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Trial registered on ANZCTR


Registration number
ACTRN12617001541392
Ethics application status
Approved
Date submitted
24/10/2017
Date registered
7/11/2017
Date last updated
10/06/2021
Date data sharing statement initially provided
10/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing the outcomes of patients who undergo spinal cord stimulation compared to patients who undergo spinal fusion surgery for the treatment of chronic low back pain.
Scientific title
Assessing the effectiveness of spinal cord stimulation versus spinal fusion surgery for the treatment of chronic low back pain: a prospective randomised study.
Secondary ID [1] 293191 0
FVS2016
Universal Trial Number (UTN)
U1111-1204-1725
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Low Back Pain 305189 0
Condition category
Condition code
Musculoskeletal 304507 304507 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be randomised to either a spinal cord stimulation arm or a spinal fusion arm.
Spinal cord stimulation (SCS) arm: SCS uses a surgically implanted electrical device positioned near the spine that delivers a pulsed current to the spinal cord. The current then suppresses the pain signals being sent to the brain or replaces them with a sensation often described as a tingling, not unpleasant feeling (paraesthesia). A spinal cord stimulation trial is performed first. This involves a surgical procedure where trial (temporary) leads are placed near the spine and stimulation via an external device is performed for 7-10 days to ascertain whether or not pain relief is obtained. If greater than 50% pain relief is obtained, then a permanent implant will be offered which involves the placement of permanent leads and an implantable pulse generator. If pain relief is not obtained with a spinal cord trial, a subject will be withdrawn from the study and offered fusion. If the spinal cord implant does not maintain pain relief after 6 months, a spinal fusion will be offered. If the spinal fusion does not maintain pain relief after 6 months, reactivation of the SCS will be offered.
Spinal fusion arm: Spinal fusion is a surgical technique that stabilises the spinal vertebrae and the disc between the vertebrae. Lumbar fusion surgery has been in use for many decades and is designed to create solid bone between the adjoining vertebrae, eliminating any movement between the bones. The goal of the surgery is to reduce pain and nerve irritation. If spinal fusion does not maintain pain relief 6 months after surgery, a spinal cord stimulation will be offered. If greater than 50% pain relief is obtained from the trial, the subject will be offered a permanent spinal cord stimulation implant. A neurosurgeon will perform spinal fusion or spinal cord stimulation procedures and pain management doctors will perform spinal cord stimulation procedures.
Intervention code [1] 299447 0
Treatment: Devices
Intervention code [2] 299448 0
Treatment: Surgery
Comparator / control treatment
Two treatments will be compared in this study - spinal cord stimulation and spinal fusion.
Control group
Active

Outcomes
Primary outcome [1] 303746 0
The primary endpoint is the Numerical Pain Rating Scale.
Timepoint [1] 303746 0
6 months except for patients randomised to the spinal cord stimulation treatment and fail the 7-10 day trial. For the 7-10 day trial spinal cord stimulation failure patients the primary endpoint is 7-10 days.
Secondary outcome [1] 340053 0
Proportion of subjects who respond to SCS of fusion, where a responder is defined as greater than or equal to 50% pain relief.
Timepoint [1] 340053 0
6 months post implant or spinal fusion procedure.
Secondary outcome [2] 340054 0
Patient's belief of treatment efficacy as determined by Patient Global Impression of Change (PGIC).
Timepoint [2] 340054 0
6 months post implant or spinal fusion procedure.
Secondary outcome [3] 340055 0
Patient disability as measured by the Oswestry Disability Index (ODI).
Timepoint [3] 340055 0
6 months post implant or spinal fusion procedure.
Secondary outcome [4] 340056 0
Patient depression, anxiety and stress as measure by the Depression, Anxiety and Stress Scale (DASS21). This is a composite secondary outcome.
Timepoint [4] 340056 0
6 months post implant or spinal fusion procedure.
Secondary outcome [5] 340057 0
Health outcomes from baseline as determined by changes in the EuroQol five dimensions questionnaire (EQ-5D)
Timepoint [5] 340057 0
6 months post implant or spinal fusion procedure.
Secondary outcome [6] 340058 0
Patient functionality and activities of daily living (ADL) as determined by sitting, standing and walking tolerance times. This is a composite secondary outcome.
Timepoint [6] 340058 0
6 months post implant or spinal fusion procedure.
Secondary outcome [7] 340059 0
Adverse events will be collected for all subjects. Possible adverse events for spinal cord stimulation include:
• pain,
• potential risk of infection,
• bleeding or bruising,
• nerve damage,
• pain and inflammation at the surgical site,
• lead fractures, migrations or disconnections, and
• lack of response to treatment.

Possible adverse events for spinal fusion include:
• pain,
• potential risk of infection,
• bleeding or bruising,
• nerve damage,
• pain and inflammation at the surgical site,
• bone fusion failure, and
• lack of response to treatment.

These will be assessed by a study doctor.
Timepoint [7] 340059 0
These will be followed up for 18 months post the most recent procedure.

