Trial registered on ANZCTR


Trial ID
ACTRN12617000059369
Ethics application status
Approved
Date submitted
4/01/2017
Date registered
11/01/2017
Date last updated
5/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Pregabalin for acute whiplash
Scientific title
Pregabalin vs placebo in targeting pronociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals – feasibility study for a randomised controlled trial.
Secondary ID [1] 290804 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Whiplash Injury 301453 0
Condition category
Condition code
Musculoskeletal 301176 301176 0 0
Other muscular and skeletal disorders
Injuries and Accidents 301258 301258 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be provided with an advice booklet Whiplash Injury Recovery: A Self Help Guide (2nd edition) published by the Motor Accident Insurance Commission (MAIC), Qld. It provides information about whiplash; assurance about prognosis; advice to stay active and resume working as well as information on correct posture; pictorial descriptions of specific exercises for the neck and upper limbs and information on resuming functional daily activities. This second edition of the booklet was written based on consumer and health care professional feedback via focus groups. The booklet is based on the recommendations of the current Australian Guidelines for Whiplash Management.

Patients randomized to the experimental arm of the study will receive 1 pregabalin capsule (75 mg) orally twice daily with the first dose taken before discharge during the initial ED presentation. Patients will continue on this dose for 3 days after which time the dose could be titrated to 150mg twice daily if the previous dose is well tolerated. The dose could be further increased to 300 mg twice daily after the second week if 150 mg twice daily is well tolerated. The dose will be reduced to the previously tolerated level if the higher dose is not well tolerated after 3 days. The study medication will be continued for 28 days, after which a dose of 300 mg twice daily will be weaned to 150 mg twice daily for 3 days and then 75 mg twice daily for 3 days, a dose of 150 mg twice daily will be weaned to 75 mg twice daily for 6 days and a dose of 75 mg twice daily continued for 6 days. Dose de-escalation in lower maximum tolerated doses will use proportionately lower doses over the same time schedule. The dose escalation/reduction regimen for our trial has been used in previous pregabalin trials. All patients will be asked to continue taking the medicines (active or placebo) for a period of 28 days with a subsequent 6 days of weaning. The prescription of pregabalin in this way is standard clinical practice.
Adherence will be measured by self-report in patient diaries and pill counts.
Intervention code [1] 296721 0
Treatment: Drugs
Comparator / control treatment
Patients in the control group will also receive the information booklet described above. A placebo will be administered as a control and this will be compared to the pregabalin drug administration.. Both drugs and administration regimes will be identical to ensure blinding.
Control group
Placebo

Outcomes
Primary outcome [1] 300594 0
Neck pain intensity at 3 months post randomisation from baseline between the treatment groups. Neck pain intensity is measured on the continuous numeric rating scale (NRS) of 0 to 10, and will represent the patient's self-report of average pain intensity during last 24 hours.
Timepoint [1] 300594 0
Neck pain intensity will be assessed at 3 months post randomisation.
Secondary outcome [1] 330369 0
1. Neck pain intensity (NRS 24 hours) at 6-and 12-month follow-up from baseline between the treatment groups;
Timepoint [1] 330369 0
6 month and 12 month followup
Secondary outcome [2] 330371 0
Neck Disability Index (NDI) scores 3, -6 and 12-months from baseline, compared between the treatments
Timepoint [2] 330371 0
3, 6 months and 12 months from baseline
Secondary outcome [3] 330372 0
Pain Catastrophising Scale (PCS) scores at follow-up from baseline, compared between treatments
Timepoint [3] 330372 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [4] 330373 0
Between treatment differences in Posttraumatic Stress Diagnostic Scale (PDS) symptom score, measured during follow-up
Timepoint [4] 330373 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [5] 330374 0
Between treatment differences in Depression, Anxiety & Stress scale (DASS), measured during follow-up
Timepoint [5] 330374 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [6] 330375 0
Generic measure of health status scores (SF-12) during follow-up between the treatment groups
Timepoint [6] 330375 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [7] 330376 0
Comparison of proportion of patients who lodge a compensation claim during follow-up, between the treatment groups. This will be self-reported on the followup questionnaires
Timepoint [7] 330376 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [8] 330403 0
Number of doses of break through medication. Self reported by the patients.
Timepoint [8] 330403 0
At the 5-week, 3-month, 6-month, 12-month follow ups
Secondary outcome [9] 341082 0
Feasibility by estimating rates of:
i. Recruitment (number of patients approached, number consenting to participate, and number eligible to be randomised);
ii. Missing data and participant attrition.
Timepoint [9] 341082 0
At the end of the trial
Secondary outcome [10] 341083 0
Recruitment strategies tested and a model for recruitment to a full trial developed.


