Clinical trial NCT06650839: POC for the Treatment of Subjects with Moderate AS Using Valvosoft® Non-Invasive Ultrasound Therapy
Official title: Proof of Concept Clinical Investigation for the Treatment of Subjects with Moderate Aortic Valve Stenosis Using Valvosoft® Non-Invasive Ultrasound Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Moderate Aortic Valve Stenosis
Keywords: aortic stenosis
moderate
aortic valve
balloon valvuloplasty
TAVR
SAVR
Ultrasound
FUS
PCUT
NIUT
Lead sponsor: Cardiawave SA
Sponsor class: INDUSTRY
Collaborators: name: Micro Cro
name: TWrite
First posted: 2024-10-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a proof of concept looking at the safety of treating subjects with moderate aortic stenosis using a Non-Invasive Ultrasound Therapy.

Detailed description: Valvosoft, Ultrasound guided Non-Invasive Ultrasound Therapy (NIUT) medical device, delivers focused and controlled, short ultrasound pulses (\<20μsec), directed trans-thoracically at a high acoustic intensity (measured in watts per square centimeter (W/cm2), to produce non-thermal mechanical tissue softening of the targeted calcified aortic valve.

Echocardiographic live imaging enables to follow valve movements in real-time and thus target the therapeutic ultrasound on the calcified valve with great precision. This is first in human or proof of concept study.

Eligibility criteria: Inclusion Criteria:

1. Aortic Valve Area (AVA) ≥1.0 cm2 ≤ 1.5 cm2 and either mean aortic Pressure Gradient (mPG) of \>25 - \< 40 mmHg or maximum velocity (Vmax) ≥3 ≤4 m/sec in normal flow conditions; or
2. Normal-flow, low-gradient aortic stenosis (AS) with preserved ejection fraction (mean aortic Pressure Gradient (mPG) \<40 mmHg, Aortic Valve Area (AVA) ≥0.8 ≤1.0 cm2, Left Ventricular Ejection Fraction (LVEF) ≥50%, Stroke Volume Index (SVi) \>35 mL/m2);
3. Age ≥18 years;

Exclusion Criteria:

1. mPG ≥40 mmHg; or
2. Severe aortic valve stenosis or other severe valve diseases; or
3. Subject with severe aortic regurgitation; or
4. Subjects with implanted mechanical or bioprosthetic valve in aortic position, or mechanical valve in any other positions; or
5. Heart failure with a NYHA 3 or 4; or
6. Cardiogenic shock or other hemodynamic instability; or
7. LVEF ≤50%; or
8. History of heart transplant; or
9. Subject with a significant kidney disease (eGFR ≤30 mL/min/1.73 m2) or subject is on dialysis; or
10. Subject with uncontrolled hypertension defined as systolic Blood Pressure (BP) ≥160 mmHg and/or a diastolic BP ≥100 mmHg (mean of 3 measurements for both assessments); or
11. Cardiac imaging evidence of vegetation; or
12. Current endocarditis; or 13 Subject has a documented history of cardiac amyloidosis; or

14. Acute Myocardial Infarction (MI) ≤1 month prior to enrolment; or 15. Stroke or Transient Ischemic attack (TIA) ≤1 month prior to enrollment; or 16. Balloon Aortic Valvuloplasty (BAV) ≤3 months prior to enrollment; or 17. Leukopenia (WBC \<4000 cell/μL), anemia (Hgb \< 8 g/dL), thrombocytopenia (platelet count \<50.000 cell/μL), or history of coagulopathy or hypercoagulable state.

Primary outcomes:
measure: Rate of MACE
timeFrame: from baseline to 30 days FU
measure: Improvement in leaflet mobility
timeFrame: at 6 months FU compared to baseline
Secondary outcomes:
measure: Rate of MACE
timeFrame: at 6 , 12 , 18 , 24 months
measure: Rate of all Serious Adverse Events
timeFrame: peri-procedural and at 30 days, 3 , 6 , 12 , 18 , 24 months
measure: Rate of Stroke
timeFrame: at 30 days, 3 , 6 , 12 , 18 , 24 months
measure: Change of AS
timeFrame: at 30 days, 3 , 6 , 12 , 18 , 24 months compared to Baseline;
measure: Change in Quality of Life by means of KCCQ
timeFrame: at 30 days, 3 , 6 , 12 , 18 , 24 months compared to Baseline;
measure: Change in Quality of Life by means of EQ-5D
timeFrame: at 30 days, 3 , 6 , 12 , 18 , 24 months compared to Baseline;
measure: Change in Exercise capacity
timeFrame: at 30 days, 6 , 12 , 18 , 24 months compared to Baseline;
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: University Clinical Centre Serbia
Study officials:
affiliation: University Clinical Centre Serbia
name: Milos Velinovic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Clinical Centre Serbia
name: Danijela Trifunovic-Zamklar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: