Pain, AcutePhase 3MAGPIENCT03215056
Methoxyflurane Analgesia for Paediatric Injuries
A Phase 3 study testing Methoxyflurane and Normal saline in people with Pain, Acute, run by Medical Developments International Limited at 11 sites in 2 countries.
Trial summary
This is a randomised, double-blind, multicentre, placebo controlled study to evaluate the safety and efficacy of methoxyflurane (Penthrox®) for the treatment of acute pain in children and adolescents from 6 to less than 18 years of age (presenting to an Emergency Department with minor trauma). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Pain, Acute
- What is being tested?
- Methoxyflurane and Normal saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 14 Aug 2017to 15 Jun 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients aged 6 to less than 18 years.
- Attending ED following minor trauma.
- Evidence of signed and dated informed consent/assent document indicating that the patient (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study*.
- Pain scores 55 to 85 mm as measured using VAS or 6 to 8 using Wong-Baker FACES Pain Rating scale.
- Note: the range for VAS pain scores was widened from 60 to 80 mm to 55 to 85 mm to improve patient recruitment but very few patients were recruited after that amendment.
Who cannot join
- Critical, life-or limb-threatening condition requiring immediate management.
- Open fractures.
- Patients with any other clinical condition that may, in the opinion of the Investigator, impact the patient's ability to participate in the study, or the study results.
- Patients deemed not cognitively capable of effectively self-administering the study drug using the PENTHROX® inhaler.
- Treatment with any analgesic agent within 5 hours prior to randomisation, except Entonox (50% nitrous oxide and 50% oxygen mixture) which is prohibited within 30 minutes prior to randomisation, diclofenac which is prohibited within 8 hours prior to randomisation or oral morphine which is prohibited within 10 hours prior to randomisation.
- Patients with chronic pain.
Show all 18Show fewer
- Patients having received an Investigational Medicinal Product (IMP) in the preceding 3 months.
- Known pregnancy or breastfeeding females.
- Personal or familial hypersensitivity to PENTHROX® or any fluorinated anaesthetics.
- Patients requiring oxygen therapy.
- Patients with known or genetic susceptibility to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
- Clinically evident respiratory depression.
- Previous use of methoxyflurane (including as an IMP).
- History of signs of liver damage including after previous PENTHROX® (methoxyflurane) use or halogenated hydrocarbon anaesthesia.
- Known significant renal impairment.
- Altered level of consciousness due to any cause including head injury, drugs, or alcohol.
- Known significant cardiovascular instability (e.g., pathological arrhythmia).
- Inability to participate in telephonic follow-up on (Day 14 ± 2 days) as per study requirement
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United Kingdom10 sites
Royal Aberdeen Children's Hospital
Aberdeen, Aberdeenshire, AB25 2ZG
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
Royal Alexandra Children's Hospital
Brighton, East Sussex, BN2 5BE
Bristol Royal Hospital for Children
Bristol, Avon, BS2 8BJ
Royal Devon and Exeter Hospital (Wonford)
Exeter, Devon, EX2 5DW
Leicester Royal Infirmary
Leicester, LE1 5WW
Alder Hey Children's Hospital
Liverpool, Merseyside, L12 2AP
Royal London Hospital
London, Greater London, E1 1BB
Nottingham University Hospitals City Campus
Nottingham, Notttinghamshire, NG5 1PB
Ormskirk District Hospital
Ormskirk, L39 2AZ
About this study
Official title: A Randomised, Double-blind, Multicentre, Placebo Controlled Study to Evaluate the Safety and Efficacy of Methoxyflurane (PENTHROX®) for the Treatment of Acute Pain in Children and Adolescents from 6 to Less Than 18 Years of Age (presenting to an Emergency Department with Minor Trauma)
This is a randomised, double-blind, multicentre, placebo controlled study to evaluate the safety and efficacy of methoxyflurane (Penthrox®) for the treatment of acute pain in children and adolescents from 6 to less than 18 years of age (presenting to an Emergency Department with minor trauma). It is conducted as part of the Paediatric Investigation Plan (PIP) agreed with the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).
The study aims to provide evidence under blinded controlled conditions that Penthrox is safe and effective in patients aged 6 to less than 18 years presenting to ED with pain associated with minor trauma.
