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Trial registered on ANZCTR


Registration number
ACTRN12624000659505
Ethics application status
Approved
Date submitted
9/05/2024
Date registered
22/05/2024
Date last updated
13/10/2024
Date data sharing statement initially provided
22/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Embolisation with NeoCast for Chronic Subdural Hematoma
Scientific title
First in Human Study of the Safety and Feasibility of Middle Meningeal Artery (MMA) Embolisation with the Arsenal Medical NeoCast Embolic System for the Treatment of Chronic Subdural Hematoma (cSDH)
Secondary ID [1] 312107 0
Sponsor Trial Number: EMBO-02
Universal Trial Number (UTN)
U1111-1305-9758
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurological 333748 0
Condition category
Condition code
Neurological 330431 330431 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants diagnosed with chronic subdural hematoma (cSDH) will undergo embolisation with a novel embolic agent, NeoCast (formerly Distal Penetrating Embolic, or DPE) in a procedure performed by a board-certified neurointerventional radiologist. A subdural hematoma develops when tiny blood vessels that run between the surface of the brain and its outermost covering (the dura) tear and begin to leak. Embolisation is a procedure that blocks off the blood supply in the leaky vessels by injecting an embolic agent into the blood vessels to form a plug within the vessels to stop blood flow. The embolisation procedure will be done in an operating room and is expected to take about 2 hours. The embolisation procedure may be done under conscious sedation or general anesthesia. Before the procedure starts, baseline computed tomography (CT) imaging is done to take pictures of the blood vessels in the brain that supply the hematoma. A catheter (a thin, flexible tube) is inserted into a small incision in the inner thigh or wrist and advanced through the blood vessels into the brain. During this time contrast dye will be injected into the catheter and x-ray images (digital subtractive angiography) are taken. Once the catheter is placed at the vessel which needs to be embolised, NeoCast is injected until the material fills the blood vessel and stops the blood leaking to the hematoma. X-ray images (digital subtractive angiography) will be taken of the embolised blood vessel(s). At the end of the procedure CT imaging is repeated to record the placement of the embolic material.
A Sponsor representative who is a technical expert on NeoCast will attend the embolisation procedure and make sure the protocol is being followed and all the information about the procedure is recorded according to the protocol. The CT and X-ray images from the procedure will be reviewed by an Imaging Core Lab to make sure the embolisation procedure was successful in placing NeoCast where it was needed to stop the blood leakage, and that no NeoCast was placed where it was not needed. The NeoCast procedure may not be repeated if post-embolisation CT imaging indicates failure of the initial procedure. Separately, study participants may have their hematoma surgically drained either before or after embolisation. This separate surgical procedure would be done by a neurosurgeon according to hospital standard of care.
Participants will be followed through 6 months post-embolisation, with CT imaging repeated at a 6-week follow-up visit and a 3-month follow-up visit, and finally at a 6-month follow-up visit if the cSDH has not resolved. The imaging will be used to measure changes from baseline in hematoma thickness, hematoma volume, and degree of midline shift.
Intervention code [1] 328551 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338180 0
The primary safety endpoint is freedom from device related disabling stroke or neurological death within 30 days of the embolisation procedure as adjudicated by an independent physician adjudicator (IPA).
Timepoint [1] 338180 0
Within 30 days of embolisation procedure
Primary outcome [2] 338181 0
The primary feasibility endpoint is defined as the successful injection of NeoCast into the middle meningeal artery, resulting in complete occlusion at or distal to the point of embolysate injection.
Timepoint [2] 338181 0
Post-embolisation CT image taken within 24 hours of the embolisation procedure
Secondary outcome [1] 434829 0
Degree of target vessel occlusion as assessed by Imaging Core Lab
Timepoint [1] 434829 0
Immediate post-embolisation imaging at Baseline Visit
Secondary outcome [2] 434830 0
Embolic penetration (before mid-line, at mid-line, or past mid-line) as assessed by Imaging Core Lab
Timepoint [2] 434830 0
Post-embolisation CT imaging (within 24 hours of embolisation procedure)
Secondary outcome [3] 434831 0
Presence of embolic outside middle meningeal artery region as assessed by Imaging Core Lab
Timepoint [3] 434831 0
Post-embolisation CT scan (within 24 hours of embolisation procedure)
Secondary outcome [4] 434832 0
Change in hematoma thickness from baseline as assessed by Imaging Core Lab
Timepoint [4] 434832 0
Baseline and follow-up timepoints (6 weeks, 3 months, or 6 months post-embolisation).
Secondary outcome [5] 434833 0
Change in hematoma volume from Baseline as assessed by the Core Imaging Lab
Timepoint [5] 434833 0
Baseline and follow-up timepoints (6 weeks, 3 months, or 6 months post-embolisation)
Secondary outcome [6] 434834 0
Change in midline shift from baseline as assessed by Imaging Core Lab
Timepoint [6] 434834 0
Baseline and follow-up timepoints (6 weeks, 3 months, or 6 months post-embolisation)
Secondary outcome [7] 434835 0
Patient-reported pain assessment (NRS scale) of pain during the embolisation procedure
Timepoint [7] 434835 0
Post-embolisation at the Baseline Visit
Secondary outcome [8] 434836 0
Modified Rankin score (mRS) degree of neurological disability at all timepoints
Timepoint [8] 434836 0
Screening Visit, Baseline Visit (pre embolisation and within 24 hours post embolisation), Surgery (pre-surgery and within 24 hours post-surgery, if surgery is performed), Discharge, the 6 week follow-up visit post embolisation, the 3 month follow up visit post embolisation, and the 6 months follow up visit post embolisation.
Secondary outcome [9] 434837 0
Markwalder cSDH Severity Score at selected timepoints
Timepoint [9] 434837 0
Baseline Visit (pre embolisation and within 24 hours post embolisation), Surgery (pre-surgery and within 24 hours post-surgery, if surgery is performed), discharge, the 6 week follow-up visit post embolisation, the 3 month follow up visit post embolisation, and the 6 months follow up visit post embolisation.
Secondary outcome [10] 434838 0
Quality of Life Questionnaire at selected timepoints
Timepoint [10] 434838 0
Baseline and follow-ups at 6 weeks, 3 months and 6 months
Secondary outcome [11] 434839 0
Length of hospital stay in days
Timepoint [11] 434839 0
Discharge
Secondary outcome [12] 434840 0
Incidence of hospital readmissions
Timepoint [12] 434840 0
Discharge through 6 month follow-up
Secondary outcome [13] 434841 0
Incidence of residual or re-accumulation of subdural hematoma. This will be assessed as a composite outcome consisting of the hematoma volume.
Timepoint [13] 434841 0
Post-embolisation CT compared to CT at follow-ups at 6 weeks, 3 months, and (optionally) 6 months, or unplanned CT due to adverse events or symptoms
Secondary outcome [14] 434842 0
Incidence of re-operation or surgical rescue. This will be assessed as a composite outcome consisting of any unplanned surgical intervention.
Timepoint [14] 434842 0
Baseline embolisation through the 6-month follow-up
Secondary outcome [15] 434843 0
NeoCast useability questionnaire for neurointerventionalist
Timepoint [15] 434843 0
Baseline Visit post-embolisation
Secondary outcome [16] 434844 0
Adjunctive surgery details for cSDH
Timepoint [16] 434844 0
Details of any planned surgery that occurs after the participant has entered the study at Baseline through the final 6-month follow-up visit will be captured
Secondary outcome [17] 435162 0
Length of ICU stay in days
Timepoint [17] 435162 0
The timepoints will be Baseline through Discharge
Secondary outcome [18] 435163 0
Rescue surgery details for cSDH
Timepoint [18] 435163 0
Details of any unplanned surgery that occurs after the participant has entered the study at Baseline through the final 6-month follow-up visit will be captured

