Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001359527
Ethics application status
Approved
Date submitted
23/09/2024
Date registered
13/11/2024
Date last updated
13/06/2025
Date data sharing statement initially provided
13/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Effectiveness of PReventing chronic pain after whiplash Road Traffic Injury (PRioRTI)
Scientific title
A Phase III triple-blind randomised placebo-controlled trial to evaluate effectiveness of early treatment with pregabalin to prevent chronic pain after whiplash road traffic injury. (PRioRTI: Trial).
Secondary ID [1] 312590 0
none
Universal Trial Number (UTN)
Trial acronym
PRioRTI Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute whiplash associated disorders 334423 0
Condition category
Condition code
Musculoskeletal 331053 331053 0 0
Other muscular and skeletal disorders
Injuries and Accidents 331924 331924 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PReventing chronic pain after whiplash Road Traffic Injury (PRioRTI) is a randomised, triple-blinded, placebo-controlled, multi-centre Phase III trial to evaluate the effectiveness of early (within 96 hours of injury) treatment with pregabalin to prevent chronic pain after whiplash injury.

The trial intervention will be pregabalin oral capsule twice a day (BD) for the below planned dosage schedule:

- 75mg BD for 3 days
- Titrated up to 150mg BD for 11 days if tolerated
- Titrated up to 300mg BD for 14 days if tolerated
- Titrated down to 150mg BD for 7 days
- 75mg BD for 7 days.

If participants do not tolerate an up-titrated dose (i.e., 150mg or 300mg), they will remain at the maximal dose previously tolerated (e.g., if 300 mg BD not tolerated, they will remain at 150 mg BD until their scheduled down-titration to 75mg BD). Adherence will be monitored by a self-report dosage checklist, telehealth follow ups by the UQ Telehealth Team, and medication bottle return after completion of the treatment period

The intervention will be delivered concurrent to evidence-based advice in the form of a booklet 'Whiplash Injury Recovery: a self-help guide (3rd edition)' which reflects current Australian Guidelines (i.e., Australian Clinical Guidelines for Health Professionals Managing People with Whiplash-Associated Disorders, 3rd edition, NSW State Insurance Regulatory Authority). This booklet was developed by the UQ research team and published by the Queensland Motor Accident Insurance Commission (available at https://maic.qld.gov.au/for-injured-people/rehabilitation-advice/whiplash-injury-recovery/) and is publicly available. It was not designed specifically for this study
Intervention code [1] 329054 0
Treatment: Drugs
Intervention code [2] 329651 0
Treatment: Other
Comparator / control treatment
The control intervention will be a placebo capsule Avicel (hydroxypropyl methylcellulose capsule filled with microcrystalline cellulose powder). It will be matched to the pregabalin medication in appearance, weight and dosage – 1 capsule BD up to 4 capsules BD, in line with the pregabalin titration schedule.

The intervention will be delivered concurrent to evidence-based advice in the form of a booklet 'Whiplash Injury Recovery: a self-help guide (3rd edition)' which reflects current Australian Guidelines.
Control group
Placebo

