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Not yet recruitingNCT07742007PAIN-THROXUpdated Aug 3, 2026

Methoxyflurane Versus Usual Care for Non-Traumatic Pain in Emergency Departments

A Phase 3 interventional study of Analgesic management with Methoxyflurane as first-line treatment and Pain treatment according to the usual analgesic management protocol of the emergency department of the participating center. in Pain Management, sponsored by University Hospital, Tours. Not yet recruiting at 3 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-03.

Sponsored by University Hospital, Tours · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
164
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Pain is one of the most frequent patient-reported symptoms in emergency departments (EDs). Pain management could be very challenging, notably for patients that must wait in an ED waiting room. In such context, antalgic drugs that could be used are mainly oral medications with the paracetamol (acetaminophen), the non-steroidal anti-inflammatory drugs and the weak and strong opioid drugs as the main available options, depending on the degree of pain. Those commonly used painkillers, with oral administration, need a delay (approximatively 20 to 30 minutes) before the full analgesic effect could be observed. Methoxyflurane is a self-administered inhaled analgesic used for over 40 years in countries such as Australia. Methoxyflurane has a rapid onset of action, is well tolerated and is widely used for moderate to severe traumatic pain, with several trials that have investigated it efficacy in such indication. However, no data are available concerning the management of non-traumatic painful diseases. Thus, the aim of the open-label, multicenter, and two parallel-arms superiority PAIN-THROX randomized controlled trial is to assess how using self-administered inhaled Methoxyflurane could reduce the time to pain relief comparatively with oral analgesic medications for patients seeking in an ED for non-traumatic painful diseases and who could wait in an ED waiting room.

Read the detailed description

Patients seeking in an ED for a non-traumatic painful disease and with a condition allowing staying in waiting room will be randomly allocated in a 1:1 ratio between Methoxyflurane (intervention group) or oral standard analgesic medications according to the degree of pain and based on the ED pain-management protocol.

Primary outcome will be the time to pain relief within the 30 minutes after randomization. Pain will be measured using the visual analogue scale. Secondary outcomes will be the time to pain relief within 3 subgroups according to the degree of pain at time to randomization (moderate, strong and intolerable), the evolution of the pain between 30 min and 2 hours post randomization, the need for rescue analgesic therapies and the occurrence adverse events.

02

Conditions studied

  • Pain Management

Keywords

  • Non-traumatic pain
  • methoxyflurane
  • Emergency department
  • analgesic management
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adult ≥ 18 years
  • Acute non-traumatic pain of moderate to severe intensity (VAS strictly greater than 39 mm)
  • Able to independently assess their pain using a VAS and to record it independently on paper.
  • Affiliated to a social security system
  • Having signed informed consent

Exclusion criteria

Exclusion Criteria:

  • Age \< 18 years

    • Contraindications to methoxyflurane as stated in the Summary of Product Characteristics:
    • Hypersensitivity to the active substance or to any other fluorinated anesthetic or to any excipient.

      • Malignant hyperthermia: known malignant hyperthermia or genetic predisposition.
      • History of serious adverse reactions (patient or relatives) after administration of inhaled anesthetics.
      • History of signs of liver injury after use of methoxyflurane or halogenated hydrocarbons.
      • Clinically significant renal impairment
      • Altered level of consciousness regardless of cause, including head trauma, drug or alcohol use
      • Clinical evidence of cardiovascular instability
      • Clinical evidence of respiratory depression
    • Hemodynamically unstable patient (SBP \< 100 mmHg, DBP \< 30 mmHg)
    • Patient having already received Methoxyflurane on the same day
    • Patient having taken analgesic treatment prior to emergency consultation within 4 hours of admission.
    • Pain ≤ 39 mm
    • Pregnant, breastfeeding.
    • Women of childbearing potential not using a highly effective method of contraception throughout the study. The absence of pregnancy must be confirmed by performing a pregnancy test. Patients who are unable to provide a urine sample at the time of inclusion will not be enrolled in the study.
    • Subject under legal protection
    • Patients currently within the exclusion period of another clinical trial.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
164 participants (estimated)

Study arms

  • Experimental
    Experimental Group

    analgesic management with Methoxyflurane as first-line treatment

    Drug: Analgesic management with Methoxyflurane as first-line treatment

  • Other
    Control group

    Pain treatment according to the usual analgesic management protocol of the emergency department of the participating center.

