Investigation of the ALLEGRA THV System With a New Delivery System in Patients With Aortic Stenosis or Failed Surgical Bioprosthesis (EMPIRE)

Investigation of the Safety and Performance of the NVT ALLEGRA THV System With a New Delivery System in Patients With Severe Calcified Aortic Stenosis or Failed Surgical Aortic Bioprosthesis

The EMPIRE study confirms the technical performance of the new IMPERIA Delivery System and evaluates the safety and efficacy of the entire ALLEGRA THV System.

The primary endpoint is device success rate at 7 days (discharge from index procedure or 7 days post implant, whichever comes first), as defined by VARC 2.

Based on the outcomes of a study with a similar device and considering a drop-out rate of 5%, 107 patients need to be enrolled in the study.

Study Overview

• Status: Active, not recruiting
• Conditions: Transcatheter Aortic Valve Implantation
• Intervention / Treatment: Device: (ALLEGRA Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Bad Rothenfelde, Niedersachsen, Germany, 49214
      • Schüchtermann Klinik
• Spain
  • Vigo, Spain, 36213
    • Hospital Álvaro Cunqueiro

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:

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 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. Pregnancy or intend to become pregnant during study participation

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

23. Unicuspid or bicuspid aortic valve
24. Non-calcified aortic stenosis
25. Predominant aortic regurgitation > grade 3

26. Distance between native aortic valve basal plane and the orifice of the lowest coronary artery <8 mm

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

27. Low position of the coronary ostia, especially in combination with shallow sinuses (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: treatment; TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis	Device: (ALLEGRA Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis; Implantation of the ALLEGRA Transcatheter Heart Valve in failing surgical bioprosthesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device success at 7 days	Absence of procedural mortality AND; Correct positioning of a single device in the proper anatomical location (site-reported) AND; Intended performance of the prosthetic heart valve (as determined by an independent Echo Core Lab at discharge from index procedure or 7 days post implant, whichever comes first)Indexed Effective Orifice Area (iEOA) > 0.85 cm2/m2 for BMI < 30kg/m2 and iEOA > 0.70 cm2/m2 for BMI ≥ 30kg/m2Mean aortic valve gradient <20 mmHg or peak velocity <3 m/sNo moderate or severe prosthetic valve regurgitation	7 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		up to 12 months
Cardiovascular mortality		up to 12 months
All stroke		up to 12 months
TIA		up to 12 months
Procedural success	Successful vascular access, delivery and deployment of the ALLEGRA THV including re- positioning if required and successful retrieval of the IMPERIA Delivery System (site- reported); Correct position of the ALLEGRA THV (site-reported); Only one ALLEGRA THV implanted in proper anatomical position (site-reported)	assessed immediately after the procedure
Effective orifice area (EOA) as assessed by transthoracic echocardiogram (TTE)		up to 12 months
Transvalvular mean and peak pressure gradient as assessed by transthoracic echocardiogram (TTE)		up to 12 months
Trans- and paravalvular regurgitation as assessed by transthoracic echocardiogram (TTE)		up to 12 months
NYHA classification		30 days, 6 months, and 12 months
Early safety	All-cause mortality; All stroke (disabling and non-disabling); Life-threatening bleeding; Acute kidney injury-Stage 2 or 3 (including renal replacement therapy); Coronary artery obstruction requiring intervention; Major vascular complication; Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR)	up to 30 days
Time-related valve safety	Structural valve deterioration; Valve-related dysfunction (mean aortic valve gradient20 mmHg, EOA ≤0.9-1.1 cm2c and/or DVI <0.35 m/s, AND/OR moderate or severe prosthetic valve regurgitation); Requiring repeat procedure (TAVI or SAVR); Prosthetic valve endocarditis; Prosthetic valve thrombosis; Thrombo-embolic events (e.g. stroke); VARC bleeding, unless clearly unrelated to valve therapy (e.g. trauma)	up to 12 months
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.	up to 12 months
New pacemaker implantation		up to 12 months
Delivery system related AEs		discharge from index procedure or 7 days post implant, whichever comes first

Collaborators and Investigators

• Sponsor: NVT GmbH

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Actual): December 20, 2023
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Aortic valve stenosis; TAVI; ALLEGRA; IMPERIA
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Fexofenadine
• Other Study ID Numbers: NVT05EMP

Drug and device information, study documents

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