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Trial registered on ANZCTR
Registration number
ACTRN12613000530729
Ethics application status
Approved
Date submitted
22/04/2013
Date registered
13/05/2013
Date last updated
7/04/2017
Type of registration
Prospectively registered
Titles & IDs
Public title
PRECISE: pregabalin in addition to usual care for sciatica.
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Scientific title
PRECISE, a two arm, double blind randomised controlled trial of pregabalin in addition to usual care compared to placebo with usual care for reducing leg pain in patients with sciatica.
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Secondary ID [1]
282382
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None
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Universal Trial Number (UTN)
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Trial acronym
PRECISE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Sciatica
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Condition category
Condition code
Musculoskeletal
289295
289295
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0
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Other muscular and skeletal disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Arm 1 pregabalin plus usual care.
Pregabalin is a drug to treat neuropathic pain.
Initial dose of 150mg/day, divided over 2 dosed and may be increased to a maximium dose of 600mg/day with gradual titration over a four week period. Discontinuation is to reduce the dose over >7 days.
It is administered in capsule form.
The participants will be monitored over the 8 week treatment by a study doctor period.The study doctor will amend the dosage based on the patient’s ‘adequate improvement’ to the study medicine. Adequate improvement is defined as a pain rating of 0 or 1 out of 10, for leg pain, for a minimum of 72 hours, with none or tolerable side effects. If ‘adequate improvement’ has not occurred, the study doctor may increase the study medicine dosage. If ‘adequate improvement’ is reported, the dose can remain the same until the end of the study. The maximum tolerated dose for each participant will be maintained for 4 weeks or up to ‘adequate improvement’or if achieved before the 8 week standard treatment regimen is completed, early titration down to cessation. All patients will be titrated down to cessation to complete the study treatment period.
In addition to receiving the study medicines and advice (patient reassurance, staying active and avoiding bed rest) participants will receive usual care. This can consist of physical or manual therapies and other analgesic medications (except adjuvant analgesics), if deemed appropriate by the study doctor.
The total invention time is 8 weeks. The follow up includes up to 9 participant consultations with the study doctor study to begin treatment, monitor progress and adjust the dose of the study medication. Outcomes measures will be collected at baseline and weeks 2, 4, 8, 12, 26 and 52.
Adherence will be achieved through study doctor training, participant consultations, data collected from the participant by research assistants. Procedures for monitoring adherence include Adherence to study medication will be documented through a self-reported daily medication diary and by counting the returned medicine, compared to the prescribed regimen as recorded by the study doctor. Participants will be asked to return unused medicines via a reply paid post satchel at the end of the 8-week treatment period.
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Intervention code [1]
287012
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Treatment: Drugs
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Comparator / control treatment
Placebo plus usual care.
The placebo capsule consists of
lactose, maize starch, purified talc, gelatin, titanium dioxide, sodium lauryl sulfate, colloidal anhydrous silica, red iron oxide CI77491.
Its duration, control and follow up is the same as the intervention treatment of pregbalin ( as described above)
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Control group
Placebo
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Outcomes
Primary outcome [1]
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Average leg pain intensity over the last 24 hours measured by the numeral pain rating scale.
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Assessment method [1]
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Timepoint [1]
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Time point: baseline, week 2, 4, 8, 12, 26, 52.
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Secondary outcome [1]
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Back pain intensity using the Numerical Pain Rating Scale.
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Assessment method [1]
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Timepoint [1]
302408
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Time point: baseline and weeks 2, 4, 8, 12, 26 and 52.
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Secondary outcome [2]
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Disability by the Roland Disability Questionnaire for Sciatica.
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Assessment method [2]
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Timepoint [2]
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Time point: baseline and weeks 2, 4, 8, 12, 26 and 52.
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Secondary outcome [3]
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Quality of Life (SF-12v2) questionnaire.
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Assessment method [3]
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Timepoint [3]
302410
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Time point: baseline and weeks 2, 4, 8, 12, 26 and 52.
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Secondary outcome [4]
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Global Perceived Effect, which asks the participant to compare their leg pain to when this episode of sciatica first started.
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Assessment method [4]
302411
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Timepoint [4]
302411
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Time point: baseline and weeks 2, 4, 8, 12, 26 and 52.
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Secondary outcome [5]
302412
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Work and health utilization questions to report the use of health services and amount of hours missed from paid employment because of sciatica.
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Assessment method [5]
302412
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Timepoint [5]
302412
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Time point: baseline and weeks 4, 12, 26 and 52.
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Eligibility
Key inclusion criteria
Eligible participants will meet all of the following criteria:
Radiating pain into one leg below the knee.
