None listed
Conditions
Brief summary
Current evidence on optimal pain management in the ED is limited, with opioids often prescribed without robust data on safety and effectiveness. Some studies have suggested that opioids, like oxycodone, can increase the risk of adverse events, and potential risks of misuse and dependency. There is a need to establish whether non-opioid analgesics can provide effective pain relief. ADAPT-ED addresses these gaps by testing multiple analgesic strategies within a single trial framework and adopting an adaptive design that enables efficient identification of effective treatments and early discontinuation of ineffective ones.
Interventions
Participants will be randomly allocated to one of five arms:
1. NSAID: Ibuprofen 400mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with ibuprofen 400mg tablets to be taken 3 times per day at 8-, 16-, 24-,32-, 40-, 48-, 56- and 64 hours post initial dose.
2. NSAID: Ketorolac trometamol 10 mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with ketorolac trometamol 10m
Participants will be randomly allocated to one of five arms: 1. NSAID: Ibuprofen 400mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with ibuprofen 400mg tablets to be taken 3 times per day at 8-, 16-, 24-,32-, 40-, 48-, 56- and 64 hours post initial dose. 2. NSAID: Ketorolac trometamol 10 mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with ketorolac trometamol 10mg tablets to be taken four times per day at 6-, 12-, 18-, 24-, 30-, 36-, 42-, 48-, 54-, 60- and 66 hours post initial dose. 3. Corticosteroid: Prednisolone 50mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with prednisolone 25 mg tablets to be taken twice per day at 12-, 24-, 36-, 48-, and 60 hours post initial dose. 4. Muscle relaxant: Orphenadrine Citrate 100 mg blinded capsule to be taken at 0 hours. Following this, participants will transition to open-label treatment with orphenadrine citrate 100 mg tablets to be taken twice per day at 12-, 24-, 36-, 48-, and 60 hours post initial dose. Participants will receive a single fixed, blinded dose at 0 hours to ensure consistent therapeutic exposure throughout the primary assessment window (0-4 hours). All discharged participants will receive a supply of their assigned treatment, intended for use within 66 hours of the initial dose. To ensure that the medication schedule during the open label phase (4-72 hours) is comparable across intervention arms, participants in the ibuprofen, ketorolac and orphenadrine arms will also receive paracetamol 1000 mg to be taken four times daily at 6-, 12-, 18-, 24-, 30-, 36-, 42-, 48-, 54-, 60-, and 66 hours post initial dose. All participants will also receive a 3-day supply of FlexeEze Heat Wraps - air activated heat patches that provide continuous low-level heat therapy for up to 12 hours. The initial heat wrap will be applied during the ED visit, with subsequent wraps used as directed over the following three days. Study staff will encourage participants to maintain the prescribed appropriate schedule of treatment with the study intervention without interruption, if it is safe to do so. Where treatment is missed or discontinued for any reason, relevant information should be documented within the participant's medical record and/or reported within the study electronic CRF. The adaptive nature of the design supports ethical and resource-efficient trial conduct by minimising exposure to inferior treatment and reallocating participants towards more promising arms. Two interim analysis will be conducted after 50% and 75% of the patients have information available (i.e have 4-hour pain measurements). At each of the two interim analyses, each of the four non-opioid arms will be compared to the common control arm. The resulting test statistics will be compared to pre-specified efficacy and futility boundaries. The opioid arm will be retained throughout the trial as the common control. Participants already randomised to the discontinued arm will stop further study treatment and revert to usual care as prescribed by the ED physician or GP if discharged. All participants will continue planned follow-up for outcomes and safety.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged greater than or equal to 18 years who present to the ED of a participating hospital, between normal business hours (local time 8am – 6pm, Monday to Friday or during the site’s alternative recruitment window documented at activation). 2. Primary complaint of back pain (defined as pain felt between the costal margins and the inferior gluteal folds) with or without leg pain. 3. Pain intensity is moderate to severe (i.e. greater than or equal to 4 out of 10, as assessed using the NRS). 4. Pain onset within last 7 days (new acute, or acute on chronic back pain defined as an acute exacerbation of chronic back pain, where chronic back pain is pain persisting for greater than or equal to 3 months). 5. Emergency department triage categories 2–5 (based on Australasian Triage Scale [ATS]). 6. Emergency physician plans to treat the patient in the ED with oral analgesics. 7. Participants must be willing to provide written informed consent (on paper, or electronically) and to complete trial assessments including English language surveys, delivered electronically to a mobile phone or conducted via phone with research staff.
Exclusion criteria
1. Lumbar radiculopathy with progressive neurological symptoms. 2. Received trial medications (excluding paracetamol), or medications in same drug class within 4 hours prior to randomisation (to ensure participants would be suitable for any of the trial drug regimens). 3. If the maximum recommended daily dose of paracetamol (4000 mg in 24 hours) has been reached or will be exceeded based on the current dosing schedule. 4. Use of interacting medications, known allergy, or any medical condition contraindicating trial medicines. Contraindications include: a. known drug allergies including to any NSAID eg aspirin, ibuprofen, diclofenac b. active peptic ulcer disease or gastrointestinal bleeding c. moderate-to-severe renal or hepatic impairment d. uncontrolled cardiovascular disease e.g cardiac failure, concurrent anti-hypertensive use e. respiratory depression or severe asthma f. severe psychiatric illness g. myasthenia gravis, glaucoma, urinary retention h. Diabetes requiring insulin therapy (participants with diet-controlled or oral-agent-treated type 2 diabetes may be included, with advice provided regarding potential risks and signs of hyperglycaemia) i. systemic infections j. use of interacting medications such as monoamine oxidase (MAO) inhibitors, anticoagulants, anticholinergic drugs such as amitriptyline, darifenacin or solifenacin (these two used for urinary incontinence) 5. Confirmed or suspected spinal or systemic pathologies as the cause of back pain (e.g. infection, fracture, kidney disease, malignancy). 6. Confirmed pregnancy or are breastfeeding. 7. Regular NSAID, paracetamol or opioid use (e.g. greater than or equal to 3 days/week), or substance dependence. 8. Has not previously taken part in the ADAPT-ED trial
Outcome results
None listed