Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001157460
Ethics application status
Approved
Date submitted
22/08/2016
Date registered
25/08/2016
Date last updated
7/11/2022
Date data sharing statement initially provided
7/11/2022
Date results information initially provided
7/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Case Series Study: Surgical Repair of Peripheral Nerve Injury with CelGro "Registered Trademark" Collagen Scaffold.
Scientific title
Case Series Study: Surgical Repair of Peripheral Nerve Injury with CelGro "Registered Trademark"Collagen Scaffold.
Secondary ID [1] 289988 0
CG-006
Universal Trial Number (UTN)
U1111-1186-7168
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral nerve injury 299996 0
Condition category
Condition code
Surgery 299888 299888 0 0
Surgical techniques
Injuries and Accidents 299889 299889 0 0
Other injuries and accidents
Neurological 299890 299890 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Surgical Repair of Peripheral Nerve Injury with CelGro "Registered Trademark" Collagen Scaffold:
CelGro "Registered Trademark is a next-generation porcine collagen membrane manufactured in Australia from locally-produced source material. It is classified as a Class III Medical Device and is intended for use in surgical applications such as tendon and soft tissue repair and guided tissue regeneration.
This is an open label pilot study where adult patients who have a traumatic injury to one or more of the peripheral nerves of the upper limb or hand that requires surgical repair will receive a single surgical implantation of CelGro "Registered Trademark at the site of the nerve end repair to be used as a conduit for nerve repair. The implantation will be performed by an Orthopaedic surgeon. The length of surgery time and recovery will depend on the number of nerves damaged and the size of the nerve gap.

Haemostasis of the nerve ends will be achieved prior to placement of CelGro"Registered Trademark". Tensionless repair will be achieved using atraumatic sutures to secure the CelGro"Registered Trademark" scaffold to the epineurium of each nerve end, resulting in a tube of CelGro"Registered Trademark" connecting and encasing the nerve ends. The site of CelGro"Registered Trademark" attachment to each nerve end will be a distance approximately greater than or equal to the nerve diameter. Fibrin glue may be used to assist with adhesion. The size of the CelGro"Registered Trademark" scaffold used will depend on the size of the nerve gap.
CelGro"Registered Trademark" is a classified as a medical device and is delivered in a sterile sealed pouch and presents as a white to off white sheet with a smooth and a slightly rough side and is intended for single use only.
Intervention code [1] 295688 0
Treatment: Surgery
Intervention code [2] 295689 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299370 0
Adverse events related to study treatment or procedures.

Adverse events will be assessed by clinical examination and participant interview at each study visit. Intensity will be graded as either: mild. moderate, severe, or extreme.

Adverse events related to study treatment may include infection at the surgical site and allergic reaction to the investigational device. Adverse events related to surgery may include discomfort and swelling, and other standard risks associated with anaesthesia and surgery of this kind.
Timepoint [1] 299370 0
Assessments will occur at 1, 6, 12 and 24 months post-treatment.
Primary outcome [2] 299371 0
Additional surgical or significant medical intervention required as a result of treatment failure (assessed at each study visit by the treating investigator).
Timepoint [2] 299371 0
Up to 24 months post-treatment.
Primary outcome [3] 333040 0
Motor function assessment (MRC criteria).
Timepoint [3] 333040 0
1, 6, 12, and 24 months post treatment
Secondary outcome [1] 326964 0
Sensory assessment (static and moving two-point discrimination)
Timepoint [1] 326964 0
1, 6, 12, and 24 months post treatment.
Secondary outcome [2] 326996 0
Upper limb function as assessed by the QuickDASH score.
Timepoint [2] 326996 0
6, 12, and 24 months post treatment.
Secondary outcome [3] 327063 0
Visual analogue scale (VAS) pain score
Timepoint [3] 327063 0
7-14 days, and months 1, 6, 12, and 24 post treatment.
Secondary outcome [4] 327064 0
Quality of life as assessed by the AQoL-6D score.
Timepoint [4] 327064 0
6, 12, and 24 months post treatment.
Secondary outcome [5] 327065 0
Nerve damage as assessed by Tinel’s sign.
Timepoint [5] 327065 0
7-14 days, and months 1, 6, 12, and 24 post treatment.

Eligibility
Key inclusion criteria
Male or female aged 18-50 years.
Traumatic injury to one or more peripheral nerves of the upper limb or hand requiring surgical repair.
Nerve gap <20mm.
Able to require to the requirements of the protocol.
Able to give informed consent or has legally acceptable representative who can give informed consent in accordance with ICH/GCP.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Nerve gap >20mm
Active infection or systemic pathology including inflammatory joint disease, HIV, uncontrolled or poorly controlled diabetes, hepatitis or neoplastic disorders.
Known hypersensitivity to the study treatment or its excipients or known relevant medication allergy.
Female participant who is pregnant or lactating.
Known substance abuse.
Participation in another study with an investigational product within the last 3 months of study treatment date.
Concurrent medical condition which precludes the administration of the study treatment.
Other clinically significant disease (including psychological disorders) or medical condition that would, in the opinion of the Investigator, compromise the safety of the participant or the outcome of the study.

