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Trial registered on ANZCTR


Registration number
ACTRN12618000882224
Ethics application status
Approved
Date submitted
4/04/2018
Date registered
25/05/2018
Date last updated
13/02/2019
Date data sharing statement initially provided
13/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does metal plating reduce the degree of disc collapse following anterior spinal surgery
Scientific title
Subsidence after plating in anterior cervical discectomy and fusion for cervical spondylosis: A phase 3, single-blinded randomised control trial.
Secondary ID [1] 294492 0
None/Nil known
Universal Trial Number (UTN)
U1111-1211-7182
Trial acronym
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Cervical Spondylosis
307260 0
Cervical degenerative disease 307261 0
Condition category
Condition code
Surgery 306379 306379 0 0
Surgical techniques
Musculoskeletal 306380 306380 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible patients will undergo an anterior cervical discetomy and fusion based on the Smith-Robinson technique, which is well described in the literature.
Arm 1 (Exposure) = Anterior Cervical Plate (ACP) group
Arm 2 (Control) = Standalone Cage (ASA) group

Arm 1:
- All patients receive information regarding the clinical trial, including an information sheet regarding operative details.
- Patients will all undergo preoperative and postoperative assessment, including the completion of clinical metrics that evaluate preoperative disability. This activity is delivered via an electronic survey and paper-based checklists. This occurs once pre-operatively, as well as at the 3, 6 and 12 month mark post-operatively.
- Patients will then undergo an ACDF as per the technique described above. Intraoperatively, patients in Arm 1 will have an anterior cervical metallic plate placed. This procedure is completed by a consultant neurosurgeon who is a fellow with the Royal Australasian College of Surgeons (RACS).
- All interventions will occur at Calvary Healthcare Lenah Valley, a private hospital.

- Monitoring fidelity to the intervention is not applicable because the intervention is delivered intra-operatively with regards to whether or not a patient receives the surgical implant described. Patient follow up will be facilitated by email/phone call reminders to attend outpatient clinics.


Intervention code [1] 300788 0
Treatment: Surgery
Intervention code [2] 300789 0
Treatment: Devices
Comparator / control treatment
Arm 2:
- All patients receive information regarding the clinical trial, including an information sheet regarding operative details.
- Patients will all undergo preoperative and postoperative assessment, including the completion of clinical metrics that evaluate preoperative disability. This activity is delivered via an electronic survey and paper-based checklists. This occurs once pre-operatively, as well as at the 3, 6 and 12 month mark post-operatively.
- Patients will then undergo an ACDF as per the technique described above. Intraoperatively, patients in Arm 2 will not have an anterior cervical metallic plate placed, instead proceeding with the standalone cage. This procedure is completed by a consultant neurosurgeon who is a fellow with the Royal Australasian College of Surgeons (RACS).
- All interventions will occur at Calvary Healthcare Lenah Valley, a private hospital.
Control group
Active

Outcomes
Primary outcome [1] 305390 0
Absolute interbody height loss (IHBL), measured in millimetres, as well as its derivative measure, the percentage of interbody height loss, herein referred to as the cage subsidence ratio (CSR).

This is the distance between two vertebral bodies measured on lateral cervical x-rays
Timepoint [1] 305390 0
This is measured at 3, 6 and 12 months post-operatively. The primary timepoint is 3 months post-operatively.
Secondary outcome [1] 345039 0
Changes in cervical spinal sagittal alignment over time, including the change between pre and post intervention, as well as the change in cervical sagittal alignment over the follow up period.

Cervical sagittal alignment is an angle expressed in degrees and is calculated as the angle between the intersection of two lines drawn perpendicular to the C2 and C7 endplate respectively. This is done manually utilising the tools within a picture archiving and communication system (PACS)
Timepoint [1] 345039 0
This is measured at 3, 6 and 12 months postoperatively.
Secondary outcome [2] 345040 0
Mean Neck Disability Index (NDI) score, including the change between pre- and post- intervention, as well as the change in NDI over the follow up period. This is measured using the widely described NDI survey
Timepoint [2] 345040 0
This will be measured at 3, 6 and 12 months postoperatively
Secondary outcome [3] 345930 0
Mean Short Form 12 (SF-12) score, including the change between pre- and post- intervention, as well as the change in SF-12 over the follow up period. This is measured using the widely described SF-12 survey. This is being utilised specifically to assess a composite secondary outcome of quality of life and functionality pre- intervention and post- intervention.
Timepoint [3] 345930 0
This will be measured at 3, 6 and 12 months postoperatively

Eligibility
Key inclusion criteria
Patients greater than 18 years of age
Patients prescribed one or two level ACDF for cervical degenerative disease by the treating surgeons
Patients requiring both single level and multi-level fusions will be eligible
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- ACDFs performed for traumatic injury of the spinal column
- Patients with prior anterior cervical spine surgery
- Patients who do not provide informed consent

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)
Sealed, opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation generated by computer software

Allocation is stratified based on the surgeon operating, so that each surgeon operates on equal numbers of patients allocated to the treatment and control arms.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Considering retrospective data, the population of patients who have undergone an ACDF experienced a mean interbody height loss (IBHL) of 5.0mm plus or minus 6.26mm. As the minimal clinically relevant difference in this study is deemed to be 3.0mm, the standardised difference is 0.48. By using a standardised nomogram that is well-established in the literature, we can see that to achieve a power of 80%, the sample size required to observe a statistically significant difference, if present, is in the order of 120-140 levels operated on per group. The exact number is likely to be 130 levels operated on per group. This number is attainable from a single site.

