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

Not Applicable
Recruiting
Conditions
Symptomatic Aortic Stenosis
Interventions
Device: Vienna Aortic Valve SE System
Registration Number
NCT04861805
Lead Sponsor
P+F Products + Features GmbH
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The clinical trial is completed after all 150 patients (including 10 patients from FIH study), that are not prematurely withdrawn, have completed their 5-year follow-up visit involving all specified assessments.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
Inclusion Criteria

Not provided

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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Vienna Aortic ValveVienna Aortic Valve SE Systemtranscatheter aortic valve implantation (TAVI)
Primary Outcome Measures
NameTimeMethod
All Cause Mortality (30 days)up to 30 days

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

Secondary Outcome Measures
NameTimeMethod
Life-threatening bleedingUp to 1 year

Life-threatening bleeding (at 30 days, 3 months, 6 months and 1 year post-implantation).

RehospitalizationUp 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)

New York Heart Association (NYHA) classificationUp 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)

All-cause, cardiovascular and non-cardiovascular mortalityup 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 death72 hours

Incidence of peri-procedural death (to capture intra-procedural events that result in immediate or consequent death ≤72 h post-procedure)

Cerebrovascular eventUp 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.

Clinical Efficacy1 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 efficacyUp 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)

Incidence of TAVI-related complicationsperiprocedural 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)

Conduction disturbances requiring permanent pacemaker implantationUp 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)

Change in exercise capacity measured as the 6-minute walk distance (6-MWD)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)

Device Success72 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 successup 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

Change in quality of life as assessed by the Kansas City Cardiomyopathy1 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

Trial Locations

Locations (23)

Instituto Estadual De Cardiologia Aloysio De Castro

🇧🇷

Rio de Janeiro, Brazil

Instituto Dante Pazzanese De Cardiologia

🇧🇷

São Paulo, Brazil

Hospital Clinic De Barcelona

🇪🇸

Barcelona, Spain

Hospital Dr Sotero Del Rio De Santiago

🇨🇱

Santiago, Chile

Hospital Santa Marta

🇵🇹

Lisboa, Portugal

Hospital Privado Sur (FUMEBA)

🇦🇷

Bahia Blanca, Argentina

Hospital César Milstein

🇦🇷

Buenos Aires, Argentina

Hospital Dr. Fernandez

🇦🇷

Buenos Aires, Argentina

Centro Hospitalar de Vila Nova de Gaia

🇵🇹

Vila Nova De Gaia, Portugal

Fundación Favaloro

🇦🇷

Buenos Aires, Argentina

Hospital Italiano De Buenos Aires

🇦🇷

Buenos Aires, Argentina

Hospital of Lithuanian University of Health Sciences Kauno klinikos

🇱🇹

Kaunas, Lithuania

Hospital Del Torax De Santiago

🇨🇱

Santiago, Chile

Hospital Las Higueras - Talcahuano

🇨🇱

Talcahuano, Chile

Instituto Do Coração (InCor) De São Paulo

🇧🇷

São Paulo, Brazil

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Puerta De Hierro

🇪🇸

Majadahonda, Madrid, Spain

Hospital Universitario Bellvtige

🇪🇸

Barcellona, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

Hospital Clinico San Carlos

🇪🇸

Madrid, Spain

Hospital Torrejon

🇪🇸

Madrid, Spain

Hospital Virgen De La Victoria

🇪🇸

Málaga, Spain

University Clinical Hospital of Valladolid

🇪🇸

Valladolid, Spain

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