Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Multi-centre randomised control trial comparing the clinical and cost effectiveness of trans-foraminal epidural steroid injection to surgical microdiscectomy for the treatment of chronic radicular pain secondary to prolapsed intervertebral disc herniation: NErve Root Block VErsus Surgery (NERVES)

    Summary
    EudraCT number
    		 2014-002751-25
    Trial protocol
    		 GB  
    Global end of trial date
    09 Jul 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Jul 2020
    First version publication date
    18 Jul 2020
    Other versions
    Summary report(s)
    		 NERVES stats analysis report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RG112-14
    Additional study identifiers
    ISRCTN number
    		 ISRCTN04820368
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Walton Centre NHS Foundation Trust
    Sponsor organisation address
    Lower Lane, Liverpool, United Kingdom, L9 7LJ
    Public contact
    NERVES Trial, Liverpool Clinical Trials Centre, University of Liverpool, 0044 151 7949768, nerves@liverpool.ac.uk
    Scientific contact
    NERVES Trial, Liverpool Clinical Trials Centre, University of Liverpool, 0044 151 7949768, nerves@liverpool.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Nov 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Feb 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study is designed to provide evidence to potentially inform future treatment of sciatica secondary to prolapsed disc. Transforaminal epidural steroid injection is recognised as a treatment alternative to surgical microdiscectomy, but it is not known how effective and cost effective this treatment is in comparison. This trial will compare the epidural steroid injection and microdiscectomy, and examine the impact of the different treatments on several outcomes such as Oswestry Disability Questionnaire scores, other back and leg pain questionnaires, and health economic analyses. The primary outcome will be the Oswestry Disability Questionnaire (ODQ; a condition specific outcome measure with over 30 years of scientific validation) at 18 weeks follow up (approx. 3 months after treatment).
    Protection of trial subjects
    The written informed consent and the completed baseline CRF to confirm and assess eligibility was authorised by an appropriately qualified doctor. Participants were also be asked to complete a questionnaire booklet (incorporating ODQ, Roland-Morris, COMI, numerical rating scores for leg and back pain, and a health economic assessment) with support from a health professional if needed. The participant completed questionnaires were completed prior to randomisation but after provision of consent.
    Background therapy
    		 - Standard NHS care. - Participants in the study also received a small exposure to ionizing radiation in both arms of the trial. This was required to provide imaging for verification of the treatment level for both microdiscectomy and TFESI. The ionizing radiation exposure was required as part of the normal care pathway and the same exposure would be necessary outside of this clinical trial context. There was no additional ionizing radiation exposure to participants as a result of trial participation.
    Evidence for comparator
    		 Surgical microdiscectomy for acute sciatica.
    Actual start date of recruitment
    04 Mar 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Scientific research
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 163
    Worldwide total number of subjects
    163
    EEA total number of subjects
    163
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    162
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This trial took place in 12 centres; 11 centres randomised at least 1 participant. Patients were recruited from units receiving patients from pooled tertiary referrals from GPs, allied health professionals and non-spinal consultants. The first patient was randomised on 06 March 2015 and the last patient was randomised on 21 December 2017.

    Pre-assignment
    Screening details
    		 A total of 1055 subjects were assessed for eligibility, of which 892 subjects were excluded. Of these, 723 subjects did not meet the inclusion criteria, 168 subjects declined and 1 value was missing. This left a total of 163 subjects to be randomised.

    Pre-assignment period milestones
    Number of subjects started
    		 1055 [1]
    Number of subjects completed
    		 163

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Not meeting inclusion criteria: 723
    Reason: Number of subjects
    		 Eligiblity yes/ no missing: 1
    Reason: Number of subjects
    		 Not approached/ declined to participate: 168
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of patients who started the pre-assignment period (screened - 1055) is larger than the number who enrolled in the trial (randomised -163).
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Surgery
    Arm description
    		 Standard surgical lumbar microdiscectomy.
    Arm type
    		 Standard microdiscectomy

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 TFESI
    Arm description
    		 Fluoroscopically guided trans-foraminal epidural steroid injection (TFESI) of a standard combination of local anaesthetic and steroid drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TFESI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Epidural use
    Dosage and administration details
    NERVES is a pragmatic trial and as such the agents used are expected to be obtained and prescribed via normal NHS routes. To minimise variability across the participating sites it is expected that the following injection regimen will be followed where possible: • Injectate: o Steroid 20 - 60 mg triamcinolone acetonide e.g., Kenalog o Local anaesthetic 0.25% levobupivacaine hydrochloride (2ml) e.g., Chirocaine For the purpose of patient safety it is expected that sites will ensure the following maximum doses are not exceeded: Injectate: Maximum Dose: Triamcinolone acetonide e.g. Kenalog: 80 mg Levobupivacaine hydrochloride e.g. Chirocaine: 10 mg Dexamethasone: 20 mg Methylprednisolone acetate e.g. Depo-Medrone: 80 mg Bupivacaine hydrochloride: 10 mg Lidocaine hydrochloride: 40 mg

    Number of subjects in period 1
    		Surgery TFESI
    Started
    83
    80
    Completed
    83
    80

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Surgery
    Reporting group description
    		 Standard surgical lumbar microdiscectomy.

