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

Overview

This is a prospective, non-randomized, single arm, multicenter, multinational two-stage FIH feasibility followed by pivotal study in symptomatic patients with severe aortic stenosis.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 2023

Detailed Description

The study consists of 7 visits spread out across two phases over 1 year. The clinical investigation will end at 30 days post-implantation. The subsequent 3-month, 6-month and 1-year follow-up (FU) visits will thus be considered post-market clinical follow-up (PMCF). The FIH study will start by evaluating the safety and feasibility of the device and study design of the Vienna Aortic Valve SE System in 10 patients with SSAS. The FIH patients must meet all study eligibility criteria. Safety and feasibility assessments for patients in the FIH period will include implantation success, hemodynamic performance and monitoring of adverse events (AEs). Early FIH data (i.e. data from the first 10 patients to have completed visit 3 at hospital discharge) will be provided to the Data and Safety Monitoring Board (DSMB) for review during which study enrollment will be paused. After reviewing the safety results from the FIH study, the DSMB will make a recommendation on whether the study may continue as planned. FIH patients will continue to be followed up for 1 year as per protocol. Data from the 10 FIH patients and the subsequent 75 patients will be analyzed together for the pivotal study endpoints. Upon a decision from the DSMB to proceed with the study, enrolment of patients will resume. The clinical investigation phase comprises 4 visits (V1 to V4). After implantation of the IMD at visit 2, early performance and safety assessment of the device will be performed at 30 days (V4). The post-market surveillance phase comprises 3 visits (V5-V7), extending from 3 months to 1 year post-implantation, to evaluate the long-term safety and performance profile of the device.

Interventions

  • Device: Vienna Aortic Valve SE System
    • The Vienna Aortic Valve SE System (valve sizes: 23, 26, 29 and 31 mm) is a biological valve system intended to be implanted percutaneously in the aortic valve via the transfemoral route. The device is made of bovine pericardium leaflets and a pericardium fabric skirt sutured on a radiopaque nitinol self-expanding stent system, designed for supra-annular positioning to optimize hemodynamic performance. The Vienna Aortic Valve SE System is repositionable and retrievable allowing a more optimal prosthesis positioning to minimize residual paravalvular regurgitation, atrioventricular conduction block/disturbances, and mitral or coronary compromise. The valve comes already pre-mounted on the delivery system, ready to be used, eliminating the need for assembly and crimping of the device prior to valve implantation.

Arms, Groups and Cohorts

  • Other: Vienna Aortic Valve
    • transcatheter aortic valve implantation (TAVI)

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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)

Participating in This Clinical Trial

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 7. The local Heart Team, including at least 1 cardiothoracic surgeon and 1 interventional cardiologist, deems the patient to be eligible for transfemoral TAVI. 8. Perimeter-based aortic annulus diameter between ≥ 18 and ≤ 29 mm measured by computed tomography (CT) performed within 90 days prior to planned implantation 9. 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 10. The distance from coronary ostia to aortic anulus > 12 mm 11. Patient (or legal representative) understands the study requirements and the treatment procedures and provides written informed consent. 12. 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. Untreated clinically significant coronary artery disease requiring revascularization at the screening visit. 7. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography within 90 days prior. 8. Patient with cardiogenic shock manifested by low cardiac output and hemodynamic instability and vasopressor dependence, or mechanical hemodynamic support 9. 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. 10. 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. 11. 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] 12. Patient with active bacterial endocarditis within 6 months of planned IMD 13. Patient has (echocardiographic/ CT and/or MRI) evidence of intra-cardiac mass, thrombus or vegetation. 14. Patient has a pre-existing prosthetic heart valve in any position (Note: mitral ring is not an exclusion). 15. Patient has severe mitral regurgitation, severe aortic regurgitation or severe tricuspid regurgitation, moderate or severe mitral stenosis. 16. Patient has a need for emergency surgery for any reason at time of screening and valve implantation. General: 17. Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. patient with contraindication to oral antiplatelet therapy) 18. 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 19. Patient with significant pulmonary disease (FEV1 < 30%) or currently on home oxygen 20. Severe pulmonary hypertension (e.g., PA systolic pressure / systemic pressure >1 or mean pulmonary pressure > 55 mmHg assessed by echocardiography) 21. Patients with evidence of an active systemic infection or sepsis 22. 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. 23. Patient has a hemoglobin < 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 24. Patient has peptic ulcer disease or history of gastrointestinal bleeding within the past 3 months. 25. Patient refuses blood transfusions. 26. 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. 27. Patient is pregnant or breast feeding. 28. 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). 29. 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 30. Patient is currently participating in another investigational drug or device study that has not reached its primary endpoint (excluding observational studies).

Gender Eligibility: All

Minimum Age: 65 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • P+F Products + Features GmbH
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Rimantas Benetis, Prof Dr, Principal Investigator, Lithuanian University of Health Sciences
    • Jose A Baz, Dr, Principal Investigator, Hospital Universitario Álvaro Cunqueiro
  • Overall Contact(s)
    • Katharina Kiss, Dr, +4369913289414, kkiss@productsandfeatures.com

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