Improving Ultrasound Images in Brain Tumour Surgery With the Use of an Acoustic Coupling Fluid Mimicking Brain Tissue.

Improving Ultrasound Images in Brain Tumour Surgery With the Use of an Acoustic Coupling Fluid Mimicking Brain Tissue: a Phase II Technical and Safety Study

Tools for improving brain tumor surgery, in particular for gliomas, are increasing. There seems to be an agreement that achieving extensive resections, when done safely without jeopardizing neurological function, improves survival.

Ultrasound is currently used as a tool for providing 2D or 3D images for tumor localization and resection control. For the use in resection control the resection cavity is filled with saline to provide acoustic coupling between the ultrasound transducer and tissue. However, attenuation of acoustic waves is very low in saline compared to the brain and this difference in attenuation is the cause of artifacts that may severely degrade the ultrasound images. Such artifacts are seen as high-intensity signal at the resection cavity wall and beyond. The artificial signal enhancement can potentially mask small tumor remnants and is generally making the interpretation of images more difficult.

This research group has developed an acoustic coupling fluid intended for use in the resection cavity instead of saline. Tests in laboratory measurements have shown that the fluid reduces artifacts and has the potential to enhance ultrasound image quality in brain tumor surgery. Three different concentrations of the acoustic coupling fluid have been tested in a phase 1 study that included 15 patients with glioblastoma. The concentration that provided the optimal ultrasound images, from qualitative and quantitative inspection, is used in the current phase II study. This study is a randomized controlled trial aiming to include 82 patients with glial brain tumours. Its purpose is to test the fluid during surgery of glial brain tumours to further investigate safety and efficacy.

Study Overview

• Status: Terminated
• Conditions: Glioma; Brain Neoplasms
• Intervention / Treatment: Biological: acoustic coupling fluid; Biological: Ringer's acetate

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway
    • Department of Neurosurgery, St Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A diffuse glial tumour (high-grade (stage 1), low-grade or high-grade (stage 2)) is suspected from the diagnostic magnetic resonance images (MRI).
• In cases where histopathology is not known from previous biopsy or resection (i.e. diagnosis is suspected based on MRI findings and not from previous surgery) a tissue sample for frozen section is necessary to confirm the diagnosis.
• Karnofsky performance status >=70

Exclusion Criteria:

• Not able to consent (e.g. severe cognitive impairment)
• Intended biopsy only (meaning: cases not suitable for resection)
• Hypersensitivity to egg protein
• Hypersensitivity to soya or peanut protein
• Hypersensitivity to glycerol
• Pregnancy of breast-feeding
• Intention to become pregnant during the time of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High grade gliomas stage 1 ACF; In the first stage 12-15 patients with high-grade gliomas will be included in the trial (acoustic coupling fluid) group.	Biological: acoustic coupling fluid; ultrasound images obtained with both ACF and Ringer's acetate; Other Names: ACF
EXPERIMENTAL: Low-high grade gliomas stage 2 ACF; If the interim safety assessments validate that the study can continue, the second stage involves inclusion in the trial (acoustic coupling fluid) group of 22-25 patients with both low-grade and high-grade glioma	Biological: acoustic coupling fluid; ultrasound images obtained with both ACF and Ringer's acetate; Other Names: ACF
ACTIVE_COMPARATOR: High grade gliomas stage 1 control; In the first stage 12-15 patients with high-grade gliomas will be included in the Ringer's acetate (control) group.	Biological: Ringer's acetate; ultrasound images obtained with Ringer's acetate only
ACTIVE_COMPARATOR: Low-high grade gliomas stage 2 control; If the interim safety assessments validate that the study can continue, the second stage involves inclusion in the Ringer's acetate (control) group of 22-25 patients with both low-grade and high-grade glioma	Biological: Ringer's acetate; ultrasound images obtained with Ringer's acetate only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference in serious adverse event rates (test minus control)	Non-inferiority (i.e. test serious adverse event rate is "not worse" than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin	72 hours
difference in serious adverse event rates (test minus control)	Non-inferiority (i.e. test serious adverse event rate is "not worse" than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin	30 days
difference in serious adverse event rates (test minus control)	Non-inferiority (i.e. test serious adverse event rate is "not worse" than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
image artefacts	during the operation; Qualitative score of ultrasound image quality (poor-medium-good)	1 day
image artefacts	during the operation; Qualitative score of artefacts in ultrasound images (none-some-much)	1 day
depiction of outline of the anatomy surrounding the resection cavity	during the operation; Qualitative score of ultrasound image quality (poor-medium-good)	1 day
depiction of outline of the anatomy surrounding the resection cavity	during the operation; Qualitative score of artefacts in ultrasound images (none-some-much)	1 day
image signal-to-noise ratio	after the operation: image analysis by quantitative measurements of signal-to-noise ratio (SNR)	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	assessed by EQ5D (generic)	1 month
Quality of Life	assessed by QLQ-C30 (cancer specific)	1 month
Quality of Life	assessed by EQ5D (generic)	6 months
Quality of Life	assessed by QLQ-C30 (cancer specific)	6 months

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: SINTEF Health Research; Norwegian National Advisory Unit for Ultrasound and Image-guided Therapy
• Investigators: Study Director: Petter Aadahl, phd md, St. Olavs Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2017
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): December 31, 2018

Study Registration Dates

• First Submitted: June 2, 2017
• First Submitted That Met QC Criteria: June 8, 2017
• First Posted (ACTUAL): June 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: surgery; brain; ultrasonography; ultrasonics
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: ACF-02; 2016-003025-42 (EUDRACT_NUMBER)

Drug and device information, study documents

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