    Reporting group title
    TFESI
    Reporting group description
    		 Fluoroscopically guided trans-foraminal epidural steroid injection (TFESI) of a standard combination of local anaesthetic and steroid drug.

    Reporting group values
    		 Surgery TFESI Total
    Number of subjects
    		 83 80 163
    Age categorical
    The numbers of subjects within each age category on both treatment arms.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 82 80 162
        From 65-84 years
    		 1 0 1
        85 years and over
    		 0 0 0
    Age continuous
    The mean and standard deviation of the ages of subjects on both treatment arms.
    Units: years
        arithmetic mean (standard deviation)
    		 43.5 ( 9.9 ) 41.2 ( 8.6 ) -
    Gender categorical
    The number of males and females allocated to both surgery and injection.
    Units: Subjects
        Female
    		 46 40 86
        Male
    		 37 40 77
    Reproductive potential
    The number of female participants who are of reproductive potential.
    Units: Subjects
        No
    		 11 5 16
        Yes
    		 35 35 70
        N/A
    		 37 40 77
    Taking Anticoagulant Medication
    The number of participants allocated to both surgery and injection taking any anticoagulant medication at the time of randomisation.
    Units: Subjects
        No
    		 82 79 161
        Yes
    		 1 1 2
    Previous surgery at disc level
    Data on whether or not the patient previously had surgery at the same intervertebral disc (Level).
    Units: Subjects
        No
    		 82 80 162
        Yes
    		 1 0 1
    Has patient taken medication for pain and symptoms?
    Has the patient used medication to help treat pain and symptoms?
    Units: Subjects
        No
    		 83 80 163
        Yes
    		 0 0 0
    Has patient modified activity?
    Has the patient modified daily activities to help pain and symptoms?
    Units: Subjects
        No
    		 0 1 1
        Yes
    		 83 79 162
    Has patient attended physiotherapy?
    Has the patient attended physiotherapy to help pain and symptoms?
    Units: Subjects
        No
    		 15 16 31
        Yes
    		 68 64 132
    Has patient had other conservative (non operative) treatment for pain and symptoms?
    Has the patient had other conservative (non operative) treatment to help pain and symptoms?
    Units: Subjects
        No
    		 49 43 92
        Yes
    		 34 37 71
    Estimated volume of canal occupied by disc prolapse
    Estimated volume of canal occupied by disc prolapse as shown on MRI scan.
    Units: Subjects
        Less than 25%
    		 43 44 87
        Between 25%-50%
    		 36 34 70
        Greater than 50%
    		 4 2 6
    Posture
    Data on whether or not the posture of each participant is normal.
    Units: Subjects
        Abnormal
    		 38 41 79
        Normal
    		 43 37 80
        Not done
    		 2 2 4
    Range of movement
    Data on whether or not the range of movement of each participant is normal.
    Units: Subjects
        Abnormal
    		 52 50 102
        Normal
    		 27 27 54
        Not done
    		 4 3 7
    Muscle strength
    Data on whether or not the muscle strength of each participant is normal.
    Units: Subjects
        Abnormal
    		 12 18 30
        Normal
    		 67 59 126
        Not done
    		 4 3 7
    Left ankle jerks present
    Data on whether or not left ankle jerks were present.
    Units: Subjects
        No
    		 13 11 24
        Yes
    		 68 66 134
        Data unobtainable
    		 2 3 5
    Right ankle jerks present
    Data on whether or not right ankle jerks were present.
    Units: Subjects
        No
    		 13 13 26
        Yes
    		 68 66 134
        Data unobtainable
    		 2 1 3
    left knee jerks present
    Data on whether or not left knee jerks were present.
    Units: Subjects
        No
    		 2 4 6
        Yes
    		 79 73 152
        Data unobtainable
    		 2 3 5
    Right knee jerks present
    Data on whether or not right knee jerks were present.
    Units: Subjects
        No
    		 3 5 8
        Yes
    		 78 74 152
        Data unobtainable
    		 2 1 3
    SLR reduction present
    Data on whether or not a SLR reduction took place.
    Units: Subjects
        No
    		 6 4 10
        Yes
    		 75 76 151
        Data unobtainable
    		 2 0 2
    Location of SLR reduction present
    Data on the location of the SLR reduction.
    Units: Subjects
        Bilateral
    		 7 9 16
        Unilateral (left)
    		 37 39 76
        Unilateral (right)
    		 31 28 59
        N/A
    		 8 4 12
    Any other abnormalities present
    Any other abnormalities noted during the physical examination?
    Units: Subjects
        No
    		 63 59 122
        Yes
    		 19 21 40
        Data unobtainable
    		 1 0 1
    Is patient currently employed?
    Is the patient currently employed?
    Units: Subjects
        No
    		 21 13 34
        Yes
    		 62 66 128
        Data unobtainable
    		 0 1 1
    Is patient currently unable to work due to sciatica
    Is the patient currently unable to attend work due to sciatica?
    Units: Subjects
        No
    		 41 34 75
        Yes
    		 21 32 53
        N/A
    		 21 14 35
    Is the patient is currently taking analgesics/ steroids/ anticoagulant medication?
    Is the patient currently taking analgesics, steroids or anticoagulant medication?
    Units: Subjects
        No
    		 7 7 14
        Yes
    		 76 73 149
    Duration of symptoms Summary
    Units: Weeks
        arithmetic mean (standard deviation)
    		 21.5 ( 10.7 ) 21.1 ( 11.2 ) -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 83.7 ( 16.8 ) 81.4 ( 20.7 ) -
    Height
    Units: centimetres
        arithmetic mean (standard deviation)
    		 171.7 ( 10.7 ) 172.6 ( 9.5 ) -
    BMI
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    		 28.2 ( 5.3 ) 27.2 ( 6.4 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Surgery
    Reporting group description
    		 Standard surgical lumbar microdiscectomy.

