BIOVALVE - I / II Clincial Investigation

Not Applicable

Completed

• Conditions: Heart Valve Diseases; Aortic Valve Stenosis
• Interventions: Device: BIOVALVE prosthesis

• Registration Number: NCT02249000
• Lead Sponsor: Biotronik AG

Brief 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

Detailed 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.

Study Timeline

• Study Start: 2014-09
• Study First Submitted: 2014-09-23
• Study First Submitted QC: 2014-09-24
• Study First Posted: 2014-09-25
• Primary Completion: 2018-03
• Status Verified: 2019-01
• Study Completion: 2023-05
• Last Update Submitted: 2024-06-10
• Last Update Posted: 2024-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIOVALVE prosthesis	BIOVALVE prosthesis	Transcatheter Aortic Valve Replacement (TAVR)

Primary Outcome Measures

Name	Time	Method
Early safety at 30 days (Acc. to VARC-2)	30 days	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)).

Secondary Outcome Measures

Name	Time	Method
Echocardiograhic (ECHO) parameters	Discharge, 30 days, 6 months, 12 months and annually through 5 years	Effective orifice area (EOA) and effective orifice area index (EOAI) Mean prosthetic valve gradient Prosthetic valve regurgitation (Acc. to VARC-1 and VARC-2)
Combined safety endpoint at 30 days (Acc. to VARC-1)	30 days	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)
Clinical efficacy after 30 days (Acc. to VARC-2):	30 days	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

Trial Locations

Locations (12)

Universitätsspital Zürich; 🇨🇭 Zurich, Switzerland

ZNA Middelheim; 🇧🇪 Antwerpen, Belgium

Städtische Kliniken Neuss - Lukaskrankenhaus; 🇩🇪 Neuss, Nordrhein-Westfalen, Germany

Segeberger Kliniken; 🇩🇪 Bad Segeberg, Schleswig-Holstein, Germany

Vivantes Klinikum; 🇩🇪 Berlin, Germany

German Heart Center; 🇩🇪 Berlin, Germany

Universitätsklinikum Halle (Saale); 🇩🇪 Halle, Germany

Asklepios Klinik St. Georg; 🇩🇪 Hamburg, Germany

University Heart Center; 🇩🇪 Köln, Germany

Herzzentrum Leipzig; 🇩🇪 Leipzig, Germany

Universitätsmedizin Rostock; 🇩🇪 Rostock, Germany

Catharina-Ziekenhuis; 🇳🇱 Eindhoven, Netherlands