Valvosoft First-In-Man Study in Severe Symptomatic Aortic Stenosis

Study Overview
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Brief Summary
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This is a prospective, controlled, single-arm clinical investigation for the treatment of subjects with severe symptomatic aortic valve stenosis using Valvosoft® Pulsed Cavitational Ultrasound Therapy (PCUT) - First-In-man

Detailed Description
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CARDIAWAVE has developed a new non-invasive, real-time image-guided, therapeutic approach to treat patients suffering from Calcified Aortic Stenosis. CARDIAWAVE's Valvosoft device is a new ultrasound therapy based on a disruptive technology involving delivering an extremely precise and focused ultrasound beam to perform a reparative effect on the aortic valve leaflets, softening the valve's tissues, restoring leaflet mobility, and therefore improving the overall clinical status related to the aortic valve stenosis. This is a FIM study

Official Title
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Prospective, Controlled, Single-arm Clinical Investigation for the Treatment of Subjects With Severe Symptomatic Aortic Valve Stenosis Using Valvosoft® Pulsed Cavitational Ultrasound Therapy (PCUT) - First-In-Man

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Ultrasound treatment of Calcified aortic valve


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects suffering from severe symptomatic aortic valve stenosis (including subjects with a bicuspid valve). Patient is not eligible for TAVR/SAVR . Age ≥18 years. Subjects who are willing to provide a written informed consent prior to participating in the study. Subjects who can comply with the study follow up or other study requirements. Subject eligible according to Clinical Review Committee - Exclusion Criteria: Subjects with any electrical device implanted. Subjects with unstable arrhythmia not controlled by medical treatment. Subjects with implanted mechanical valve in any position or bio prosthetic valve in aortic position. Subjects with complex congenital heart disease. Chest deformity. Cardiogenic shock. History of heart transplant. Subjects requiring other cardiac surgery procedures (bypass graft surgery, mitral valve procedure, tricuspid valve procedure) within one month after treatment. Thrombus in heart. Acute myocardial infarction (MI), stroke or transient ischemic attack (TIA) within one month prior to enrolment*. Subjects who are pregnant or nursing. Subjects who are participating in another research study for which the primary endpoint has not been reached. -

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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Ultrasound treatment of calcified aortic valve stenosis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound treatment<br>Ultrasound treatment of patients with symptomatic aortic valve stenosis who are not eligible for valve replacement | Device: Ultrasound treatment of Calcified aortic valve<br>* Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Rate of procedure related mortality at 30 days | Rate of procedure related mortality at 30 days | 30 days post-procedure | 
| Device performance to modify valve structure as measured by echocardiography | Ability to modify the Aortic Valve Area (mm2) | Immediately post-procedure | 
| Device performance to modify valve structure as measured by echocardiography | Ability to modify the Pressure Gradient (mmHg) | Immediately post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality and major adverse events (MAE's) | Rate of all-cause mortality and MAE's peri and postprocedure and at 1, 3, 6, 12 and 24 months post operatively. | Up to 24 months | 
| Non-disabling stroke | Rate of stroke at 1,3,6, 12 and 24 months | Up to 24 months | 
| Improvement of clinical status | Improvement of New York Heart Association class (I-IV - stage of severity of heart failure - I=no symptoms, IV= symptoms at rest) at 1,3,6,12, and 24 months. | Up to 24 months | 
| Number of all Adverse Events (AEs) | Rate of AE's reported at at 1, 3, 6, 12 and 24 months | Up to 24 months | 
| User handeling of Valvosoft | User handling (questionnaire for operator + procedure duration) immediately post-procedure | Immediately post-procedure | 
| Improvement of quality of life | Improvement of quality of life by means of Kansas City Cardiomyopathy Questionnaire at 1, 3, 6, 12 and 24 months | upto 24 months | 
| Long term maintenance of improvement of AVA and PG | Long term maintenance of improvement of AVA and PG at 3, 6, 12 and 24 months | upto 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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symptomatic, aortic valve, stenosis, ultrasound, non-invasive