Prospective, Multicentre Trial of Methoxyflurane for Acute Trauma-Related Pain in Helicopter Emergency Medical Systems and Hostile Environments: METEORA Protocol

Abstract

Introduction

The inhalational analgesic low-dose methoxyflurane has been widely used by Australian ambulance services since 1975 and is now approved in Europe for emergency relief of moderate-to-severe trauma-related pain in conscious adult patients. The use of methoxyflurane in hostile environments is of special interest given its portability, ease of use and rapid onset of action. This trial will investigate the efficacy, tolerability and practicality of use of inhaled methoxyflurane in patients with moderate-to-severe trauma-related pain rescued from hostile mountainous environments by the Helicopter Emergency Medical Service (HEMS) in Italy.

Methods

METEORA is a phase IIIb, prospective, single-arm, multicentre trial. Approximately 200 adult patients with a pain score of at least 4 on the numerical rating scale (NRS) due to limb trauma rescued by HEMS will be enrolled. Patients will receive up to 2 × 3 mL methoxyflurane, self-administered by the patient by inhalation under medical supervision. Rescue medication will be permitted if required.

Planned Outcomes

Pain intensity will be measured using a 100-mm visual analogue scale (VAS) at baseline, at 5, 10, 15, 20, 30, 45 and 60 min after the start of methoxyflurane inhalation and when positioning the patient on a spinal board or stretcher; and also using the NRS at enrolment and at 10 min. Use of rescue medication (yes/no) will be recorded. The patient will rate efficacy and the healthcare professional will rate practicality of methoxyflurane treatment at 30 and 60 min using a 5-point Likert scale. Vital signs will be measured at baseline, 10, 30 and 60 min. Assessments after 30 min will only be performed for patients using a second inhaler. Adverse events will be recorded until safety follow-up at 3 ± 1 days. The primary endpoint is the percentage of patients achieving at least 30% improvement from baseline in VAS pain intensity within the first 10 min of methoxyflurane administration.

Trial Registration

EudraCT number: 2017-004601-40.

Funding

Mundipharma Pharmaceuticals, srl.

Plain Language Summary

Plain language summary available for this article.

Electronic supplementary material

The online version of this article (10.1007/s12325-018-0816-8) contains supplementary material, which is available to authorized users.

Plain language summary

The treatment of pain is an essential part of the management of injured patients. In emergency rescue situations, rapid and effective pain relief can reduce the patient’s stress and discomfort, making it easier to assess, treat and extricate them. Currently available painkillers have limitations such as being slow to work (oral medications), requiring needles (intravenous medications) or prolonged monitoring and observation (e.g. opioids). An inhaled painkiller (methoxyflurane) is now available in Europe for emergency relief of moderate-to-severe pain in conscious adult patients with trauma (injury) and associated pain. Methoxyflurane is administered via a hand-held inhaler, which provides pain relief within 6–10 inhalations and lasts for 25–30 min, on average, when used continuously. The patient can control his/her own level of pain relief and a second inhaler may be used if required. Methoxyflurane has been widely used by Australian ambulance services since 1975 and its effectiveness and safety are well established. Considering its ease of use and rapid action, inhaled methoxyflurane may be useful in emergency situations in remote and hostile environments. A new trial (METEORA) will assess the use of methoxyflurane in 200 patients with limb injuries who are rescued from mountainous environments by the Helicopter Emergency Medical Service (HEMS) in Italy. Patients with moderate-to-severe pain will receive inhaled methoxyflurane under medical supervision. A second inhaler and/or additional pain-relieving medication will be provided if necessary. The trial will assess the reduction in pain intensity and whether additional pain-relieving medication is needed. The practicality of use of methoxyflurane in the emergency rescue situation and any side effects will also be evaluated.

Electronic supplementary material

The online version of this article (10.1007/s12325-018-0816-8) contains supplementary material, which is available to authorized users.