BIOVALVE - I / II Clincial Investigation

Aortic Valve Stenosis Clinical Trial

— BIOVALVE  

Official title:

Safety and Clinical Performance of the Self-expanding Transcatheter BIOVALVE Prosthesis in Subjects With Severe Symptomatic Aortic Stenosis Suitable for Transfemoral Transcatheter Aortic Valve Implantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249000
• Other study ID #: C1205
• Status: Completed
• Phase: N/A
• Start date: September 2014
• Est. completion date: May 2023

Study information

• Verified date: January 2019
• Source: Biotronik AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

First-in-Human clinical investigation to evaluate the safety and clinical performance of the BIOVALVE prosthesis in subjects presenting with severe symptomatic aortic valve stenosis, which are as judged by the heart team, indicated for transfemoral transcatheter aortic valve implantation

Description:

In a non-randomized, prospective, multi-center clinical investigation, approximately 86 eligible subjects will be enrolled.

Phase 1: BIOVALVE-I feasibility clinical investigation: Approximately 13 eligible subjects will be enrolled.

Phase 2: BIOVALVE-II pilot clinical investigation: Approximately 73 eligible subjects will be enrolled.

BIOVALVE-I/II subjects follow the same clinical investigation plan (CIP) in all aspects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: May 2023
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. The subject is =65 years

2. The subject has provided written informed consent

3. Subject is willing to participate in the clinical investigation and to comply with all of the study procedures and follow-up visits

4. NHYA class =II

5. High surgical risk: Logistic EuroSCORE-I =20% (or equivalence of EuroSCORE-II) or STS score =10% or co-morbidity judged by the heart team (consisting of at least one interventional cardiologist and one cardiac surgeon) to pose an absolute or relative contraindication for conventional aortic valve replacement according to VARC-2

6. Severe symptomatic calcific aortic valve stenosis characterized by mean aortic gradient >40 mm Hg or peak jet velocity >4.0 m/s or effective orifice area (EOA) of <1.0 cm2 (<0.6 cm2/m2 body surface area)

7. Annulus diameter as determined by multi-slice computed tomography (MSCT) from 23-26 mm

Exclusion Criteria:

1. Trans-esophageal echocardiogram (TEE) is contraindicated

2. Congenital bicuspid or unicuspid valve

3. Left ventricular outflow tract (LVOT) obstruction such as hypertrophic obstructive cardio myopathy (HOCM) or subject presenting with systolic anterior motion (SAM). Evidence of intra cardiac mass, thrombus or vegetation

4. Transfemoral access vessel characteristics that would preclude safe placement of a 18 French sheath

5. Vessel and/or anatomical characteristics that would preclude safe delivery of the BIOVALVE prosthesis to the ascending aorta and/or placement of the prosthesis

6. Anatomical restrictions such as shallow sinuses with heavily calcified leaflets, low height of coronary ostia, extreme tortuosity of the aortic arch, thoracic (TAA) or abdominal (AAA) aortic aneurysm, presence of endovascular stent graft

7. Severe mitral regurgitation grade >3

8. Severe mitral stenosis

9. Prosthetic mitral valve

10. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <20%

11. Hemodynamic instability

12. Percutaneous coronary intervention (PCI) within 30 days prior to index procedure and / or planned PCI during index procedure

13. Renal insufficiency (creatinine >2.5 mg/dl) or subject under dialysis and/or renal replacement therapy

14. Any cerebrovascular event or transient ischemic attack (TIA) within 180 days prior to TAVI procedure

15. Evidence of acute myocardial infarction (defined as =2 fold CK level or in absence of CK a =3 fold CKMB level above the upper range limit within =30 days prior to TAVI procedure)

16. Blood dyscrasia defined as: leucopenia (WBC <1000 mm³), thrombocytopenia (platelet count <50'000 cells/mm³), history of bleeding diathesis requiring blood transfusion

17. Ongoing sepsis or suspected active endocarditis

18. Active peptic ulcer or gastrointestinal bleeding within last 3 months that would preclude anticoagulation

19. Subject refuses blood transfusion

20. Known hypersensitivity to, or contraindication to nitinol, anticoagulation/antiplatelet regimes, any other medications required for the procedure or post-procedure as determined by the heart team, or sensitivity to contrast media which cannot be adequately pre-medicated

