The PreMeFen study is a randomized, three-arm, non-inferiority phase 3 clinical trial comparing inhaled methoxyflurane, intranasal fentanyl and intravenous morphine for the treatment of acute prehospital pain in patients aged 18 years and older with NRS ≥4 in Norway. The primary objective is the change in NRS pain scale (0-10) from baseline to 10 minutes after drug administration, with a non-inferiority margin of 1.3. Median age of patients was 61 years (IQR 47-75), basal NRS 7.6 (SD 1.8). Mean NRS changes at 10 minutes were -3.31 (SD 2.67) for methoxyflurane, -1.98 (SD 2.28) for fentanyl, and -2.74 (SD 2.12) for morphine. Adjusted for baseline, methoxyflurane was non-inferior to fentanyl (-1.33 [95% CI -2.01 to -0.64]) and morphine (-0.36 [-1.03 to 0.31]), while fentanyl was non-inferior to morphine (0.91 [0.27 to 1.55]). adverse events occurred in 24% of patients in the methoxyflurane group (111 patients), 24% in the fentanyl group (112 patients), and 24% in the morphine group (109 patients); two serious events (grade 2 respiratory depression and grade 3 loss of consciousness) occurred in one patient in the methoxyflurane group, with no treatment-related deaths. Inhaled methoxyflurane is non-inferior to intranasal fentanyl and intravenous morphine in the management of acute pain in the prehospital setting, assessed 10 minutes after administration.[4]