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

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

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

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Ultrasound treatment

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Serbia
  • Belgrad, Serbia, 11000
    • Clinical Centre of Serbia

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Ultrasound treatment; Ultrasound treatment of patients with symptomatic aortic valve stenosis who are not eligible for valve replacement	Device: Ultrasound treatment; Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacemen; Other Names: Ultrasound treatment of calcific aortic valve

What is the study measuring?

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
Rate of stroke	Rate of stroke	Up to two years
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
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
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
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

Collaborators and Investigators

• Sponsor: Cardiawave SA
• Investigators: Principal Investigator: Emmanuel Messas, MD, Hospital Georges Pompidou, Paris, France

Publications and helpful links

General Publications

• Messas E, Ijsselmuiden A, Trifunovic-Zamaklar D, Cholley B, Puymirat E, Halim J, Karan R, van Gameren M, Terzic D, Milicevic V, Tanter M, Pernot M, Goudot G. Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study. Lancet. 2023 Dec 16;402(10419):2317-2325. doi: 10.1016/S0140-6736(23)01518-0. Epub 2023 Nov 14.
• Trifunovic-Zamaklar D, Velinovic M, Kovacevic-Kostic N, Messas E. Systematic brain magnetic resonance imaging and safety evaluation of non-invasive ultrasound therapy for patients with severe symptomatic aortic valve stenosis. Eur Heart J Cardiovasc Imaging. 2023 Jun 21;24(7):e108-e109. doi: 10.1093/ehjci/jead089. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2019
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): May 23, 2024

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: ultrasound; non-invasive; stenosis; aortic valve; symptomatic
• 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
• Other Study ID Numbers: CW19-01RS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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