Treatment of acute trauma-related pain in children and adolescents with methoxyflurane (Penthrox®) compared to placebo (MAGPIE): A randomised clinical trial
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Authors
Hartshorn, Stuart
Barrett, Michael J.
Bloom, Benjamin
Lyttle, Mark D.
Walton, Emily
Steel, Kim
Yee, Sue Anne
Irvine, Alan
Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI)
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Issue Date
2025
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Article
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IMPORTANCE: Methoxyflurane, an inhalational analgesic, has proven safety and efficacy in clinical trials and clinical practice. This double-blind, well-controlled study aimed to establish the benefit-risk of methoxyflurane in a paediatric population. OBJECTIVE: To evaluate the safety and efficacy of methoxyflurane in children with minor trauma and acute pain presenting to emergency departments (ED). DESIGN: Randomised, double-blind, multicentre, placebo-controlled study (MAGPIE). SETTING: Conducted at 11 EDs in the UK and Ireland. PARTICIPANTS: Participants aged from 6-<18 years of age with minor trauma and pain scores of 60-80 mm on a visual analogue scale (VAS), or 6-8 on a Wong Baker Pain Scale, were recruited. INTERVENTIONS: Methoxyflurane 3 mL or placebo (normal saline, 5 mL) via a Penthrox® inhaler device, with a second inhaler upon request. MAIN OUTCOME(S) AND MEASURE(S): Primary: change in VAS pain intensity from baseline to 15-minutes in participants aged 9-<18 years (secondary: included the total Intent-To-Treat (ITT) population, aged 6-<18 years). RESULTS: 4513 patients screened, 249 participants randomised (127 methoxyflurane, 122 placebo), 192 treated (92 methoxyflurane, 100 placebo). Mean (standard deviation (SD)) age 11.1 (2.45) years; 108/192 (56 %) were male. At 15-minutes, the mean change from baseline in VAS was -20.0 mm (methoxyflurane) and -13.2 mm (placebo); least squares (LS) mean difference in 9-<18-year old's -6.8 mm [95 % CI -12.5 to -1.2 mm], p = 0.018, which was similar to the total ITT population. Fewer methoxyflurane participants required rescue medication (9.8 % vs 30.0 %). There were statistically significant odds of better global medication performance assessments for the methoxyflurane group compared to the placebo group, based on physician (OR 5.29, 95 % CI 3.02 to 9.45, p < 0.001) and research nurse assessments (OR 5.78, 95 % CI 3.32 to 10.27, p < 0.001). Adverse events were more common with methoxyflurane (64 %) vs. placebo (55 %). Common treatment emergent adverse events (TEAEs) included dizziness (methoxyflurane 41 %, placebo 12 %) and euphoric mood (methoxyflurane 12 %, placebo 0 %). Discontinuations due to TEAEs occurred in 8 methoxyflurane and 1 placebo participant. There were no serious adverse events related to methoxyflurane. CONCLUSIONS AND RELEVANCE: In this pivotal placebo-controlled trial, methoxyflurane was efficacious for treatment of acute trauma-related pain in paediatrics, with a safety profile consistent with adults. TRIAL REGISTRATION: NCT03215056.
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Journal
Injury
Volume
56
Issue
11