Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units (InMEDIATE)

Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.

Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used in usual clinical practice, in patients with trauma and associated pain, treated in Spanish emergency units.

Study Overview

• Status: Completed
• Conditions: Acute Pain Due to Trauma
• Intervention / Treatment: Drug: Methoxyflurane; Drug: Standard of care

Detailed Description

Open, randomized clinical trial to compare emergency pain relief between methoxyflurane and standard of care in patients with trauma and associated pain, treated in Spanish emergency units.

Methoxyflurane is a fluorinated ethyl methyl ether, with the chemical name 2:2-dichloro-1:1-difluoroethyl methyl ether. It belongs to the fluorinated hydrocarbon group of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations to achieve an analgesic effect for the management of pain.

In Europe countries, where methoxyflurane is already marketed, it is indicated for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain.

On the other hand, current clinical practice includes a variety of analgesic agents, with the choice of which to employ based on consideration of the risk-benefit factors of each class of drug, as well as the type of pain, its severity, and the risk of adverse effects.

The main objective of this study is to assess Methoxyflurane's significant advantage in terms of anaglesic effectiveness, as it is known as a rapidly acting, non-narcotic analgesic for the treatment of emergency pain.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain, 03010
    • Hospital General de Alicante
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28045
    • SUMMA - Comunidad de Madrid
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
  • Valladolid, Spain, 47006
    • Hospital Campo Grande
  • Zamora, Spain, 49022
    • Complejo Asistencial de Zamora
  • Barcelona
    • Viladecans, Barcelona, Spain, 08840
      • Hospital de Viladecans
  • León
    • Ponferrada, León, Spain, 24404
      • Hospital del Bierzo
  • Madrid
    • Coslada, Madrid, Spain, 28823
      • Hospital Asepeyo Coslada
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Puerta de Hierro
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Álvaro Cunqueiro
  • Vizcaya
    • Gernika-Lumo, Vizcaya, Spain, 48300
      • Hospital Gernika-Lumo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients: ≥ 18 years of age
• Moderate to severe pain (NRS 0-10; >=4) secondary to trauma
• Without anticipating surgery due to the trauma, requiring hospitalization (hospital stay 12h)
• Conscious patient.
• Giving informed consent in writing

Exclusion Criteria:

• Hypersensitivity to methoxyflurane (MEOF) or any fluorinated anaesthetic.
• Malignant hyperthermia: patients with known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
• Patients who have a history of showing signs of liver damage after previous MEOF use or halogenated hydrocarbon anaesthesia
• Known clinically significant renal impairment
• Known pregnant or likely to be pregnant women at the time of inclusion.
• Clinically evident cardiovascular instability
• Clinically evident respiratory depression
• Patients taken any analgesic for the traumatic pain before inclusion
• Altered level of consciousness due to any cause, including head injury, drugs or alcohol
• Degenerative diseases, mental illness or other conditions that could affect ability of valuing pain intensity
• Patients to be unable to understand the purpose of the study and perform self-assessments, following investigator's criteria.
• Participation in another clinical trial within 30 days prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methoxyflurane; Patients will be supplied with up to two inhalers containing 3 mL methoxyflurane. A member of the research team will train the patient to self-administer methoxyflurane	Drug: Methoxyflurane; Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.; Other Names: No other interventions
Active Comparator: Standard of Care (SoC); Patients will be treated following standard of care (SoC) of the hospital, for emergency relief of trauma and associated pain. Any kind of analgesia administered by any route will be valid. Only administration of one analgesic (or fixed combinations) at baseline will considered SoC. Other required analgesics will be considered rescue medication.	Drug: Standard of care; Any kind of analgesia, administered by any route for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain; Other Names: No other interventions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain relief	Change in mean pain intensity over 20 min from start of administration (STA) and time to first pain relief, measured by numeric scale (0-10)	At baseline, 3, 5, 10, 15 and 20 minutes from STA
Analgesia effectiveness	Difference between arms related to analgesia effectiveness	Change from baseline to 3, 5, 10, 15, 20 and 30 min
Analgesia speed of action	Difference between arms related to speed of action of analgesia for all patients	From time of randomization up to 20 minutes
Safety for patients with severe pain, treated with second or third step analgesics	Difference between arms related to safety for patients with severe pain (NRS >7), treated with second or third step analgesics	Up until 14 days from STA
Patient-averaged summed pain intensity difference 15 min after STA	Patient-averaged summed pain intensity difference 15 min after STA	from baseline to 3, 5, 10 and 15 minutes post dose
Pain Responders	Pain Responders (with >30% pain relief compared to baseline) at 20 min	from baseline to 20 minutes post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigators and patients satisfaction	Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)	30 min from start of administration
Patient and investigators' fulfillment of expectations	Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale	30 min from start of administration
Patients' Global Impression of Change with the treatments	Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale	Up until 30 minutes from STA
Treatment cost of pain relief	Treatment cost of pain relief, measured considering use of fungible material; need of nurse to administer iv treatments; time to discharge	Up until 60 minutes from randomization
Safety rates of treatment emergent adverse events	Safety rates of treatment emergent adverse events (TEAE) in both arms, including alterations in biochemical and blood count.	Up until 14 days from STA

Collaborators and Investigators

• Sponsor: Mundipharma Pharmaceuticals S.L.
• Collaborators: Spanish Clinical Research Network - SCReN; Spanish Society for Emergency Medicine (SEMES)
• Investigators: Study Director: Alberto Borobia, MD, PhD, La Paz University Hospital

Publications and helpful links

General Publications

• Borobia AM, Collado SG, Cardona CC, Pueyo RC, Alonso CF, Torres IP, Gonzalez MC, Casal Codesido JR, Betegon MA, Barcela LA, Andicoechea AO, Testa AF, Colina JT, Dorribo AC, Del Arco Galan C, Martinez Avila JC, Lugilde ST, Carcas Sansuan AJ; InMEDIATE Investigators Group. Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments. Ann Emerg Med. 2020 Mar;75(3):315-328. doi: 10.1016/j.annemergmed.2019.07.028. Epub 2019 Oct 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2017
• Primary Completion (Actual): March 6, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: emergency; Methoxyflurane; trauma pain; inhaled analgesia
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Emergencies; Wounds and Injuries; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Methoxyflurane
• Other Study ID Numbers: MR311-3502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No