Investigation of the NVT ALLEGRA Plus THV System in Patients With Severe Aortic Stenosis or Failed Surgical Aortic Bioprosthesis

Transcatheter Aortic Valve Implantation Clinical Trial

— EMPIRE-II  

Official title:

InvEstigation of the Safety and Performance of the NVT ALLEGRA Plus THV SysteM in Patients With Severe aortIc Stenosis or Failed suRgical Aortic bioprosthEsis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05804903
• Other study ID #: NVT06EMP2
• Status: Recruiting
• Phase: N/A
• Start date: November 24, 2023
• Est. completion date: December 31, 2029

Study information

• Verified date: February 2024
• Source: NVT GmbH
• Contact: Calvin Bahr
• Phone: +41 78 251 8084
• Email: c.bahr[@]biosensors.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The EMPIRE II study evaluates the safety and performance of the entire ALLEGRA THV System.

The primary safety endpoint is composite of all-cause mortality or stroke rates at 12 months. And the primary performance endpoint is device success at 7 days.

Based on the outcomes of a study with a similar device and considering a drop-out rate of 5%, 177 patients need to be enrolled in the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 177
• Est. completion date: December 31, 2029
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Symptomatic severe calcific stenosis of a native aortic valve with an AVA =1.0 cm2 (or AVA index =0.6 cm2/m2), AND mean aortic pressure gradient = 40mmHg OR maximal transaortic velocity =4.0m/s OR Doppler velocity index =0.25 on site-reported echocardiography OR symptomatic patients with degeneration of a surgical bioprosthetic valve (stenosis +/- insufficiency) on site-reported echocardiography

2. Local multi-disciplinary Heart Team and Central Screening Committee (CSC) agree on indication and eligibility for TAVI

3. Age =18 years

4. Patient has signed the Patient Informed Consent Form

5. Patient is willing and able to comply with requirements of the study, including all follow-up visits

Exclusion Criteria:

Patient will not be included if ANY one of the following conditions exists:

General:

1. Mean aortic annulus diameter as measured by pre-procedural CT or internal diameter of the bioprosthesis is <16.5 mm or >27 mm

2. Echocardiographic evidence of intracardiac thrombus or vegetation (site-reported)

3. Significant disease of the aorta that would preclude safe advancement of the ALLEGRA Plus THV System

4. Severe ilio-femoral vessel disease that would preclude safe placement of an 18 Fr introducer sheath or make endovascular access impossible

5. Porcelain aorta

6. Severe left ventricular dysfunction with ejection fraction (EF) <20% (site-reported)

7. Evidence of active endocarditis or other acute infections

8. Renal failure requiring continuous renal replacement therapy

9. Untreated clinically significant coronary artery disease requiring revascularization

10. Any percutaneous interventional procedure (e.g. PCI with stenting) within 14 days prior of the index procedure

11. Acute MI =30 days prior to the index procedure

12. Symptomatic carotid or vertebral artery disease requiring intervention or carotid/vertebral intervention within the preceding 45 days

13. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) =6 months or prior CVA with moderate or severe disability (e.g. modified Rankin scale score >2)

14. History of bleeding diathesis or coagulopathy; acute blood dyscrasias as defined:

thrombocytopenia (platelets <80,000/µl), acute anemia (hemoglobin <10 g/dl), leukopenia (WBC <3000/ µl)

15. Active peptic ulcer or gastrointestinal (GI) bleeding =3 months

16. Severe (greater than 3+) mitral insufficiency (site-reported)

17. Uncontrolled atrial fibrillation

18. Required emergency surgery for any reason

19. Known hypersensitivity to contrast media, which cannot be adequately pre-medicated or contraindication to anticoagulant or anti-platelet medication or to nitinol alloy or to bovine tissue

20. Life expectancy =12 months due to other medical illness

21. Currently participating in another investigational drug or device study

22. Hypertrophic obstructive cardiomyopathy

23. Pregnancy or intend to become pregnant during study participation

Specific exclusions in patients with native aortic valve disease (site-reported):

24. Unicuspid or bicuspid aortic valve

25. Non-calcified aortic stenosis

26. Identified risk of coronary occlusion due to Sinus of Valsalva anatomy and/or bulky calcified aortic valve leaflets in close proximity to coronary ostia

Specific exclusions in patients with degenerated surgical bioprosthetic aortic valves (valve-in-valve) (site-reported):

27. High risk of coronary occlusion

28. Partially detached leaflets that may obstruct a coronary ostium

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Transcatheter Aortic Valve Implantation

Intervention

Device:
• (ALLEGRA Plus Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis
Implantation of the ALLEGRA Plus Transcatheter Heart Valve in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis

Locations

Country	Name	City	State
Finland	Oulu University Hospital	Oulu
Germany	Deutsches Herzzentrum Berlin	Berlin
Poland	Klinika Kardiochirurgii	Gdansk
Poland	III Katedra Kardiologii	Katowice
Spain	Reina Sofia Hospital	Córdoba
Spain	Hospital La Paz	Madrid
Switzerland	Herzzentrum - Luzerner Kantonsspital	Luzern

Sponsors (1)

Lead Sponsor	Collaborator
NVT GmbH

Countries where clinical trial is conducted

Finland,  Germany,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of all-cause mortality or stroke rates		12 months
Secondary	All-cause mortality rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Cardiovascular mortality rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Any stroke rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Transient ischemic attack rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Device success rate	Device success at 30 days (In-hospital may be used if 30-day data are not available): Technical success; Freedom from mortality; Freedom from surgery or intervention related to the device (excluding permanent pacemaker) or to a major vascular or access-related or cardiac structural complication; Intended performance of the valve‡(mean gradient<20 mmHg, peakvelocity<3 m/s, Doppler velocity index =0.25, and less than moderate aortic regurgitation	30 days
Secondary	Effective orifice area (EOA) as assessed by transthoracic echocardiogram (TTE)	as determined by an independent Echo Core Lab	7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Transvalvular mean and peak pressure gradient as assessed by transthoracic echocardiogram (TTE)	as determined by an independent Echo Core Lab	7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Transvalvular mean and peak pressure gradient as assessed by transthoracic	as determined by an independent Echo Core Lab	7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	NYHA classification		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Life-threatening/major bleeding (BARC 3b or more)		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Major vascular complications according to VARC-3		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	Early safety profile according to VARC-3		30 days
Secondary	Quality of life as assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)	Assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Patients are asked questions about physical limitation, symptom frequency, quality of life, and social limitation. Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health.	7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Secondary	New pacemaker implantation rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years