VALVOSOFT® Pivotal Study

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

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

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Aortic Valve Calcification
• Intervention / Treatment: Device: VALVOSFT intervention

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France
    • CHU Lille Insitut Coeur Poumon
  • Paris, France
    • Hôpital Européen Georges Pompidou
  • Paris, France
    • Hopital Bichat Claude-Bernard
  • Reims, France
    • CHU Reims Hopital Robert Debre
  • Rouen, France
    • CHU Rouen Hopital Charles Nicole
  • Toulouse, France, 31076
    • Clinique Pasteur
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik
  • Hamburg, Germany
    • Marienkrankenhaus
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • OLVG
  • Breda, Netherlands
    • Amphia Hospital
  • Nijmegen, Netherlands, 6525 AG
    • Radboudumc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subject suffering from severe symptomatic calcific aortic valve stenosis as defined by ESC/EACTS guidelines for the management of valvular heart disease 2021; and
2. Subject is not recommended by the local HEART Team for immediate TAVR/SAVR; or
3. Subject who refuses TAVR/SAVR, documented by local HEART Team (not allowed in France); and
4. Age ≥18 years; and
5. Subject willing to provide a written informed consent prior to participating in the study; and
6. Subject who can comply with the study follow-up or other study requirements; and
7. Subject is eligible for the Valvosoft procedure according to Clinical Review Committee (CRC).

Exclusion Criteria:

1. Subject with severe aortic regurgitation; or
2. Subject with unstable arrhythmia not controlled by medical treatment; or
3. Subjects with implanted mechanical valve in any position or bio-prosthetic valve in aortic position; or
4. Subject has a chest deformity not allowing optimal placement of Valvosoft Applicator and visualization of the aortic valve; or
5. Cardiogenic shock or other hemodynamic instability; or
6. Left Ventricular Ejection Fraction ≤30%; or
7. Subject with mean AVAI <0,24 cm²/m2; or
8. History of heart transplant; or
9. Subject requiring other cardiac surgery procedures (bypass graft surgery, mitral valve procedure, tricuspid valve procedure) within one month after Valvosoft procedure; or
10. Cardiac imaging evidence of vegetation; or
11. Acute myocardial infarction (MI) within one month prior to enrolment; or
12. Valve depth not suitable for NIUT (depth >125mm with respect to the Valvosoft imaging probe); or
13. Stroke or transient ischemic attack (TIA) ≤1 month prior to enrollment; or
14. Subject who is pregnant, or plan to become pregnant during the 12-months study follow-up period; or
15. Subject who is participating in another research study for which the primary endpoint has not been reached; or
16. Balloon aortic valvuloplasty (BAV) ≤3 months prior to enrollment; or
17. Current endocarditis; or
18. 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
19. Life expectancy < 6 months due to non-cardiac co-morbid conditions; or
20. Other medical, psychological, or social condition which, in the opinion of the investigator, precludes the subject from study participation; or
21. Subjects who do not have Social Security and who are under legal restraint; or
22. Subjects who cannot read or write or are mentally not or partially capable of giving informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cardiawave SA
• Collaborators: QbD Clinical
• Investigators: Principal Investigator: Christian Spaulding, MD, PhD, HEGP, Paris, France

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 11, 2022

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; Aortic Valve Stenosis; Stenosis; Aortic Valve; non invasive; Aortic Valve Calcification
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Calcium Metabolism Disorders; Aortic Valve Stenosis; Constriction, Pathologic; Calcinosis
• Other Study ID Numbers: CW21-02

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