Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA).

INTRODUCTION: Low-dose methoxyflurane, administered via a hand-held inhaler, has been used for short-term pain relief in emergency medicine in Australia and New Zealand for over 40 years, and was recently approved in Europe for the rapid relief of moderate-to-severe trauma-related pain in adults. There is currently a lack of data for methoxyflurane versus active comparators, therefore this trial will investigate the efficacy and safety of inhaled methoxyflurane compared with standard of care (SoC) in the treatment of acute trauma-related pain in pre-hospital and ED settings in Italy.

METHODS: MEDITA (Methoxyflurane in Emergency Department in ITAly) is a Phase IIIb, prospective, randomised, active-controlled, parallel-group, open-label, multicentre trial. A total of 272 adult patients with moderate-to-severe pain [score ≥ 4 on the Numerical Rating Scale (NRS)] due to limb trauma will be randomised 1:1 to receive 3 mL methoxyflurane (self-administered by the patient via inhalation under supervision of a trained person) or medications that currently comprise the SoC in Italy [intravenous (IV) morphine for severe pain (NRS ≥ 7); IV paracetamol or ketoprofen for moderate pain (NRS 4-6)], administered as soon as possible after randomisation.

PLANNED OUTCOMES: Pain intensity will be measured using a 100-mm visual analogue scale (VAS) at baseline (time of randomisation) and at intervals up to 30 min. Time of onset of pain relief as reported by the patient and use of rescue medication will be recorded. The patient will rate the efficacy and the healthcare professional will rate the practicality of study treatment at 30 min after randomisation using a 5-point Likert scale. Adverse events will be recorded until safety follow-up at 14 ± 2 days. Vital signs will be measured at baseline, 10 and 30 min. The primary aim is to demonstrate non-inferiority of methoxyflurane versus SoC for the change in VAS pain intensity from baseline (randomisation) to 3, 5 and 10 min.

TRIAL REGISTRATION: EudraCT number: 2017-001565-25. Clinicaltrials.gov identifier: NCT03585374.

FUNDING: Mundipharma Pharmaceuticals srl.