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

Symptomatic Aortic Stenosis Clinical Trial

— VIVA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04861805
• Other study ID #: CTP-VIE-001
• Status: Recruiting
• Phase: N/A
• Start date: July 3, 2023
• Est. completion date: October 2030

Study information

• Verified date: October 2023
• Source: P+F Products + Features GmbH
• Contact: Katharina Kiss, Dr
• Phone: +4369913289414
• Email: kkiss[@]productsandfeatures.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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clinical trial is completed after all 150 patients (including 10 patients from FIH study), that are not prematurely withdrawn, have completed their 5-year follow-up visit involving all specified assessments.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

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 2030
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Symptomatic Aortic Stenosis

Intervention

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

Locations

Country	Name	City	State
Argentina	Hospital Privado Sur (FUMEBA)	Bahia Blanca
Argentina	Fundación Favaloro	Buenos Aires
Argentina	Hospital César Milstein	Buenos Aires
Argentina	Hospital Dr. Fernandez	Buenos Aires
Argentina	Hospital Italiano De Buenos Aires	Buenos Aires
Brazil	Instituto Estadual De Cardiologia Aloysio De Castro	Rio de Janeiro
Brazil	Instituto Dante Pazzanese De Cardiologia	São Paulo
Brazil	Instituto Do Coração (InCor) De São Paulo	São Paulo
Chile	Hospital Del Torax De Santiago	Santiago
Chile	Hospital Dr Sotero Del Rio De Santiago	Santiago
Chile	Hospital Las Higueras - Talcahuano	Talcahuano
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas
Portugal	Hospital Santa Marta	Lisboa
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova De Gaia
Spain	Hospital Universitario Bellvtige	Barcellona
Spain	Hospital Clinic De Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Torrejon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Puerta De Hierro	Majadahonda	Madrid
Spain	Hospital Virgen De La Victoria	Málaga
Spain	University Clinical Hospital of Valladolid	Valladolid

Sponsors (2)

Lead Sponsor	Collaborator
P+F Products + Features GmbH	Meditrial USA Inc.

Countries where clinical trial is conducted

Argentina,  Brazil,  Chile,  Lithuania,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cause Mortality (30 days)	All-cause mortality at 30 days from the index procedure.	up to 30 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Life-threatening bleeding	Life-threatening bleeding (at 30 days, 3 months, 6 months and 1 year post-implantation).	Up to 1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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-moderate; Patient prosthesis mismatch (PPM) insignificant*; Mean gradient < 20 mmHg	up to 30 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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