Timepoint [10] 341083 0
At the end of the trial
Secondary outcome [11] 341084 0
Relevant factors identified that could create barriers to subsequent study completion, and strategies developed to overcome these
Timepoint [11] 341084 0
At end of the trial
Secondary outcome [12] 341085 0
Qualitative feedback obtained from ED clinicians, GPs, and patients on their experience with the trial and areas for improvement to inform a full scale trial.
Timepoint [12] 341085 0
At end of the trial

Eligibility
Key inclusion criteria
1. Individuals with Grade II WAD and within 48 hours of injury.
2. Experiencing at least moderate pain (VAS>=5/10) on first measurement by ambulance or on arrival in ED.
3. Age 18-65 years
4. Proficient in written and spoken English
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known or suspected serious spinal pathology (e.g. metastatic disease of the spine);
2. Confirmed fracture or dislocation at time of injury (WAD IV);
3. WAD III (neurological compromise eg decreased reflexes, muscle power);
4. Previous whiplash injury or neck pain condition requiring treatment;
5. Patient Health Questionnaire-2 score of 3 or more
6. Patients using gabapentin/pregabalin;
7. Patients with known peripheral neuropathy;
8. Known hypersensitivity to pregabalin use (hives, blisters, rash, dyspnea and wheezing);
9. History of renal insufficiency; liver disease?
10. Women who are pregnant or breastfeeding;
11. History of psychiatric illness or substance abuse;
12. Inability to speak and write in English (participants will be required to complete questionnaires written in English only).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All analyses will be conducted on an intention to treat basis and by a statistician blinded to group allocation. The primary outcome of change in neck pain intensity at 3 months from baseline will be compared between the treatment groups using standard analysis of variance technique, and the 95% confidence intervals of changes between the groups will be presented. Analyses of data from earlier studies and our simulation studies suggest approximate normality of the distribution of change in intensity score. Missing data will be examined for its randomness and addressed with multiple imputations, if required.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 7175 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 14936 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 295228 0
Government body
Name [1] 295228 0
NHMRC Centre of Research Excellence in Road Traffic Injury Recovery
Address [1] 295228 0
GPO Box 1421 Canberra ACT 2601
Country [1] 295228 0
Australia
Funding source category [2] 295230 0
University
Name [2] 295230 0
Menzies Health Institute of Queensland
Address [2] 295230 0
G40 Griffith Health Centre, Level 8.86
Gold Coast campus
Griffith University QLD 4222
Country [2] 295230 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Faculty of Health and Behavioural Sciences, The University of Queensland
Level 7, UQ Oral Health Centre, 288 Herston Road, Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 294058 0
None
Name [1] 294058 0
Address [1] 294058 0
Country [1] 294058 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296573 0
Gold Coast Hospital and Health Service Human Research Ethics Committee (HRECs)
Ethics committee address [1] 296573 0
1 Hospital Boulevard
Southport QLD 4215
Ethics committee country [1] 296573 0
Australia
Date submitted for ethics approval [1] 296573 0
10/11/2016
Approval date [1] 296573 0
07/12/2016
Ethics approval number [1] 296573 0
HREC/16/QGC/296

Summary
Brief summary
We will conduct a feasibility study for a randomised controlled trial examining the effectiveness of pregabalin to prevent chronic pain following whiplash injury in ‘at-risk’ individuals. This feasibility study will hone eligibility criteria, test recruitment strategies, and develop a model for recruitment for the subsequent full scale trial. The primary aim of this current study is to assess the feasibility of the RCT by measuring recruitment rates (number of patients approached, number consenting to participate, and number eligible to to be randomised; missing data and participant attrition). and obtaining qualitative feedback from patients and doctors about their experience of the trial and suggestions for improvement.

The secondary aims are to: 1) Investigate the effectiveness of pregabalin to decrease disability, depression, posttraumatic stress symptoms, and pain catastrophizing; 2) To conduct an economic evaluation of the pregabalin intervention.

We hypothesise that pregabalin used in acute whiplash injury will prevent or modulate pro-nociceptive mechanisms and improve health outcomes for this treatment resistant condition, and that the study will be feasible.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71338 0
Prof Michele Sterling
Address 71338 0
Recover Injury Research Centre, Faculty of Health and Behavioural Sciences, The University of Queensland
Level 7, UQ Oral Health Centre, 288 Herston Road, Herston QLD 4006
Country 71338 0
Australia
Phone 71338 0
61 488 196 862
Fax 71338 0
Email 71338 0
m.sterling@uq.edu.au
Contact person for public queries
Name 71339 0
Dr Jane Nikles
Address 71339 0
Recover Injury Research Centre, Faculty of Health and Behavioural Sciences, The University of Queensland
Level 7, UQ Oral Health Centre, 288 Herston Road, Herston QLD 4006
Country 71339 0
Australia
Phone 71339 0
61 408 599 033
Fax 71339 0
Email 71339 0
uqjnikle@uq.edu.au
Contact person for scientific queries
Name 71340 0
Dr Jane Nikles
Address 71340 0
Recover Injury Research Centre, Faculty of Health and Behavioural Sciences, The University of Queensland
Level 7, UQ Oral Health Centre, 288 Herston Road, Herston QLD 4006
Country 71340 0
Australia
Phone 71340 0
61 408 599 033
Fax 71340 0
Email 71340 0
catherine.nikles@uq.edu.au