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Trial registered on ANZCTR


Registration number
ACTRN12623001039673
Ethics application status
Approved
Date submitted
7/08/2023
Date registered
26/09/2023
Date last updated
15/09/2024
Date data sharing statement initially provided
26/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Scaffold for Temporal Hollowing in children with craniosynostosis.
Scientific title
Assessment of 3D-printed patient specific scaffolds for the treatment of temporal hollowing following cranial vault remodelling surgery in children with craniosynostosis.
Secondary ID [1] 310324 0
N/A
Universal Trial Number (UTN)
Trial acronym
2023-THSCAFFOLD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Temporal Hollowing 331045 0
Condition category
Condition code
Surgery 327840 327840 0 0
Surgical techniques
Reproductive Health and Childbirth 328131 328131 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial evaluates the use of patient specific 3D-printed medical grade polycaprolactone-tricalciumphosphate (mPCL-TCP) with the addition of bone marrow aspirate (BMA) and injectable Platelet Rich Fibrin (I-PRF) to augment the fronto-temporal region in patients with temporal hollowing.
Patient with craniosynostosis who have developed clinically appreciable temporal hollowing after cranial vault remodelling will be candidates for inclusion in the trial.

Serial computed tomography (CT) scans will be taken for the participants enrolling in this study. All patients will have had a CT prior to temporal hollowing correction as per standard of care and then again at 12 months following insertion of the scaffold. The CT scans will be used to assess bone volume formed within the scaffold and the volume of bone formed.

The participant specific scaffolds will be designed following an existing published workflow as described by Bartnikowski M, Vaquette C and Ivanovski S (Bartnikowski et al., 2020). Firstly, the participant’s de-identified CT data is loaded into the Materialise Mimics software (Materialise, Belgium) and a mask is created using the threshold tool to isolate the bone of the participant. This threshold can be adjusted depending on the quality of the scan. Next, noise from the mask (a result from scan or metallic artefacts) is cleaned using the multiple slice edit and region grow tools and bones can be separated using the split mask tool. Once the temporal bone has been isolated and scan artefacts have been removed it can be exported into 3-Matic (Materialise, Belgium) for further processing and the creation of the patient specific scaffold outline. Note that in 3-Matic the bony anatomy of the frontotemporal region bone can be smoothed using the smooth tool if appropriate and re-meshed to minimise the presence of surface artefacts from the STL conversion process. To compensate for potential dimensional errors in the subsequent processes and manufacturing step, the part is wrapped using the wrap tool. The area to undergo onlay bone augmentation is then identified by the treating clinician and the area is traced using a curve tool. Surgeons will use their experience to guide the degree of augmentation required. For unilateral cases (unifrontal orbital advancement) the unaffected (contralateral side) geometry may be duplicated, mirrored in reference to its sagittal plane, and virtually placed over the temporal hollowing side to guide design of the anatomical template.

The solid geometry is then saved and exported as an STL file. The anonymised scaffold outline will then be sent to Osteopore for manufacturing of the mPCL-TCP scaffold. The Osteopore mPCL-TCP are made of an FDA approved polymer (K051093) PCL that is bioresorbable, slow-degrading and possesses adequate mechanical strength, similar to that of trabecular bone. The mPCL-TCP scaffold will be manufactured using additive manufacturing to produce accurate and reproducible participant-specific implants.

Surgical placement of the scaffold will be performed under a general anaesthetic at the QCH by the Principal Investigator Dr Yun Phua and the Plastic and Reconstructive Surgery team.

For scaffold placement, the bicoronal incision (used for their previous cranial vault remodelling surgery) will be used for surgical access. Note that, depending on the size of the temporal fossa implant, a more limited portion of the previous incision may be used.
After the skin incision and elevation of the scalp flap in a sub-galeal or sub-periosteal flap, the lateral frontal region and temporal fossa will be dissected sub-periosteally. Where the temporalis muscle is malpositioned, the upper portion of the muscle may be raised as part of this dissection. A rigid endoscope may be required in cases where a more limited incision has been utilised to facilitate dissection of the temporal fossa. The scaffold will then be inserted and secured with one or several degradable screws (SonicWeld, Delta etc.) through premade flanges.

Thereafter, autologous haemoderivate (i-PRF) and BMA will be injected in the scaffold.

