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CompletedNCT03256903InMEDIATEUpdated Aug 20, 2018

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

A Phase 3 interventional study of Methoxyflurane and Standard of care in Acute Pain Due to Trauma, sponsored by Mundipharma Pharmaceuticals S.L.. Completed at 14 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-20.

Sponsored by Mundipharma Pharmaceuticals S.L. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
310
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Acute Pain Due to Trauma

Keywords

  • Methoxyflurane
  • emergency
  • trauma pain
  • inhaled analgesia
03

Who can participate

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

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
310 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugMethoxyflurane

    Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.

    Also known as: No other interventions

  • DrugStandard 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

    Also known as: No other interventions

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: At baseline, 3, 5, 10, 15 and 20 minutes from STA

  2. Analgesia effectiveness

    Difference between arms related to analgesia effectiveness

    Time frame: Change from baseline to 3, 5, 10, 15, 20 and 30 min

  3. Analgesia speed of action

    Difference between arms related to speed of action of analgesia for all patients

    Time frame: From time of randomization up to 20 minutes

  4. 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

    Time frame: Up until 14 days from STA

  5. Patient-averaged summed pain intensity difference 15 min after STA

    Patient-averaged summed pain intensity difference 15 min after STA

    Time frame: from baseline to 3, 5, 10 and 15 minutes post dose

  6. Pain Responders

    Pain Responders (with \>30% pain relief compared to baseline) at 20 min

    Time frame: from baseline to 20 minutes post dose

Secondary outcomes

  1. Investigators and patients satisfaction

    Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)

    Time frame: 30 min from start of administration

  2. Patient and investigators' fulfillment of expectations

    Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale

    Time frame: 30 min from start of administration

  3. Patients' Global Impression of Change with the treatments

    Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale

    Time frame: Up until 30 minutes from STA

  4. 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

    Time frame: Up until 60 minutes from randomization

  5. 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.

    Time frame: Up until 14 days from STA

06

Study locations

14 sites
  • Hospital de Viladecans
    Viladecans, Barcelona 08840, Spain
  • Hospital del Bierzo
    Ponferrada, León 24404, Spain
  • Hospital Asepeyo Coslada
    Coslada, Madrid 28823, Spain
  • Hospital Puerta de Hierro
    Majadahonda, Madrid 28222, Spain
  • Hospital Álvaro Cunqueiro
    Vigo, Pontevedra 36312, Spain
  • Hospital Gernika-Lumo
    Gernika-Lumo, Vizcaya 48300, Spain
  • Hospital General de Alicante
    Alicante, 03010, Spain
  • Hospital Universitario La Princesa
    Madrid, 28006, Spain
  • Hospital Clínico San Carlos
    Madrid, 28040, Spain
  • SUMMA - Comunidad de Madrid
    Madrid, 28045, Spain
  • Hospital La Paz
    Madrid, 28046, Spain
  • Hospital Virgen del Rocío
    Sevilla, 41013, Spain
  • Hospital Campo Grande
    Valladolid, 47006, Spain
  • Complejo Asistencial de Zamora
    Zamora, 49022, Spain
07

References and documents

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. PubMed 31623936 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03256903
Lead sponsor
Mundipharma Pharmaceuticals S.L.
Collaborators
Spanish Society for Emergency Medicine (SEMES), Spanish Clinical Research Network - SCReN
Responsible party
Alberto M. Borobia (MD, PhD, Hospital Universitario La Paz) — Principal investigator
First posted
Aug 22, 2017
Start date
Jul 7, 2017
Primary completion
Mar 6, 2018
Completion
Jul 31, 2018
Last update
Aug 20, 2018

Study contacts

Alberto Borobia, MD, PhD
study director · La Paz University Hospital

Oversight

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