Read the detailed description
This is a randomised, double-blind, multicentre, placebo-controlled study in children and adolescents aged 6 to less than 18 years presenting to an ED requiring analgesia for acute pain, with visual analogue scale (VAS) score of 55 to 85 mm or Wong-Baker Faces score of 6 to 8 associated with minor trauma. In the context of the current study, minor trauma refers to "a non-critical and non-limb threatening physical wound or injury of the tissues", such as, soft tissue injuries, fractures of the extremities, burns, penetration by foreign bodies, lacerations, dislocation, contusions, etc.
This study will include screening and enrolment, followed by treatment and day 14 ± 2 day safety follow-up post treatment. The procedure for screening and enrolment including obtaining consent/assent is to occur on the same day. The expected duration for each patient in the study is up to 16 days.
The clinician/research nurse must ascertain that the patient has not been pre-medicated with an analgesic within 5 hours prior to randomisation, except Entonox (50% nitrous oxide and 50% oxygen mixture) which is prohibited within 30 minutes prior to randomisation, diclofenac which is prohibited within 8 hours prior to randomisation or oral morphine which is prohibited within 10 hours prior to randomisation.
At least 220 eligible children and adolescents aged 9 to < 18 years (110 children aged 9 to < 12 years and 110 adolescents aged 12 to < 18 years) were to be randomised in a 1:1 ratio to receive either methoxyflurane or placebo from the PENTHROX inhaler. Additionally, at least 36 eligible children aged 6 to < 9 years were to be randomized in a 1:1 ratio. Randomisation was stratified by age group (6 to < 9 years; 9 to < 12 years; 12 to < 18 years).
Pain scores will be assessed using the VAS or Wong-Baker FACES® Pain Rating scale in younger children who cannot utilise the VAS tool. A pain score will be measured at screening to establish study eligibility. After randomisation, a baseline pain score will be recorded between 5 to 60 minutes after the screening pain score and will act as a validation score. If the baseline pain score falls outside the range of 55 to 85 mm on the VAS or 6 to 8 on Wong-Baker FACES Pain Rating scale, the patient will be withdrawn from the study (randomised, but not treated). Patients who have a pain score between 55 and 85 mm on the VAS or 6 to 8 on Wong-Baker FACES Pain Rating scale at screening and baseline will be eligible to receive treatment. In order to improve patient recruitment, a protocol amendment in July 2019 widened the range of the eligible VAS pain score from 60 to 80 mm to 55 to 85 mm. However, this amendment was quite late in study conduct and shortly prior to the COVID pandemic, hence the majority of patients were recruited under the original criterion (60 to 80mm).
Following enrolment and initial assessments, the research nurse will assist the patient to self administer ten successive inhalations of PENTHROX® (methoxyflurane) or placebo. The research nurse, the treating clinician and the patient will be blind to the treatment administered.
Patients/parents/legal guardians will be advised that rescue medication will be available immediately on request at any time during or after the completion of the treatment. The rescue medication to be used will be at the discretion of the blinded clinician. Rescue analgesia should be near the potency equivalence of active PENTHROX. Depending on the standard practice of the participating site, this may include intranasal fentanyl, intranasal diamorphine, intranasal ketamine, Entonox (50% nitrous oxide and 50% oxygen mixture), intravenous morphine, or oral morphine.
- Conditions
- Pain, Acute
- Being tested
- Methoxyflurane, Normal saline
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethoxyfluraneDrug
Also called Penthrox®
PENTHROX 3mL inhalation vapour, liquid
Normal salineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| PENTHROX® (methoxyflurane) | Experimental | PENTHROX® (methoxyflurane) administered as a liquid for inhalation and should be self-administered under supervision of research nurse trained in its administration, using the hand held PENTHROX® inhaler.
One vial of 3 mL PENTHROX® is to be vaporised in a PENTHROX® inhaler. On finishing the 3 mL dose, another 3 mL may be used.
Dose of PENTHROX® should not exceed 6 mL in a single administration.
The patient is instructed to inhale ten successive inhalations of PENTHROX® (methoxyflurane) followed by additional intermittent inhalations as required.
The maximum dose administered will not exceed 6 mL of methoxyflurane. Receives: Drug: Methoxyflurane |
| Normal saline | Placebo comparator | Normal saline will be administered as a liquid for inhalation and should be self-administered under supervision of research nurse trained in its administration, using the hand held PENTHROX® inhaler.
One vial of 5 mL of normal saline is to be vaporised in a PENTHROX® inhaler. On finishing the 5 mL dose, another 5 mL may be used.
Dose of normal saline should not exceed 10 mL in a single administration.
In this study, the patient is instructed to inhale ten successive inhalations of placebo followed by additional intermittent inhalations as required.
The maximum dose administered will not exceed 10 mL of placebo (2 × 5 mL) Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in pain intensity between methoxyflurane and placebo as measured by change from baseline in VAS pain scores at 15 minutes for patients aged 9 to < 18 years.
The primary analysis was conducted using an analysis of covariance (ANCOVA) model with change from baseline in pain score at 15 minutes as the dependent variable, continuous baseline pain, treatment and age group (9 to < 12 years versus 12 to < 18 years) as fixed effects and centre (site) as a random effect. Missing pain scores at 15 (± 2) minutes were imputed using worst observation carried forward (WOCF) and pain scores taken after the initiation of rescue medication were included.
Note the population for the primary analysis was changed in the protocol following an amendment to the sample size across the age groups due to difficulties recruiting patients into the youngest (6 to < 9 years) age group and agreement with agencies to focus the primary analysis on 9 to < 18-year-olds.
Measured: Baseline to 15 minutes
Secondary outcomes (12)
Difference in pain intensity between methoxyflurane and placebo as measured by change from baseline in VAS pain scores at 15 minutes in the ITT Population (patients aged 6 to <18 years).
This analysis used the same statistical model (ANCOVA) as the primary analysis.
Measured: Baseline to 15 minutes
Responder analysis - number of responders, who achieve 30% reduction in VAS score compared to baseline, at 15 minutes in the ITT population (patients aged 6 to <18 years).
Patients with missing data at baseline or 15 minutes were regarded as non-responders. Data were analysed using a logistic regression model adjusted for continuous baseline pain score, age group and treatment. Number and percentage of responders are presented for each treatment group. Treatment effect is presented as the OR with the corresponding 95% CI and p-value.
Measured: Baseline to 15 minutes
Longitudinal analysis of VAS pain scores at 5, 10, 15, and 20 minutes following commencement of treatment in the ITT population (patients aged 6 to <18 years).
Data were analysed using a mixed model repeated measure (MMRM) approach with age group, continuous baseline pain score, assessment time (5, 10, 15 and 20 minutes), treatment group, and assessment time by treatment group interaction.
Measured: Baseline to 5, 10, 15 and 20 minutes
Number of inhalations taken before first pain relief is summarised by category (1 to 10 inhalations, 11 to 20 inhalations, 21 to 30 inhalations, >30 inhalations, or no relief recorded) in the ITT population (patients aged 6 to <18 years).
Additionally, for patients with pain relief documented prior to discharge, continuous descriptive summaries are presented for the number of inhalations.
Measured: From baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission.
Rescue medication requested within 20 (+2 minutes) minutes of start of treatment and any time during treatment in the ITT population (patients aged 6 to &amp;lt;18 years).
These endpoints were analysed using a logistic regression model as described for the pain responder analysis.
Measured: From baseline until request of rescue medication, assessed until point of either Emergency Department discharge or inpatient admission.
The time to request for rescue medication in the ITT population (patients aged 6 to &lt;18 years).
Patients who did not receive rescue medication were censored. Data was analysed using a Cox proportional hazards model stratified by age group and adjusted for treatment and continuous baseline VAS score to obtain an estimate of the hazard ratio (methoxyflurane/placebo) and the corresponding two-sided 95% CI. The p-value was obtained from a stratified log-rank test (stratified by age group).
Measured: From baseline until time at which rescue medication is first requested, assessed up to time of Emergency Department discharge or inpatient admission.
The time to first pain relief derived as time in minutes since start of study treatment until first pain relief in the ITT population (patients aged 6 to &lt;18 years).
Patients who did not experience pain relief by the time of discharge were censored at their time of discharge (or last VAS assessment date if date of discharge is missing). This endpoint was analysed using a Cox PH model as described above for time (minutes) to request rescue medication.
Measured: From baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission.
Number of inhalations taken before first pain relief split by whether the hole was covered at least once or not covered in the ITT population (patients aged 6 to &lt;18 years).
Data was summarised using the same categories as for number of inhalations taken before first pain relief split by dilutor hole covered at least once/not covered.
Measured: Baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission..
Global medication performance assessment by patient, clinician and research nurse: 0 = poor to 4 = excellent, measured after completion of treatment.
An ordinal logistic regression was performed with adjustments for continuous baseline pain score, age group and treatment. Number and percentage of patients per response score per treatment group are presented. Treatment effect is presented as the OR with the corresponding 95% CI and p-value (obtained using profile likelihood).