Nerve root/spinal nerve involvement evidenced by at least one of the following clinical features:
a) Myotomal weakness,
b) Dermatomal sensory deficits,
c) Diminished reflexes,
d) Leg pain radiating in a dermatomal distribution.
Leg pain severe enough to cause at least moderate pain or moderate interference with normal work or daily activities over the last week (measured by adaptations of items 7 and 8 in the SF-36 questionnaire).
Pain duration of current episode of at least 1 week and up to 1 year.
Age 18 years and over.
Sufficient understanding of the English language or interpretation assistance available to complete the study treatment and assessments.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Patients will be excluded if they meet any of the following criteria:
Known or suspected serious spinal pathology (e.g. cauda equina syndrome, spinal fracture).
Pregnant or breastfeeding women, and males or females planning conception during the 8 week treatment period.
Scheduled or being considered for spinal surgery or interventional procedures for sciatica during the 8 week treatment period.
Contraindications to pregabalin (known allergy to pregabalin or significant renal impairment. Pregabalin is predominantly renally excreted, so patients with an estimated creatinine clearance of < 60 ml/min will be excluded).
Already taking an anticonvulsant medication, a medication for neuropathic pain, a tricyclic antidepressant or a sedative and unable to cease the medication.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be recruited from patients in the community who consult a study general practitioner (GP) or medical specialist (e.g. orthopaedic surgeon, neurosurgeon, neurologist or rheumatologist). Other sources will be patients seeking care from physiotherapists and chiropractors, or patients who respond to a community advertisement. Potential participants are then referred to a study GP to complete screening and enrolment.
Allocating treatment- the study medication (pregabalin or placebo) will be prepared by the study pharmacy according to a randomisation schedule generated a priori, then sealed and supplied to the recruiting doctor (blinded). The doctor will provide each eligible and consenting participant with a sealed study medication pack, thus randomising them to either the treatment or control group.
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A researcher not involved in participant recruitment or data collection will generate a randomisation schedule a priori using a computer derived random number sequence. Study medication will be prepared according to the randomisation schedule by the study pharmacy, then sealed and supplied to the study doctors. Upon recruitment, the doctor (blinded) will provide the medication pack to the participant (blinded), thus randomising the participant to one of two groups: pregabalin with usual care or placebo with usual care. Placebo capsules will have an identical appearance to the active pregabalin capsules. The randomisation process will ensure concealed allocation and blinding of the doctor, participant and outcome assessor.
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
Safety/efficacy
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Statistical methods / analysis
Treatment effectiveness analyses will be blinded and by intention-to-treat. A two-tailed p-value of < 0.05 will be considered statistically significant. Longitudinal linear models including all post-baseline measurements available will be used to assess the effect of treatment group on the primary and secondary outcomes with the baseline measurement and symptom duration as covariates. In case of significant missing data, sensitivity analyses will be conducted using multiple imputation, where reasonable. A secondary analysis will assess the presence of neuropathic pain features, measured by the PainDETECT questionnaire at baseline, as a modifier of treatment effects.
Economic evaluation will be conducted in two ways. Firstly a cost-effectiveness study using leg pain intensity as a measure of effectiveness and secondly a cost-utility analysis where health state utilities (quality-adjusted life-years or QALY) will be based on measures obtained from the SF-12 and transformed into utilities via the SF-6D algorithm. The primary analysis will be conducted from the health sector’s perspective, where healthcare services will be valued at standard rates published by the Australian Government (e.g. the Medical Benefits Scheme standard fees, the Pharmaceutical Benefits Scheme costs). Private non-medical healthcare services (e.g. physiotherapy) will be valued at standard rates published by the relevant professional body or third party payer. An additional analysis will entail a societal perspective in which costs associated with the use of community services (e.g. community hydrotherapy classes) and work absenteeism due to sciatica will be included. Costs of community services will be based on the self-reported costs. Costs of absenteeism from paid employment will be estimated by the number of days absent from work multiplied by the average wage rate. Sensitivity analysis will test uncertainty in key parameters such as the selection of cost weights and statistical variation in quality of life scores.
We have calculated the required sample size using a standard algorithm. The primary outcome is leg pain at week 8. A sample size of 204 participants (102 per group) will provide 90% power to detect a difference of 1.5 out of 10 units of leg pain on the Numerical Pain Rating Scale, assuming a standard deviation of 2.5, a two-tailed alpha of 0.05, and allowing for 10% of dropouts and 20% non-compliance. There is no robust evidence for the smallest worthwhile effect in pain reduction in sciatica. We have based the sample size calculation on a between-group difference of 1.5/10 in leg pain from previous trials of pregabalin for neuropathic pain. The sample size also has 90% power to detect a difference of 3 out of 23 at week 8 on our key secondary outcome, the Roland Disability Questionnaire for Sciatica. This is based on the between-group difference (3/23) and standard deviation from one of our previous sciatica trials (4/23) and the same assumptions taken for the primary outcome calculation.
