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Trial registered on ANZCTR


Registration number
ACTRN12612000353897
Ethics application status
Approved
Date submitted
26/03/2012
Date registered
28/03/2012
Date last updated
19/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
When reconstructing defects in the skull is it safer and more cost effective to use a patients own bone or a custom made titanium plate
Scientific title
A single blinded randomised controlled trial comparing the safety efficacy and cost effectiveness of autologous bone compared with custom made titanium for reconstructive cranioplasty
Secondary ID [1] 280221 0
Nil
Universal Trial Number (UTN)
U1111-1129-4840
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic brain injury 286165 0
Stroke 286166 0
Subarachnoid haemorrhage 286167 0
Condition category
Condition code
Surgery 286360 286360 0 0
Surgical techniques
Neurological 286373 286373 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cranioplasty with either custom made titanium or autologous bone in patients requiring reconstruction of a skull defect. The surgical procedure in either case takes approximately one hour. The number of procedures performed will be no differant to what usually occurs because all patients who have a large skull defect will need to have a cranioplasty procedure in order to restore the cosmetic and protective function of the skull
Intervention code [1] 284551 0
Treatment: Surgery
Intervention code [2] 284564 0
Treatment: Devices
Comparator / control treatment
Usual method of reconstruction which is the patients own bone (Autologous cranioplasty). The bone that has been removed is stored in a designated refridgerator until the pathological process that caused the acute brain swelling has subsided. (e.g. traumatic brain injury, ischaemic stroke, Subarachnoid haemorrhage). Once the brain swelling has resolved the patient is taken back to theatre and the previous incision is reopened and the bone replaced and secured with miniplates. The procedure takes approximately one hour. Only one procedure is required
Control group
Active

Outcomes
Primary outcome [1] 286818 0
The primary outcome measures will be failure of the cranioplasty such that it requires removal (due to infection, resorption, dislodgement or severe cosmetic failure), as well as any significant adverse events attributable to treatment allocation. The patients will be followed up in the outpatients department at 3, 6, and 12 months post surgery. The patients will be clinically examined to assess adverse events such as wound breakdown, infection and cosmetic deformity. At twelve months a CT scan of the brain will assess whether the autologous bone has undergone significant resorption
Timepoint [1] 286818 0
One year post surgery
Secondary outcome [1] 296728 0
Total hospital costs incurred by the two groups of patients over a one year period. This will include manufacture of the custom made cranioplasties (both as a primary and for those that fail as a secondary procedure), length of additional hospital days due to complications (excluding ongoing hospital inpatient requirements), antibiotics, theatre time and follow up appointments.
Timepoint [1] 296728 0
One year post surgery
Secondary outcome [2] 296729 0
Quantitative bone volume loss between early post-op CT and CT at one year using BrainLAB stereotactic software.
Timepoint [2] 296729 0
One year post surgery
Secondary outcome [3] 296730 0
Quality of life as measured by SF-36
Timepoint [3] 296730 0
One year post surgery

Eligibility
Key inclusion criteria
Adult patients in Western Australia who have undergone craniectomy and who are awaiting a cranioplasty procedure.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have had a previous cranial infection and patients who do not have an autologous bone flap
available

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible patients will be identified in the in the neurosurgical clinic or neurosurgical ward and they will be approached by the study investigators. After informed consent is given and documented, each will be randomised using online randomisation software approximately eight weeks prior to their intended date for surgery. Research participants and assessment staff will be blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised according to a random number sequence generated by a random number software and all randomisation numbers are concealed inside sequentially numbered sealed envelopes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/04/2012
Actual
2/04/2012
Date of last participant enrolment
Anticipated
2/04/2015
Actual
7/08/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 284972 0
Government body
Name [1] 284972 0
Western Australian State Health Research Advisory Council
Country [1] 284972 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Wellington Street
Perth WA 6001
Country
Australia
Secondary sponsor category [1] 283839 0
None
Name [1] 283839 0
Address [1] 283839 0
Country [1] 283839 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286978 0
Royal Perth Hospital HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 286978 0
Wellington Street
Perth WA 6001
Ethics committee country [1] 286978 0
Australia
Date submitted for ethics approval [1] 286978 0
Approval date [1] 286978 0
28/02/2012
Ethics approval number [1] 286978 0
EC 2012/126
Ethics committee name [2] 292843 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [2] 292843 0
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
Perth WA 6000
Ethics committee country [2] 292843 0
Australia
Date submitted for ethics approval [2] 292843 0
14/03/2012
Approval date [2] 292843 0
30/05/2012
Ethics approval number [2] 292843 0
2012-052

Summary
Brief summary
Cranial bone defects are often left following brain surgery usually to allow swelling of the brain to recover before subsequently re-implanting protective covering of the brain at a later time (cranioplasty). These procedure are performed anywhere over the the cranial vault, either unilaterally or bilaterally. The original piece of bone (autologous bone plate = bone flap) is placed in a sterile container and stored in a refrigerator at temperature of -40degrees celcius.