Measured: From baseline, assessed up to Emergency Department discharge or inpatient admission.
Heart rate
Absolute and change from baseline in heart rate [bpm], at each scheduled protocol timepoint, were listed and plotted (boxplots) by scheduled protocol timepoint.
Measured: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Respiratory rate
Absolute and change from baseline in respiratory rate [breaths/min] at each scheduled protocol timepoint, were listed and plotted (boxplots) by scheduled protocol timepoint.
Measured: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Oxygen saturation
Absolute and change from baseline in oxygen saturation [%] at each scheduled protocol timepoint, were listed and plotted (boxplots) by scheduled protocol timepoint.
Measured: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study start14 Aug 2017
- Primary completion15 Jun 2022
- Study completion15 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pain, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Developments International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pediatric Emergency Research in the UK and Ireland (PERUKI), Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Stuart Hartshorn, Principal investigator, Birmingham Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03215056
- Sponsor's protocol ID
- MEOF-002
- Other IDs
- 2016-004290-41, 2016
- Acronym
- MAGPIE
- Status last verified
- Jul 2024
- First submitted
- 2 Jul 2017
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hartshorn S, Barrett MJ, Lyttle MD, Yee SA, Irvine AT; in collaboration with Paediatric Emergency Research in the UK and Ireland (PERUKI). Inhaled methoxyflurane (Penthrox(R)) versus placebo for injury-associated analgesia in children-the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial. Trials. 2019 Jul 4;20(1):393. doi: 10.1186/s13063-019-3511-4.
PubMed 31272493Hartshorn S, Barrett MJ, Bloom B, Lyttle MD, Walton E, Steel K, Yee SA, Irvine A; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI). Treatment of acute trauma-related pain in children and adolescents with methoxyflurane (Penthrox(R)) compared to placebo (MAGPIE): A randomised clinical trial. Injury. 2025 Dec;56(12):112830. doi: 10.1016/j.injury.2025.112830. Epub 2025 Oct 20.
PubMed 41242203
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Multicentre, Placebo Controlled Study to Evaluate the Safety and Efficacy of Methoxyflurane (PENTHROX®) for the Treatment of Acute Pain in Children and Adolescents from 6 to Less Than 18 Years of Age (presenting to an Emergency Department with Minor Trauma)
- ClinicalTrials.gov ID
- NCT03215056
- Acronym / sponsor ID
- MAGPIE / MEOF-002
- Conditions
- Pain, Acute
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Medical Developments International LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Pediatric Emergency Research in the UK and Ireland (PERUKI), Quintiles, Inc.
- Study start
- 14 Aug 2017 (actual)
- Primary completion
- 15 Jun 2022 (actual)
- Study completion
- 15 Jun 2022 (actual)
- First posted
- 12 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomised, double-blind, multicentre, placebo controlled study to evaluate the safety and efficacy of methoxyflurane (Penthrox®) for the treatment of acute pain in children and adolescents from 6 to less than 18 years of age (presenting to an Emergency Department with minor trauma). It is conducted as part of the Paediatric Investigation Plan (PIP) agreed with the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).
The study aims to provide evidence under blinded controlled conditions that Penthrox is safe and effective in patients aged 6 to less than 18 years presenting to ED with pain associated with minor trauma.
Detailed description
This is a randomised, double-blind, multicentre, placebo-controlled study in children and adolescents aged 6 to less than 18 years presenting to an ED requiring analgesia for acute pain, with visual analogue scale (VAS) score of 55 to 85 mm or Wong-Baker Faces score of 6 to 8 associated with minor trauma. In the context of the current study, minor trauma refers to "a non-critical and non-limb threatening physical wound or injury of the tissues", such as, soft tissue injuries, fractures of the extremities, burns, penetration by foreign bodies, lacerations, dislocation, contusions, etc.
This study will include screening and enrolment, followed by treatment and day 14 ± 2 day safety follow-up post treatment. The procedure for screening and enrolment including obtaining consent/assent is to occur on the same day. The expected duration for each patient in the study is up to 16 days.
The clinician/research nurse must ascertain that the patient has not been pre-medicated with an analgesic within 5 hours prior to randomisation, except Entonox (50% nitrous oxide and 50% oxygen mixture) which is prohibited within 30 minutes prior to randomisation, diclofenac which is prohibited within 8 hours prior to randomisation or oral morphine which is prohibited within 10 hours prior to randomisation.