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
1/07/2013
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Actual
3/09/2013
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Date of last participant enrolment
Anticipated
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Actual
27/03/2015
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Date of last data collection
Anticipated
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Actual
21/03/2016
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Sample size
Target
204
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Accrual to date
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Final
207
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment postcode(s) [1]
8068
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2093 - Balgowlah
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Recruitment postcode(s) [2]
8069
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2200 - Bankstown
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Recruitment postcode(s) [3]
8070
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2119 - Beecroft
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Recruitment postcode(s) [4]
8071
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2153 - Bella Vista
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Recruitment postcode(s) [5]
8072
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2148 - Blacktown
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Recruitment postcode(s) [6]
8073
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2134 - Burwood
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Recruitment postcode(s) [7]
8074
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2570 - Camden
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Recruitment postcode(s) [8]
8075
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2560 - Campbelltown
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Recruitment postcode(s) [9]
8076
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2166 - Canley Heights
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Recruitment postcode(s) [10]
8077
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2230 - Cronulla
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Recruitment postcode(s) [11]
8078
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2099 - Dee Why
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Recruitment postcode(s) [12]
8079
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2113 - East Ryde
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Recruitment postcode(s) [13]
8080
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2233 - Engadine
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Recruitment postcode(s) [14]
8081
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2759 - Erskine Park
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Recruitment postcode(s) [15]
8082
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2768 - Glenwood
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Recruitment postcode(s) [16]
8083
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2077 - Hornsby
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Recruitment postcode(s) [17]
8084
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2220 - Hurstville
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Recruitment postcode(s) [18]
8085
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2066 - Lane Cove
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Recruitment postcode(s) [19]
8086
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2070 - Lindfield
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Recruitment postcode(s) [20]
8087
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2035 - Maroubra
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Recruitment postcode(s) [21]
8088
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2204 - Marrickville
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Recruitment postcode(s) [22]
8089
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2160 - Merrylands
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Recruitment postcode(s) [23]
8090
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2137 - Mortlake
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Recruitment postcode(s) [24]
8091
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2152 - Northmead
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Recruitment postcode(s) [25]
8092
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2021 - Paddington
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Recruitment postcode(s) [26]
8093
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2124 - Parramatta
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Recruitment postcode(s) [27]
8094
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2120 - Pennant Hills
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Recruitment postcode(s) [28]
8095
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2750 - Penrith
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Recruitment postcode(s) [29]
8096
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2011 - Potts Point
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Recruitment postcode(s) [30]
8097
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2009 - Pyrmont
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Recruitment postcode(s) [31]
8098
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2031 - Randwick
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Recruitment postcode(s) [32]
8099
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2143 - Regents Park
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Recruitment postcode(s) [33]
8100
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2216 - Rockdale
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Recruitment postcode(s) [34]
8101
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2560 - Rosemeadow
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Recruitment postcode(s) [35]
8102
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2039 - Rozelle
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Recruitment postcode(s) [36]
8103
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2112 - Ryde
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Recruitment postcode(s) [37]
8104
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2000 - Sydney
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Recruitment postcode(s) [38]
8105
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2573 - Tahmoor
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Recruitment postcode(s) [39]
8106
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2084 - Terrey Hills
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Recruitment postcode(s) [40]
8107
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2570 - The Oaks
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Recruitment postcode(s) [41]
8108
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2146 - Toongabbie
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Recruitment postcode(s) [42]
8109
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2017 - Waterloo
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Recruitment postcode(s) [43]
8110
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2145 - Wentworthville
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Recruitment postcode(s) [44]
8111
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2153 - Winston Hills
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Recruitment postcode(s) [45]
8112
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2500 - Wollongong
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Funding & Sponsors
Funding source category [1]
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Government body
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Name [1]
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National Health and Medical Research Council (NHMRC).
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Address [1]
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Level 1, 16 Marcus Clarke St,
Canberra, NSW, 2601, Australia.
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Country [1]
287154
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Australia
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Primary sponsor type
Other Collaborative groups
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Name
The George Institute for Global Health
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Address
PO Box M201
Missenden Rd, NSW 2050.
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Country
Australia
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Secondary sponsor category [1]
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University
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Name [1]
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Sydney Medical School, University of Sydney.
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Address [1]
285919
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Edward Ford Building,
University of Sydney,
Cnr Physics Rd & Fisher Rd,
Camperdown, NSW, 2006.
