SonoClear Acoustic Coupling Fluid (ACF) Mimicking Brain Tissue

Study Overview
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Brief Summary
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The objective of this clinical investigation is to assess the safety and performance of the SonoClear Acoustic Coupling Fluid (ACF). The performance will be assessed by analysis of the contrast-to-noise ratio (CNR) and assessment of image quality by using the Surgeon Image Rating (SIR) Scale. This is a prospective, multi-centre single-arm study where the performance of SonoClear ACF relative to routinely used acoustic coupling fluid is investigated by each patient being their own control. Patients with the diagnosis of HGG and LGG at up to 10 sites will be included. Additionally, safety data are collected at 30 days and 6 months post-procedure.

Detailed Description
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Ultrasound images will be obtained at different timepoints during the operation. First timepoint being after craniotomy (no fluids involved). Second timepoint being when some tumour is left in the bottom of the deeper part of the resection cavity (approximately 80% of tumour removed), and third timepoint being when the surgeon deems resection of the tumour to be completed. At the second and third timepoint ultrasound acquisition will be performed twice at each timepoint. Once with routinely used saline / Ringer's solution and once with SonoClear ACF. There are two performance related primary endpoints, based on core lab assessments: To show that ultrasound images obtained with SonoClear ACF are less influenced by image artefacts compared to images obtained with standard of care saline or Ringer´s solution, by measuring the contrast-to-noise ratio (CNR). The CNR is a measure of the relative noise in the image. To achieve this endpoint, the use of SonoClear ACF must lead to superior image quality in comparison with Saline/Ringer´s solution. Superior image quality is defined as the CNR being statistically different between the images obtained with saline/Ringer and SonoClear ACF respectively, i.e., significantly less noise in the images obtained with SonoClear ACF. To show that ultrasound images obtained with SonoClear ACF are of better quality compared to images obtained with standard of care Saline/Ringer's solution, by using a qualitative assessment, called the Surgeons Image Rating (SIR) scale. A Panel of Experts will assess the quality of the obtained images by answering 3 questions for each image. The SIR a 1-10 numeric rating scale, is used to measure the quality of the image according to three questions to be answered at the three different timepoints during the operation. This SIR is designed to explore whether SonoClear ACF, having shown to provide better quantitative image quality in the CNR analysis, allows surgeons to detect this improved image quality. Eventually this improved image quality should result in better decision-making during surgery about margins of excision and residual tumour resection. Primary Safety Endpoint The primary safety hypothesis is to prove the primary safety event rate is less than 10%. The primary safety event is defined as any core lab determined major MRI finding when post-operative MRI is compared to pre-operative MRI that was found by the DMC to be serious and probably or definitely related to the study device OR any DMC determined serious adverse event that is probably or definitely related to the study device that occurs within 30 days of the procedure. Success is demonstrated by observing 0 of these events out of 37 subjects exposed to SonoClear ACF. This is equivalent to a two-sided p-value less 0.05 for the alternative hypothesis that the primary safety event rate in subjects undergoing tumor resection using ACF is less than 10%.

Official Title
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Ultrasound Imaging in Brain Tumour Surgery With the Use of SonoClear Acoustic Coupling Fluid (ACF) Mimicking Brain Tissue

Conditions
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Brain Tumour, High Grade Glioma, Low-grade Glioma, Glioblastoma

Intervention / Treatment
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* Device: SonoClear ACF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diffuse malignant glial tumour (high (grade III and IV) or low grade (grade I-II) is suspected from the diagnostic MRI scan A tumour that extends at least 3 cm in depth from the surface of the brain (confirmed by MRI) Pre- or peri-procedural confirmed histopathology of glioma ≥18 years of age Karnofsky performance status ≥ 70 Life expectancy of more than 30 days at the time of the procedure Negative pregnancy test for female subjects of childbearing potential Exclusion Criteria: Not able to give consent (e.g. severe cognitive impairment) History of brain radiation therapy Recent meningitis (within 6 months prior to screening visit) Other active infection (within 30 days prior to screening visit) Immuno-incompetent patient (e.g. failing immune system due to AIDS) Patients taking immune-suppressive medication Intended biopsy only (meaning: cases not suitable for resection) Known hypersensitivity to egg protein Known hypersensitivity to soybean or peanut protein Known Hypersensitivity to glycerol Known Hypersensitivity to polysorbates Pregnant or lactating females or females who intend to become pregnant during the time of the study

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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: A prospective, multi-centre single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SonoClear acoustic coupling fluid (ACF) mimicking brain tissue<br>SonoClear | Device: SonoClear ACF<br>* The SonoClear ACF is intended to be used as an acoustic coupling fluid during ultrasound imaging in brain surgery of human beings<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contrast-to-Noise Ratio (CNR) to quantify the reduction in noise | To show that ultrasound images obtained when using SonoClear ACF are less influenced by image artefacts compared to images obtained when using routinely used saline solution measuring the contrast-to-noise ratio (CNR) in the images. | During ultrasound guided brain tumour resection | 
| Surgeons Image Rating (SIR) to assess the image quality | Quality assessment of the images is done by the core-lab in a blinded manner using the Surgeon Image Rating (SIR) scale, a 1-10 rating scale to score the quality of the image according to 3 questions at different time points during the operation. First timepoint being after craniotomy (no fluids involved). The second time point is when some tumour is left in the bottom of the deeper part of the resection cavity (approximately 80% of tumour removed), and the third time point being when the surgeon deems resection of the tumour to be completed. | During ultrasound guided brain tumour resection | 
| Adverse events up to 30 days post procedure | The primary safety hypothesis is to prove the primary safety event rate is less than 10%. A primary safety event is defined as any core lab determined major MRI finding when post-operative MRI is compared to pre-operative MRI that was found by the DMC to be serious and probably or definitely related to the study device OR any DMC determined serious adverse event that is probably or definitely related to the study device that occurs within 30 days of the procedure. Success is demonstrated by observing 0 of these events out of 37 subjects exposed to SonoClear ACF. This is equivalent to a two-sided p-value less 0.05 for the alternative hypothesis that the primary safety event rate in subjects undergoing tumor resection using ACF is less than 10%. | safety data are collected up to 30 days post procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acoustic Coupling Fluid (ACF), Ultrasound imaging in brain tumour surgery, brain tumour surgery