    Reporting group title
    TFESI
    Reporting group description
    		 Fluoroscopically guided trans-foraminal epidural steroid injection (TFESI) of a standard combination of local anaesthetic and steroid drug.

    Subject analysis set title
    ODQ Extended Model Surgery
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the surgery arm included in the extened model for ODQ

    Subject analysis set title
    ODQ Extended Model TFESI
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the TFESI arm included in the extened model for ODQ

    Subject analysis set title
    ODQ Sensitivity MI Surgery
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the surgery arm included in the sensitivity analyis of the primary outcome using multiple imputations.

    Subject analysis set title
    ODQ Sensitivity MI TFESI
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the TFESI arm included in the sensitivity analyis of the primary outcome using multiple imputations.

    Subject analysis set title
    ODQ post-hoc Model Surgery
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the surgery arm included in the post-hoc extened model for ODQ which also included level of disc prolapse

    Subject analysis set title
    ODQ post-hoc Model TFESI
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Number of subjects in the TFESI arm included in the post-hoc extened model for ODQ which also included level of disc prolapse

    Primary: ODQ (primary outcome)

    		 Close Top of page
    End point title
    		 ODQ (primary outcome)
    End point description
    The primary outcome (ODQ score at 18 weeks post-randomisation) was compared between groups using a linear regression model, adjusted for the stratification variable centre, baseline ODQ score, and other (specified in advance) variables considered to be potential confounders.
    End point type
    Primary
    End point timeframe
    ODQ score at 18 weeks post randomisaiton (+/- 6 weeks).
    End point values
    		 Surgery TFESI ODQ Extended Model Surgery ODQ Extended Model TFESI ODQ Sensitivity MI Surgery ODQ Sensitivity MI TFESI ODQ post-hoc Model Surgery ODQ post-hoc Model TFESI
    Number of subjects analysed
    61 [1]
    63 [2]
    56 [3]
    53 [4]
    83 [5]
    79 [6]
    54 [7]
    52 [8]
    Units: Score
    arithmetic mean (standard deviation)
        Baseline
    49.39 ( 17.81 )
    53.74 ( 19.35 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Week 18
    22.30 ( 19.83 )
    30.02 ( 24.38 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Difference
    -26.74 ( 21.35 )
    -24.52 ( 18.89 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    Notes
    [1] - Baseline: n = 83 n missing = 0 Week 18: n = 61 n missing/ invalid = 22
    [2] - Baseline: n=79 n missing=1 Week 18: n=63 n missing/invalid=17
    [3] - Baseline and week 18 summaries not included for this analysis
    [4] - Baseline and week 18 summaries not included for this analysis
    [5] - Baseline and week 18 summaries not included for this analysis
    [6] - Baseline and week 18 summaries not included for this analysis
    [7] - Baseline and week 18 summaries not included for this analysis
    [8] - Baseline and week 18 summaries not included for this analysis
    Statistical analysis title
    		 ODQ primary analysis
    Statistical analysis description
    The primary outcome (ODQ score at 18 weeks post-randomisation) was compared between groups using a linear regression model, adjusted for the stratification variable centre and baseline ODQ score.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.221
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.09
         upper limit
    		 2.59
    Statistical analysis title
    		 ODQ Extended model
    Statistical analysis description
    As well as the model specified for our primary outcome analysis, we also considered if any of the following baseline variables adjusted our estimate of treatment effect by adding them to our mixed effects model as fixed effects: Age, Sex, BMI, Duration of symptoms, Estimated volume of canal occupied.
    Comparison groups
    ODQ Extended Model TFESI v ODQ Extended Model Surgery
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1991
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -5.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.76
         upper limit
    		 2.7
    Statistical analysis title
    		 ODQ primary analysis - Sensitivity
    Statistical analysis description
    Sensitivity analyses was carried out as the amount of missing data was greater than 10%. Multiple imputation was used to assess the robustness of the analysis to missing primary outcome data.
    Comparison groups
    ODQ Sensitivity MI TFESI v ODQ Sensitivity MI Surgery
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.393
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.16
         upper limit
    		 3.99
    Notes
    [9] - Sensitivity analyses
    Statistical analysis title
    		 ODQ Extended model - post-hoc
    Statistical analysis description
    As well as the model specified for our primary outcome analysis, we also considered if any of the following baseline variables adjusted our estimate of treatment effect by adding them to our mixed effects model as fixed effects: Age, Sex, BMI, Duration of symptoms, Estimated volume of canal occupied. As a post-hoc analysis the level of disc prolapse was also added to this model.
    Comparison groups
    ODQ post-hoc Model Surgery v ODQ post-hoc Model TFESI
    Number of subjects included in analysis
    106
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.215
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.81
         upper limit
    		 2.93

