Clinical Trial Results:
A randomised controlled trial of adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica.
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Summary
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EudraCT number |
2015-000636-15 |
Trial protocol |
GB |
Global end of trial date |
22 Sep 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Oct 2019
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First version publication date |
18 Oct 2019
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Other versions |
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Summary report(s) |
2018 SCIATiC lessons learnt SCIATiC HTA report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
12/201/02
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Additional study identifiers
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ISRCTN number |
ISRCTN14569274 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bangor University,
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Sponsor organisation address |
School of Healthcare Sciences, Fron Heulog , Bangor, United Kingdom, LL57 2EF
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Public contact |
Dr Nefyn Williams, Bangor University, 44 01248383141, nefyn.williams@bangor.ac.uk
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Scientific contact |
Dr Nefyn Williams, Bangor University, 1248382442 01248383141, nefyn.williams@bangor.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Dec 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Sep 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Sep 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the effectiveness of subcutaneous injections of adalimumab plus physiotherapy compared with placebo injection of saline plus physiotherapy for patients with sciatica who have failed first line primary care treatment and
been referred to an outpatient physiotherapy clinic. The primary effectiveness outcome will be sciatica related health status using the Oswestry Disability Index.
To evaluate the costeffectiveness of subcutaneous injections of adalimumab plus physiotherapy, compared with placebo injection of saline plus physiotherapy for patients with sciatica who have failed first line primary care treatment
and been referred to an outpatient physiotherapy clinic, from a health service and personal social care perspective.
The primary economic outcome will be the incremental cost per Quality Adjusted Life Year (QALY) gained. QALYs will be estimated by administering the EQ5D5L at each followup visit.
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Protection of trial subjects |
Eligible participants who gave initial consent had blood tests to exclude haematological and biochemical abnormalities (FBC, U+E, eGFR, LFT, Hba1c). They received tuberculosis (TB) screening including a plain chest radiograph, biological agents counselling and magnetic resonance imaging (MRI) to exclude serious spinal pathology ideally within 2-3 weeks of their initial visit. When MRI has excluded serious spinal pathology, TB screening, pregnancy test for eligible women and biological agent counselling has been completed. A letter was sent to the participant’s GP by the treatment site to inform them that the participant was taking part in the trial and request that the GP make a note of this in the patient record. In addition GP's were requested to inform the trial team if they became aware the participant experienced an adverse event or serious adverse event during the trial. Once the participants completed their course of physiotherapy, if their symptoms have settled or improvied no further intervention was organised. They were discharged to the care of their general practitioner and followed up by the research team as described in this protocol. If troublesome symptoms persisted then further treatment was planned as appropriate by referral to musculoskeletal interface clinics or secondary care specialists according to local arrangement in each of the centres. Further treatment was at the discretion of the treating clinicians and may have included epidural corticosteroid injections or referral for disc surgery. The full result of the MRI scan would be made available if a spinal surgery referral was being contemplated
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Background therapy |
All participants were randomised to receive an 80-mg adalimumab subcutaneous injection followed 2 weeks later by a 40-mg injection in the posterior thigh, or an equivalent volume of 0.9% sodium chloride. Both groups received a concurrent course of physiotherapy over a period of 12 weeks | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
6
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
patients identified in three ways: a) By their GP Identified during the primary care consultation with suspected sciatica. b) Following a search of the general practice patient record database c) After referral to local musculoskeletal services | |||||||||
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Pre-assignment
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Screening details |
Invited to participate by letter. Those who were interested were contacted by telephone and, if fitted the inclusion criteria, were given an appointment in a research clinic run by a research physiotherapist. At the research clinic all potential participants were assessed by the research physiotherapist for eligibility, and consent obtained | |||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
Not possible to supply indistinguishable ampoules of adalimumab and 0.9% Sodium Chloride placebo because the adalimumab is only available in its own unique injection device. Not possible to blind the pharmacy or the person administering the injection. blinding will be maintained until all data entry and processing are complete and the database has been locked. In an emergency situation an on-call pharmacist will be available at all times to unmask the treatment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Adalimumab injections compared with control | |||||||||
Arm description |
to test whether injections of adalimumab plus physiotherapy were more effective and cost-effective than injections of saline plus physiotherapy, for patients with sciatica. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
L04AB04
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Other name |
Humira
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Pharmaceutical forms |
Solution for injection in pre-filled injector
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
80mg injection will be given on the day of randomisation or within three days from randomisation, a 40mg injection will be given two weeks later
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Arm title
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Adalimumab injections compared with control | |||||||||
Arm description |
To test whether injections of adalimumab plus physiotherapy were more effective and cost-effective than injections of saline plus physiotherapy, for patients with sciatica. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
PL1
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Other name |
0.9% Sodium Chloride.
