Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001002673p
Ethics application status
Not yet submitted
Date submitted
7/08/2023
Date registered
13/09/2023
Date last updated
13/09/2023
Date data sharing statement initially provided
13/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Scaffold for Nasoalveolar Augmentation
Scientific title
Assessment of 3D-printed patient specific scaffolds for nasoalveolar augmentation in patients with cleft lip-related paranasal maxillary deformities.
Secondary ID [1] 310318 0
N/A
Universal Trial Number (UTN)
Trial acronym
2023-NASCAFFOLD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nasoalveolar Augmentation 331037 0
Condition category
Condition code
Surgery 327835 327835 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will utilise a patient specific 3D-printed medical grade polycaprolactone-tricalciumphosphate (mPCL-TCP) scaffold for the purpose of paranasal maxillary augmentation in patients with a unilateral cleft lip. The PCL-TCP scaffolds used will be augmented through the addition of bone marrow aspirate (BMA) and injectable Platelet Rich Fibrin (i-PRF).

Cleft lip patients with paranasal maxillary deficiencies associated with nasal alar base retrusion will be candidates for inclusion in the trial. Scaffold placement will be timed to coincide with either their secondary alveolar bone graft or their rhinoplasty (intermediate or secondary). The standard of care at our institution for a nasal base deformity is placing an onlay cancellous bone graft along the piriform rim and superior maxillary alveolus at the cleft margin. The long-term persistence of cancellous bone graft volume and position, however, is generally considered poor and its direct effect on nasal base form is largely unknown. As such, the scaffold will replace the onlay bone graft, not adding any time to the standard of care procedure.

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 maxilla 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 maxilla 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. The non-cleft maxilla (contralateral side) geometry is duplicated, mirrored in reference to its sagittal plane, and virtually placed over the cleft 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. The protocol for device manufacturing will be following that of the Osteopore Patient Specific Implant (PSI) which has already been used at QCH.

Serial computed tomography (CT) or cone beam CT (CBCT) scans will be taken for the participants enrolling in this study. All patients will have had a CT or CBCT prior to their alveolar bone graft as per standard of care and then again at approximately 12 months following secondary alveolar bone grafting insertion of the scaffold. This is part of the standard of care for alveolar bone graft patients. The CT scans will be used to assess bone volume formed within the scaffold and the volume of bone formed


Surgical placement of the scaffold will be performed under a general anaesthetic at QCH by the treating clinician (all treating clinicians are part of the study team) at the same time as bone grafting of the alveolar cleft or rhinoplasty.

A. Scaffold placement at the time of alveolar bone graft:
For patients having scaffold placement at the time of alveolar bone grafting, surgery involves incisions along the cleft margin, raising gingivoperiosteal flaps to close the nasal floor and palatal defect (roof of the alveolar cleft). Iliac crest cancellous bone graft is then harvest via a short incision posterior to the anterior superior iliac spine and this is packed into the alveolar cleft. A broad superiorly based gingivoperiosteal flap is then raised distal to the cleft (from the lesser alveolar segment) and this is advanced with a backcut in the region of the first molar to close the anterior wall of the cleft. Vicryl sutures are used to close mucosa. This is the standard approach amongst all cleft surgeons in the unit and will not differ in patients undergoing scaffold placement.
Following placement of iliac crest cancellous bone graft, a scaffold will be inserted to sit along the piriform margin. The amount of overlap from the piriform margin and across the superior alveolus will be determine pre-operatively based on the patient’s imaging. It is anticipated that there will be some overlap over both the piriform and grafted superior alveolus to adequately support the alar base. The scaffold extension for nasal alar support will be sutured to the fibrofatty tissue of the alar base. Small perforations in the maxilla deep to the region of scaffold placement, avoiding unerupted teeth or tooth roots, will be performed to encourage bony bleeding. The scaffold will then be inserted and secured with one or several degradable screws (e.g. Sonic WeldTM (KLS Martin) or Delta system (Stryker)) through premade flanges. Thereafter, BMA and autologous i-PRF will be injected in the scaffold.
Once the scaffold has been secured, the lateral gingivoperiosteal flap will be advanced in the standard manner as all other patients undergoing an alveolar bone graft and closed tension free.
The participant will be admitted 1-2 nights for observation. Post-operative oral antibiotics will continue for 24 hours, and chlorhexidine mouthwash will be prescribed for all participants to be used for 2 weeks as per standard protocol.
B. Scaffold placement at the time of rhinoplasty:
For patients having scaffold placement at the time of a rhinoplasty, a standard open tip rhinoplasty will be carried out by the treating clinician. A separate incision will then be made in either the alar crease or the upper gingivolabial sulcus, allowing access and subperiosteal dissection of the piriform margin and superior alveolus.
The patient specific implant will then be inserted and secured in the same manner described above. Thereafter, BMA and autologous I-PRF will be injected in the scaffold.
The participant will be admitted 1-2 nights for observation. Post-operative oral antibiotics will continue for 24 hours.

