ANZCTR - Registration

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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]

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

Condition category

Condition code

Surgery

Surgical techniques

Injuries and Accidents

Other injuries and accidents

Musculoskeletal

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]

Treatment: Surgery

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

This will be performed every 3 months during the 36 month study period.

Secondary outcome [1]

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]

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]

Short Musculoskeletal Function Assessment (SMFA) questionnaire score

Timepoint [2]

Every 6 months throughout the study period (36 months)

Secondary outcome [3]

36-item Short Form Quality of Life Survey

Timepoint [3]

This form will be completed prior to surgical intervention and every 6 months throughout the study period post intervention (36 months)

Secondary outcome [4]

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]

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]

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]

The first time at which union is achieved in the study period (up to 36 months).

Secondary outcome [6]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Princess Alexandra Hospital - Woolloongabba

Recruitment postcode(s) [1]

4102 - Woolloongabba

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Osteopore International Pty Ltd

Address [1]

2 Tukang Innovation Grove, #09-06 MedTech Hub, Singapore 618305

Country [1]

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]

University

Name [1]

Australian Centre for Complex Integrated Surgical Solutions (ACCISS)

Address [1]

Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102

Country [1]

Australia

Other collaborator category [1]

University

Name [1]

Centre for Biomedical Technologies, School of Mechanical, Medical, and Process Engineering, Faculty of Engineering, Queensland University of Technology

Address [1]

60 Musk Avenue, Kelvin Grove QLD 4059

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Metro South Human Research and Ethics Committee (HREC)

Ethics committee address [1]

Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

31/10/2019

Approval date [1]

15/05/2020

Ethics approval number [1]

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

Dr Michael Wagels

Address

Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102

Country

Australia

Phone

+61 7 3176 2111

Fax

michael.wagels@health.qld.gov.au

Contact person for public queries

Name

Michael Wagels

Address

Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102

Country

Australia

Phone

+61 7 3176 2111

Fax

michael.wagels@health.qld.gov.au

Contact person for scientific queries

Name

Michael Wagels

Address

Australian Center for Complex Integrated Surgical Solutions
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba, QLD, 4102

Country

Australia

Phone

+61 7 3176 2111

Fax

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

Source	Title	Year of Publication	DOI
Dimensions AI	Protocol 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 transfer	2023	https://doi.org/10.1136/bmjopen-2021-056440

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically