<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03256903</url>
  </required_header>
  <id_info>
    <org_study_id>MR311-3502</org_study_id>
    <nct_id>NCT03256903</nct_id>
  </id_info>
  <brief_title>Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units</brief_title>
  <acronym>InMEDIATE</acronym>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mundipharma Pharmaceuticals S.L.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spanish Society for Emergency Medicine (SEMES)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Spanish Clinical Research Network - SCReN</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mundipharma Pharmaceuticals S.L.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used&#xD;
      in usual clinical practice, in patients with trauma and associated pain, treated in Spanish&#xD;
      emergency units.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open, randomized clinical trial to compare emergency pain relief between methoxyflurane and&#xD;
      standard of care in patients with trauma and associated pain, treated in Spanish emergency&#xD;
      units.&#xD;
&#xD;
      Methoxyflurane is a fluorinated ethyl methyl ether, with the chemical name&#xD;
      2:2-dichloro-1:1-difluoroethyl methyl ether. It belongs to the fluorinated hydrocarbon group&#xD;
      of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations&#xD;
      to achieve an analgesic effect for the management of pain.&#xD;
&#xD;
      In Europe countries, where methoxyflurane is already marketed, it is indicated for emergency&#xD;
      relief of moderate to severe pain in conscious adult patients with trauma and associated&#xD;
      pain.&#xD;
&#xD;
      On the other hand, current clinical practice includes a variety of analgesic agents, with the&#xD;
      choice of which to employ based on consideration of the risk-benefit factors of each class of&#xD;
      drug, as well as the type of pain, its severity, and the risk of adverse effects.&#xD;
&#xD;
      The main objective of this study is to assess Methoxyflurane's significant advantage in terms&#xD;
      of anaglesic effectiveness, as it is known as a rapidly acting, non-narcotic analgesic for&#xD;
      the treatment of emergency pain.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 7, 2017</start_date>
  <completion_date type="Actual">July 31, 2018</completion_date>
  <primary_completion_date type="Actual">March 6, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Phase IIIb open randomized clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain relief</measure>
    <time_frame>At baseline, 3, 5, 10, 15 and 20 minutes from STA</time_frame>
    <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)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Analgesia effectiveness</measure>
    <time_frame>Change from baseline to 3, 5, 10, 15, 20 and 30 min</time_frame>
    <description>Difference between arms related to analgesia effectiveness</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Analgesia speed of action</measure>
    <time_frame>From time of randomization up to 20 minutes</time_frame>
    <description>Difference between arms related to speed of action of analgesia for all patients</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety for patients with severe pain, treated with second or third step analgesics</measure>
    <time_frame>Up until 14 days from STA</time_frame>
    <description>Difference between arms related to safety for patients with severe pain (NRS &gt;7), treated with second or third step analgesics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient-averaged summed pain intensity difference 15 min after STA</measure>
    <time_frame>from baseline to 3, 5, 10 and 15 minutes post dose</time_frame>
    <description>Patient-averaged summed pain intensity difference 15 min after STA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain Responders</measure>
    <time_frame>from baseline to 20 minutes post dose</time_frame>
    <description>Pain Responders (with &gt;30% pain relief compared to baseline) at 20 min</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Investigators and patients satisfaction</measure>
    <time_frame>30 min from start of administration</time_frame>
    <description>Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient and investigators' fulfillment of expectations</measure>
    <time_frame>30 min from start of administration</time_frame>
    <description>Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' Global Impression of Change with the treatments</measure>
    <time_frame>Up until 30 minutes from STA</time_frame>
    <description>Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment cost of pain relief</measure>
    <time_frame>Up until 60 minutes from randomization</time_frame>
    <description>Treatment cost of pain relief, measured considering use of fungible material; need of nurse to administer iv treatments; time to discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety rates of treatment emergent adverse events</measure>
    <time_frame>Up until 14 days from STA</time_frame>
    <description>Safety rates of treatment emergent adverse events (TEAE) in both arms, including alterations in biochemical and blood count.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">310</enrollment>
  <condition>Acute Pain Due to Trauma</condition>
  <arm_group>
    <arm_group_label>Methoxyflurane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care (SoC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methoxyflurane</intervention_name>
    <description>Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.</description>
    <arm_group_label>Methoxyflurane</arm_group_label>
    <other_name>No other interventions</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of care</intervention_name>
    <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</description>
    <arm_group_label>Standard of Care (SoC)</arm_group_label>
    <other_name>No other interventions</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients: ≥ 18 years of age&#xD;
&#xD;
          -  Moderate to severe pain (NRS 0-10; &gt;=4) secondary to trauma&#xD;
&#xD;
          -  Without anticipating surgery due to the trauma, requiring hospitalization (hospital&#xD;
             stay 12h)&#xD;
&#xD;
          -  Conscious patient.&#xD;
&#xD;
          -  Giving informed consent in writing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to methoxyflurane (MEOF) or any fluorinated anaesthetic.&#xD;
&#xD;
          -  Malignant hyperthermia: patients with known or genetically susceptible to malignant&#xD;