    Secondary: Secondary efficacy endpoint 1 – ODQ (18, 30, 42, 54 weeks)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 1 – ODQ (18, 30, 42, 54 weeks)
    End point description
    Change from baseline summaries (ODQ score at follow up - baseline) are presented in this section where both the baseline ODQ questionnaire and follow up questionnaire were completed. A lower ODQ scores represents lower levels of disability therefore a decrease from baseline represents an improvement. Questionnaires are only included in the summaries if they were completed at the protocol specified time points post randomisation (+/- 2 weeks for week 18, week 30 and week 42 and 54-62 weeks for week 54 questionnaire). The study design defines questionnaires to be measured a specific time-points, however measurements that are not taken at per-protocol time-points were still included in this mixed model analysis as the time in weeks was included in the model to directly account for the time between baseline and completed follow up questionnaires. The ODQ is only considered valid if at least 8 out of 10 items were answered.
    End point type
    Secondary
    End point timeframe
    Weeks 18, 30, 42 and 52 post randomisation
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    75 [10]
    72 [11]
    Units: Scores
    arithmetic mean (standard deviation)
        Week 18 ODQ summary
    -27.18 ( 22.31 )
    -24.29 ( 18.28 )
        Week 30 ODQ summary
    -26.62 ( 19.12 )
    -23.25 ( 17.45 )
        Week 42 ODQ summary
    -31.40 ( 17.22 )
    -25.51 ( 23.74 )
        Week 54 ODQ summary
    -30.38 ( 17.77 )
    -31.10 ( 24.35 )
    Notes
    [10] - 18 n=46 n inval/miss=37 30 n=40 n inval/miss=43 42 n=40 n inval/miss=43 54 n=48 n inval/miss=35
    [11] - 18 n=51 n inval/miss=29 30 n=30 n inval/miss=50 42 n=34 n inval/miss=46 54 n=42 n inval/miss=38
    Statistical analysis title
    		 Parameter estimates for ODQ longitudinal model
    Statistical analysis description
    A repeated measures random effects model was fitted. The dependent variable was post baseline ODQ. Covariates were: baseline ODQ, treatment arm, time (fitted as a continuous variable), and a time-treatment arm interaction. Centre was fitted as a random effect. The time-treatment interaction was dropped if it was found to be non-significant (p<0.05).
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.123 [12]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.61
         upper limit
    		 1.28
    Notes
    [12] - A time-treatment interaction was tested and was found to be non-significant so was excluded from the model, below the treatment effect (estimated mean difference in ODQ) is reported together with a 95% CI and a p-value.
    Statistical analysis title
    		 Post-hoc: parameter estimates for ODQ joint model
    Statistical analysis description
    As a post-hoc analysis, joint modelling of the longitudinal outcome (as above) and the time to study dropout was done to consider the possibility of informative dropout. The longitudinal model was fitted as mixed effects model with a random intercept and random slope for participant. The parameter estimates are found below, the standard errors were calculated from 246 bootstrapped samples (4 failed to converge).
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    147
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.108
    Method
    		 Joint modelling
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.84
         upper limit
    		 1.27

