Intranasal fentanyl spray versus intravenous opioids for the treatment of severe pain in patients with cancer in the emergency department setting: A randomized controlled trial

OBJECTIVE: Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. METHODS: We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (≥7, scale: 0 “none” to 10 “worst pain”). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). RESULTS: At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (<pain relief) mean change in the IVH group. Finally, assuming all subjects in the IVH group had maximum pain at T0 and that T0 pain for the INF group remained unchanged from randomization, the lower bound of the 90% CL for mean pain decrease in the INF group extended 1.37 points below (<pain relief) mean decrease in the IVH group. Time (minutes) from randomization until T0 was longer for the IVH (Median 23, IQR 12) versus INF (Median 15, IQR 11) group (P<0.001). CONCLUSIONS: Two of three analyses supported non-inferiority of INF versus IVH, while one analysis was inconclusive. Compared to IVH, INF had the advantage of shorter time to administration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02459964