Comparison of inhalational methoxyflurane, intranasal fentanyl, and intravenous morphine for treatment of prehospital acute pain in Norway (PreMeFen): a randomised, non-inferiority, three-arm, phase 3 trial.
Randi Simensen, Lars Olav Fjose, Kjetil Thorsen et al.
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In 30 seconds
PreMeFen was a randomised, open-label, three-arm phase 3 non-inferiority trial in Norwegian ambulance services, comparing inhaled methoxyflurane with intranasal fentanyl and intravenous morphine for acute traumatic or medical pain. Among 281 patients in the per-protocol analysis, mean pain-score reductions at 10 minutes were -3·31, -1·98, and -2·74, respectively. Methoxyflurane was non-inferior to both comparators; fentanyl was not non-inferior to morphine. Adverse-event rates were similar across groups, although two serious events occurred in one methoxyflurane-treated patient.
Key findings
- At 10 minutes, mean NRS changes were -3·31 (SD 2·67) with methoxyflurane, -1·98 (2·28) with fentanyl, and -2·74 (2·12) with morphine.
- Methoxyflurane was non-inferior to fentanyl (-1·33 [95% CI -2·01 to -0·64]) and morphine (-0·36 [-1·03 to 0·31]).
- Intranasal fentanyl was not non-inferior to morphine at 10 minutes (0·91 [0·27 to 1·55]).
- Adverse events occurred in 22% of methoxyflurane, 24% of fentanyl, and 24% of morphine recipients; two serious events occurred in one methoxyflurane recipient.
Why it matters
Prehospital pain treatment may need to begin before intravenous access is available. These trial findings indicate that inhaled methoxyflurane can provide short-term pain relief comparable to the studied fentanyl and morphine regimens, supporting its consideration as a non-intravenous option in early ambulance care. The serious events observed also underscore the importance of monitoring and interpreting safety alongside analgesic efficacy.
What to keep in mind
The trial was open-label, and the primary endpoint was assessed at 10 minutes; the abstract does not establish comparative longer-term pain control.