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 Cleft-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] 326697 0
Treatment: Devices
Intervention code [2] 326698 0
Treatment: Surgery
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335682 0

Radiological evidence of bone regeneration and the quality of regenerate bone in the scaffold, these outcomes will be analysed together as a composite outcome.
Timepoint [1] 335682 0
Radiological evidence of bone regeneration within the scaffold based on a CT taken at 12 months post-implantation.
Primary outcome [2] 335683 0
Change in nasal form following paranasal augmentation
Timepoint [2] 335683 0
Change in nasal alar position and morphology based on standard pre- and post-operative 3D photography 12 months after surgery.
Secondary outcome [1] 425177 0
Change in patient reported outcome measures (from cleft-Q questionnaire) related to nasolabial form following surgery analysed as composite outcome.
Timepoint [1] 425177 0
Patient reported outcome measure questionnaire (select questions from the CLEFT-Q questionnaire specific to nasolabial form) [completed at enrolment and 12 months post-implantation.

Eligibility
Key inclusion criteria
Patients must fulfil all the following criteria to be eligible for the trial:
• Patients being treated at the Queensland Children’s Hospital scheduled to undergo a secondary alveolar bone graft or rhinoplasty.
• Sagittal bony projection discrepancy of the piriform region of the maxilla on the cleft side greater than 2mm compared to the non-cleft side following palatal expansion and dental arch alignment.
• Adequate nasal closure for the scaffold when placed along and potentially overlapping the piriform margin.
• Patients aged between 4 and 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
4 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 lead Dr Yun Phua, 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
Single group
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 (as described in the schedule of assessment). The bone volume will be analysed using Mimics (Materialise, Belgium) software.

Comparison analysis of Cleft-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
15/01/2024
Actual
Date of last participant enrolment
Anticipated
15/08/2025
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] 25345 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 41053 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 314525 0
Commercial sector/Industry
Name [1] 314525 0
Osteopore Limited
Country [1] 314525 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] 316476 0
None
Name [1] 316476 0
Address [1] 316476 0
Country [1] 316476 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 313567 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC)
Ethics committee address [1] 313567 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] 313567 0
Australia
Date submitted for ethics approval [1] 313567 0
09/10/2023
Approval date [1] 313567 0
Ethics approval number [1] 313567 0

Summary
Brief summary
The aim of this study is to use a 3D-printed scaffold made specifically for the patient to help improve the visual appearance and symmetry of their nose. The current treatment to improve symmetry to the nostril base is to use either bone graft which is prone to resorb with time or to use an artificial material which doesn’t grow with the child. We hope to overcome these shortcomings by implanting a biodegradable scaffold under the base of the nose to improve nostril shape. The scaffold will be placed during the same surgery as the patient’s secondary alveolar bone grafting procedure or secondary rhinoplasty. The scaffold is made from a material (polycaprolactone-tricalciumphosphate (mPCL-TCP)) that degrades over time allowing for their own tissue to grow into it leaving them with just their own tissue once the scaffold has fully degraded. The scaffold will typically fully degrade in 24 months.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128574 0
Dr Yun Phua
Address 128574 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128574 0
Australia
Phone 128574 0
+61 0730682581
Fax 128574 0
Email 128574 0
yun.phua@health.qld.gov.au
Contact person for public queries
Name 128575 0
Dr Yun Phua
Address 128575 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128575 0
Australia
Phone 128575 0
+61 0730682581
Fax 128575 0
Email 128575 0
yun.phua@health.qld.gov.au
Contact person for scientific queries
Name 128576 0
Dr Yun Phua
Address 128576 0
Queensland Children’s HospitalLevel 7501 Stanley StreetSouth BrisbaneQLD 4101
Country 128576 0
Australia
Phone 128576 0
+61 0730682581
Fax 128576 0
Email 128576 0
yun.phua@health.qld.gov.au

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.