARC Type 2-4 bleeding secondary to or exacerbated by antiplatelet or anticoagulant agents, used specifically for valve-related concerns (e.g. clinically apparent leaflet thrombosis)	Up to 5 years
New York Heart Association (NYHA) classification	Change in heart failure symptoms from baseline as assessed by the New York Heart Association (NYHA) classification (at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation)	Up to 5 years
Change in quality of life as assessed by the Kansas City Cardiomyopathy	Scale from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent	1 year
Change in exercise capacity measured as the 6-minute walk distance (6-MWD)	Change in exercise capacity from baseline measured as the 6-minute walk distance (6-MWD) (at 30 days, 3 months, 6 months and 1 year post-implantation)	1 year

Collaborators and Investigators

• Sponsor: P+F Products + Features GmbH
• Collaborators: Meditrial USA Inc.
• Investigators: Principal Investigator: Rimantas Benetis, Prof Dr, Lithuanian University of Health Sciences; Principal Investigator: Ignacio J Amato Santos, Dr, Hospital Clínico Universitario de Valladolid

Publications and helpful links

Helpful Links

• Meditrial Clinical Research Organization
• Products & Features, manufacturer of VIVA Transcatheter Aortic Valve System

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: heart disease; aortic valve; heart valve; SSAS; symptomatic severe aortic stenosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: CTP-VIE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No