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

• ClinicalTrials.gov Identifier: NCT04861805
• Recruitment Status: Recruiting
• First Posted: April 27, 2021
• Last Update Posted: November 1, 2023
• Sponsor: P+F Products + Features GmbH
• Collaborator: Meditrial USA Inc.
• Information provided by (Responsible Party): P+F Products + Features GmbH

Tracking Information

• First Submitted Date: April 20, 2021
• First Posted Date: April 27, 2021
• Last Update Posted Date: November 1, 2023
• Actual Study Start Date: July 3, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2023)

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

All-cause mortality at 30 days from the index procedure.

Original Primary Outcome Measures (submitted: April 22, 2021)

• Percentage of participants with early safety events [ Time Frame: up to 30 days ]
  To determine early safety of the Vienna Aortic Valve SE System
• All-cause mortality [ Time Frame: up to 30 days ]
  All-cause mortality within 30 days or during index procedure hospitalization, if the postoperative length of stay is longer than 30 days

Current Secondary Outcome Measures (submitted: October 27, 2023)

• All-cause, cardiovascular and non-cardiovascular mortality [ Time Frame: up to 5 years ]
  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.
• Periprocedural death [ Time Frame: 72 hours ]
  Incidence of peri-procedural death (to capture intra-procedural events that result in immediate or consequent death ≤72 h post-procedure)
• Incidence of TAVI-related complications [ Time Frame: periprocedural and during index hospitalization ]
  Incidence of TAVI-related complications:

  1. Valve-related complication requiring repeat procedure
  2. Vascular complications resulting in interventions
  3. Ventricular septal perforation ≤7 days after IMD implantation
  4. Acute kidney injury-Stage 2 or 3 ≤7 days post IMD implantation
  5. Coronary artery obstruction requiring intervention
  6. Atrio-ventricular block requiring pacemaker implantation
  7. Mitral valve apparatus damage or dysfunction
  8. Evidence of a new pericardial effusion/ tamponade related to the TAVI procedure
  9. Prosthetic valve endocarditis
  10. Prosthetic valve thrombosis
  11. Prosthetic valve mispositioning
  12. Prosthetic valve embolization
  13. 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)
• Cerebrovascular event [ Time Frame: Up to 5 years ]
  Cerebrovascular event (at 30 days, 3 months, 6 months, 1 year and every year thereafter up to 5 years post-implantation):

  1. 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
  2. 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.
• Life-threatening bleeding [ Time Frame: Up to 1 year ]
  Life-threatening bleeding (at 30 days, 3 months, 6 months and 1 year post-implantation).
• Conduction disturbances requiring permanent pacemaker implantation [ Time Frame: Up to 5 years ]
  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)
• Rehospitalization [ Time Frame: Up to 5 years ]
  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)
• Device Success [ Time Frame: 72 hours ]
  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
• Technical success [ Time Frame: up to 30 days ]
  Technical success defined as

  1. successful vascular access, delivery and deployment of the IMD and successful retrieval of the delivery system; and
  2. correct positioning of a single prosthetic investigational heart valve in the proper anatomical location
  3. in patients alive at 30 days with implanted Vienna valve:
     1. Total aortic regurgitation of none/trace/mild/mild-moderate
     2. Patient prosthesis mismatch (PPM) insignificant*
     3. Mean gradient < 20 mmHg
• Clinical Efficacy [ Time Frame: 1 year ]
  Clinical efficacy (at 1 year and thereafter)

  1. Freedom from all-cause mortality
  2. Freedom from all stroke
  3. Freedom from hospitalization for procedure- or valve-related causes
  4. Freedom from KCCQ Overall Summary Score <45 or decline from baseline of >10 point (i.e. Unfavourable Outcome)
• Valve-related clinical efficacy [ Time Frame: Up to 5 years ]
  Valve-related clinical efficacy

  1. Freedom from bioprosthetic Valve Failure (defined as: Valve-related mortality OR Aortic valve re-operation/re-intervention OR Stage 3 haemodynamic valve deterioration)
  2. Freedom from stroke or peripheral embolism (presumably valve-related, after ruling out other non-valve aetiologies)
  3. 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)
• New York Heart Association (NYHA) classification [ Time Frame: Up to 5 years ]
  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)
• Change in quality of life as assessed by the Kansas City Cardiomyopathy [ Time Frame: 1 year ]
  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
• Change in exercise capacity measured as the 6-minute walk distance (6-MWD) [ Time Frame: 1 year ]
  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)

Original Secondary Outcome Measures (submitted: April 22, 2021)

