VALVOSOFT® Pivotal Study

Study Overview
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Brief Summary
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The objective of the study is to evaluate the safety and performance of a new non-invasive ultrasound therapy (NIUT) with Valvosoft in the treatment of Calified Aortic Stenosis

Official Title
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Prospective, Single-arm Pivotal Study for the Treatment of Subjects With Severe Symptomatic Calcific Aortic Valve Stenosis Using Valvosoft® Non-Invasive Ultrasound Therapy (NIUT)

Conditions
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Aortic Valve Calcification, Aortic Valve Stenosis

Intervention / Treatment
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* Device: VALVOSFT intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject suffering from severe symptomatic calcific aortic valve stenosis as defined by ESC/EACTS guidelines for the management of valvular heart disease 2021; and Subject is not recommended by the local HEART Team for immediate TAVR/SAVR; or Subject who refuses TAVR/SAVR, documented by local HEART Team (not allowed in France); and Age ≥18 years; and Subject willing to provide a written informed consent prior to participating in the study; and Subject who can comply with the study follow-up or other study requirements; and Subject is eligible for the Valvosoft procedure according to Clinical Review Committee (CRC). Exclusion Criteria: Subject with severe aortic regurgitation; or Subject with unstable arrhythmia not controlled by medical treatment; or Subjects with implanted mechanical valve in any position or bio-prosthetic valve in aortic position; or Subject has a chest deformity not allowing optimal placement of Valvosoft Applicator and visualization of the aortic valve; or Cardiogenic shock or other hemodynamic instability; or Left Ventricular Ejection Fraction ≤30%; or Subject with mean AVAI <0,24 cm²/m2; or History of heart transplant; or Subject requiring other cardiac surgery procedures (bypass graft surgery, mitral valve procedure, tricuspid valve procedure) within one month after Valvosoft procedure; or Cardiac imaging evidence of vegetation; or Acute myocardial infarction (MI) within one month prior to enrolment; or Valve depth not suitable for NIUT (depth >125mm with respect to the Valvosoft imaging probe); or Stroke or transient ischemic attack (TIA) ≤1 month prior to enrollment; or Subject who is pregnant, or plan to become pregnant during the 12-months study follow-up period; or Subject who is participating in another research study for which the primary endpoint has not been reached; or Balloon aortic valvuloplasty (BAV) ≤3 months prior to enrollment; or Current endocarditis; or Leukopenia (WBC <4000 cell/μL), anemia (Hgb <8 g/dL), thrombocytopenia (platelet count <15.000 cell/μL), or history of coagulopathy or hypercoagulable state; or Life expectancy < 6 months due to non-cardiac co-morbid conditions; or Other medical, psychological, or social condition which, in the opinion of the investigator, precludes the subject from study participation; or Subjects who do not have Social Security and who are under legal restraint; or Subjects who cannot read or write or are mentally not or partially capable of giving informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Valvosoft<br>Treatment with VALVOSOFT device | Device: VALVOSFT intervention<br>* Treatment of the calcific aorta valve by non-invasive ultrasound therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoint | Rate of MACE < 25% | at 30 days post-procedure | 
| Performance endpoint | Improvement in clinical status assessed by means of a decrease in NHYA functional class | at 30 days post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of MACE | Rate of major adverse and cerebral events | peri-procedureal, and at 3-, 6- and 12 months post procedure | 
| All cause mortality | All cause mortality | 30 days, 3-, 6- and 12-months post procedure | 
| Rate of Stroke | Rate of stroke (disabling and non-disabling; ischemic and hemorrhagic) | 30 days, 3-, 6- and 12-months post procedure; | 
| AVA change at 30 days | Change of 10% in of aortic stenosis by means of aortic valve area (AVA) (assessed by the independent echocardiographic Central Core Laboratory) 30 days post procedure compared to baseline | 30 days post procedure | 
| AVA change in severity | Change in severity of aortic stenosis by means of aortic valve area (AVA) (assessed by the independent echocardiographic Central Core Laboratory) at 6- and 12 months compared to baseline | at 6- and 12 months | 
| NYHA improvement | Change in clinical status assessed by means of a decrease in NYHA functional class | 3-, 6- and 12-months | 
| Change in 6 minutes walk test | Change in 6-minutes' walk test | 30 days, 6- and 12 months | 
| Improvement of quality of life by Kansas City Cardiomyopathy Questionnaire (KCCQ) | Improvement of quality of life by means of KCCQ. KCCQ is a 23-item, self-administered questionnaire | 30 days, 6-, and 12-months | 
| Improvement of quality of life by EQ-5D | Improvement of quality of life by means of EQ-5D. The EQ-5D descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. | 30 days, 6-, and 12-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Stenosis, Aortic Valve Calcification, Aortic Valve, Stenosis, Ultrasound, non invasive