    Secondary: Secondary efficacy endpoint 2 - Leg pain (18,30, 42 and 54 weeks)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 2 - Leg pain (18,30, 42 and 54 weeks)
    End point description
    Change from baseline summaries (Numerical rating of leg pain at follow up - baseline) are presented in this section where the numerical rating for leg pain were completed. A lower leg pain rating (0-100) represents lower overall pain so a decrease from baseline represents an improvement. Questionnaires were only included in the summaries if they were completed at protocol specified time points post randomisation (+/- 2 weeks for week 18, week 30 and week 42 and 54-62 weeks for week 54 questionnaire). The study design defines questionnaires to be measured a specific time-points, measurements that are not taken at per-protocol time-points were still included in this mixed model analysis as the time in weeks was included in the model to directly account for the time between baseline and completed follow up questionnaire.
    End point type
    Secondary
    End point timeframe
    Weeks 18, 30, 42 and 54 post randomisation
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    70 [13]
    70 [14]
    Units: rating
    arithmetic mean (standard deviation)
        Week 18 leg pain summary
    -58.31 ( 34.51 )
    -43.55 ( 32.52 )
        Week 30 leg pain summary
    -54.37 ( 27.05 )
    -42.70 ( 35.27 )
        Week 42 leg pain summary
    -55.81 ( 31.66 )
    -47.12 ( 42.28 )
        Week 54 leg pain summary
    -55.44 ( 33.57 )
    -47.08 ( 33.06 )
    Notes
    [13] - 18 n=45 n inval/miss=38 30 n=38 n inval/miss=45 42 n=37 n inval/miss=46 54 n=43 n inval/miss=40
    [14] - 18 n=49 n inval/miss=31 30 n=30 n inval/miss=50 42 n=33 n inval/miss=47 54 n=39 n inval/miss=41
    Statistical analysis title
    		 Leg pain longitudinal model
    Statistical analysis description
    A repeated measures random effects model was fitted. The dependent variable was post baseline numerical rating scores for leg pain. Covariates were: baseline numerical rating scores for leg pain, treatment arm, time (fitted as a continuous variable), and a time-treatment arm interaction. Centre was fitted as a random effect. The time-treatment interaction was dropped if it was found to be non-significant (p<0.05). In addition to this, effect estimates, 95% CIs and a p-value at T18 were reported.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.115 [15]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -7.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.81
         upper limit
    		 1.73
    Notes
    [15] - A time-treatment interaction was tested and was found to be non-significant so was excluded from the model, below the treatment effect (estimated mean difference in numerical rating of leg pain) is reported together with a 95% CI and a p-value.
    Statistical analysis title
    		 Parameter estimates for leg pain joint model
    Statistical analysis description
    As a post-hoc analysis, joint modelling of the longitudinal outcome and the time to study dropout was done to consider the possibility of informative dropout. The longitudinal model was fitted as mixed effects model with a random intercept for participant. The random intercept and slope model failed to converge and the model improvement was marginal. The parameter estimates are found below, the standard errors were calculated from 250 bootstrapped samples.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    140
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.098
    Method
    		 Joint modelling
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -7.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.82
         upper limit
    		 0.86

    Secondary: Secondary efficacy endpoint 3 - Back pain (18, 30, 42 and 54 weeks)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 3 - Back pain (18, 30, 42 and 54 weeks)
    End point description
    Change from baseline summaries (Numerical rating of back pain at follow up - baseline) are presented in this section where the numerical rating for back pain were completed. A lower score for back pain represents lower overall pain so a decrease from baseline represents an improvement. Questionnaires were only included in the summaries if they were completed at protocol specified time points (+/- 2 weeks for week 18, week 30 and week 42 and 54-62 weeks for week 54 questionnaire). The study design defines numerical rating for back pain be measured a specific time-points, measurements that are not taken at per-protocol time-points will still be included in this mixed model analysis as time in weeks will be included in the model to directly account for the time between baseline and follow up questionnaires
    End point type
    Secondary
    End point timeframe
    Weeks 18, 30, 42 and 54 post randomisation.
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    71 [16]
    70 [17]
    Units: Rating
    arithmetic mean (standard deviation)
        Week 18 back pain summary
    -26.02 ( 32.83 )
    -23.41 ( 27.69 )
        Week 30 back pain summary
    -25.00 ( 32.04 )
    -24.33 ( 31.95 )
        Week 42 back pain summary
    -20.81 ( 37.43 )
    -23.00 ( 37.29 )
        Week 54 back pain summary
    -23.07 ( 34.54 )
    -22.90 ( 29.11 )
    Notes
    [16] - 18 n=45 n inval/miss=38 30 n=38 n inval/miss=45 42 n=37 n inval/miss=46 54 n=42 n inval/miss=41
    [17] - 18 n=49 n inval/miss=31 30 n=30 n inval/miss=50 42 n=33 n inval/miss=47 54 n=39 n inval/miss=41
    Statistical analysis title
    		 Back pain rating longitudinal model
    Statistical analysis description
    A repeated measures random effects model was fitted. The dependent variable was post baseline numerical rating scores for back pain. Covariates were: baseline numerical rating scores for back pain, treatment arm, time (fitted as a continuous variable), and a time-treatment arm interaction. Centre was fitted as a random effect. The time-treatment interaction was dropped if it was found to be non-significant (p<0.05). In addition, effect estimates, 95% CIs and a p-value at T18 were reported.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.473 [18]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.29
         upper limit
    		 5.26
    Notes
    [18] - A time-treatment interaction was tested and was found to be non-significant so was excluded from the model, below the treatment effect (estimated mean difference in numerical rating of back pain) is reported together with a 95% CI and a p-value.
    Statistical analysis title
    		 Parameter estimates for back pain joint model
    Statistical analysis description
    As a post-hoc analysis, joint modelling of the longitudinal outcome (as above) and the time to study dropout was done to consider the possibility of informative dropout. The longitudinal model was fitted as mixed effects model with a random intercept and random slopes for participant. The parameter estimates are found below, the standard errors were calculated from 197 bootstrapped samples (53 failed to converge).
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    141
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.457
    Method
    		 Joint modelling
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.58
         upper limit
    		 3.16