Eligibility
Key inclusion criteria
• Have been diagnosed with chronic low back pain that has persisted for at least 90 days
• Pain clinically suspected to be generated from single level lumbar disc disease as assessed by an investigator
• Be 18 years of age or older
• Have an average pain intensity of at least 6 out of 10 on the Numerical Pain Rating Scale at enrolment.
• Willing and able to complete health questionnaires and pain scales as specified in the protocol
• Willing and able to sign the study-specific Patient Informed Consent form
• Have private health insurance
• No previous open back surgery
• No previous SCS treatment
• No RF treatment in past 12 months
• Be on stable pain medications, as determined by the Investigator, for at least 28 days prior to enrolling in this study.
• Be willing to not increase pain medication, until 6 months after SCS or fusion surgery. This excludes post and peri-operative analgesia administered as per the centres’ standard practice for up to 3 months following surgery.
• Imaging, as per standard of care, to ensure suitability for spinal fusion surgery and SCS therapy (MRI +/- CT, +/- X-ray).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Have plans to enroll in another clinical study during their participation in this study, or are currently enrolled in an interventional clinical study that could interfere in participation in the trial or affect the scientific soundness of this study
• Have a medical condition or pain in other area(s), not intended to be treated with SCS or fusion, that could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints, as determined by the Investigator (such as primary headache diagnosis and fibromyalgia).
• Clinical back instability with surgically unstable spondylolisthesis as determined by the investigator
• Have evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of pain, compliance of intervention and/or ability to evaluate treatment outcome, as determined by a psychologist or the physician
• Have a current diagnosis of a progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, rapidly progressive diabetic peripheral neuropathy, brain or spinal cord tumor, and/or central deafferentation syndrome.
• Have a current diagnosis of a coagulation disorder, bleeding diathesis that would put patient at any increased risk of bleeding during SCS or fusion procedure, progressive peripheral vascular disease or uncontrolled diabetes mellitus.
• Having any clinical evidence of mechanical instability or progressive neurologic pathology that warrants surgical intervention.
• Any previous history of surgery on the posterior elements (laminectomy, posterior fusion) that would disrupt/obliterate the posterior epidural space.
• Have a condition currently requiring or likely to require the use of MRI or diathermy.
• Have metastatic malignant disease or active local malignant disease.
• Have a life expectancy of less than 1 year.
• Have an active systemic or local infection.
• Be pregnant (if female and sexually active, subject must be using a reliable form of birth control, be surgically sterile or be at least 2 years post-menopausal).

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)
Central randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Subjects will be assigned to a SCS arm or a fusion arm. Depending on the outcome of these treatments, the subjects could then follow other arms. There are 9 sub-arms within the study. These include:
1.1a Positive SCS trial and implant.
1.1b Positive SCS trial, negative SCS implant, positive fusion
1.1c Positive SCS trial, negative SCS implant, negative fusion, positive SCS reactivation.
1.1d Positive SCS trial, negative SCS implant, negative fusion, negative SCS reactivation
1.2 Failed SCS trial.
2a Positive fusion
2b Negative fusion, positive SCS trial, positive SCS implant.
2c Negative fusion, positive SCS trial, negative SCS implant.
2d Negative fusion, negative SCS trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
NRS back pain will be analysed with analysis of covariance (ANCOVA) with baseline as the covariate. The use of ANCOVA will reduce the standard deviation for NRS back pain relative to baseline SD, and relative to change in NRS SD. Therefore, based on the estimates for the standard deviation (1.6 and 3.0 ) a reasonable estimate for the standard deviation of NRS back pain at final analysis is 2.0.
For the sample size calculation the level of significance was set to 0.05 with a 2-sided test, the difference between mean NRS back pain for the SCS and Spinal Fusion groups was set to 1.5 with a common standard deviation of 2.0. With these settings a sample size of 29 patients per arm, so 58 in total, is required to achieve a power of 80%.
The null hypothesis shall be that mean NRS for the SCS arm is equal to mean NRS for the Spinal Fusion arm. The alternative hypothesis shall be that the NRS means are not equal. The assumptions of the ANCOVA of Normality and constant variance will be assessed graphically with quantile-quantile plots and residual versus fitted plots. If necessary rectifying transformations will be applied. The continuous secondary efficacy variables will be analysed as per the primary efficacy variable analysis.
Binary and categorical variables with greater than 2 outcomes will be reported as frequencies and percentages.
Binary secondary efficacy variables, such as success or failure with respect to a 50% improvement in NRS, will be analysed with logistic regression. Odds-ratios and relative risks with 95% CI will be used as measures of the strength of the Treatment effect. The null hypothesis shall be appropriate for each binary variable. For example, for the secondary efficacy variable of the proportion of patients whose NRS improves by greater than or equal to 50% the null hypothesis shall be that the proportion of patients with greater than or equal to 50% in their NRS shall be equal for the SCS arm, and the Spinal fusion arm. The alternative hypothesis is that the 2 proportions are not equal. The hypothesis test will be conducted with the log-likelihood ratio statistic.
Categorical secondary efficacy variables with greater than 2 outcomes, such as PGIC, will be analysed with a log-linear model. Odds-ratio with 95% CI will be used as measures of the strength of the Treatment effect. The null hypothesis shall be that there is no association between Treatment and the Categorical secondary efficacy variable. The alternative hypothesis shall be that there is an association. The hypothesis test will be conducted with the log-likelihood ratio statistic.


Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
covid-19
Date of first participant enrolment
Anticipated
15/01/2018
Actual
Date of last participant enrolment
Anticipated
20/01/2020
Actual
Date of last data collection
Anticipated
20/07/2022
Actual
Sample size
Target
58
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 17900 0
3168 - Clayton
Recruitment postcode(s) [2] 17901 0
3004 - St Kilda Road Melbourne

Funding & Sponsors
Funding source category [1] 297821 0
Commercial sector/Industry
Name [1] 297821 0
Boston Scientific
Country [1] 297821 0
Netherlands
Primary sponsor type
Other
Name
Monash Clinical Research
Address
271 Clayton Road, Clayton, Victoria, 3168
Country
Australia
Secondary sponsor category [1] 296862 0
None
Name [1] 296862 0
Address [1] 296862 0
Country [1] 296862 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298875 0
Bellberry Limited
Ethics committee address [1] 298875 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 298875 0
Australia
Date submitted for ethics approval [1] 298875 0
14/11/2016
Approval date [1] 298875 0
04/10/2017
Ethics approval number [1] 298875 0
2016-09-690
Ethics committee name [2] 298878 0
Epworth Healthcare Human Research Ethics Committee
Ethics committee address [2] 298878 0
89 Bridge Road, Richmond, Victoria, 3121
Ethics committee country [2] 298878 0
Australia
Date submitted for ethics approval [2] 298878 0
Approval date [2] 298878 0
Ethics approval number [2] 298878 0

Summary
Brief summary
The main purpose of this study is to determine whether or not patients that are treated by spinal cord stimulation have the same or different treatment outcomes as patients that undergo spinal fusion in a group of patients that have received no treatment in the past for chronic low back pain. The outcomes are measured by pain scores, depression, anxiety and stress scores, patient impression of change, patient functionality, health outcomes assessments and disability scores. The patients' belief in the efficacy of the treatment will also be collected. There is also an aspect of the study that will look at whether spinal cord stimulation in conjunction with spinal fusion leads to better patient outcomes. Eligible subjects will be randomised to either the spinal cord stimulation arm or the fusion arm. Subjects randomised to the spinal cord stimulation arm will undergo an initial spinal cord stimulation trial. If this trial is positive (relieves pain by at least 50%), the subject will then be offered a spinal cord implant. If the trial is not positive, the subject will be withdrawn from the study and offered spinal fusion. If the implant is positive (pain relief of at least 50% is maintained) 6 months post implant, a subject will be followed for a further 12 months. If the implant is negative, the subject will be offered spinal fusion. Outcomes of the fusion will be assessed 6 months after surgery. If the fusion is positive (pain relief of at least 50% is maintained), the subject will be followed for a further 12 months. If the fusion is negative, the subject will be offered reactivation of the spinal cord stimulator. The subject will then be followed for 18 months post reactivation. Subjects randomised to the spinal fusion arm will be assessed 6 months post procedure. If the spinal fusion is positive (pain relief of at least 50% is maintained) , subjects will be followed for a further 12 months. If the spinal fusion is negative, subjects will then be offered a spinal cord stimulation trial. If this trial is positive (at least 50% of pain relief is obtained), subjects will be offered a spinal cord stimulation implant. Subjects will be followed for 18 months post implant (whether positive or negative). If the spinal cord stimulation trial is negative, subjects will be followed for 18 months post the spinal fusion procedure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78522 0
Dr Bruce Mitchell
Address 78522 0
Metro Pain Group
271 Clayton Road
Clayton
Victoria 3168
Country 78522 0
Australia
Phone 78522 0
+61 3 9595 6111
Fax 78522 0
+61 3 9595 6110
Email 78522 0
[email protected]
Contact person for public queries
Name 78523 0
Merylyn Ryan
Address 78523 0
Monash Clinical Research
271 Clayton Road
Clayton
Victoria 3168
Country 78523 0
Australia
Phone 78523 0
+61 3 9595 6111
Fax 78523 0
+61 3 9595 6110
Email 78523 0
[email protected]
Contact person for scientific queries
Name 78524 0
Merylyn Ryan
Address 78524 0
Monash Clinical Research
271 Clayton Road
Clayton
Victoria 3168
Country 78524 0
Australia
Phone 78524 0
+61 3 9595 6111
Fax 78524 0
+61 3 9595 6110
Email 78524 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.