Please see Noordzij et al. 2011, ‘Sample size calculations’, Nephron Clin Pract, 118(4):c319-23 as a reference for the above calculations.

With regards to considering the relationship between radiological endpoints and patient spinal QoL outcomes, it will be difficult to calculate a sample size as this has not been investigated in-depth before. It has been suggested by the statistician that at least 10 individuals will be required for every explanatory variable included in the logistic regression model for QoL measures.

Statistical Methods
Clinical outcome will be measured pre-operatively versus postoperatively using the Oswestry Disability Index (ODI) and Short Form 12 (SF-12) All analyses will be based on 2-sided tests with values of P<0.05 considered significant with Bonferroni correction when appropriate (for repeated measures tests). Correlation studies will be performed using Pearson’s coefficients to investigate relations between changes in radiologic parameters and improvements in ODI and SF-12. If logistic regression analysis is performed, then approximately 10 individuals will be required for every explanatory variable included in a logistic regression model of neck and arm related pain and disability. All data analysis and statistical evaluations will be performed using the SPSS Statistics 23 (IBM Corporation, Armonk, NY, USA).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
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)
TAS
Recruitment hospital [1] 10542 0
Calvary Health Care Tasmania - Hobart - Lenah Valley
Recruitment postcode(s) [1] 22261 0
7008 - Lenah Valley

Funding & Sponsors
Funding source category [1] 299290 0
Other
Name [1] 299290 0
Tasmanian Spine Service
Address [1] 299290 0
49 Augusta Road
Lenah Valley
Hobart, Tasmania
7008
Country [1] 299290 0
Australia
Primary sponsor type
Individual
Name
Mr. Nova Thani
Address
Tasmanian Spine Service
Calvary Healthcare Lenah Valley
49 Augusta Road
Lenah Valley TAS 7008
Country
Australia
Secondary sponsor category [1] 298375 0
None
Name [1] 298375 0
Address [1] 298375 0
Country [1] 298375 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300049 0
Tasmanian Health and Medical HREC
Ethics committee address [1] 300049 0
University of Tasmania
Building 1, 1st Floor, 301 Sandy Bay Road
Hobart TAS 7001
Ethics committee country [1] 300049 0
Australia
Date submitted for ethics approval [1] 300049 0
17/07/2017
Approval date [1] 300049 0
06/03/2018
Ethics approval number [1] 300049 0
H0016583

Summary
Brief summary
The Anterior Cervical Discectomy and Fusion (ACDF) is one of the most common operations utilised in treating cervical degenerative disc disease. This involves removal of an intervertebral disc and cartilage with surrounding bone removal to release compressed spinal nerves. Once the disc has been removed, an implant known as an ‘inter-body cage’ is introduced into the disc space to restore disc height with restoration of physiological alignment and create an environment to achieve bony fusion. Overall, this procedure aims to improve neck pain and nerve pain via neural decompression and improved stabilisation.

One of the inherent problems with introducing an implant that is more resistant to compressive forces (i.e. an increased bulk modulus) when compared to vertebral bodies is subsidence. Subsidence involves the ‘sinking’ of an implant postoperatively into vertebral bodies over time. Radiologically, this is the distance measured between two vertebral bodies at the segment of interest. This can result in narrowing if the neural exit foramen and development of pathological alignment leading to recurrence of symptoms. Furthermore, adjacent levels are subjected to abnormal biomechanical stresses, ultimately leading to development of further issues. Early subsidence can also lead to increased mobility in the segment and lead to failure in fusion. Currently, there lacks consensus on the definition of subsidence, with reported parameters of radiological subsidence varying amongst publications, thus making comparison between studies difficult. Generally, it is accepted that subsidence has occurred when there is an absolute loss of 2-4mm in interbody height, or a 10% reduction in interbody height, when compared to cervical x-rays performed immediately postoperatively.

Subsequent to the introduction of the ACDF utilising a standalone cage, the operation has been augmented by the addition of a metal, anterior cervical plate. By bridging the anterior aspect of a fused segment, this was shown to supplement the cage leading to increased fusion rates and better stability. However, some of the disadvantages associated with use of a plate included post-operative dislodgement, soft-tissue injury and dysphagia. Currently, there is no consensus over whether anterior cervical plating offers any added benefit, hence the need for this trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82390 0
Mr Nova Thani
Address 82390 0
Tasmanian Spine Service
49 Augusta Road
Lenah Valley
TAS 7008
Country 82390 0
Australia
Phone 82390 0
+61362283777
Fax 82390 0
Email 82390 0
clinical@tasmanianspineservice.com.au
Contact person for public queries
Name 82391 0
Mr Nova Thani
Address 82391 0
Tasmanian Spine Service
49 Augusta Road
Lenah Valley
TAS 7008
Country 82391 0
Australia
Phone 82391 0
+61362283777
Fax 82391 0
Email 82391 0
clinical@tasmanianspineservice.com.au
Contact person for scientific queries
Name 82392 0
Mr Nova Thani
Address 82392 0
Tasmanian Spine Service
49 Augusta Road
Lenah Valley
TAS 7008
Country 82392 0
Australia
Phone 82392 0
+61362283777
Fax 82392 0
Email 82392 0
clinical@tasmanianspineservice.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Single centre pilot study.
What supporting documents are/will be available?
No other documents available
Summary results
No Results