Weeks or months later, when the brain is relaxed, the scalp well healed, and the patient’s medical condition permits, the individual is taken back to the operating theatre and the bone is reimplanted (A procedure known as an autologous cranioplasty). The aim of the procedure is to restore cosmesis and protection to the underlying brain and it can sometimes also improve neurological symptoms by unknown mechanisms. Unfortunately these aims are not always achieved and whilst technically straightforward the procedure is known to be associated with a number of complications. Two of the most significant of which are infection (such that the bone flap needs to be removed and replaced) and resorption (such that the protective function is compromised). A less severe but cosmetically significant complication is injury to the frontal branch of the facial nerve during cranioplasty leading to weakness of eyebrow elevation.

Between 2004 and 2009 in Western Australia 164 patients required either a unilateral (n = 78) or bilateral (n = 86) decompressive craniectomy for trauma. Of those patients that survived 138 had a cranioplasty procedure and in this cohort there was a high rate of infection and bone flap resorption.

Infection
A number of reports have now documented the higher than expected incidence of infection following decompressive craniectomy and subsequent cranioplasty. Within the Western Australian state-wide neurosurgical service the overall infection rate for cranial procedures has been consistently audited at 1 – 2%, however within the post-traumatic craniectomy/cranioplasty cohort of 138 patients, sixteen (11.6%) had to have the bone flap removed because of infection. It is not known why the infection rate is so high but a number of reasons have been proposed e.g. skin colonisation whilst in hospital, factors relating to long-term storage of the bone flap, immune compromise following trauma and reoperation. Some studies have reported lower rates of infection when using custom made titanium or ceramic cranioplasty plates however, meaningful interpretation of the published literature is difficult because other studies have demonstrated precisely the opposite.

Bone flap resorption
The incidence of bone flap resorption has been reported between 10% and 50% Within our post traumatic cohort, 10% of the bone flaps were so severely resorbed that they needed to be replaced. A further 12% showed significant radiological resorption and whilst these were not replaced they could be adjudged to have failed because there is concern that they do not provide adequate protection.

In each case of absolute cranioplasty failure (overall approximately 20%) the patient requires readmission, a second operation to remove the bone flap, prolonged antibiotic therapy (in the case of infection), a custom-made titanium plate constructed and readmission for a third surgical procedure. The question addressed in this study is whether it would be more efficacious and cost effective to insert a custom-made titanium cranioplasty as a primary procedure.
Trial website
Trial related presentations / publications
Honeybul, S., Ho, K.M., Lind, C.R.P., and Gillett G. The retrospective application of a prediction model to patients who have had a decompressive craniectomy for trauma. J. Neurotrauma. 26: 2179, 2009.

Honeybul, S., Ho, K.M., Lind, C.R.P., and Gillette G. Observed versus predicted outcome for decompressive craniectomy: A population based study. J. Neurotrauma. 27: 1225, 2010.

Honeybul, S., and Ho, K.M. Long-term complications of decompressive craniectomy for head injury. J Neurotrauma. 28: 929, 2011.

Honeybul, S. Sudden death following cranioplasty: a complication of decompressive craniectomy for head injury. Br. J. Neurosurg. 25: 343, 2011.
Public notes

Contacts
Principal investigator
Name 33978 0
Mr Stephen Honeybul
Address 33978 0
Department of Neurosurgery
Sir Charles Gairdner
Hospital Avenue
Nedlands
Perth WA 6000

Royal Perth Hospital
Wellinton Street
Perth WA 6001
Country 33978 0
Australia
Phone 33978 0
+61 8 93463333
Fax 33978 0
+61 8 93463824
Email 33978 0
[email protected]
Contact person for public queries
Name 17225 0
Stephen Honeybul
Address 17225 0
Sir Charles Gairdner Hospital
Hospital Avenue, Nedlands, Perth WA 6009

Royal Perth Hospital
Wellington Street, Perth WA 6001
Country 17225 0
Australia
Phone 17225 0
+61 8 9346 3333
Fax 17225 0
Email 17225 0
[email protected]
Contact person for scientific queries
Name 8153 0
Stephen Honeybul
Address 8153 0
Sir Charles Gairdner Hospital
Hospital Avenue, Nedlands, Perth WA 6009

Royal Perth Hospital
Wellington Street, Perth WA 6001
Country 8153 0
Australia
Phone 8153 0
+61 8 9346 3333
Fax 8153 0
Email 8153 0
[email protected]

No information has been provided regarding IPD availability


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
EmbaseA randomized controlled trial comparing autologous cranioplasty with custom-made titanium cranioplasty.2017https://dx.doi.org/10.3171/2015.12.JNS152004
N.B. These documents automatically identified may not have been verified by the study sponsor.