A Phase III triple-blind randomised placebo-controlled trial to evaluate effectiveness of early treatment with pregabalin to reduce pain severity after whiplash road traffic injury: study protocol for the PRioRTI Trial {1}

BACKGROUND: There are few effective treatments for acute whiplash-associated disorder (WAD) following a road traffic crash. Early clinical features of central sensitisation, for example widespread hyperalgesia, predict poor recovery. Pregabalin's effects on central sensitisation suggest the potential to prevent or modulate these processes after whiplash injury and prevent later chronic pain. Preliminary evidence indicates that pregabalin provided in the Emergency Department and within 96 hours of injury shows promise to prevent chronic pain. This trial aims to definitively evaluate, in patients at risk for poor recovery following whiplash injury, the effectiveness of early (within 96 hours of injury) pregabalin, compared to placebo, to reduce pain severity.

METHODS: The PReventing chronic pain after whiplash Road Traffic Injury (PRioRTI) study is a 12-month randomised, placebo-controlled, triple-blind trial. Individuals with acute WAD (aged 18-70 years) and at risk of poor recovery (pain ≥ 5/10) will be recruited from hospital Emergency Departments in Australia. Participants will be randomly assigned 1:1 to receive pregabalin or placebo. All participants will additionally receive an evidence-based advice booklet. Pregabalin will be commenced at 75 mg bd and titrated to 300 mg bd over 4 weeks, then weaned for 2 weeks. Participants will complete online questionnaires at 6 weeks and 3, 6 and 12 months post-randomisation. The primary outcome will be average pain intensity over 24 hours (0-10 numerical rating scale) at 3 months post-randomisation. Secondary outcomes include disability, patient global impression of recovery, psychological distress, quality of life and the number of adverse events. A cost-effectiveness analysis will be conducted. Potential mediators of treatment effects will be explored. A process evaluation will be conducted to explore barriers and facilitators for future implementation.

DISCUSSION: There are few effective treatments for acute WAD. To address this gap, the PRioRTI trial aims to improve health outcomes by targeting central nociceptive processes very soon after whiplash injury using a readily available medication, pregabalin. If successful, the results of this trial will address an urgent unmet need to reduce pain severity after injury and will have clear implications for the early treatment of patients with whiplash injury. TRIAL REGISTRATION {2A AND 2B}: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12624001359527. Registered 13th November 2024.