Valvosoft First-In-Human 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-Human

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. In this study, a brai-MRI is performed before the procedure and 24-72 hours after the procedure to detect cerebrovascular events.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-Human

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Ultrasound treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects suffering from severe symptomatic aortic valve stenosis according to ESC 2017 definition, including subjects with a bicuspid valve. Patient is not eligible for TAVR/SAVR according to local Heart Team. 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. Patient is eligible for the Valvosoft procedure according to CRC. 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 calcific aortic 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<br>* Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacemen<br>* Other names: Ultrasound treatment of calcific aortic valve;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Rate of procedure related mortality | Rate of procedure related mortality at 30 days | Up to 30 days | 
| Device performance to modify valve structure as measured by echocardiography | Ability to modify the Left Ventricular Ejection Fraction (%) | Immediately after the procedure | 
| Device performance to modify valve structure as measured by echocardiography | Ability to modify the Mean Pressure Gradient (mmHg) | Immediately after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Number of patients that die during the course of the study and if so, how long aftre the procedure | Up to two years | 
| Rate of stroke | Rate of stroke | Up to two years | 
| Change of severity of heart failure | Change 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 | 
| Major Adverse Events | Rate of Major Adverse Events (MAE) and number of patients with one or more MAE during the course of the study, an MAE defined as: Disabling stroke, Myocardial infarction or any clinically significant changes in biomarkers (CK, Troponin I - T) that would indicate damage to the heart structure, or clinically significant conduction disturbances requiring pacemaker implantation or persistent arrhythmias | Up to 2 years | 
| Adverse events | Rate of all Adverse Events | Up to 2 years | 
| User Handeling | User handling (questionnaire for operator + procedure duration | Immediately after the procedure | 
| Long term maintenance of improvement of Aortic Valve area and mean Pressure Gradient | Long term maintenance of improvement of AVA and PG | At 1, 3, 6,1 2 and 24 months | 
| quality of life measured through Kansas City Cardiomyopathy Questionnaire | Improvement of quality of life by means of KCCQ | at 1, 3, 6, 12 and 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