Valvosoft First-In-Man 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-Man

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

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Ultrasound treatment of Calcified aortic valve

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. This is a FIM study

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
• Netherlands
  • Breda, Netherlands, 4818CK
    • Amphia Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects suffering from severe symptomatic aortic valve stenosis (including subjects with a bicuspid valve).
2. Patient is not eligible for TAVR/SAVR .
3. Age ≥18 years.
4. Subjects who are willing to provide a written informed consent prior to participating in the study.
5. Subjects who can comply with the study follow up or other study requirements.

6. Subject eligible according to Clinical Review Committee

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Exclusion Criteria:

1. Subjects with any electrical device implanted.
2. Subjects with unstable arrhythmia not controlled by medical treatment.
3. Subjects with implanted mechanical valve in any position or bio prosthetic valve in aortic position.
4. Subjects with complex congenital heart disease.
5. Chest deformity.
6. Cardiogenic shock.
7. History of heart transplant.
8. Subjects requiring other cardiac surgery procedures (bypass graft surgery, mitral valve procedure, tricuspid valve procedure) within one month after treatment.
9. Thrombus in heart.
10. Acute myocardial infarction (MI), stroke or transient ischemic attack (TIA) within one month prior to enrolment*.
11. Subjects who are pregnant or nursing.

12. Subjects who are participating in another research study for which the primary endpoint has not been reached.

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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 of Calcified aortic valve; Ultrasound treatment of calcified aortic valve causing symptomatic aortic valve stenosis in patients who are not eligible for valve replacement

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cardiawave SA
• Investigators: Principal Investigator: Emmanuel Messas, MD, HGEP Paris, France

Publications and helpful links

General Publications

• Messas E, IJsselmuiden A, Goudot G, Vlieger S, Zarka S, Puymirat E, Cholley B, Spaulding C, Hagege AA, Marijon E, Tanter M, Bertrand B, Remond MC, Penot R, Ren B, den Heijer P, Pernot M, Spaargaren R. Feasibility and Performance of Noninvasive Ultrasound Therapy in Patients With Severe Symptomatic Aortic Valve Stenosis: A First-in-Human Study. Circulation. 2021 Mar 2;143(9):968-970. doi: 10.1161/CIRCULATIONAHA.120.050672. Epub 2021 Jan 25. No abstract available.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): January 15, 2022
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 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: CW19-01

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