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Trial registered on ANZCTR


Registration number
ACTRN12620001007921
Ethics application status
Approved
Date submitted
19/05/2020
Date registered
6/10/2020
Date last updated
26/08/2022
Date data sharing statement initially provided
6/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial evaluating a novel scaffold-based method for regenerating bone in lower limb reconstruction
Scientific title
The BONE-RECON trial: A single-arm feasibility trial evaluating the mPCL-TCP scaffold system with corticoperiosteal tissue transfer for reconstruction of critical sized lower limb bone defects
Secondary ID [1] 298564 0
None
Universal Trial Number (UTN)
Trial acronym
BONE-RECON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acquired intercalary defect of the femur or tibia 318550 0
Condition category
Condition code
Surgery 311948 311948 0 0
Surgical techniques
Injuries and Accidents 311949 311949 0 0
Other injuries and accidents
Musculoskeletal 311953 311953 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A medical-grade Polycaprolactone Tricalcium Phosphate (mPCL-TCP) 3D printed scaffold (Osteopore, Pty. Ltd. Singapore) will be used in this project. The device has FDA approval and has been used in a single selected case in Australia with Special Access Scheme TGA approval. This will be used alongside a free or pedicled tissue transfer of corticoperiosteal tissue to regenerate bone sufficient to bridge a critical sized bone defect in the lower limb. The corticoperiosteal flap surgical approach is already used in reconstructive surgery. The combination of the two methods for lower limb reconstruction is the novelty related to this trial.

Briefly, for patients that meet eligibility criteria for segmental bone defect repair of the lower limb, a customised (personalised) 3D printed scaffold (Osteopore, Pty. Ltd. Singapore) will be manufactured based on preoperative imaging data. Implant-related pre-operative planning and simulated scaffold implantation training is performed by the surgical team in the weeks leading up to each surgery to optimize the surgical outcome. This is performed as a single 60-minute training session led by the research principal investigator Dr Michael Wagels at the Australian Center for Complex Integrated Surgical Solutions (ACCISS) located at the Translational Research Facility in Woolloongabba, Brisbane. At the Princess Alexandra Hospital, the patient will undertake surgical reconstruction of the lower limb defect through the use of the scaffold to match the bone that is lost, alongside vascularised tissue transfer (“free flap”) of corticoperiosteal tissue (“corticoperiosteal flap”) to be placed inside the scaffold to enhance bone regeneration (regenerative matching axial vascularisation). Additionally, a bone growth factor (bone morphogenic protein -7) will be impregnated inside the scaffold to enhance scaffold-based bone regeneration. A team of experienced surgeons will perform the surgery over a period of 8 hours. Clinical follow up will occur over a 36 month period after the initial reconstruction, and further surgical interventions may be required during this period to optimise the outcome (as is done normally in lower limb reconstruction).
Intervention code [1] 314901 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320609 0
Safety and Tolerability of the novel intervention. Specific reporting on safety and tolerability will include adverse events that occur during the study period as related to both the scaffold and surgical approach. Reporting will be performed as an ‘adverse event’ and ‘near adverse event’, as per the Australian Therapeutic Goods Administration (TGA) guidelines on Medical Device Adverse Event Reporting. Monitoring of the safety of the intervention will be conducted by the Data Monitoring Committee as part of an audit of medical records.
Timepoint [1] 320609 0
This will be performed every 3 months during the 36 month study period.
Secondary outcome [1] 372183 0
Time to partial (touch) weight bearing on the affected limb. This is determined by the treating surgical team when union is considered sufficient for partial load-bearing (ie. touch weight bearing of the foot with crutches).
Timepoint [1] 372183 0
Patients are assessed weekly for the first month post discharge, then fortnightly for the 2 months following, then 3 monthly until 36 months post surgery.
Secondary outcome [2] 372184 0
Short Musculoskeletal Function Assessment (SMFA) questionnaire score
Timepoint [2] 372184 0
Every 6 months throughout the study period (36 months)
Secondary outcome [3] 372187 0
36-item Short Form Quality of Life Survey
Timepoint [3] 372187 0
This form will be completed prior to surgical intervention and every 6 months throughout the study period post intervention (36 months)
Secondary outcome [4] 386603 0
Time to full weight bearing on affected limb. This is determined by the treating surgical team when union is considered sufficient for full weight bearing (normal ambulation with full "normal" loading of the limb through the gait cycle).
Timepoint [4] 386603 0
Patients are assessed weekly for the first month post discharge, then fortnightly for the 2 months following, then 3 monthly until 36 months post surgery.
Secondary outcome [5] 413409 0
Time to union (radiological and/or clinical). Union will be assessed by a dedicated radiology consultant involved in the trial and scored using the radiological union score (RUS) and the computed tomographic union score (TUS). Clinically, union will be assessed by both the consultant orthopaedic surgeon and plastic surgeon using a combination of clinical examination alongside assessment of weight bearing status and gait where applicable.
Timepoint [5] 413409 0
The first time at which union is achieved in the study period (up to 36 months).
Secondary outcome [6] 413410 0
Time to full weight bearing (ie. full weight on treated limb) on the affected limb. This is determined by the treating surgical team when union is considered sufficient for full weight bearing (ie. full weight on limb without supports like crutches, single point stick etc).
Timepoint [6] 413410 0
Patients are assessed weekly for the first month post discharge, then fortnightly for the 2 months following, then 3 monthly until 36 months post surgery.