21. Need for emergency TAVI intervention, or other medical, social, or psychological conditions that in the opinion of the heart team precludes the subjects from appropriate consent or adherence to protocol required follow-up exams

22. Expectation that subject will not improve despite treatment of aortic stenosis

23. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbidities

24. Severe pulmonary hypertension (> 60 mm Hg assessed by continuous wave Doppler, TTE) or clinical signs of acute severe right ventricular dysfunction

25. Currently participating in another investigational drug or device study where primary endpoint has not been reached yet

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Heart Valve Diseases

Intervention

Device:
• BIOVALVE prosthesis
Transcatheter Aortic Valve Replacement (TAVR)

Locations

Country	Name	City	State
Belgium	ZNA Middelheim	Antwerpen
Germany	Segeberger Kliniken	Bad Segeberg	Schleswig-Holstein
Germany	German Heart Center	Berlin
Germany	Vivantes Klinikum	Berlin
Germany	Universitätsklinikum Halle (Saale)	Halle
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	University Heart Center	Hamburg
Germany	University Heart Center	Köln
Germany	Herzzentrum Leipzig	Leipzig
Germany	Städtische Kliniken Neuss - Lukaskrankenhaus	Neuss	Nordrhein-Westfalen
Germany	Universitätsmedizin Rostock	Rostock
Netherlands	Catharina-Ziekenhuis	Eindhoven
Switzerland	Universitätsspital Zürich	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
Biotronik AG	Medstar Health Research Institute

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands,  Switzerland, 

References & Publications (3)

Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB; Valve Academic Research Consortium-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. EuroIntervention. 2012 Nov 22;8(7):782-95. doi: 10.4244/EIJV8I7A121. — View Citation

Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip DE, Kappetein AP, Krucoff MW, Mack M, Mehran R, Miller C, Morel MA, Petersen J, Popma JJ, Takkenberg JJ, Vahanian A, van Es GA, Vranckx P, Webb JG, Windecker S, Serruys PW. Standardized endpoint definitions for Transcatheter Aortic Valve Implantation clinical trials: a consensus report from the Valve Academic Research Consortium. J Am Coll Cardiol. 2011 Jan 18;57(3):253-69. doi: 10.1016/j.jacc.2010.12.005. Epub 2011 Jan 7. — View Citation

Treede H, Lubos E, Conradi L, Deuschl F, Asch FM, Weissman NJ, Schofer N, Schirmer J, Koschyk D, Blankenberg S, Reichenspurner H, Schaefer U. Thirty-day VARC-2 and performance data of a new self-expanding transcatheter aortic heart valve. EuroIntervention — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early safety at 30 days (Acc. to VARC-2)	A composite of all-cause mortality, all stroke (disabling/non-disabling), life-threatening bleeding, acute kidney injury stage 2 or 3 (including renal replacement therapy), coronary artery obstruction requiring intervention, major vascular complication and valve-related dysfunction requiring repeat procedure (balloon aortic valvuloplasty (BAV), transcatheter aortic valve implantation (TAVI), or surgical aortic valve replacement (SAVR)).	30 days
Secondary	Combined safety endpoint at 30 days (Acc. to VARC-1)	A composite of all-cause mortality, major stroke, life-threatening (or disabling) bleeding, acute kidney injury stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, major vascular complication and repeat procedure for valve-related dysfunction (surgical or interventional therapy)	30 days
Secondary	Clinical efficacy after 30 days (Acc. to VARC-2):	A composite of all-cause mortality, all stroke (disabling and non-disabling), requiring hospitalizations for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV, valve-related dysfunction (mean aortic valve gradient =20 mm Hg, effective orifice area (EOA) =0.9-1.1 cm2 * and/or Doppler velocity index (DVI) <0.35 m/s, and/or moderate or severe prosthetic valve regurgitation **).; * depending on body surface area; ** refers to VARC-2 definitions	30 days
Secondary	Echocardiograhic (ECHO) parameters	Effective orifice area (EOA) and effective orifice area index (EOAI) Mean prosthetic valve gradient Prosthetic valve regurgitation (Acc. to VARC-1 and VARC-2)	Discharge, 30 days, 6 months, 12 months and annually through 5 years