Preparation of the injectable platelet rich fibrin (i-PRF) will be conducted on the day of surgery during the same procedure as scaffold implantation. The i-PRF preparation is performed in the operating theatre at the same time of the surgery and in the same surgical theatre using a commercially available clinical centrifuge (for example a Duo Centrifuge, Fixed angle rotor/radius 110 mm, Biomedent Australia) and under sterile surgical operation conditions. This protocol is already utilised in the clinical setting for various applications and predominantly in the dental and maxillofacial area. Sample tracking using participant labels will be used throughout the protocol. 10mL of autologous whole blood will be collected via an intravenous line already set-up for the maintenance and induction of anaesthesia. The blood is collected into a sterile vacuum blood tube and centrifuged at 700 rpm (60 g) for 3 min. Following centrifugation, the orange supernatant, representing the liquid i-PRF, will be aspirated using a sterile syringe fitted with a 21G needle and placed in a sterile 6-well-plate until natural pre-gelation occurs. Thereafter, the i-PRF is injected in the polycaprolactone scaffold and gelation is finalised.

The BMA will be harvested from the iliac crest using a bone marrow aspiration needle (e.g. Stryker Imbibe Bone Marrow Aspiration Needles) as per standard of care for bone augmentation procedures in craniofacial reconstruction. A small incision lateral to the anterior or posterior iliac crest will be made to allow for insertion of the trocar needle and cannula assembly which are advanced into the iliac crest. Once in placed the trocar needle is replaced by the aspiration needle and sufficient BMA is aspirated as required as per standard of care for bone augmentation procedures in craniofacial reconstruction. The harvested BMA will then be injected into the scaffold.

Once the scaffold has been secured, temporalis will be re-suspended with Vicrryl or PDS sutures. Total surgical procedure will be approximately 3 hours (1.5 hours per side). The participant will be admitted 1-2 nights for observation and post-operative antibiotics continued for 24 hours or per the consultant surgeon’s preference.


After surgery, the patient will return to standard of care, and return for visits to the QCH outpatient clinic for a review as per standard of care after 2 weeks, 3 months, 6 months and 12 months. At these visits everything will as per standard of care except for the Face-Q questionnaire that the patient will fill out at the enrolment visit and at the 12 month visit. The patient will then continue to be under the care of their treating clinician until they reach maturity and leave the care of the QCH as per standard of care.
Intervention code [1] 326725 0
Treatment: Surgery
Intervention code [2] 326726 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335689 0
Radiological evidence of bone regeneration and quality of regenerate bone in the scaffold, these outcomes will be analysed together as a composite outcome.
Timepoint [1] 335689 0
Radiological evidence of bone regeneration within the scaffold based on a CT taken at 12 months post-implantation.
Primary outcome [2] 335690 0
Change in forehead contour following temporal augmentation.
Timepoint [2] 335690 0
Change in forehead morphology based on standard pre- and post-operative 3D photography.
Secondary outcome [1] 425190 0
Change in patient reported outcome measures (from Face-Q questionnaire) related to forehead appearance following surgery, analysed as composite outcome. Children over 8 years of age will complete FACE-Q themselves. A parent or guardian will complete FACE-Q on behalf of their child in those under 8 years of age (or for those with developmental delay).

Appearance of forehead will be evaluated using the Face-Q questionnaire - appearance of forehead section, which gives an equivalent RASCH Transformed score as per the Face-Q survey (McMaster University)
Timepoint [1] 425190 0
Patient reported outcome measure questionnaire (select questions from the Face-Q questionnaire specific to forehead appearance) completed at baseline (pre-implantation at the enrolment visit) and 12 months post-implantation.

Eligibility
Key inclusion criteria
Patients must fulfil all the following criteria to be eligible for the trial:
• Clinically appreciable temporal hollowing with a temporal defect (bony and/or soft tissue) evident on CT imaging.
• Patients aged 2 to 18 years of age.
• Patient, and their parent/guardian if applicable, willing and able to comply with the study requirements.
• Guardian (or patient if Gillick competent) capable of providing valid informed consent
Minimum age
2 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting any of the following criteria will be excluded from the trial:
• Current smokers.
• Syndromes associated with poor wound healing.
• Patient or guardian unwilling or unable to provide fully informed consent.
• Patient with a known history of immunodeficiency including HIV, concomitant systemic corticosteroid therapy, chemotherapy, synchronous haematological malignancy, or other cause for secondary/primary immunodeficiency.
• Known severe concurrent or inter-current illness including but not limited to cardiovascular, respiratory, or immunological illness, psychiatric disorders, or possible allergies (including allergy to PCL) that, at the discretion of the clinical leads, would compromise the participant safety or compliance, or interfere with interpretation of study results.
• Unable or unwilling to comply with the study requirements.
• Unreliable follow up record (i.e. multiple failed attendances for their regular follow-up appointments).

