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

NCT07742007 | Not Yet Recruiting Phase 3

• 2 other identifiers: DR250268 - PAIN-THROX2025-525001-21-00
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Pain Management

Keywords

Non-traumatic pain; methoxyflurane; Emergency department; analgesic management

Outcome Measures

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).

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

Secondary Outcomes (5)

• Evaluate the effect of methoxyflurane based on pain intensity

  from baseline to 30 minutes after randomization

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

  At 60 minutes after randomization, 90 minutes and 120 minutes

• Use of Rescue Analgesic Treatment After 30 Minutes Post-Randomization

  More than 30 minutes after randomization

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

  More than 30 minutes after randomization

• Adverse Events and Serious Adverse Events

  From baseline to 24 hours

Study Arms (2)

Experimental Group

EXPERIMENTAL

analgesic management with Methoxyflurane as first-line treatment

Drug: Analgesic management with Methoxyflurane as first-line treatment

Control group

OTHER

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

Analgesic management with Methoxyflurane as first-line treatment DRUG

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.

Experimental Group

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

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

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (3)

CHRU Hôpitaux de Tours - Urgences de l'Hôpital Trousseau

Tours, CHRU de Tours, 37170, France

Location

CHU d'Angers

Angers, 49100, France

Location

CHU d'Orléans

Orléans, 45100, France

Location

MeSH Terms

Conditions

Agnosia; Emergencies

Interventions

Methoxyflurane

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Ethyl Ethers; Ethers; Organic Chemicals; Methyl Ethers

Central Study Contacts

Mickael SOLETCHNIK, Dr.

CONTACT

0247471014; mickael.soletchnik@gmail.com

Amélie DELAGE

CONTACT

0247473933; a.delage@chu-tours.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: August 3, 2026
• Study Start (Estimated): September 16, 2026
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): September 16, 2027
• Last Updated: August 3, 2026

Record last verified: 2026-07

Locations

FR (3)