MEDAL

Primary Objective:
To assess which analgesic ladder is the most effective in the management and resolution of pain in those presenting with either 1) Acute LBP, 2) Acute LBP and referred somatic leg pain, or 3) Neuropathic leg pain (sciatica) +/- acute LBP.

Secondary Objectives:
To assess which analgesic ladder:

• Best improves function
• Best allows normalisation of sleep
• Best allows an earlier return to work and/or usual daily activities
• Best reduces feelings of depression and anxiety
• Most quickly resolves symptoms

 The trial will also:

• Compare the relative cost-effectiveness of the different analgesic ladders
• Explore views and experiences of those with LBP, and those who work with people who have LBP

A multi-centre, open label, individually randomised controlled, adaptive platform trial in Primary Care, recruiting patients from three separate clinical scenarios with an integrated health economic evaluation and internal pilot with embedded qualitative process evaluation.

We aim to recruit 3960 adults with symptoms of less than 3 months duration that class as either (1) Acute LBP (2) Acute LBP with referred somatic leg pain or (3) Neuropathic leg pain (sciatica) +/- acute LBP.

Inclusion Criteria

• Aged 18 years or over
• A clinical diagnosis of acute LBP +/- low back related leg pain, or sciatica, of no more than 3 months duration
• Must understand spoken and written English
• Must provide informed consent

Exclusion Criteria

• More than 3 months of pain symptoms in this episode of pain
• Inability to take any of the medications to be used in the study for any reason (e.g. specified co-morbidities, drug interactions, known allergies) or any contraindication to treatment with the study IMP as per approved SmPC
• Other previously diagnosed spinal pathology (e.g. scoliosis, kyphosis, spondylolisthesis, spinal stenosis, systemic inflammatory disease)
• Neurological deficit requiring an urgent surgical assessment (e.g. cauda equina syndrome or ‘foot drop’)
• Clinical suspicion (red flags) or known diagnosis of spinal malignancy, infection or fracture
• History of drug misuse
• Currently taking regular analgesia (not including paracetamol and ibuprofen that could be bought OTC) that has been prescribed by a health care professional
• Already enrolled in another trial
• Onset of pain following significant trauma, such as a road traffic collision
• Ongoing litigation for spinal or MSK pain
• Undergoing active chemotherapy for cancer
• Listed on a palliative care register at a general practice or hospital
• Woman of childbearing potential (WOCBP)
  • Currently pregnant, intending to become pregnant in the next 8 weeks
  • Not willing to use effective methods of contraception
  • Not providing a negative pregnancy test at screening
  • Not willing to follow the pregnancy testing requirements during the trial, or
  • Currently breastfeeding

Primary Outcome
A time to event outcome when, using the Patient Global Impression of Change (PGIC) scale daily, measures of self-scoring are ≥4 points (a change from ‘no improvement’ to at least ‘quite a lot better’) for 5 consecutive days.

Secondary Outcomes
To be measured daily:

• The intensity of pain using a Numerical Rating Scale (NRS) of pain
• The number and type of serious side effects
• The amount of each prescribed medication taken as instructed

To be measured at 4, 8 and 26 weeks:

• Patient self-assessment of resolution of symptoms (yes/no)
• The level of back-related function and disability during daily activities using the Oswestry Disability Index (ODI).
• If their pain has disturbed their sleep in the past week (Yes/No).
• Percent overall work impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire.
• Mental health using the Depression, Anxiety and Positive Outlook Scale (DAPOS).
• Health-related quality of life using the EQ-5D-5L.
• Relapse of pain. Determined by asking if pain has relapsed after the end of the medication.
• Admission to hospital related to this episode of back pain/leg pain/sciatica or the medications given.

 We will also record and report descriptively, without making formal comparisons:

• The number and type of side effects/adverse events
• The type, and quantity, of other treatments, outside of the analgesic ladder, taken on top of the medication in the trial (physical, topical, other medications / analgesics etc.)