Outcomes
Primary outcome [1] 338818 0
Neck pain intensity
Assessment method [1] 338818 0
Self reported neck pain intensity over the previous 24 hours using a numeric rating scale (NRS 0 no pain – 10 worst possible pain)
Timepoint [1] 338818 0
The primary time point will be 3 months post-randomisation
Secondary outcome [1] 437572 0
Neck pain intensity
Assessment method [1] 437572 0
Self reported pain intensity over the previous 24 hours using a numeric rating scale (NRS 0 no pain – 10 worst possible pain)
Timepoint [1] 437572 0
Baseline, 6 weeks, 6 months and 12 months post-randomisation
Secondary outcome [2] 437573 0
Pain location
Assessment method [2] 437573 0
Body chart: patients are asked to indicate where on a body chart they are experiencing pain/symptoms
Timepoint [2] 437573 0
Baseline, 6 weeks, Day 21, Day 42, 3 months, 6 months, 12 months post-randomisation.
Secondary outcome [3] 437574 0
Pain-related disability
Assessment method [3] 437574 0
Neck Disability Index: 10 item questionnaire that scores on a 0-100% scale, such that 0% is no neck-pain related disability and 100% is total disability
Timepoint [3] 437574 0
6 weeks, 3 months, 6 months, 12 months post-randomisation.
Secondary outcome [4] 437577 0
Patient overall improvement (perceived recovery, or global impression of recovery)
Assessment method [4] 437577 0
Global Impression of Recovery Scale: 11-point (-5 to +5) global rating of change scale, where , 0 represents no change in a patient’s overall condition, negative values denote worsening, and positive values denote improvement
Timepoint [4] 437577 0
6 weeks, 3 months, 6 months, 12 months post-randomisation
Secondary outcome [5] 437581 0
Quality of life
Assessment method [5] 437581 0
Assessment of Quality of Life 8D (AQoL-8D): s a 35 item questionnaire that will assess quality of life, spanning eight domains: Independent Living, Happiness, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses. Responses from these items will be computed to produce aggregate scores for quality of life, normalised to Australian population data
Timepoint [5] 437581 0
Baseline, 6 weeks, 3 months, 6 months, 12 months post-randomisation
Secondary outcome [6] 437582 0
Post-traumatic stress symptoms
Assessment method [6] 437582 0
PTSD Checklist for DSM-5 (PCL-5): a 20-item self-report measure that assesses the 20 DSM-5 symptoms of post traumatic stress disorder. Respondents are asked to rate how bothered they have been by each of 20 items in the past month on a 5-point Likert scale ranging from 0-4. A total summary score is calculated, ranging 0-80 (higher scores denote worse symptoms).
Timepoint [6] 437582 0
6 weeks, 3 months, 6 months, 12 months post-randomisation
Secondary outcome [7] 437585 0
Sleep quality
Assessment method [7] 437585 0
To assess sleep quality as a potential mediator of treatment effect, we will use the brief sleep survey reported by Beaudoin et al (Transl Psychiatry 2023;13:4) . This is assessed using three items: “Over the last few nights, how much of a problem have you had falling asleep?”, “Over the last few nights, how much of a problem have you had staying asleep all night?” and “Over the last few nights, how much of a problem have you had waking up too early in the morning?”. Each item is rated on a 0–4 scale (0=None, 1=A little, 2=Some, 3=A lot, 4=Extremely), with total score ranging 0-12
Timepoint [7] 437585 0
As a mediating variable, sleep will be assessed at Day 21 and at Day 42 6 weeks post-randomisation.
Secondary outcome [8] 437588 0
Cold hyperalgesia (i.e., increased perception of pain with a cold stimulus)
Assessment method [8] 437588 0
Cold hyperalgesia will be assessed using the ice cube test, as described by Maxwell and Sterling (Man Ther 2013 18:172-174). This test involves placing a small plastic bag with two ice cubes inside on the skin of the participant for 10 s. Participants are asked to rate on 0-10 numerical rating scale the pain they experienced during the test. A pain rating >5/10 is indicative of cold hyperalgesia. This test will be performed via telehealth
Timepoint [8] 437588 0
As a mediating variable, cold hyperalgesia will be assessed at Day 21 and at Day 42 post-randomisation.
Secondary outcome [9] 437589 0
Nociplastic pain characteristics
Assessment method [9] 437589 0
Study-specific survey (developed based on international clinical classification criteria): an 8 item questionnaire comprising self-report Yes/No questions regarding elements of nociplastic pain (i.e., sensitivity to touch, warm, cold and movement, sensitivity to light/sound, fatigue, cognitive problems)
Timepoint [9] 437589 0
As a mediating variable, the survey will be assessed at Day 21 and Day 42 post-randomisation.
Secondary outcome [10] 437907 0
Participant qualitative experience of intervention
Assessment method [10] 437907 0
Semi-structured interviews of a subset of 25-30 trial participants (in-person or by zoom, to maximise participation), to understand their experiences of the treatment. Interviews will be ~40 mins to 1 hour and conducted by trial staff with expertise in qualitative research. Interviews will explore patients’ experience of participating in the clinical trial, the treatment, barriers and facilitators to the use and prescription of pregabalin, and any perceived impacts on their treatment goals and outcomes. Participants who consented to being approached to participate in a qualitative interview will be contacted by email and provided with further information. Sampling will be purposive to ensure diversity of participants regarding gender, age, and location.
Timepoint [10] 437907 0
Interviews will be undertaken after completion of the intervention (i.e. after 6 weeks post-randominsation)
Secondary outcome [11] 439541 0
Clinical staff qualitative experience of intervention
Assessment method [11] 439541 0
Semi-structured interviews of a subset of 25-30 healthcare staff involved in the trial (in-person or by zoom, to maximise participation), to understand their experiences and perceptions of the treatment. Interviews will be ~40 mins to 1 hour and conducted by trial staff with expertise in qualitative research. Over 2 phases, interviews will explore staff experience of the clinical trial, the treatment, barriers and facilitators to the use and prescription of pregabalin, and challenges and solutions regarding trial processes in the Emergency Department. Expression of Interest (EOI) in participating in a qualitative interview will be sought at the time of signing the trial delegation log. A selection of staff will be contacted by email and provided with further information. Sampling will be purposive to ensure diversity of participants regarding employment location, disciplinary background, and level of seniority.
Timepoint [11] 439541 0
Interviews to occur ) from 6 months post trial commencement, or once 50% of recruitment is complete, whichever is sooner (Phase 1), and from ~1.5 years post commencement (Phase 2).
Secondary outcome [12] 440450 0
Psychological functioning – Anxiety symptoms
Assessment method [12] 440450 0
Depression, Anxiety and Stress Scale 21: This 21 item questionnaire has three subscales that allow calculation of separate scores for depression, anxiety and stress symptoms; higher scores indicate higher levels of psychological symptoms. The anxiety subscale will be used to assess anxiety symptoms.
Timepoint [12] 440450 0
Baseline, 6 weeks, 3 months, 6 months, 12 months post-randomisation, plus Day 21 and Day 42 post-randomisation for mediation analysis.
Secondary outcome [13] 440451 0
Psychological functioning – Stress symptoms
Assessment method [13] 440451 0
Depression, Anxiety and Stress Scale 21: This 21 item questionnaire has three subscales that allow calculation of separate scores for depression, anxiety and stress symptoms; higher scores indicate higher levels of psychological symptoms. The stress subscale will be used to assess stress symptoms.
Timepoint [13] 440451 0
Baseline, 6 weeks, 3 months, 6 months, 12 months post-randomisation.
Secondary outcome [14] 440452 0
Psychological functioning – Depression symptoms
Assessment method [14] 440452 0
Depression, Anxiety and Stress Scale 21: This 21 item questionnaire has three subscales that allow calculation of separate scores for depression, anxiety and stress symptoms; higher scores indicate higher levels of psychological symptoms. The depression subscale will be used to assess depression symptoms.
Timepoint [14] 440452 0
Baseline, 6 weeks, 3 months, 6 months, 12 months post-randomisation.