Eligibility
Key inclusion criteria
• Subject whose age is greater than or equal to 18 years and less than or equal to 90 years;
• Subject whose pre-morbid mRS score is less than or equal to 2
• Confirmed diagnosis of a symptomatic chronic subdural hematoma that measures greater than or equal to 10 mm in greatest thickness
• Subject is planned for Middle Meningeal Artery embolisation for cSDH, either adjunctive to surgery or as part of medical management
• Subject understands the nature of the procedure, consents to participation in the study and provides a signed informed consent form;
• Subject (woman of child-bearing potential) with a current negative pregnancy test who has agreed to an appropriate method of contraception throughout the trial;
• Subject is willing to return to the investigational site for follow-up visits.
Baseline Inclusion Criteria:
• A negative pregnancy test is required at baseline for a woman of child-bearing potential
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Screening Exclusion Criteria:
• Diagnosed with acute SDH
• Subject with prior embolisation of either MMA
• Subject with urgent or emergent (within 1 hour of assessment) subdural hematoma evacuation needed
• Subject who presents with a meningioma greater than or equal to 1 cm or less than 1 cm with mass effect
• Subject currently undergoing radiation therapy for carcinoma or sarcoma of the head or neck region
• Structural pathology causing the cSDH (e.g., dural AV fistula, AVM, tumor, arachnoid cyst, ventriculoperitoneal shunt)
• Presumed microbial superinfection
• Subject who is breastfeeding
• Subject with life expectancy of less than 1 year
• Patients with acute renal impairment that the investigator assesses could be at risk for contrast induced nephropathy
• Subject with a life-threatening allergy to radiographic contrast (unless treatment for allergy is tolerated or can be managed medically)
• Participant is allergic to any of the materials used in the NeoCast device
• Planned embolisation procedure that would require use of a microcatheter with lumen diameter < 0.016 in
• Subject who is currently participating or planning to participate within 6 months in another non-observational clinical research study
Baseline Exclusion Criteria:
• Digital subtractive angiography (DSA) demonstrates potentially dangerous anatomic variations leading to increased procedural risk or unsafe access for MMA embolisation (i.e., MMA originating from ophthalmic artery)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The EMBO-02 study is a prospective, multi-center, first in human clinical study. This single-arm, open-label evaluation will enroll up to 10 participants at up to 5 sites in Australia to evaluate the early safety and feasibility of the Arsenal Medical NeoCast embolic (formerly Distal Penetrating Embolic, or DPE) for the treatment of chronic subdural hematoma.

The study is considered an early feasibility study, and as such no control arm is included and no hypothesis is utilised for statistical testing. The sample size of ten participants will be used to evaluate early safety and feasibility only.

The primary safety endpoint of this study is freedom from device related disabling stroke or neurological death within 30 days of the embolisation procedure as adjudicated by an independent physician adjudicator (IPA). Since this is an early feasibility study, safety assessments are important and appropriate measurements. A DMC is being utilised to ensure review of safety data at periodic points during study enrollment and to recommend if the study should be continued, revised or closed.

The primary feasibility endpoint is defined as the successful injection of NeoCast into the middle meningeal artery, resulting in complete occlusion at or distal to the point of embolysate injection.
The primary feasibility endpoint will be assessed by the Imaging Core Lab based on the post-embolisation imaging. This endpoint is appropriate given that the study is an early feasibility study. Additional endpoints are more quantitative and include the change from baseline in hematoma volume, hematoma thickness, and degree of midline shift.

As a first in human study, the choice of the number of participants is not statistically based. The enrollment of 10 participants is supported by evidence of the safety of NeoCast for use in the embolisation of chronic subdural hematomas based on preclinical testing and animal studies performed by Arsenal Medical.

The data analysis will consist of descriptive statistics. Participant data listings and tabular and graphical presentations of results will be provided.

Participant demographics, clinical information, and procedural characteristics will be summarised. Continuous variables will be presented as mean, standard deviation, and 95% confidence intervals for the mean. Discrete variables will be presented as frequencies, percentages and exact 95% confidence intervals for discrete variables.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/10/2024
Actual
7/10/2024
Date of last participant enrolment
Anticipated
15/02/2025
Actual
Date of last data collection
Anticipated
15/08/2025
Actual
Sample size
Target
10
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26522 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 27193 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 42563 0
3168 - Clayton
Recruitment postcode(s) [2] 43276 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 316465 0
Commercial sector/Industry
Name [1] 316465 0
Arsenal Medical, Inc.
Country [1] 316465 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arsenal Medical Australia Pty Ltd.
Address
Country
Australia
Secondary sponsor category [1] 318640 0
None
Name [1] 318640 0
Address [1] 318640 0
Country [1] 318640 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315255 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 315255 0
https://monashhealth.org/research/resources/resource-library/
Ethics committee country [1] 315255 0
Australia
Date submitted for ethics approval [1] 315255 0
10/04/2024
Approval date [1] 315255 0
21/06/2024
Ethics approval number [1] 315255 0

Summary
Brief summary
The EMBO-02 study is a first-in-human study for treatment of chronic subdural hematomas, which is a collection of blood and blood breakdown products, like a blood clot. A hematoma that is subdural is located between the surface of the brain and its outermost covering (the dura). A subdural hematoma develops when tiny blood vessels that run between the dura and surface of the brain tear and begin to leak. Participants in this study may benefit from “embolisation” to stop the blood vessels from leaking. This research study is testing a new investigational device that is an embolic agent called the NeoCast Embolic System (“NeoCast”).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134146 0
Dr Lee-Anne Slater
Address 134146 0
Monash Medical Centre Monash Imaging 246 Clayton Road Clayton, VIC, 3168
Country 134146 0
Australia
Phone 134146 0
+61 3 9594 7649
Fax 134146 0
Email 134146 0
[email protected]
Contact person for public queries
Name 134147 0
Lee-Anne Slater
Address 134147 0
Monash Medical Centre Monash Imaging 246 Clayton Road Clayton, VIC, 3168
Country 134147 0
Australia
Phone 134147 0
+61 3 9594 7649
Fax 134147 0
Email 134147 0
[email protected]
Contact person for scientific queries
Name 134148 0
Lee-Anne Slater
Address 134148 0
Monash Medical Centre Monash Imaging 246 Clayton Road Clayton, VIC, 3168
Country 134148 0
Australia
Phone 134148 0
+61 3 9594 7649
Fax 134148 0
Email 134148 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
10-patient first in human feasibility trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.