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
Demographic data will be displayed and summary statistics used to describe the study population

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2016
Actual
20/12/2016
Date of last participant enrolment
Anticipated
1/07/2018
Actual
23/04/2020
Date of last data collection
Anticipated
1/07/2020
Actual
18/03/2022
Sample size
Target
20
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 6519 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [2] 6520 0
St John of God Hospital, Murdoch - Murdoch
Recruitment postcode(s) [1] 14092 0
6008 - Subiaco
Recruitment postcode(s) [2] 14093 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 294361 0
Commercial sector/Industry
Name [1] 294361 0
Orthocell Ltd
Country [1] 294361 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Orthocell Ltd
Address
Building 191
Murdoch University
South Street
Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 293202 0
None
Name [1] 293202 0
Address [1] 293202 0
Country [1] 293202 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295779 0
St John of God Health Care HREC
Ethics committee address [1] 295779 0
12 Salvado Road
Subiaco
WA 6009
Ethics committee country [1] 295779 0
Australia
Date submitted for ethics approval [1] 295779 0
05/09/2016
Approval date [1] 295779 0
12/10/2016
Ethics approval number [1] 295779 0
SJOG HREC 1036

Summary
Brief summary
CelGro "Registered Trademark is an acellular type I/III collagen matrix of porcine origin. The product consists of natural collagen bundles without cross-linking or chemical additives. It is free from animal-derived DNA and pathogens.
Treatment of injuries to peripheral nerves is a challenging surgical issue. The primary aim of surgical repair is to guide regenerating axons correctly into place in the distal nerve, with minimal loss of nerve fibres at the site of repair. This results in reinnervation of distal tissues, and restores autonomic, sensory and motor function.
Direct, tensionless, end-to-end repair using epineural microsutures (neurorhaphy) provides the most favourable outcomes. Tensionless repair is acknowledged as a major factor in successful recovery of sensorimotor function. However, if a tensionless repair cannot be achieved, autologous nerve grafting is the gold standard treatment for surgical treatment of nerve gaps. However, autologous nerve grafting results in significant donor-site morbidity; is more technically difficult to perform; requires more operative time; and elevates treatment costs.
The search for alternatives to nerve grafting has resulted in the development of nerve conduits, which are tubes fashioned of biocompatible materials. The proximal and distal ends of the severed nerve are inserted into the tube and sutured in place. The conduit provides gross alignment for the regenerating nerve, and retains fluids leaking from the nerve ends, enriching the microenvironment with neurotrophic growth factors. Conduits manufactured from bioabsorbable materials are preferred as non-degradable materials such as silicone require additional surgery for removal, and may have detrimental effects on nerve regeneration.
Collagen is one of the most commonly used biomaterials for construction of nerve conduits. Key advantages of collagen are that it is biocompatible and has a natural structure that has been shown to support and guide tissue regeneration in vivo. Clinical studies have shown that digital nerve gaps of up to 40mm can be bridged with collagen conduits, resulting in good to excellent sensory outcomes in up to 75% of patients.

CelGro"registered trademark" is a next-generation membrane that is manufactured using collagen originating from animals bred and exclusively raised in Australia, eliminating disease transmission concerns associated with foreign products. Additionally, the collagen bundle structure of CelGro"registeris mechanically stronger and more elastic than other collagen membrane products of this type.
The main complication related to conduit implantation is protrusion or extrusion of the conduit. This is most common when the repair occurs across a joint or where the quality of covering soft tissue is reduced. However, in a systematic review of digital nerve repair using resorbable FDA- and CE-approved nerve conduits, protrusion or extrusion of collagen conduits was not observed
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68442 0
Dr Alex O'Beirne
Address 68442 0
Western Orthopaedic Clinic
Suite 213
25 McCourt Street
Subiaco
WA 6009
Country 68442 0
Australia
Phone 68442 0
+618 9489 8799
Fax 68442 0
Email 68442 0
[email protected]
Contact person for public queries
Name 68443 0
Dr Alex O'Bierne
Address 68443 0
Western Orthopaedic Clinic
Suite 213
25 McCourt Street
Subiaco
WA 6009
Country 68443 0
Australia
Phone 68443 0
+618 9489 8799
Fax 68443 0
Email 68443 0
[email protected]
Contact person for scientific queries
Name 68444 0
Dr Clair Lee
Address 68444 0
Clinical Research Manager
Orthocell Ltd
Building 191 Murdoch University
South Street
Murdoch WA 6150
Country 68444 0
Australia
Phone 68444 0
+61 8 6360 2888
Fax 68444 0
+61 8 9360 2899
Email 68444 0
[email protected]

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 efficacy/safety line listings.
When will data be available (start and end dates)?
After publication, no end date.
Available to whom?
Researchers who provide a methodologically and scientifically sound research proposal that has received Human Research Ethics Committee approval, as assessed on a case by case basis.
Available for what types of analyses?
Meta-analysis.
How or where can data be obtained?
Subject to approval from the Principal Investigator and Sponsor.

Email: [email protected]


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.