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Country [1]
285919
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Australia
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
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University of Sydney Research Ethics Committee
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Ethics committee address [1]
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Level 6 Jane Foss Russell Building-G02,
The University of Sydney, NSW, 2006, Australia.
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Ethics committee country [1]
289151
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Australia
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Date submitted for ethics approval [1]
289151
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Approval date [1]
289151
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07/11/2012
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Ethics approval number [1]
289151
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Summary
Brief summary
Patients with sciatica experience low back pain, with pain radiating into the leg and possible neurological deficits. Sciatica is associated with substantial pain and chronic disability. The lack of evidence supporting effective treatments for sciatica makes clinical management difficult.
The aim of the study is to determine the efficacy and cost effectiveness of adding pregabalin to usual care for reducing leg pain intensity in patients with sciatica.
PRECISE is a prospectively registered, double blind, randomized placebo controlled trial of pregabalin, in addition to usual care in people with sciatica. Participants will be recruited from patients in the community who consult a study general practitioner (GP) or medical specialist (e.g. orthopaedic surgeon, neurosurgeon, neurologist or rheumatologist) with moderate to severe sciatica. GPs and specialists will be recruited from the Sydney metropolitan area (Australia). Other referral sources include physiotherapists and chiropractors that may identify potential participants and then refer the patient to a study GP. Participant inclusion criteria include low back pain that radiates below the knee, neurological compromise, interference with normal daily activities and pain duration of 1 week to 1 year. Participants will not be eligible if they are scheduled for spinal surgery, have known serious pathology, are pregnant, have contraindications to pregabalin or taking certain prescribed medicines. Participants will be randomised to receive either pregabalin with usual care (n=102) or the placebo with usual care (n=102) for 8 weeks. The medicine dosage will be titrated up to the participant’s optimal dose, to a maximum 600 mg per day. Usual care, if deemed appropriate by the study doctor may include analgesic medication or physical and manual therapy. Participants, doctors and researchers collecting participant data will be blinded. The primary outcome is leg pain. Secondary outcomes include back pain, disability and quality of life. Treatment effectiveness analysis will be blinded and by intention-to-treat. A p-value of < 0.05 will be considered statistically significant. A parallel economic evaluation will be conducted from the societal perspective.
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Trial website
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Trial related presentations / publications
Mathieson S, Maher CG, McLachlan AJ, Latimer J, Koes BW, Hancock MJ, Harris I,
Day RO, Billot L, Pik J, Jan S, Lin CC. Trial of Pregabalin for Acute and Chronic
Sciatica. N Engl J Med. 2017 Mar 23;376(12):1111-1120. doi:10.1056/NEJMoa1614292. PubMed PMID: 28328324.
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Public notes
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Contacts
Principal investigator
Name
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Dr Chung-Wei Christine LIN
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Address
39490
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The George Institute for Global Health,
PO Box M201,
Missenden Rd, NSW 2050.
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Country
39490
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Australia
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Phone
39490
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+612 8238 2437
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Fax
39490
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+612 9657 0301
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Email
39490
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[email protected]
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Contact person for public queries
Name
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Ms Stephanie MATHIESON
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Address
39491
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The George Institute for Global Health,
PO Box M201,
Missenden Rd, NSW 2050.
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Country
39491
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Australia
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Phone
39491
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+612 9657 0300
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Fax
39491
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+612 9657 0301
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Email
39491
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[email protected]
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Contact person for scientific queries
Name
39492
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Dr Chung-Wei Christine LIN
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Address
39492
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The George Institute for Global Health,
PO Box M201,
Missenden Rd, NSW 2050.
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Country
39492
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Australia
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Phone
39492
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+612 8238 2437
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Fax
39492
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+612 9657 0301
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Email
39492
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[email protected]
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
Healthcare expenditure and its predictors in a cohort of Australians living with sciatica.
2021
https://dx.doi.org/10.1007/s00586-020-06605-2
Embase
In moderate-to-severe sciatica, pregabalin did not reduce leg pain intensity or improve quality of life.
2017
https://dx.doi.org/10.7326/ACPJC-2017-167-2-004
Embase
Trial of pregabalin for acute and chronic sciatica.
2017
https://dx.doi.org/10.1056/NEJMoa1614292
Embase
PRECISE - pregabalin in addition to usual care: Statistical analysis plan.
2016
https://dx.doi.org/10.1186/s13063-016-1174-y
Embase
PRECISE - pregabalin in addition to usual care for sciatica: Study protocol for a randomised controlled trial.
2013
https://dx.doi.org/10.1186/1745-6215-14-213
N.B. These documents automatically identified may not have been verified by the study sponsor.
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