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All participants registered for the trial will be accounted for in the analysis (intention to treat). The primary outcome of measuring the degree of bone formation into the scaffold will be measured by calculating the bone volume in the scaffold from deidentified CT data taken 12 months post scaffold implantation (as described in the schedule of assessment). The bone volume will be analysed using Mimics (Materialise, Belgium) software.

Comparison analysis of FACE-Q questionnaire results between time points will be analysed using univariate Cox regression analysis due to the small sample size. Statistical significance will be defined as P < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
1/04/2026
Actual
Date of last data collection
Anticipated
15/01/2027
Actual
Sample size
Target
5
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 25346 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 41055 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 314530 0
Commercial sector/Industry
Name [1] 314530 0
Osteopore Limited
Country [1] 314530 0
Singapore
Primary sponsor type
Commercial sector/Industry
Name
Osteopore Limited
Address
2 Tukang Innovation Grove #09-06/07, JTC MedTech Hub, Singapore 618305
Country
Singapore
Secondary sponsor category [1] 316480 0
None
Name [1] 316480 0
Address [1] 316480 0
Country [1] 316480 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313572 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC)
Ethics committee address [1] 313572 0
Human Research Ethics CommitteeCentre for Children’s Health ResearchQueensland Children’s Hospital PrecinctLevel 7, 62 Graham StreetSouth Brisbane QLD 4101
Ethics committee country [1] 313572 0
Australia
Date submitted for ethics approval [1] 313572 0
09/10/2023
Approval date [1] 313572 0
21/11/2003
Ethics approval number [1] 313572 0

Summary
Brief summary
Craniosynostosis is a condition where the bones in a baby’s skull fuse too early causing an unusual head shape. Most children with this condition undergo cranial vault remodeling surgery within the first 2 years of life. This operation is generally effective in normalising the overall shape of the skull, however, a common issue after surgery is hollowing of the temples just in front of the hairline (temporal hollowing).

The current way that temporal hollowing is corrected involves using artificial materials (for example, a bone substitute putty or plastic-like implant) but they have some limitations and can only been used when the child is in their teenage years and their skull has stopped growing.

A new approach to fix this problem uses a specially made, degradable tissue scaffold. This scaffold is designed to fit in the affected area and can be placed through a smaller incision. The benefits of using this scaffold include the potential for further growth, which is not possible with current materials used for correction. The scaffold is made of a material called Polycarprolactone (PCL) which is the same material that some dissolving sutures are made of and is known to support tissue growth. The scaffold will also have a compound called Tricalcium Phosphate added which encourages bone to form. Eventually the scaffold will be replaced by the patient’s own bone as the scaffold slowly degrades.

These scaffolds have been studied extensively and are currently being used in Australia in trials for other types of reconstruction (eg skull defects, leg bone defects, and jaw bone defects).



Aims of the study:

The main aim of the study is see how effective a tissue scaffold is at improving the appearance of the temporal region and forehead in children with temporal hollowing. The study will also investigate how much new bone forms within the scaffold.



Importance of the findings:

Tissue scaffolds have been used in other parts of the face, but this will be the first time they have been used in the temporal region, laid on top of the bone. This study will therefore tell us how effective scaffolds are at augmenting bone. This is relevant for many children with congenital conditions that affect the face, where the facial bones do not grow normally and may need to be augmented.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128594 0
Dr Yun Phua
Address 128594 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128594 0
Australia
Phone 128594 0
+61 0730682581
Fax 128594 0
Email 128594 0
[email protected]
Contact person for public queries
Name 128595 0
Yun Phua
Address 128595 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128595 0
Australia
Phone 128595 0
+61 0730682581
Fax 128595 0
Email 128595 0
[email protected]
Contact person for scientific queries
Name 128596 0
Yun Phua
Address 128596 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128596 0
Australia
Phone 128596 0
+61 0730682581
Fax 128596 0
Email 128596 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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.