ANZCTR - Registration

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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]

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

Stroke

Subarachnoid haemorrhage

Condition category

Condition code

Surgery

Surgical techniques

Neurological

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]

Treatment: Surgery

Intervention code [2]

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]

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]

One year post surgery

Secondary outcome [1]

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]

One year post surgery

Secondary outcome [2]

Quantitative bone volume loss between early post-op CT and CT at one year using BrainLAB stereotactic software.

Timepoint [2]

One year post surgery

Secondary outcome [3]

Quality of life as measured by SF-36

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Western Australian State Health Research Advisory Council

Address [1]

Western Australian Department of Health
189 Royal Street
East Perth
6004

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Perth Hospital

Address

Wellington Street
Perth WA 6001

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Perth Hospital HUMAN RESEARCH ETHICS COMMITTEE

Ethics committee address [1]

Wellington Street
Perth WA 6001

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

28/02/2012

Ethics approval number [1]

EC 2012/126

Ethics committee name [2]

Sir Charles Gairdner Hospital Human Research Ethics Committee

Ethics committee address [2]

Sir Charles Gairdner Hospital 
Hospital Avenue
Nedlands
Perth WA 6000

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

14/03/2012

Approval date [2]

30/05/2012

Ethics approval number [2]

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

Mr Stephen Honeybul

Address

Department of Neurosurgery
Sir Charles Gairdner
Hospital Avenue
Nedlands
Perth WA 6000

Royal Perth Hospital
Wellinton Street
Perth WA 6001

Country

Australia

Phone

+61 8 93463333

Fax

+61 8 93463824

stephen.honeybul@health.wa.gov.au

Contact person for public queries

Name

Stephen Honeybul

Address

Sir Charles Gairdner Hospital
Hospital Avenue, Nedlands, Perth WA 6009

Royal Perth Hospital
Wellington Street, Perth WA 6001

Country

Australia

Phone

+61 8 9346 3333

Fax

stephen.honeybul@health.wa.gov.au

Contact person for scientific queries

Name

Stephen Honeybul

Address

Sir Charles Gairdner Hospital
Hospital Avenue, Nedlands, Perth WA 6009

Royal Perth Hospital
Wellington Street, Perth WA 6001

Country

Australia

Phone

+61 8 9346 3333

Fax

stephen.honeybul@health.wa.gov.au

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

Source	Title	Year of Publication	DOI
Embase	A randomized controlled trial comparing autologous cranioplasty with custom-made titanium cranioplasty.	2017	https://dx.doi.org/10.3171/2015.12.JNS152004

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

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Documents added manually

Documents added automatically