Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children - The MAGPIE trial (MEOF-002): Study protocol for a randomised controlled trial

Hartshorn, Stuart; Barrett, Michael J.; Lyttle, Mark D.; Yee, Sue Anne; Irvine, Alan T.

Abstract

Background
Pain from injuries is one of the commonest symptoms in children attending emergency departments (EDs), and this is often inadequately treated in both the pre-hospital and ED settings, in part due to challenges of continual assessment and availability of easily administered analgesic options. Pain practices are therefore a key research priority, including within the field of paediatric emergency medicine. Methoxyflurane, delivered via a self-administered Penthrox® inhaler, belongs to the fluorinated hydrocarbon group of volatile anaesthetics and is unique among the group in having analgesic properties at low doses. Despite over 30 years of clinical acute analgesia use, and a large volume of evidence supporting its safety and efficacy, there is a paucity of randomised controlled trial data for Penthrox®.

Methods
This is an international multi-centre randomised, double-blind, placebo-controlled phase III trial assessing the efficacy and safety of methoxyflurane delivered via the Penthrox® inhaler for the management of moderate to severe acute traumatic pain in children and young people aged 6–17 years. Following written informed consent, eligible participants are randomised to self-administer either inhaled methoxyflurane (maximum dose of 2 × 3 ml) or normal saline placebo (maximum dose 2 × 5 ml). Patients, treating clinicians and research nurses are blinded to the treatment. The primary outcome is the change in pain intensity at 15 min after the commencement of treatment, as measured by the Visual Analogue Scale (VAS) or the Wong-Baker FACES® Pain Rating scale, with the latter converted to VAS values. Secondary outcome measures include the number and proportion of responders who achieve a 30% reduction in VAS score compared to baseline, rescue medication requested, time and number of inhalations to first pain relief, global medication performance assessment by the patient, clinician and research nurse, and evaluation of adverse events experienced during treatment and during the subsequent 14 ± 2 days. The primary analysis will be by intention to treat. The total sample size is 110 randomised and treated patients per treatment arm.

Discussion
The Methoxyflurane AnalGesia for Paediatric InjuriEs (MAGPIE) trial will provide efficacy and safety data for methoxyflurane administered via the Penthrox® inhaler, in children and adolescents who present to EDs with moderate to severe injury-related pain.

Trial registration
EudraCT, 2016–004290-41. Registered on 11 April 2017.
ClinicalTrials.gov, NCT03215056. Registered on 12 July 2017.

Citation

Hartshorn, S., Barrett, M. J., Lyttle, M. D., Yee, S. A., & Irvine, A. T. (2019). Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children - The MAGPIE trial (MEOF-002): Study protocol for a randomised controlled trial. Trials, 20, Article 393 (2019). https://doi.org/10.1186/s13063-019-3511-4

• Journal Article Type: Article
• Acceptance Date: Jun 10, 2019
• Online Publication Date: Jul 4, 2019
• Publication Date: Jul 4, 2019
• Deposit Date: Jul 14, 2020
• Publicly Available Date: Jul 14, 2020
• Journal: Trials
• Print ISSN: 1745-6215
• Electronic ISSN: 1745-6215
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Article Number: 393 (2019)
• DOI: https://doi.org/10.1186/s13063-019-3511-4
• Keywords: Medicine (miscellaneous); Pharmacology (medical)
• Public URL: https://uwe-repository.worktribe.com/output/6137312
• Additional Information: Received: 19 February 2019; Accepted: 10 June 2019; First Online: 4 July 2019; : The protocol, PIS, consent form and all relevant documentation for this clinical trial were approved for the UK by the South Central (Oxford A) Research Ethics Committee (17/SC/0039) and, in a separate process, for Ireland by Our Lady’s Children’s Hospital, Crumlin (GEN/539/17). All participating centres confirm capacity prior to commencing recruitment.For patients under the age of 16 years, written informed consent is sought from the patient’s parent or legal guardian, together with verbal assent from the patient. Competent 16 and 17 year olds provide their own written consent. Given the short timeframe for recruiting patients in EDs, a summary PIS is used. Parents have the opportunity to read this and are given the full PIS to take home. This approach was approved by the ethic committees.; : Not applicable.; : The authors declare that they have no competing interests.