The Medal Trial - MEDications in Acute Low back pain

Research question: Which analgesic ladder is the most effective to resolve pain for (i) acute low back pain, (ii) acute low back pain and somatic leg pain, or (iii) neuropathic pain (sciatica) ± acute low back pain, measured using the Patient Global Impression of Change scale recording ‘Quite a lot better’ for 5 consecutive days. Background: Back pain and leg pain / sciatica are common in primary care and cause many lost work days in the UK (2). Management of the acute pain is challenging. Current NICE guidance (11) limits medication options available for lack of evidence. Rapid resolution of an acute episode gets people out of pain and back to work, preventing symptom chronicity (7). There is a need for robust evidence for the medication options in these groups. Aims and objectives: To test 6 analgesic ladders in the 3 different diagnostic groups ((i) acute low back pain, (ii) acute low back pain and referred somatic leg pain, or (iii) neuropathic pain (sciatica) ± acute low back pain) to find the best ladder for rapid pain relief along with better function, return to activity, work and sleep. Also, explore the cost effectiveness of the interventions and to seek the views of participants and the professionals involved. Methods: Design: A multi-centre, open, individually randomised controlled, adaptive platform trial using 6 pre-defined analgesic ladders for 3 different diagnostic groups, with remote electronic data collection and interim analyses the allow the dropping of ineffective arms with an internal pilot and integrated health economic analysis. Participants: Adults with less than 3 months of symptoms randomised to 6 arms (maximum of 220 per diagnostic groups per arm). Interventions: One of 6 pre-defined analgesic ladders. Escalation of medication if required after 72 hours for a maximum of 8 weeks from randomisation. Outcomes: The primary outcome is the time to recording ‘Quite a lot better’ for 5 consecutive days on the validated Patient Global Impression of Change scale. Other outcomes are a rating of pain severity (NRS), level of function (ODI), work impairment (WAPI), mental health (DAPOS), quality of life (EQ-5D-5L) and questions on sleep, side effects / adverse events and other treatments also used. Analysis: The primary analysis will be on an intention to treat principle. Bayesian methods will be used for interim and final analyses (time to event modelling) including appropriate minimisation factors. Posterior probability distributions will be used to identify the most favourable intervention in each diagnostic group. We will also explore the use of hierarchical modelling across the groups. Other outcomes will be modelled longitudinally. Sensitivity analyses will be performed to assess the effect of data loss from incomplete follow from drop out. Public patient involvement: PPI input has been extensive and will shape every aspect of the trial including conduct, recruitment, and qualitative data interpretation. Timelines for delivery: Total of 60 months: 7 mths set up, 6 mths internal pilot, 29 mths main recruitment, 11 mths FU up from last recruitment; 6 mths analysis and writing. Anticipated impact and dissemination: The results will inform prescribers of the most effective medication(s) for the management of acute low back pain / leg pain and sciatica. This will inform future NICE guidelines in this field. Dissemination will be through the media, conferences, journal articles and future clinical guidelines.