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

Primary Purpose

Acute Pain Due to Trauma

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Methoxyflurane
Standard of care
Sponsored by
Mundipharma Pharmaceuticals S.L.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pain Due to Trauma focused on measuring Methoxyflurane, emergency, trauma pain, inhaled analgesia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital de Viladecans
  • Hospital del Bierzo
  • Hospital Asepeyo Coslada
  • Hospital Puerta de Hierro
  • Hospital Álvaro Cunqueiro
  • Hospital Gernika-Lumo
  • Hospital General de Alicante
  • Hospital Universitario La Princesa
  • Hospital Clínico San Carlos
  • SUMMA - Comunidad de Madrid
  • Hospital La Paz
  • Hospital Virgen del Rocío
  • Hospital Campo Grande
  • Complejo Asistencial de Zamora

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Methoxyflurane

Standard of Care (SoC)

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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)
Analgesia effectiveness
Difference between arms related to analgesia effectiveness
Analgesia speed of action
Difference between arms related to speed of action of analgesia for all patients
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
Patient-averaged summed pain intensity difference 15 min after STA
Patient-averaged summed pain intensity difference 15 min after STA
Pain Responders
Pain Responders (with >30% pain relief compared to baseline) at 20 min

Secondary Outcome Measures

Investigators and patients satisfaction
Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)
Patient and investigators' fulfillment of expectations
Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
Patients' Global Impression of Change with the treatments
Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
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
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.

Full Information

First Posted
May 30, 2017
Last Updated
August 16, 2018
Sponsor
Mundipharma Pharmaceuticals S.L.
Collaborators
Spanish Society for Emergency Medicine (SEMES), Spanish Clinical Research Network - SCReN
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1. Study Identification

Unique Protocol Identification Number
NCT03256903
Brief Title
Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units
Acronym
InMEDIATE
Official Title
Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
July 7, 2017 (Actual)
Primary Completion Date
March 6, 2018 (Actual)
Study Completion Date
July 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mundipharma Pharmaceuticals S.L.
Collaborators
Spanish Society for Emergency Medicine (SEMES), Spanish Clinical Research Network - SCReN

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pain Due to Trauma
Keywords
Methoxyflurane, emergency, trauma pain, inhaled analgesia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Phase IIIb open randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
310 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methoxyflurane
Arm Type
Experimental
Arm Description
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
Arm Title
Standard of Care (SoC)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methoxyflurane
Other Intervention Name(s)
No other interventions
Intervention Description
Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.
Intervention Type
Drug
Intervention Name(s)
Standard of care
Other Intervention Name(s)
No other interventions
Intervention Description
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
Primary Outcome Measure Information:
Title
Pain relief
Description
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
Title
Analgesia effectiveness
Description
Difference between arms related to analgesia effectiveness
Time Frame
Change from baseline to 3, 5, 10, 15, 20 and 30 min
Title
Analgesia speed of action
Description
Difference between arms related to speed of action of analgesia for all patients
Time Frame
From time of randomization up to 20 minutes
Title
Safety for patients with severe pain, treated with second or third step analgesics
Description
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
Title
Patient-averaged summed pain intensity difference 15 min after STA
Description
Patient-averaged summed pain intensity difference 15 min after STA
Time Frame
from baseline to 3, 5, 10 and 15 minutes post dose
Title
Pain Responders
Description
Pain Responders (with >30% pain relief compared to baseline) at 20 min
Time Frame
from baseline to 20 minutes post dose
Secondary Outcome Measure Information:
Title
Investigators and patients satisfaction
Description
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
Title
Patient and investigators' fulfillment of expectations
Description
Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
Time Frame
30 min from start of administration
Title
Patients' Global Impression of Change with the treatments
Description
Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
Time Frame
Up until 30 minutes from STA
Title
Treatment cost of pain relief
Description
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
Title
Safety rates of treatment emergent adverse events
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Borobia, MD, PhD
Organizational Affiliation
La Paz University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Hospital de Viladecans
City
Viladecans
State/Province
Barcelona
ZIP/Postal Code
08840
Country
Spain
Facility Name
Hospital del Bierzo
City
Ponferrada
State/Province
León
ZIP/Postal Code
24404
Country
Spain
Facility Name
Hospital Asepeyo Coslada
City
Coslada
State/Province
Madrid
ZIP/Postal Code
28823
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Álvaro Cunqueiro
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36312
Country
Spain
Facility Name
Hospital Gernika-Lumo
City
Gernika-Lumo
State/Province
Vizcaya
ZIP/Postal Code
48300
Country
Spain
Facility Name
Hospital General de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital Universitario La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
SUMMA - Comunidad de Madrid
City
Madrid
ZIP/Postal Code
28045
Country
Spain
Facility Name
Hospital La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Campo Grande
City
Valladolid
ZIP/Postal Code
47006
Country
Spain
Facility Name
Complejo Asistencial de Zamora
City
Zamora
ZIP/Postal Code
49022
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31623936
Citation
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.
Results Reference
derived

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

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