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

Официальное название

Methoxyflurane Versus Usual Care for Non-Traumatic Pain in Emergency Departments: the Multicenter, Open-label, Superiority PAIN-THROX Randomized Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Analgesic 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
• Препарат Pain 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.

Первичные конечные точки

• Time to Pain Reduction of at Least 30 mm on the Visual Analog Scale (VAS) [Срок оценки: At Inclusion An at 3, 5, 10, 15, 20, 25, and 30-minutes post randomisation]

Вторичные конечные точки (5)

• Evaluate the effect of methoxyflurane based on pain intensity [Срок оценки: from baseline to 30 minutes after randomization]
• Compare the prolonged analgesic effect (ranging from 30 minutes to 2 hours) of methoxyflurane [Срок оценки: At 60 minutes after randomization, 90 minutes and 120 minutes]
• Use of Rescue Analgesic Treatment After 30 Minutes Post-Randomization [Срок оценки: More than 30 minutes after randomization]
• Class of Rescue Analgesic Treatment Used After 30 Minutes Post-Randomization [Срок оценки: More than 30 minutes after randomization]
• Adverse Events and Serious Adverse Events [Срок оценки: From baseline to 24 hours]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Франция · 3 центра

• CHRU Hôpitaux de Tours - Urgences de l'Hôpital Trousseau — Tours
• CHU d'Angers — Angers
• CHU d'Orléans — Orléans

Идентификаторы

NCT: NCT07742007 · DR250268 - PAIN-THROX · 2025-525001-21-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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