    Secondary: Secondary efficacy endpoint 4 - Likert scale for satisfaction with care

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 4 - Likert scale for satisfaction with care
    End point description
    The Likert scale for satisfaction with care was used to assess patients’ satisfaction with the care received during the study and this was assessed at 54 weeks post randomisation. Lower scores over the 2 questions indicated higher levels of satisfaction.
    End point type
    Secondary
    End point timeframe
    Week 54
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    61 [19]
    58 [20]
    Units: scores
    median (inter-quartile range (Q1-Q3))
        week 54
    1 (1 to 2)
    1.5 (1 to 3)
    Notes
    [19] - n=61 n missing=22
    [20] - n=58 n missing=22
    Statistical analysis title
    		 Mann-Whitney results
    Statistical analysis description
    Patient treatment satisfaction scores at 54 weeks were compared between groups using the Mann-Whitney U test. A blind review of the data was undertaken and the distribution of the Likert score at 54 weeks was found to be non-normal.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.021
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Secondary efficacy endpoint 5 - Roland-Morris (18, 30, 42, 54 weeks)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 5 - Roland-Morris (18, 30, 42, 54 weeks)
    End point description
    Change from baseline summaries (Roland-Morris at follow up - baseline) are presented in this section where the modified Roland-Morris (MRM) was completed at both time points. A Lower MRM score relates to lower levels of disability so a decrease from baseline represents an improvement. Questionnaires are only included in the summaries if they were completed at protocol specified time points (+/- 2 weeks for week 18, week 30 and week 42 and 54-62 weeks for week 54 questionnaire). The study design defines numerical rating for back pain be measured a specific time-points, measurements that are not taken at per-protocol time-points will still be included in this mixed model analysis as time in weeks will be included in the model to directly account for the time between baseline and follow up questionnaires.
    End point type
    Secondary
    End point timeframe
    Weeks 18, 30, 42 and 54 post randomisation
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    74 [21]
    72 [22]
    Units: scores
    arithmetic mean (standard deviation)
        Week 18 MRM summary
    -9.09 ( 6.27 )
    -7.73 ( 5.91 )
        Week 30 MRM summary
    -9.58 ( 5.60 )
    -7.48 ( 6.68 )
        Week 42 MRM summary
    -9.56 ( 5.86 )
    -8.35 ( 8.56 )
        Week 54 MRM summary
    -9.74 ( 6.65 )
    -9.24 ( 6.68 )
    Notes
    [21] - 18 n=47 n inval/miss=36 30 n=40 n inval/miss=43 42 n=39 n inval/miss=44 54 n=47 n inval/miss=36
    [22] - 18 n=51 n inval/miss=29 30 n=31 n inval/miss=49 42 n=34 n inval/miss=46 54 n=42 n inval/miss=38
    Statistical analysis title
    		 MRM longitudinal model
    Statistical analysis description
    A repeated measures random effects model was fitted. The dependent variable was post baseline MRM outcome score for sciatica. Covariates were: baseline MRM outcome score for sciatica, treatment arm, time (fitted as a continuous variable), and a time-treatment arm interaction. Centre was fitted as a random effect. The time-treatment interaction was dropped if it was found to be non-significant (p<0.05). In addition to this, effect estimates, 95% CIs and a p-value at T18 were reported.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054 [23]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.67
         upper limit
    		 0.03
    Notes
    [23] - A time-treatment interaction was tested and was found to be non-significant so was excluded from the model, below the treatment effect (estimated mean difference in MRM) is reported together with a 95% CI and a p-value.
    Statistical analysis title
    		 Post-hoc: parameter estimates for MRM joint model
    Statistical analysis description
    As a post-hoc analysis, joint modelling of the longitudinal outcome (as above) and the time to study dropout was done to consider the possibility of informative dropout. The longitudinal model was fitted as mixed effects model with a random intercept and random slopes for participant. The parameter estimates are found below, the standard errors were calculated from 250 bootstrapped samples.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    146
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.063
    Method
    		 Joint modelling
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.44
         upper limit
    		 0.1

