A Randomized Controlled Trial of a Combination of Analgesics for Pain Management in Children With a Suspected Fracture at Triage (CAST Trial)

Pain management for children with a suspected fracture is suboptimal in the Emergency Department (ED). This type of musculoskeletal injury (MSK-I) often generates moderate to severe pain (> 49 mm on 0 to 100 mm Visual Analogue Scale (VAS)), and requires rapid and sustained pain management for the duration of the physical examination, diagnostic imaging (X-Ray), immobilization and occasionally fracture reduction. Current standard care includes the use of oral ibuprofen (IBU), a non-steroidal anti-inflammatory drug (NSAID), for mild-to-moderate MSK-I pain in the ED. However, ibuprofen has been shown to be inadequate for moderate-to-severe pain when used alone. A number of small/single centre studies suggest that intranasal fentanyl (INF) is effective for rapidly decreasing MSK-I related pain in children with a quick onset of 10 minutes and a peak action of 20 minutes. However, the duration of its analgesic effect is limited to a maximum of 60 minutes, which does not provide an optimal pain management for the duration of the ED stay, which typically lasts up to three hours. Typically, patients with a fracture have sustained pain throughout their ED stay due to imaging, splinting and repeated physical exams. Our objective is to examine the efficacy of a combination of intranasal and oral analgesics for pain management in children presenting to the ED with a suspected fracture. Our primary research question: For children presenting to the ED with a suspected fracture, is a combination of INF1.0 (1.0 mcg/kg, maximum dose of 100 mcg) and IBU (10 mg/kg, maximum dose of 600 mg) more efficacious than a combination of INF2.0 (2.0 mcg/kg, maximum dose of 100 mcg) and oral ibuprofen (10 mg/kg, maximum dose of 600 mg) to decrease pain at 15 minutes post-administration? Our primary hypothesis is: A combination of INF2.0 and IBU will be more efficacious than a combination of INF1.0 and IBU to decrease pain at 15 minutes post-administration.

Methods. Design: This study is a single-blind, two-arm, three-centre RCT of a combination of analgesics for pain management of children presenting to the ED with a suspected fracture will be performed. Settings: Children will be recruited in the following EDs: CHU Sainte-Justine (Montreal, QC), Stollery Children's Hospital (Edmonton, AB), and Children's Hospital of the London Health Sciences Centre (London, ON). Sample. Inclusion criteria: Will be include children: (a) with a pain score >49 mm on VAS at triage, (b) between the ages of 7 and 17 years, (c) presenting to the ED with a suspected fracture of the upper or lower limb, and (d) who can communicate in either French or English. Exclusion criteria: Will be exclude children with (a) known allergy to fentanyl or ibuprofen, (b) triage nurse suspicion of child abuse, (c) inability to self-report pain, (d) chronic pain that necessitates daily analgesic use, (e) NSAID or opioid analgesic use within the three hours prior to ED presentation, (f) trauma to >1 limb, (g) known hepatic or renal disease/dysfunction, (h) known bleeding disorder, (i) neuro-cognitive disability that precludes assent and/or participating in the study, (j) known history of obstructive sleep apnea (k) a suspected fracture of the nose, or (l) significant head injury, as determined by the clinical team/triage nurse.

Allocation and Randomization: A biostatistician, independent to our study team, will generate the randomization scheme that will consist of a computer-generated random listing of the treatment using a 1:1 allocation scheme. Randomization will be stratified by center using block-randomization (with permuted block sizes). Enrolled children will be allocated to (a) INF 1.0 mcg/kg (up to a maximum of 100 mcg) via intranasal atomization + oral IBU 10 mg/kg (up to a maximum of 600 mg) OR (b) INF 2.0 mcg/kg (up to a maximum of 100 mcg) via intranasal atomization + oral IBU 10 mg/kg (up to a maximum of 600 mg.

Sample Size: Accounting for a 10% attrition rate, we determined that enrollment of 172 participants would provide at least 90 % power to detect a 10 mm absolute difference in mean pain scores between groups at 15 minutes post-medication administration (T-15), at an alpha level of 5 %.

Primary efficacy outcome: Mean difference in pain scores between groups at 15 minutes post-medication administration (T-15) using the Visual Analogue Scale (VAS). Secondary outcomes: (a) Mean differences in pain scores between groups at 30 min (T-30), 60 min (T-60), 90 min (T-90), 120 min (T-120) after medication administration, during the medical examination (T-ME), and during radiographic procedure (T-XR), (b) the proportion of children administered a rescue analgesic in the 60 minutes following administration of study medication, (c) the proportion of children with adverse events at T-15, T-30, T-60, T-90, T-120, T-ME and T-XR, (d) the proportion of children with serious adverse events at T-15, T-30, T-60, T-90, T-120, T-ME and T-XR, (e) the proportion of children in each group with an RSS score > 3 (f) satisfaction of children and parents regarding pain management (T-120).