Eligibility
Key inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply:
1. Neck or upper back pain (Whiplash Associated Disorder (WAD) Grade II)
2. Within 96 hours of road traffic injury
3. Pain of at least 5/10 on numerical rating scale of pain intensity
4. Aged 18-70 years
5. Not admitted as a hospital inpatient (Emergency Deptment short stay units acceptable)
6. Participant is able to provide written informed consent and is willing to participate for the duration of the study and to follow study procedures
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. Serious spinal pathology (e.g., fracture/dislocation WAD Grade IV, metastatic disease)
2. Neurological compromise (e.g., decreased reflexes, muscle power – WAD Grade III)
3. Peripheral neuropathy
4. Chronic pain condition for which patient is currently seeking treatment
5. Using gabapentin/pregabalin/other anticonvulsants
6. Known hypersensitivity to pregabalin (hives, blisters, rash, dyspnoea, wheezing)
7. Known renal disease causing renal insufficiency
8. Pregnancy or breastfeeding
9. History of psychiatric illness or substance abuse
10. History of depression or scoring 3 or greater on the PHQ-2
11. Inability to speak and write in English (to complete questionnaires)

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)
A unique kit number will be displayed on all trial intervention. Only those who hold the unblinded allocation tables will be able to link the unique kit number to the intervention group
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent statistician will generate the randomisation list, blocks with 1:1 ratio, which will be directly supplied to Syntro, the manufacturer. The manufacturer prepares the medication kits according to the list.
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
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/07/2025
Actual
Date of last participant enrolment
Anticipated
12/07/2027
Actual
Date of last data collection
Anticipated
12/07/2028
Actual
Sample size
Target
258
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 26796 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 26797 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 26798 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 42847 0
4032 - Chermside
Recruitment postcode(s) [2] 42848 0
2050 - Camperdown
Recruitment postcode(s) [3] 42849 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 316881 0
Government body
Name [1] 316881 0
Department of Health and Aged Care: Medical Research Future Fund (MRFF) – 2021 Clinical Trials Activity
Country [1] 316881 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Country
Australia
Secondary sponsor category [1] 319212 0
None
Name [1] 319212 0
Country [1] 319212 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315641 0
Metro North Health HREC (EC00172)
Ethics committee address [1] 315641 0
Ethics committee country [1] 315641 0
Australia
Date submitted for ethics approval [1] 315641 0
27/03/2024
Approval date [1] 315641 0
12/07/2024
Ethics approval number [1] 315641 0
HREC/2024/MNHB/106754

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 135354 0
Prof Michele Sterling
Address 135354 0
RECOVER Injury Research Center, The University of Queensland, Level 7 296 Herston Road, Herston QLD 4029
Country 135354 0
Australia
Phone 135354 0
+61733464793
Email 135354 0
m.sterling@uq.edu.au
Contact person for public queries
Name 135355 0
Lisa Ferguson
Address 135355 0
RECOVER Injury Research Center, The University of Queensland, Level 7 296 Herston Road, Herston QLD 4029
Country 135355 0
Australia
Phone 135355 0
+61 404026350
Email 135355 0
lisa.ferguson@uq.edu.au
Contact person for scientific queries
Name 135356 0
Michele Sterling
Address 135356 0
RECOVER Injury Research Center, The University of Queensland, Level 7 296 Herston Road, Herston QLD 4029
Country 135356 0
Australia
Phone 135356 0
+61733464793
Email 135356 0
m.sterling@uq.edu.au

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Data obtained through this trial may be provided to qualified researchers with an interest in whiplash pain management.

Conditions for requesting access:
• -

What individual participant data might be shared?
• Data shared will be non-identifiable IPD of published trial results only, coded with no protected health information included.

What types of analyses could be done with individual participant data?
• For related analyses on management of pain (e.g., IPD meta-analysis etc).

When can requests for individual participant data be made (start and end dates)?
From:
Immediately after article publication and the data will be made accessible for up to 60 months.

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Non-identifiable IPD can be obtained by contacting Prof Sterling (m.sterling@uq.edu.au) and will be provided following ethical review and approval of a research proposal and Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA).

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.