    Secondary: Secondary efficacy endpoint 6 - COMI (18, 30, 42 and 54 weeks)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 6 - COMI (18, 30, 42 and 54 weeks)
    End point description
    Change from baseline summaries (COMI at follow up – baseline COMI) are presented in this section where the numerical rating for leg pain were completed. Lower leg pain rating represents lower overall pain so a decrease from baseline represents an improvement. Questionnaires were only included in the summaries if they were completed at protocol specified time points (+/- 2 weeks for week 18, week 30 and week 42 and 54-62 weeks for week 54 questionnaire). The study design defines questionnaires to be measured a specific time-points, measurements that are not taken at per-protocol time-points were still included in this mixed model analysis as the time in weeks was included in the model to directly account for the time between baseline and completed follow up questionnaires. Only COMI questionnaires with all items answered were included in the summaries. If a COMI questionnaire was missing an item then it was recorded as missing.
    End point type
    Secondary
    End point timeframe
    Weeks 18, 30, 42 and 54 post randomisaiton.
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    65 [24]
    67 [25]
    Units: Rating
    arithmetic mean (standard deviation)
        Week 18 COMI summary
    -3.93 ( 2.80 )
    -3.05 ( 2.69 )
        Week 30 COMI summary
    -4.49 ( 2.44 )
    -3.33 ( 2.35 )
        Week 42 COMI summary
    -4.92 ( 2.18 )
    -3.45 ( 3.14 )
        Week 54 COMI summary
    -5.02 ( 2.32 )
    -3.93 ( 2.81 )
    Notes
    [24] - 18 n=42 n inval/miss=41 30 n=32 n inval/miss=51 42 n=33 n inval/miss=50 54 n=39 n inval/miss=44
    [25] - 18 n=47 n inval/miss=33 30 n=27 n inval/miss=53 42 n=32 n inval/miss=48 54 n=37 n inval/miss=43
    Statistical analysis title
    		 COMI longitudinal model
    Statistical analysis description
    A repeated measures random effects model was fitted. The dependent variable was post baseline COMI scores. Covariates were: baseline COMI scores, treatment arm, time (fitted as a continuous variable), and a time-treatment arm interaction. Centre was fitted as a random effect. The time-treatment interaction was dropped if it was found to be non-significant (p<0.05). In addition to this, effect estimates, 95% CIs and a p-value at T18 were reported.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.059 [26]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.58
         upper limit
    		 0.03
    Notes
    [26] - A time-treatment interaction was tested and was found to be non-significant so was excluded from the model, below the treatment effect (estimated mean difference in COMI score) is reported together with a 95% CI and a p-value.
    Statistical analysis title
    		 Post-hoc: parameter estimates for COMI joint model
    Statistical analysis description
    As a post-hoc analysis, joint modelling of the longitudinal outcome (as above) and the time to study dropout was done to consider the possibility of informative dropout. The longitudinal model was fitted as mixed effects model with a random intercepts and random slopes for participant. The parameter estimates are found below, the standard errors were calculated from 250 bootstrapped samples.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    132
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.046
    Method
    		 Joint modelling
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.54
         upper limit
    		 -0.02

    Secondary: Secondary efficacy endpoint 7 – Work Status (Baseline)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 7 – Work Status (Baseline)
    End point description
    The number of patients that are employed/not employed at baseline are presented in this section by treatment group. Of those patients who are employed, the number of patients that are off work/at work are also presented by treatment group.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    83
    80
    Units: subjects
        Unemployed
    21
    13
        Employed
    62
    66
        Working
    41
    34
        Not working
    21
    32
        Missing/ can't tell
    0
    1
    No statistical analyses for this end point

    Secondary: Secondary efficacy endpoint 7 – Work Status (Week 18)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 7 – Work Status (Week 18)
    End point description
    The number of patients that are employed/ not employed at week 18 are presented in this section by treatment group. Of those patients who are employed, the number of patients that are off work/at work are also presented by treatment group.
    End point type
    Secondary
    End point timeframe
    Week 18
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    51
    53
    Units: subjects
        Unemployed
    18
    16
        Employed
    54
    53
        Working
    45
    44
        Not working
    6
    9
        Missing/ can't tell
    14
    11
    Statistical analysis title
    		 Chi-square test of association - week 18
    Statistical analysis description
    Work status (at work or off work) at 18 weeks post randomisation was compared between groups using a chi-square test. The chi-square statistic and p-value were presented. In addition to this, the relative risk and 95% confidence interval were presented.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.449
    Method
    		 Chi-squared
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.81

    Secondary: Secondary efficacy endpoint 7 – Work Status (Week 54)