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Pharmaceutical forms |
Solution for infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
80mg injection will be given on the day of randomisation or within three days from randomisation, a 40mg injection will be given two weeks late
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
8 participants in total recruited and randomised to the trial | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adalimumab injections compared with control
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Reporting group description |
to test whether injections of adalimumab plus physiotherapy were more effective and cost-effective than injections of saline plus physiotherapy, for patients with sciatica. | ||
Reporting group title |
Adalimumab injections compared with control
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Reporting group description |
To test whether injections of adalimumab plus physiotherapy were more effective and cost-effective than injections of saline plus physiotherapy, for patients with sciatica. | ||
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End point title |
Primary Outcome | ||||||||||||
End point description |
The primary effectiveness analysis would have been linear mixed models for repeated measures to measure the effects of time and group allocation. An internal pilot study would have involved the first 50 participants recruited across all centres. The primary economic analysis would have been a cost utility analysis.
The original intention was to use a linear mixed model approach to assess the effects of time, group and time*group. This was not possible since data were only available for eight randomised participants on trial closure.
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End point type |
Primary
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End point timeframe |
Outcomes were measured at baseline, six weeks, and six months follow-up. Originally intended to collect outcomes at 12 months but due to the early termination of the study this was not completed.
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Statistical analysis title |
Results | ||||||||||||
Statistical analysis description |
Due to low recruitment, four in each group, no statistical analysis was performed. The intention was to perform a linear mixed model in order to assess the effects of randomised group and timepoint. The data for all eight patients were presented as the analysis.
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Comparison groups |
Adalimumab injections compared with control v Adalimumab injections compared with control
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Number of subjects included in analysis |
8
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
< 0.05 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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| Notes [1] - Due to low recruitment, four in each group, no statistical analysis was performed. The intention was to perform a linear mixed model in order to assess the effects of randomised group and timepoint. The data for all eight patients were presented as the analysis. [2] - Due to low recruitment, four in each group, no statistical analysis was performed. The intention was to perform a linear mixed model in order to assess the effects of randomised group and timepoint. The data for all eight patients were presented. |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All adverse events, including non-serious adverse events, were recorded in the participant’s medical records and on their case
report form. All adverse events were reported up to 1 month after the conclusion of the physiotherapy intervention.
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Adverse event reporting additional description |
The following were not included as adverse events:
l medical or surgical procedures in which the condition that led to the procedure was the adverse event
l pre-existing disease or conditions present before treatment that did not worsen
l overdose of medication without signs or symptoms
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
18
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No adverse events observed in any of the 8 patients recruited. Study was terminated early due to low recruitment |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Jun 2015 |
Generic GP letter given to all eligible participants to inform them about the study and ask if they would like to participate, also a generic template covering letter that can be sent to participants with the relevant questionnaire at 6 weeks, 6 moths and 12 months and also a generic questionnaire reminder letter for the 6 weeks, 6 months and 12 month questionnaires |
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22 Mar 2016 |
Amendment made to the following documents:
• Baseline quality of life- addition of pain trajectory question from case report form to quality of life
• GP letter to participant- additional methods of contact
• Patient information sheet- Clarification of travelling expenses, clarification of contact by qualified member of research team
• Addition of new appointment letter- participants who have shown an interest in the trial
• Addition of a physiotherapy letter- participants who may be eligible for the trial via physiotherapy
• Participant Leaflet - Additional methods of contact
• Participant Poster- Additional methods of contact
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