             hyperthermia or a history of severe adverse reactions in either patient or relatives.&#xD;
&#xD;
          -  Patients who have a history of showing signs of liver damage after previous MEOF use&#xD;
             or halogenated hydrocarbon anaesthesia&#xD;
&#xD;
          -  Known clinically significant renal impairment&#xD;
&#xD;
          -  Known pregnant or likely to be pregnant women at the time of inclusion.&#xD;
&#xD;
          -  Clinically evident cardiovascular instability&#xD;
&#xD;
          -  Clinically evident respiratory depression&#xD;
&#xD;
          -  Patients taken any analgesic for the traumatic pain before inclusion&#xD;
&#xD;
          -  Altered level of consciousness due to any cause, including head injury, drugs or&#xD;
             alcohol&#xD;
&#xD;
          -  Degenerative diseases, mental illness or other conditions that could affect ability of&#xD;
             valuing pain intensity&#xD;
&#xD;
          -  Patients to be unable to understand the purpose of the study and perform&#xD;
             self-assessments, following investigator's criteria.&#xD;
&#xD;
          -  Participation in another clinical trial within 30 days prior to randomization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alberto Borobia, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>La Paz University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de Viladecans</name>
      <address>
        <city>Viladecans</city>
        <state>Barcelona</state>
        <zip>08840</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Bierzo</name>
      <address>
        <city>Ponferrada</city>
        <state>León</state>
        <zip>24404</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Asepeyo Coslada</name>
      <address>
        <city>Coslada</city>
        <state>Madrid</state>
        <zip>28823</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Puerta de Hierro</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Álvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <state>Pontevedra</state>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Gernika-Lumo</name>
      <address>
        <city>Gernika-Lumo</city>
        <state>Vizcaya</state>
        <zip>48300</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUMMA - Comunidad de Madrid</name>
      <address>
        <city>Madrid</city>
        <zip>28045</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Campo Grande</name>
      <address>
        <city>Valladolid</city>
        <zip>47006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Asistencial de Zamora</name>
      <address>
        <city>Zamora</city>
        <zip>49022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>May 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>August 16, 2018</last_update_submitted>
  <last_update_submitted_qc>August 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitario La Paz</investigator_affiliation>
    <investigator_full_name>Alberto M. Borobia</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Methoxyflurane</keyword>
  <keyword>emergency</keyword>
  <keyword>trauma pain</keyword>
  <keyword>inhaled analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Emergencies</mesh_term>
    <mesh_term>Acute Pain</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methoxyflurane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03256903
org study id: MR311-3502
nct id: NCT03256903
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase IIIb open randomized clinical trial
primary purpose: Treatment
masking: None (Open Label)
measure: Pain relief
time frame: At baseline, 3, 5, 10, 15 and 20 minutes from STA
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)
measure: Analgesia effectiveness
time frame: Change from baseline to 3, 5, 10, 15, 20 and 30 min
description: Difference between arms related to analgesia effectiveness
measure: Analgesia speed of action
time frame: From time of randomization up to 20 minutes
description: Difference between arms related to speed of action of analgesia for all patients
measure: Safety for patients with severe pain, treated with second or third step analgesics
time frame: Up until 14 days from STA
description: Difference between arms related to safety for patients with severe pain (NRS >7), treated with second or third step analgesics
measure: Patient-averaged summed pain intensity difference 15 min after STA
time frame: from baseline to 3, 5, 10 and 15 minutes post dose
description: Patient-averaged summed pain intensity difference 15 min after STA
measure: Pain Responders
time frame: from baseline to 20 minutes post dose
description: Pain Responders (with >30% pain relief compared to baseline) at 20 min
measure: Investigators and patients satisfaction
time frame: 30 min from start of administration
description: Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)
measure: Patient and investigators' fulfillment of expectations
time frame: 30 min from start of administration
description: Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
measure: Patients' Global Impression of Change with the treatments
time frame: Up until 30 minutes from STA
description: Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
measure: Treatment cost of pain relief
time frame: Up until 60 minutes from randomization
description: Treatment cost of pain relief, measured considering use of fungible material; need of nurse to administer iv treatments; time to discharge
measure: Safety rates of treatment emergent adverse events
time frame: Up until 14 days from STA
description: Safety rates of treatment emergent adverse events (TEAE) in both arms, including alterations in biochemical and blood count.
arm group label: Methoxyflurane
arm group type: Experimental
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 group label: Standard of Care (SoC)
arm group type: Active Comparator
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: Methoxyflurane
description: Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.
arm group label: Methoxyflurane
other name: No other interventions
intervention type: Drug
intervention name: Standard of care
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
arm group label: Standard of Care (SoC)
other name: No other interventions
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alberto Borobia, MD, PhD
role: Study Director
affiliation: La Paz University Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Hospital Universitario La Paz
investigator full name: Alberto M. Borobia
investigator title: MD, PhD
mesh term: Emergencies
mesh term: Acute Pain
mesh term: Wounds and Injuries
mesh term: Methoxyflurane
sharing ipd: Undecided