Efficacy and Safety of Methoxyflurane (Penthrox) for the Treatment of Acute Pain in Minor Trauma (STOP!)

A Randomised, Double Blind, Multi-centre, Placebo Controlled Study to Evaluate the Efficacy and Safety of Methoxyflurane (Penthrox) for the Treatment of Acute Pain in Patients Presenting to an Emergency Department With Minor Trauma

This study investigates the treatment of acute pain, an unpleasant feeling caused by an injury. The overall purpose of the study is to gain more information that the pain relief medicine Penthrox(Methoxyflurane) administered using the Penthrox Inhaler(a distinctive green, whistle like object that you breathe through) is safe and works at relieving pain in patients aged 12 years and older who are admitted to a hospital Emergency Department with a minor injury (known as trauma).

Study Overview

• Status: Completed
• Conditions: Acute Pain Due to Trauma
• Intervention / Treatment: Drug: Methoxyflurane

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Barnsley District General Hospital
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital NHS Foundation Trust
  • Colchester, United Kingdom, CO4 5JL
    • Colchester General Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • James Cook University Hospital
  • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients 12 years of age or older who are able to give written informed consent or who are accompanied by a parent(s)/legal guardian able to provide written informed consent on their behalf.
• Evidence of signed and dated informed consent document(s) indicating that the patient (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study.
• Pain Score ≥ 4 to ≤ 7 as measured using Numerical Rating Scale (NRS) at the time of admission, due to minor trauma.

Exclusion Criteria:

• Life-threatening condition requiring immediate admission in the Operating Room or Intensive Care Unit.
• Presence of any other clinical condition(s) that may, in the opinion of the investigator, impact on the patient's ability to participate in the study, or on the study results, including history of head injury and/or altered consciousness.
• Unable to provide written informed consent.
• Known pregnancy or lactation
• Acute intoxication with drugs or alcohol, based on the judgement of the attending physician.
• Treatment with any analgesic agent within 5 hours prior to presentation to ED (except diclofenac sodium which is prohibited within 8 hours prior to presentation to ED).
• Current ongoing use of analgesics for chronic pain.
• Use of an investigational product within one month prior to presentation to ED.
• Known personal or familial hypersensitivity to fluorinated anaesthetics.
• Known personal or familial history of malignant hyperthermia.
• Clinically significant respiratory depression.
• Use of methoxyflurane in the previous 4 weeks.
• Known pre-existing clinically significant renal or hepatic impairment according to the judgement of the clinician.
• Clinically significant cardiovascular instability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal Saline	Drug: Methoxyflurane; Patients will have access to two 3 mL methoxyflurane (Penthrox) Inhalers or two 5mL placebo Inhalers to be self-administered.; Other Names: Penthrox
Experimental: Methoxyflurane	Drug: Methoxyflurane; Patients will have access to two 3 mL methoxyflurane (Penthrox) Inhalers or two 5mL placebo Inhalers to be self-administered.; Other Names: Penthrox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS Score	The difference between treatment and placebo on the VAS pain score	Twenty Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue Medication	A request for rescue medication, time of request for rescue medication and the quantity of opioid equivalent rescue medication administered will be measured	Up to a maximum of 6 hours
Time to pain relief	The number of inhalations of study treatment until pain relief is achieved and the time until pain relief is achieved.	Up to a maximum of 6 hours
Responder analysis	The number of responders will be defined	Up to a maximum of 6 hours
Safety Analysis	Evaluation of Adverse Events experienced during treatment. Evaluation of Adverse Events, including safety laboratory samples, up to 14 +/- 2 days following Emergency Department discharge	Up to 16 days

Collaborators and Investigators

• Sponsor: Medical Developments International Limited
• Collaborators: ORION Clinical Services
• Investigators: Principal Investigator: Frank M Coffey, Nottingham University Hospitals, Queen's Medical Centre Campus

Publications and helpful links

General Publications

• Hartshorn S, Dissmann P, Coffey F, Lomax M. Low-dose methoxyflurane analgesia in adolescent patients with moderate-to-severe trauma pain: a subgroup analysis of the STOP! study. J Pain Res. 2019 Feb 15;12:689-700. doi: 10.2147/JPR.S188675. eCollection 2019.
• Coffey F, Dissmann P, Mirza K, Lomax M. Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!). Adv Ther. 2016 Nov;33(11):2012-2031. doi: 10.1007/s12325-016-0405-7. Epub 2016 Aug 27.
• Coffey F, Wright J, Hartshorn S, Hunt P, Locker T, Mirza K, Dissmann P. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. Emerg Med J. 2014 Aug;31(8):613-8. doi: 10.1136/emermed-2013-202909. Epub 2014 Apr 17.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: August 11, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 19, 2011

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 30, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Pain; Analgesia; Trauma
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Wounds and Injuries; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Methoxyflurane
• Other Study ID Numbers: MEOF-001