    Drug: Pain treatment according to the usual analgesic management protocol of the emergency department of the participating center.

Interventions

  • DrugAnalgesic management with Methoxyflurane as first-line treatment

    The investigational medicinal product is methoxyflurane, presented as a liquid for vapor inhalation, supplied in 3 mL vials and marketed under the name Penthrox®. Each vial contains 3 mL of methoxyflurane at 99.9%, and includes butylated hydroxytoluene (E321) as an excipient with known effect (0.01% w/w). Each pack contains one methoxyflurane vial, an inhaler, and an activated carbon chamber. Methoxyflurane is self-administered under the supervision of a trained healthcare professional, either a physician or a nurse. Administration is performed using the provided handheld inhaler.

  • DrugPain treatment according to the usual analgesic management protocol of the emergency department of the participating center.

    Administration of oral analgesic treatment in the emergency reception area according to the protocol in force in the emergency department.

05

What researchers measure

Primary outcomes

  1. Time to Pain Reduction of at Least 30 mm on the Visual Analog Scale (VAS)

    Time from randomization to the first decrease of at least 30 mm from baseline pain score measured on a 100-mm Visual Analog Scale (VAS), assessed within the 30 minutes after randomization. The VAS is a simple pain measurement tool consisting of placing a mark on a colored ruler graduated in millimeters, thereby associating a numerical value ranging from 0 (no pain) to 100 millimeters (unbearable pain).

    Time frame: At Inclusion An at 3, 5, 10, 15, 20, 25, and 30-minutes post randomisation

Secondary outcomes

  1. Evaluate the effect of methoxyflurane based on pain intensity

    Assess the effect of methoxyflurane in each of the three subgroups defined by pain intensity and categorized as "moderate" pain (VAS between 40 and 59), "severe" pain (VAS between 60 and 79 mm), and "unbearable" pain (VAS ≥ 80 mm) at enrollment

    Time frame: from baseline to 30 minutes after randomization

  2. Compare the prolonged analgesic effect (ranging from 30 minutes to 2 hours) of methoxyflurane

    Compare the prolonged analgesic effect of methoxyflurane with that of "standard"pain management with the measurement of Pain Intensity (VAS) at 60, 90, and 120 Minutes Post-Randomization

    Time frame: At 60 minutes after randomization, 90 minutes and 120 minutes

  3. Use of Rescue Analgesic Treatment After 30 Minutes Post-Randomization

    Participants requiring any analgesic treatment due to insufficient pain relief or recurrence of pain more than 30 minutes after randomization.

    Time frame: More than 30 minutes after randomization

  4. Class of Rescue Analgesic Treatment Used After 30 Minutes Post-Randomization

    Therapeutic class of the analgesic treatment administered for insufficient pain relief or recurrence of pain more than 30 minutes after randomization.

    Time frame: More than 30 minutes after randomization

  5. Adverse Events and Serious Adverse Events

    Number of participants experiencing adverse events (AEs) and serious adverse events (SAEs) during the study period.

    Time frame: From baseline to 24 hours

06

Study locations

3 sites
  • CHRU Hôpitaux de Tours - Urgences de l'Hôpital Trousseau
    Tours, CHRU de Tours 37170, France
  • CHU d'Angers
    Angers, 49100, France
    • Aurélie FIENI, Dr · Principal investigator
  • CHU d'Orléans
    Orléans, 45100, France
    • Ayar VAITTINADA, Dr · Principal investigator
07

Registry details

Key details

Study ID
NCT07742007
Lead sponsor
University Hospital, Tours
Responsible party
Sponsor
First posted
Aug 3, 2026
Start date
Sep 16, 2026 (estimated)
Primary completion
Sep 15, 2027 (estimated)
Completion
Sep 16, 2027 (estimated)
Last update
Aug 3, 2026

Study contacts

Mickael SOLETCHNIK, Dr.
Contact
mickael.soletchnik@gmail.com
0247471014
Amélie DELAGE
Contact
a.delage@chu-tours.fr
0247473933

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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