Eligibility
Key inclusion criteria
Men or women >18 years of age and <80 years of age
Acquired intercalary defect of the femur or tibia
Patients must be willing and able to comply with the study requirements
Patients must be capable of providing valid (written and informed) consent
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Active infection of the limb at the time of study inclusion
Absence or significant disability associated with contra-lateral weight-bearing limb
Patient unwilling or unable to provide fully informed consent including patients with intellectual or mental impairment
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: cardiovascular, respiratory or immunological) illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the primary investigator, compromise their safety or compliance or interfere with interpretation of study results
Patient life expectancy < 36 months
Patient unable or unwilling to comply with the treatment protocol

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
A minimum of ten patients are required. No formal power analysis has been performed as this is not a comparative study. The number of patients required for inclusion in the trial is based on in vivo data in an ovine large animal model and is sufficient to meet the primary end-points of early feasibility, safety and tolerability.

All patients registered for the trial will be accounted for in the analysis (intention to treat).

For secondary outcome measures, statistical analysis otherwise will include a descriptive review of relevant clinical variables to the time to bony union and time to weight-bearing on the affected limb in the study period. Univariate student’s t test, X2 and multivariate Cox regression analysis will be performed where it is statistically appropriate. For such measures, statistical significance will be defined as P < 0.05. Data will be analysed and graphed using SPSS for Windows v.26 (SPSS, Chicago, Illinois, USA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/01/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14128 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 26938 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 312129 0
Commercial sector/Industry
Name [1] 312129 0
Osteopore International Pty Ltd
Country [1] 312129 0
Singapore
Primary sponsor type
Commercial sector/Industry
Name
Osteopore International Pty Ltd
Address
2 Tukang Innovation Grove, #09-06 MedTech Hub, Singapore 618305
Country
Singapore
Secondary sponsor category [1] 313649 0
University
Name [1] 313649 0
Australian Centre for Complex Integrated Surgical Solutions (ACCISS)
Address [1] 313649 0
Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country [1] 313649 0
Australia
Other collaborator category [1] 280831 0
University
Name [1] 280831 0
Centre for Biomedical Technologies, School of Mechanical, Medical, and Process Engineering, Faculty of Engineering, Queensland University of Technology
Address [1] 280831 0
60 Musk Avenue, Kelvin Grove QLD 4059
Country [1] 280831 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303648 0
Metro South Human Research and Ethics Committee (HREC)
Ethics committee address [1] 303648 0
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 303648 0
Australia
Date submitted for ethics approval [1] 303648 0
31/10/2019
Approval date [1] 303648 0
15/05/2020
Ethics approval number [1] 303648 0
HREC/2020/QMS/52837

Summary
Brief summary
The research project aims to evaluate safety and tolerability of a novel method for large volume bone reconstruction that includes a combination of a thin layer of bone with its blood supply kept in tact as well as a 3-D printed scaffold to help bone grow. This method of “growing” new bone uses a 3D printed substance similar to human bone and is already TGA approved for use in reconstruction of the bone of the skull. The novelty to the project stems from a new method of "growing" new bone in the patient by using a small amount of their own bone from another part of the body with its blood supply kept in tact using very fine surgical techniques (microsurgery) to connect the vessels. This approach is known in reconstructive surgery as a "free flap".

It is hoped that this trial will provide further evidence to support the use of this method in reconstructing large segment bone loss for a range of conditions where minimal options currently exist – the focus being on “limb salvage” where amputation can be avoided for a better functional and socially acceptable outcome for the patient.
Trial website
Trial related presentations / publications
Public notes
Sparks DS, Flavi MS, Saifzadeh S, Schuetz MA, Wagels M, Hutmacher DW. (2020) Convergence of Scaffold-Guided Bone Reconstruction and Surgical Vascularization Strategies-A Quest for Regenerative Matching Axial Vascularization. Front. Bioeng. Biotechnol. 10;7:448. doi: 10.3389/fbioe.2019.00448

Sparks, DS; Wagels, M; Taylor, GI. (2017) Bone reconstruction: a history of vascularised bone transfer. Microsurgery., http://dx.doi.org/10.1002/micr.30260

Sparks DS; et al., (2017) Vascularised bone transfer: History, blood supply and contemporary problems, JPRAS, http://dx.doi.org/10.1016/j.bjps.2016.07.12

Sparks DS, Saifzadeh S, Savi FM, Dlaska CE, Berner A, Henkel J, Reichert JC, Wullschleger M, Ren J, Cipitria A, McGovern JA, Steck R, Wagels M, Woodruff MA, Schuetz MA, Hutmacher DW. (2020) A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction. Nat. Protoc. 15(3):877-924. doi: 10.1038/s41596-019-0271-2. Epub 2020 Feb 14.

Sparks DS, Medeiros Savi F, Saifzadeh S, Wille ML, Wagels M, Hutmacher DW. Bone regeneration exploiting corticoperiosteal tissue transfer in scaffold-
guided bone regeneration. Tissue Eng Part C Methods. 2022 Mar 9. doi: 10.1089/ten.TEC.2022.0015. Epub ahead of print. PMID: 35262425.

Castrisos G, Gonzalez Matheus I, Sparks D, Lowe M, Ward N, Sehu M, Wille ML, Phua Y, Medeiros Savi F, Hutmacher D, Wagels M. Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series. J Plast Reconstr Aesthet Surg. 2022 Mar 9:S1748- 6815(22)00137-1. doi: 10.1016/j.bjps.2022.02.057. Epub ahead of print. PMID: 35370116.

Contacts
Principal investigator
Name 94390 0
Dr Michael Wagels
Address 94390 0
Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102
Country 94390 0
Australia
Phone 94390 0
+61 7 3176 2111
Fax 94390 0
Email 94390 0
michael.wagels@health.qld.gov.au
Contact person for public queries
Name 94391 0
Dr Michael Wagels
Address 94391 0
Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102
Country 94391 0
Australia
Phone 94391 0
+61 7 3176 2111
Fax 94391 0
Email 94391 0
michael.wagels@health.qld.gov.au
Contact person for scientific queries
Name 94392 0
Dr Michael Wagels
Address 94392 0
Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102
Country 94392 0
Australia
Phone 94392 0
+61 7 3176 2111
Fax 94392 0
Email 94392 0
michael.wagels@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data. All results will be made available.
When will data be available (start and end dates)?
Following publication of the clinical trial. IPD will be available 5-years post-publication.
Available to whom?
Case-by-case basis at the discretion of Primary Investigator
Available for what types of analyses?
At the discretion of Primary Investigator
How or where can data be obtained?
Following a signed data protection agreement and agreement by the Principal Investigator (Dr Michael Wagels - EMAIL: Michael.Wagels@health.qld.gov.au)


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
SourceTitleYear of PublicationDOI
Dimensions AIProtocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer2023https://doi.org/10.1136/bmjopen-2021-056440
N.B. These documents automatically identified may not have been verified by the study sponsor.