At least 220 eligible children and adolescents aged 9 to < 18 years (110 children aged 9 to < 12 years and 110 adolescents aged 12 to < 18 years) were to be randomised in a 1:1 ratio to receive either methoxyflurane or placebo from the PENTHROX inhaler. Additionally, at least 36 eligible children aged 6 to < 9 years were to be randomized in a 1:1 ratio. Randomisation was stratified by age group (6 to < 9 years; 9 to < 12 years; 12 to < 18 years).
Pain scores will be assessed using the VAS or Wong-Baker FACES® Pain Rating scale in younger children who cannot utilise the VAS tool. A pain score will be measured at screening to establish study eligibility. After randomisation, a baseline pain score will be recorded between 5 to 60 minutes after the screening pain score and will act as a validation score. If the baseline pain score falls outside the range of 55 to 85 mm on the VAS or 6 to 8 on Wong-Baker FACES Pain Rating scale, the patient will be withdrawn from the study (randomised, but not treated). Patients who have a pain score between 55 and 85 mm on the VAS or 6 to 8 on Wong-Baker FACES Pain Rating scale at screening and baseline will be eligible to receive treatment. In order to improve patient recruitment, a protocol amendment in July 2019 widened the range of the eligible VAS pain score from 60 to 80 mm to 55 to 85 mm. However, this amendment was quite late in study conduct and shortly prior to the COVID pandemic, hence the majority of patients were recruited under the original criterion (60 to 80mm).
Following enrolment and initial assessments, the research nurse will assist the patient to self administer ten successive inhalations of PENTHROX® (methoxyflurane) or placebo. The research nurse, the treating clinician and the patient will be blind to the treatment administered.
Patients/parents/legal guardians will be advised that rescue medication will be available immediately on request at any time during or after the completion of the treatment. The rescue medication to be used will be at the discretion of the blinded clinician. Rescue analgesia should be near the potency equivalence of active PENTHROX. Depending on the standard practice of the participating site, this may include intranasal fentanyl, intranasal diamorphine, intranasal ketamine, Entonox (50% nitrous oxide and 50% oxygen mixture), intravenous morphine, or oral morphine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PENTHROX® (methoxyflurane) | Experimental | Drug: MethoxyfluranePENTHROX® (methoxyflurane) administered as a liquid for inhalation and should be self-administered under supervision of research nurse trained in its administration, using the hand held PENTHROX® inhaler. One vial of 3 mL PENTHROX® is to be vaporised in a PENTHROX® inhaler. On finishing the 3 mL dose, another 3 mL may be used. Dose of PENTHROX® should not exceed 6 mL in a single administration. The patient is instructed to inhale ten successive inhalations of PENTHROX® (methoxyflurane) followed by additional intermittent inhalations as required. The maximum dose administered will not exceed 6 mL of methoxyflurane. |
| Normal saline | Placebo comparator | Drug: Normal salineNormal saline will be administered as a liquid for inhalation and should be self-administered under supervision of research nurse trained in its administration, using the hand held PENTHROX® inhaler. One vial of 5 mL of normal saline is to be vaporised in a PENTHROX® inhaler. On finishing the 5 mL dose, another 5 mL may be used. Dose of normal saline should not exceed 10 mL in a single administration. In this study, the patient is instructed to inhale ten successive inhalations of placebo followed by additional intermittent inhalations as required. The maximum dose administered will not exceed 10 mL of placebo (2 × 5 mL) |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Patients aged 6 to less than 18 years.
- Attending ED following minor trauma.
- Evidence of signed and dated informed consent/assent document indicating that the patient (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study*.
- Pain scores 55 to 85 mm as measured using VAS or 6 to 8 using Wong-Baker FACES Pain Rating scale.
- Note: the range for VAS pain scores was widened from 60 to 80 mm to 55 to 85 mm to improve patient recruitment but very few patients were recruited after that amendment.
Key exclusion criteria (18 listed)
- Critical, life-or limb-threatening condition requiring immediate management.
- Open fractures.
- Patients with any other clinical condition that may, in the opinion of the Investigator, impact the patient's ability to participate in the study, or the study results.
- Patients deemed not cognitively capable of effectively self-administering the study drug using the PENTHROX® inhaler.
- Treatment with any analgesic agent within 5 hours prior to randomisation, except Entonox (50% nitrous oxide and 50% oxygen mixture) which is prohibited within 30 minutes prior to randomisation, diclofenac which is prohibited within 8 hours prior to randomisation or oral morphine which is prohibited within 10 hours prior to randomisation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethoxyfluraneAlso: Penthrox®PENTHROX 3mL inhalation vapour, liquid | Drug | PENTHROX® (methoxyflurane) |
| Normal salinePlacebo | Drug | Normal saline |
Primary outcome
Difference in pain intensity between methoxyflurane and placebo as measured by change from baseline in VAS pain scores at 15 minutes for patients aged 9 to < 18 years.
Time frame: Baseline to 15 minutes
The primary analysis was conducted using an analysis of covariance (ANCOVA) model with change from baseline in pain score at 15 minutes as the dependent variable, continuous baseline pain, treatment and age group (9 to < 12 years versus 12 to < 18 years) as fixed effects and centre (site) as a random effect. Missing pain scores at 15 (± 2) minutes were imputed using worst observation carried forward (WOCF) and pain scores taken after the initiation of rescue medication were included. Note the population for the primary analysis was changed in the protocol following an amendment to the sample size across the age groups due to difficulties recruiting patients into the youngest (6 to < 9 years) age group and agreement with agencies to focus the primary analysis on 9 to < 18-year-olds.
12 secondary outcomes
Difference in pain intensity between methoxyflurane and placebo as measured by change from baseline in VAS pain scores at 15 minutes in the ITT Population (patients aged 6 to <18 years).
Time frame: Baseline to 15 minutes
Responder analysis - number of responders, who achieve 30% reduction in VAS score compared to baseline, at 15 minutes in the ITT population (patients aged 6 to <18 years).
Time frame: Baseline to 15 minutes
Longitudinal analysis of VAS pain scores at 5, 10, 15, and 20 minutes following commencement of treatment in the ITT population (patients aged 6 to <18 years).
Time frame: Baseline to 5, 10, 15 and 20 minutes
Number of inhalations taken before first pain relief is summarised by category (1 to 10 inhalations, 11 to 20 inhalations, 21 to 30 inhalations, >30 inhalations, or no relief recorded) in the ITT population (patients aged 6 to <18 years).
Time frame: From baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission.
Rescue medication requested within 20 (+2 minutes) minutes of start of treatment and any time during treatment in the ITT population (patients aged 6 to &amp;lt;18 years).
Time frame: From baseline until request of rescue medication, assessed until point of either Emergency Department discharge or inpatient admission.
The time to request for rescue medication in the ITT population (patients aged 6 to &lt;18 years).
Time frame: From baseline until time at which rescue medication is first requested, assessed up to time of Emergency Department discharge or inpatient admission.
The time to first pain relief derived as time in minutes since start of study treatment until first pain relief in the ITT population (patients aged 6 to &lt;18 years).
Time frame: From baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission.
Number of inhalations taken before first pain relief split by whether the hole was covered at least once or not covered in the ITT population (patients aged 6 to &lt;18 years).
Time frame: Baseline until time at which first pain relief is reported, assessed up to Emergency Department discharge or inpatient admission..
Global medication performance assessment by patient, clinician and research nurse: 0 = poor to 4 = excellent, measured after completion of treatment.
Time frame: From baseline, assessed up to Emergency Department discharge or inpatient admission.
Heart rate
Time frame: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Respiratory rate
Time frame: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Oxygen saturation
Time frame: From baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter assessed until the point of either Emergency Department discharge or inpatient admission.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 31272493Hartshorn S, Barrett MJ, Lyttle MD, Yee SA, Irvine AT; in collaboration with Paediatric Emergency Research in the UK and Ireland (PERUKI). Inhaled methoxyflurane (Penthrox(R)) versus placebo for injury-associated analgesia in children-the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial. Trials. 2019 Jul 4;20(1):393. doi: 10.1186/s13063-019-3511-4.
- Derived from this study: PubMed 41242203Hartshorn S, Barrett MJ, Bloom B, Lyttle MD, Walton E, Steel K, Yee SA, Irvine A; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI). Treatment of acute trauma-related pain in children and adolescents with methoxyflurane (Penthrox(R)) compared to placebo (MAGPIE): A randomised clinical trial. Injury. 2025 Dec;56(12):112830. doi: 10.1016/j.injury.2025.112830. Epub 2025 Oct 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Hartshorn principal investigator
Birmingham Children's Hospital
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methoxyflurane and Normal saline in people with Pain, Acute, run by Medical Developments International Limited at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in pain intensity between methoxyflurane and placebo as measured by change from baseline in VAS pain scores at 15 minutes for patients aged 9 to < 18 years. (time frame: Baseline to 15 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03215056, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.