• overall mortality [ Time Frame: up to 1 year ]
  evaluate overall mortality of patients treated with the Vienna Aortic Valve SE System concept
• general feasibility [ Time Frame: up to 30 days ]
  evaluate general feasibility of the Vienna Aortic Valve SE System design
• safety evaluation [ Time Frame: up to 1 year ]
  evaluate safety of the Vienna Aortic Valve SE System
• clinical and hemodynamic performance [ Time Frame: up to 1 year ]
  evaluate clinical and hemodynamic performance
• peri-procedural death [ Time Frame: from date of implantation until 3 days post procedure ]
  Incidence of peri-procedural death (to capture intra-procedural events that result in immediate or consequent death ≤72 h post-procedure)
• Number of participants with incidence of Valve-related complications [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Valve-related complication requiring repeat procedure (transcatheter or surgical heart valve replacement)
• Number of participants with incidence of vascular complications [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Vascular complications (aortic dissection, perforation, rupture or femoral/iliac artery complications) resulting in interventions (surgical or interventional)
• Number of participants with incidence of Coronary artery obstruction requiring intervention [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Coronary artery obstruction requiring intervention (Evidence of a new, partial or complete obstruction of a coronary ostium, either by the valve prosthesis itself, the native leaflets, calcifications, or dissection, occurring during or after the TAVI procedure)
• Number of participants with incidence of Mitral valve apparatus damage or dysfunction [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Mitral valve apparatus damage or dysfunction
• Number of participants with Evidence of a new pericardial effusion/ tamponade related to the TAVI procedure [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Evidence of a new pericardial effusion/ tamponade related to the TAVI procedure
• Number of participants with Incidence of Prosthetic valve endocarditis, thrombosis, mispositioning and/or embolization [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Prosthetic valve endocarditis, Prosthetic valve thrombosis, Prosthetic valve mispositioning and/or Prosthetic valve embolization
• Number of participants with incidence of Valve-related dysfunction [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, EOA ≤0.9-1.1 cm2 and/or DVI <0. 35 m/s, AND/OR moderate or severe prosthetic valve regurgitation)
• Device success [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  Device success measured by number of patients who are alive with intended device in place without any additional surgical or interventional procedures related to Vienna Aortic Valve.
• Technical success [ Time Frame: from date of implantation until date of discharge (equal to or less than 10 days post-procedure) ]
  The percentage of surviving participants with successful access delivery and retrieval fo the device delivery system with correct deployment and positioning of the intended device and no need for additional unplanned surgery or re-intervention related to the device or access procedure.
• Number of participants with ventricular septal perforation [ Time Frame: from date of implantation until 7 days post-procedure ]
  Ventricular septal perforation ≤7 days after IMD implantation
• Number of patients with Cerebrovascular event [ Time Frame: up to 1 year ]
  Number of patients with Cerebrovascular event ,like Stroke and Transient ischemic attack (TIA) will be assessed.
• Number of participants with Life-threatening bleeding [ Time Frame: up to 1 year ]
  Life-threatening bleeding (at 30 days, 3 months, 6 months and 1 year post-implantation)
• Conduction disturbances requiring permanent pacemaker implantation [ Time Frame: up to 1 year ]
  Conduction disturbances requiring permanent pacemaker implantation (at 30 days, 3 months, 6 months and 1 year post-implantation)
• Acute kidney injury [ Time Frame: from date of implantation until 7 days post-procedure ]
  Acute kidney injury-Stage 2 or 3 (including renal replacement therapy) ≤7 days post IMD implantation
• Valve function assessed by transthoracic echocardiography (TTE) [ Time Frame: up to 1 year ]
  Valve function assessed by transthoracic echocardiography (TTE): a. valve position, morphology, function, and evaluation of the left ventricle (LV) size and function.
• Number of participants with all-cause, cardiovascular, and non-cardiovascular mortality [ Time Frame: up to 1 year ]
  All-cause, cardiovascular, and non-cardiovascular mortality at 3 months, 6months and 1 year
• Number of participants who were re-hospitalized for valve-related complications or worsening congestive heart failure [ Time Frame: up to 1 year ]
  Re-hospitalization for valve-related complications or worsening congestive heart failure (at 30 days, 3 months, 6 months and 1 year post-implantation)
• Change in heart failure symptoms as assessed by the New York Heart Association (NYHA) classification [ Time Frame: up to 1 year ]
  Change in heart failure symptoms from baseline as assessed by the New York Heart Association (NYHA) classification (at 30 days, 3 months, 6 months and 1 year post-implantation) Values: NYHA Class I - IV Expected outcome: from NYHA class II or higher to a lower NYHA class
• Change in quality of life as assessed by the Kansas City Cardiomyopathy [ Time Frame: up to 1 year ]
  Change in quality of life from baseline as assessed by the Kansas City Cardiomyopathy questionnaire (KCCQ) (at 30 days, 3 months, 6 months and 1 year post-implantation) overall summary scores range from 0 to 100 Expected outcome: from a higher score to a smaller score
• Change in exercise capacity measured as the 6-minute walk distance (6-MWD) [ Time Frame: up to 1 year ]
  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)
• Change in number of syncope events [ Time Frame: up to 1 year ]
  Change in number of syncope events from baseline (at 30 days, 3 months, 6 months and 1 year post-implantation)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: 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.

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
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is a prospective, single arm, multicenter pivotal study in an expanding cohort of symptomatic patients with severe aortic stenosis (following the initial FIH feasibility study).

Masking: None (Open Label)
Primary Purpose: Other

• Condition: Symptomatic Aortic Stenosis

Intervention

Device: Vienna Aortic Valve SE System

Vienna Aortic Valve SE system for TAVI.

Study Arms

Vienna Aortic Valve

transcatheter aortic valve implantation (TAVI)

Intervention: Device: Vienna Aortic Valve SE System

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 27, 2023): 150
• Original Estimated Enrollment (submitted: April 22, 2021): 100
• Estimated Study Completion Date: October 2030
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Katharina Kiss, Dr; +4369913289414; kkiss@productsandfeatures.com

Contact: Monica Tocchi, MD, PhD; 9176841700; m.tocchi@meditrial.net

• Listed Location Countries: Argentina, Brazil, Chile, Lithuania, Portugal, Spain

Administrative Information

• NCT Number: NCT04861805
• Other Study ID Numbers: CTP-VIE-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: P+F Products + Features GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: P+F Products + Features GmbH
• Original Study Sponsor: Same as current
• 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

• PRS Account: P+F Products + Features GmbH
• Verification Date: October 2023