    		 Close Top of page
    End point title
    		 Secondary efficacy endpoint 7 – Work Status (Week 54)
    End point description
    The number of patients that are employed/not employed at week 54 are presented in this section by treatment group. Of those patients who are employed, the number of patients that are off work/at work are also presented by treatment group.
    End point type
    Secondary
    End point timeframe
    week 54
    End point values
    		 Surgery TFESI
    Number of subjects analysed
    45
    38
    Units: subjects
        Unemployed
    15
    13
        Employed
    49
    44
        Working
    45
    37
        Not working
    0
    1
        Missing/can't tell
    23
    29
    Statistical analysis title
    		 Chi-square test of association - week 54
    Statistical analysis description
    Work status (at work or off work) at 54 weeks post randomisation were compared between groups using a chi-square test. The chi-square statistic and p-value were presented. In addition to this, the relative risk and 95% confidence interval were presented.
    Comparison groups
    TFESI v Surgery
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.274 [27]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [27] - The relative risk of not working at 54 weeks cannot be calculate as one of the cell counts for not working is 0.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    An assessment of adverse events was undertaken at each clinical visit.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Surgery
    Reporting group description
    		 Any participant who had at least one surgery during the trial are considred in this reporting group.

    Reporting group title
    TFESI
    Reporting group description
    		 Any participant who had at least one TFESI during the trial are considred in this reporting group.

    Serious adverse events
    		 Surgery TFESI
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 105 (3.81%)
    0 / 82 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Surgical procedure repeated
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomeningocele
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Peroneal nerve palsy
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Postoperative wound infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Surgery TFESI
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 105 (13.33%)
    3 / 82 (3.66%)
    Injury, poisoning and procedural complications
    Dural tear
         subjects affected / exposed
    4 / 105 (3.81%)
    0 / 82 (0.00%)
         occurrences all number
    4
    0
    Wound complication
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Pseudomeningocele
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 82 (2.44%)
         occurrences all number
    1
    5
    Cerebrospinal fluid leakage
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Radicular pain
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Swelling
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 82 (1.22%)
         occurrences all number
    1
    1
    Sciatica
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Wound infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    Postoperative wound infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 May 2015
    Change of PI at a site.
    08 Jun 2015
    Addition of one new site.
    20 Aug 2015
    Change of PI at a site.
    13 Oct 2015
    Protocol v4.0 to v5.0: Addition of statistician sign-off and addition of IRMER (Ionising Radiation (Medical Exposure) Regulations).
    26 Nov 2015
    Addition of 9 new sites.
    08 Dec 2015
    Addition of one new site.
    17 Feb 2016
    Change of a site name.
    24 Feb 2016
    REC approval date: 23/12/2015. Update of 4 summary of product characteristics documents.
    11 May 2016
    REC approval date: 18/04/2016. Protocol v5.0 to v6.0: Change of inclusion and exclusion criteria: Duration of symptoms extended from “between 6 weeks and 6 months” to “between 6 weeks and 12 months”. Addition of CT scanning for guidance of the TFESI injection. Addition of text clarifying follow-up process and SAE assessment process. Patient information sheet and consent form (PISC) v3.0 to v4.0: Addition of CT scanning for guidance of the TFESI injection.
    07 Sep 2016
    Update of 2 summary of product characteristics documents and clarification of reference safety information.
    26 Jan 2017
    REC approval date: 02/12/2016. Addition of patient identification sites (PIC).
    21 Feb 2017
    Update of 2 summary of product characteristics documents.
    10 Apr 2017
    REC approval date: 10/04/2017 Addition of 1 site and creation of trial poster (for use in relevant clinics to raise trial awareness).
    15 Jan 2018
    REC approval date: 13/12/2017. MHRA approval date: 04/02/2018. Protocol v6.0 to v7.0: Recruitment target lowered from 200 to 148. Eligibility criteria relating to consent clarified stating written informed consent is needed. Study duration amended from 54 weeks to 54-60 weeks, list of accepted active ingredients and expected maximum doses for use in TFESI group added. Guidance on handling of non-attendance at follow-up visits added. Pharmacovigilance section modified throughout for clarification PISC v5.0 to v6.0: Clarification of data collection, sharing and data use. Health economic letter (how health economic data is collected and used) for patients. Withdrawal statement for trial website. Update of 2 summary of product characteristics documents.
    22 Aug 2018
    REC approval date: 20/08/2018 (acknowledged). Update of 4 summary of product characteristics documents.
    08 Jul 2019
    MHRA approval date: 03/06/2019. REC approval date: 08/07/2018. Protocol v7.0 to v8.0: Change in lead sponsor contact / signatory. Minor amendments for clarity. Updated withdrawal statement for website. Privacy statement i.e. how data is used and kept secure wording for the trial website.
    09 Jul 2019
    HRA approval date: 02/08/2019 MHRA approval date: 23/07/2019. Update of 1 summary of product characteristics document.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 20:45:05 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA