Introduction: Inhaled low dose methoxyflurane (MEOF) was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. ADVANCE-ED is an ongoing phase IV, prospective open label study undertaken to generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of low dose MEOF in Canadian emergency departments (EDs). Methods: This multi-centre study is enrolling adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10 ≥ 4) associated with minor trauma. To address limitations from the pivotal study, this study allows patients who were excluded in the pivotal trials: namely, those with severe (≥7) pain, and those using OTC or stably dosed analgesics for other conditions, including chronic pain. Eligible patients receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication is permitted at any time, if required. Results: Here we describe the patient demographics and treatment satisfaction (Global Medication Performance, GMP) at 50% enrolment (n = 49). Mean (SD) patient age is 48.0 (17.1) yrs and 55.1% are female. Mean pain (SD) reported at enrolment is 8.3 (1.5), with 73.4% of patients with NRS0-10 ≥ 8. Injuries are overwhelmingly limb trauma (87.8%). The most common type is sprain/strain (40.8%), followed by fracture (32.7%). At 5 minutes post-start of administration (STA) of MEOF, 80.4% of patients reported pain relief; this increased to 91.3% at 15 minutes, and 100% of patients reported pain relief by 30 minutes post-STA. GMP was assessed as “good”, “very good” or “excellent” by ≥80% of patients both 20 minutes post-start of administration (STA) of MEOF (83.3%) and at discharge (85.8%). When asked to what extent their expectation of pain relief had been met, 32.7% responded good, 26.5% responded “very good” and 22.4% responded “excellent”. Three quarters of enrolled patients (75.5%) did not require rescue medication. The most common (≥5%) treatment-related adverse events were dizziness (n = 14, 28.6%) and euphoric mood (n = 4, 8.2%). No serious adverse events have been reported. Conclusion: Based on 50% of the patients enrolled in this prospective, open label study, responses to inhaled low-dose MEOF are within expectation for both effectiveness and tolerability.

Introduction: Pain is a significant driver of demand in emergency care and 65% of adult patients with trauma also report moderate to severe pain. Inhaled low dose methoxyflurane (MEOF) a rapid-acting patient administered inhalational analgesic was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. This study will generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of MEOF in Canadian emergency departments. Methods: This is a phase IV, prospective open label, multi-centre study. Approximately 100 adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10≥4) associated with single system trauma will be enrolled at 5-10 EDs across Canada. Patients will receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication will be permitted at any time, if required. Results: Planned Assessments and Outcome Measures: Pain will be assessed using the NRS0-10 at 4 time points: screening/triage, 5 minutes and 20 minutes post-start of administration (STA) of MEOF, and when ready for discharge. Secondary assessments will include the speed of action of analgesia (from STA of MEOF); patient and physician satisfaction with treatment (as assessed through Global Medical Performance (GMP) at 20 minutes post-STA and when ready for discharge); patient and physician fulfilment of pain relief expectations (assessed when ready for discharge); use of rescue medication and treatment-emergent adverse events. Exploratory outcomes will include the time to disposition, time to readiness for discharge and responder analysis. The primary outcome measure will be the change in pain intensity over 20 minutes from the start of administration of MEOF as measured on the NRS0-10. Conclusion: We report on the methodology of a phase IV, prospective open label, multi-centre study, evaluating the use of MEOF for the management of acute traumatic pain in Canadian Emergency Departments.

Introduction: Insufficient analgesia affects around 50% of emergency department patients. The use of a protocol helps to reduce the risk of oligoanalgesia in this context. Our objective was to describe the feasibility and efficacy of a multimodal analgesia protocol (combining paracetamol, oxycodone, and inhaled low-dose methoxyflurane) initiated by triage nurse. Methods: We performed a prospective, observational study in the emergency department at Grenoble Alpes University Hospital (Grenoble, France) between October 2017 and April 2018. Non severe adult trauma patients with a numerical pain rating scale (NRS) score ≥4 and receiving MEOF were included. The primary efficacy criterion was the proportion of patients with an NRS score ≤3 at 15min post-administration. Pain intensity was measured for 60 min as well as during radiography. Data on adverse events and satisfaction were also recorded. Data are presented as median [interquartile (IQR)] and were compared using non parametric tests. Results: A total of 200 adult patients were included (age: 32 [IQR: 23–49] years; 126 men (63%)). Patients presented at triage with a pain score of 7 [IQR: 6-8]. Sixty-six patients (33%) reported an NRS score ≤3 at 15 min post-administration. The time required to achieve a decrease of at least 2 points in the NRS score was 10 [IQR 5–20] min. The pain intensity was 4 [IQR: 2–5] before radiography and 4 [IQR: 2–6] during radiography. Adverse events were frequent (n = 128, 64%), mainly dizziness. No serious adverse events were reported and 89% of minor adverse events resolved at one hour. Both patients and health care providers reported good levels of satisfaction. Conclusion: The administration of a nurse-driven multimodal analgesia protocol combining paracetamol, oxycodone, and low-dose methoxyflurane was feasible on triage. It rapidly produced long-lasting analgesia in adult trauma patients.