Investigation of the NVT ALLEGRA Plus THV System in Patients With Severe Aortic Stenosis or Failed Surgical Aortic Bioprosthesis (EMPIRE-II)

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

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.

Study Overview

• Status: Suspended
• Conditions: Transcatheter Aortic Valve Implantation
• Intervention / Treatment: Device: (ALLEGRA Plus Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Oulu, Finland, 90220
    • Oulu University Hospital
• Germany
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
• Poland
  • Gdansk, Poland, 80-214
    • Klinika Kardiochirurgii
  • Katowice, Poland, 40-635
    • III Katedra Kardiologii
• Spain
  • Córdoba, Spain, 14004
    • Reina Sofía Hospital
  • Madrid, Spain, 28046
    • Hospital La Paz
• Switzerland
  • Lucerne, Switzerland, 6000
    • Herzzentrum - Luzerner Kantonsspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of all-cause mortality or stroke rates	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Early safety profile according to VARC-3		30 days
All-cause mortality rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Cardiovascular mortality rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Any stroke rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Transient ischemic attack rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
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
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
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
NYHA classification		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Life-threatening/major bleeding (BARC 3b or more)		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
Major vascular complications according to VARC-3		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years
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
New pacemaker implantation rate		7 days, 30 days, 6 months, 12 months, 2 years, 3 years , 4 years, 5 years

Collaborators and Investigators

• Sponsor: NVT GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2023
• Primary Completion (Actual): August 31, 2025
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Aortic valve stenosis; TAVI; IMPERIA; ALLEGRA Plus; NVT
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Surgical Procedures, Operative; Cardiovascular Surgical Procedures; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Prosthesis Implantation; Heart Valve Prosthesis Implantation; Transcatheter Aortic Valve Replacement
• Other Study ID Numbers: NVT06EMP2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No