Oral Analgesic Utilization for CHildhood Musculoskeletal Injuries
Condition: Musculoskeletal Injury
MeSH terms: Wounds and Injuries
Study type: Interventional

Summary: 
      Pain management for children presenting to the emergency department (ED) with an injured limb
      is often under-treated, even though it is known that broken arms and legs cause moderate to
      severe pain. Further, children are less likely to receive appropriate pain medicine than
      adults with similar injuries. This study aims to improve the pain treatment of children who
      present to the ED with a suspected fracture, or broken bone or severe sprain. The
      investigators will compare the use of 3 different possible medication combinations (ibuprofen
      alone, oral morphine alone, or combined ibuprofen and oral morphine) to determine which
      combination is the best at treating children's pain. The investigators also plan to verify
      the safety of using these different drugs to treat children's pain.

      The investigators strongly believe that children's pain should be optimally treated in the
      ED. Adequately relieving children's pain is crucial, as inadequate pain treatment can have
      both short and longterm effects on the child. It also generates unnecessary stress for both
      the child and their caregivers/parents. Given this knowledge, the investigators feel that
      their study has the potential to impact care provided in EDs, and improve pain management
      safely, for children.
    

Detailed description: 
      Rationale. Musculoskeletal trauma (MSK-T) in children is very common and almost universally
      painful. Standards for children's pain management of MSK-T in the Emergency Department (ED)
      vary greatly between Canadian hospitals and, overall, pain is very poorly treated. This
      inadequate pain treatment can have significant acute and chronic negative effects. Previous
      studies have determined that monotherapy with ibuprofen, the most commonly prescribed oral
      analgesic in the ED, is likely providing inadequate pain management for children. In response
      to this problem, clinicians have turned back to classic oral opioids (eg morphine) and are
      experimenting with combination therapies. To date, few studies have focused on the efficacy
      of a combination of a non-steroidal anti-inflammatory drug (NSAID) (eg ibuprofen) and an
      opioid (eg morphine). Such a combination of analgesics is known to potentiate pain relief by
      blocking it at the level of both the peripheral and the central nervous system. By combining
      two drugs with different mechanisms of action, we may be able to provide additive analgesic
      effects. To our knowledge, no studies have ever studied the efficacy and safety of this
      combination of medication for MSK-T in pediatric EDs. Primary Hypothesis: For children with a
      MSK-T in the ED, the addition of morphine to ibuprofen is safe and provides better pain
      relief than either of the two drugs alone. Primary Research Question: For children with a
      MSK-T in the ED, is a combination of oral morphine (0.2 mg/kg) and oral ibuprofen (10 mg/kg)
      more efficacious than either of the two drugs, alone, in decreasing pain scores to <30 mm, 60
      minutes after administration?

      Methods. Design: This study is a double-blind, placebo-controlled, two center, three-arm,
      randomized clinical trial (RCT). Patients will be randomized to receive either: (a) ibuprofen
      (10mg/kg) + placebo or (b) morphine (0.2 mg/kg) + placebo or (c) morphine (0.2mg/kg) +
      ibuprofen (10mg/kg). Setting: Stollery Children's Hospital (Edmonton, AB) and CHU
      Ste.Justine's pediatric hospital (Montreal, PQ). Inclusion criteria: We will include
      children: (a) between the ages of 8 and 17 years; (b) visiting the ED with an injured upper
      or lower limb that is neither obviously deformed, nor neurovascularly compromised, (c) with a
      self-reported pain score >30 mm on a 0 to100mm Visual Analogue Scale (VAS), where 0 mm
      corresponds to no pain and 100 mm to the worst pain the child has experienced, and (d) who
      understand French or English. Sample Size: Based on previous studies, we expect that between
      25-52% (Clark et al., 2007, Le May et al., 2013) of children will achieve a VAS < 30 mm at 60
      minutes in the ibuprofen arm. We have conservatively set the proportion of children with VAS
      < 30 mm at 60 min to 50%. A sample size of 500 will be then necessary to provide at least 80%
      power to detect a 20% absolute difference in proportion using a two-tailed with an alpha
      level of 5%. In order to ensure an overall alpha level of 5%, a Bonferroni correction has
      been applied in order to take into account the 3 pairwise comparisons that will be performed.
      Primary Outcome and Measurement: The primary outcome measure will be pain intensity score
      under 30 mm at 60-minutes after medication administration, using the VAS). Primary Safety
      Outcomes: We will also assess clinical measures of safety by monitoring oxygen saturation at
      30 minutes intervals, up until 120 minutes. Level of sedation/alertness, as well as the
      respiratory rate, of each child will be monitored at set time points in the study, up until
      120 minutes. Participating children will be followed up (via phone call) at 24 hours, to
      record any latent side effects or adverse events. Further, acceptability of the intervention
      will be assessed.

      Relevance: Our proposed work will be the first RCT to investigate if there is some additive
      effect of a bi-therapy of pain with ibuprofen and morphine. In summary, currently available
      research supports ibuprofen as the monotherapy agent of choice. However, given concerns
      regarding its ability to provide adequate relief on its own, smaller studies looked at
      morphine as a possible alternative combined to ibuprofen. Very few studies of analgesic
      combinations exist, and as such, we have yet to identify the optimal ED pain management
      strategy for children with MSK-T. A larger trial with careful control over principal sources
      of bias and a rigorous approach to safety data collection will provide clinicians with strong
      evidence regarding efficacy and safety on new therapeutic strategies for pain management
      related to MSK-T in the pediatric EDs.
    

Intervention name(s): oral morphine and oral ibuprofen; Oral morphine; Oral ibuprofen
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The combination of oral morphine and oral ibuprofen is one of the Experimental arm group; Oral morphine 0.2 mg/kg (syrup) up to a maximum dosage of 15 mg, administered once during the study; oral ibuprofen combine to a placebo is the active comparator
Intervention MeSH terms: Ibuprofen; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: children; analgesia; musculoskeletal injury; emergency; opioids