<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/NCT01731184</url>
  </required_header>
  <id_info>
    <org_study_id>Morphine Midazolam</org_study_id>
    <nct_id>NCT01731184</nct_id>
  </id_info>
  <brief_title>Morphine-Midazolam in Pre-hospital Traumatic Patients With Severe Acute Pain</brief_title>
  <acronym>Morphine-Mida</acronym>
  <official_title>Randomized Double-blind Placebo-controlled Trial: Administration of Morphine-Placebo vs. Morphine-Midazolam in Pre-hospital Traumatic Patients With Severe Acute Pain.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier de Cornouaille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier de Cornouaille</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Administration of midazolam with morphine in patients with severe acute pain is a routine&#xD;
      practice in the management of pre- and post-operative patients but has not been evaluated in&#xD;
      pre-hospital setting. The investigators aim to evaluate the co-analgesic effect of midazolam&#xD;
      in the pre-hospital management of traumatic patients with severe acute pain.&#xD;
&#xD;
      In a multicenter prospective randomized double-blind placebo-controlled trial, the&#xD;
      investigators would like to compare the analgesic effect and safety of the intravenous&#xD;
      morphine 0.10 mg/kg and midazolam 0.04 mg/kg with the intravenous morphine 0.10 mg/kg and&#xD;
      placebo in pre-hospital traumatic adults. Assessment will be done at the baseline using a&#xD;
      validated numeric rating scale (NRS).&#xD;
&#xD;
      The primary outcome will be the proportion of patients with a pain score less than or equal&#xD;
      to 3 after 20 minutes. The secondary outcomes will be in between-group comparison of: the&#xD;
      treatment safety, pain score every 5 minutes during 30 minutes and the total morphine dose&#xD;
      required until obtaining a pain score less than or equal to 3.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patient will be included in pre-hospital setting. They must have an acute pain NRS greater&#xD;
      than or equal to 6 from a traumatic origin. The participation of the study for each patient&#xD;
      will be the time of the pre-hospital setting. The study will stop when the patient arrives at&#xD;
      the hospital.&#xD;
&#xD;
      Patient will be randomized after obtaining an informed consent. Then, the nurse will&#xD;
      administered intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg or intravenous morphine&#xD;
      0.10 mg/kg and placebo.&#xD;
&#xD;
      Only the nurse will be aware of the treatment received by the patient. Every 5 minutes, life&#xD;
      constants and pain score will be recorded on the case report form.&#xD;
&#xD;
      Assessment will be done at the baseline using a validated numeric rating scale. The primary&#xD;
      outcome will be the proportion of patients with a pain score less than or equal to 3 after 20&#xD;
      minutes. The secondary outcomes will be in between-group comparison of: the treatment safety,&#xD;
      pain score every 5 minutes during 30 minutes and the total morphine dose required until&#xD;
      obtaining a pain score less than or equal to 3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2006</start_date>
  <completion_date type="Actual">September 2010</completion_date>
  <primary_completion_date type="Actual">September 2009</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain score</measure>
    <time_frame>20 minutes</time_frame>
    <description>The primary outcome was the proportion of patients with a pain score less than or equal to 3 after 20 minutes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pain evolution</measure>
    <time_frame>every 5 minutes and at the end of the study</time_frame>
    <description>The secondary outcomes were in between-group comparison of:&#xD;
- pain score every 5 minutes during 30 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>during all the study</time_frame>
    <description>The secondary outcomes were in between-group comparison of:&#xD;
- The treatment safety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morphine total dose</measure>
    <time_frame>During all the study</time_frame>
    <description>The secondary outcomes were in between-group comparison of:&#xD;
- The total morphine dose required until obtaining pain score less than or equal to 3</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Acute Traumatic Pain</condition>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).</description>
    <arm_group_label>Midazolam</arm_group_label>
    <other_name>Midazolam (hypnovel)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 to 70 years old&#xD;
&#xD;
          -  conscient with spontaneous ventilation&#xD;
&#xD;
          -  acute pain with an traumatic origin : pain escape superior or egal to 6/10&#xD;
&#xD;
          -  taking care by French reanimation and urgency mobile services (Smur).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  younger than 18 years old or older than 70 years old&#xD;
&#xD;
          -  chronical respiratory insufficiency&#xD;
&#xD;
          -  severe hepatocellular insufficiency,&#xD;
&#xD;
          -  myasthenia&#xD;
&#xD;
          -  known allergy to morphine or benzodiazepin,&#xD;
&#xD;
          -  already treated for a chronical pain,&#xD;
&#xD;
          -  pregnant women&#xD;
&#xD;
          -  treated by morphine&#xD;
&#xD;
          -  patient unable to evaluate his/her pain&#xD;
&#xD;
          -  any acute and severe hemodynamic, respiratory or neurologic deficiency&#xD;
&#xD;
          -  needed an local analgesia&#xD;
&#xD;
          -  patient who received an other antalgic treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yannick AUFFRET, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier intercommunal de Cornouaille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Brest</name>
      <address>
        <city>Brest</city>
        <zip>29609</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de Carhaix</name>
      <address>
        <city>Carhaix</city>
        <zip>29270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hpistalier Intercommunal de Cornouaille</name>
      <address>
        <city>Quimper</city>
        <zip>29000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>November 16, 2012</last_update_submitted>
  <last_update_submitted_qc>November 16, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 21, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute traumatic pain, pre-hospital setting, Midazolam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01731184
org study id: Morphine Midazolam
nct id: NCT01731184
lead sponsor: 
collaborator: 
has dmc: No
Administration of midazolam with morphine in patients with severe acute pain is a routine
      practice in the management of pre- and post-operative patients but has not been evaluated in
      pre-hospital setting. The investigators aim to evaluate the co-analgesic effect of midazolam
      in the pre-hospital management of traumatic patients with severe acute pain.

      In a multicenter prospective randomized double-blind placebo-controlled trial, the
      investigators would like to compare the analgesic effect and safety of the intravenous
      morphine 0.10 mg/kg and midazolam 0.04 mg/kg with the intravenous morphine 0.10 mg/kg and
      placebo in pre-hospital traumatic adults. Assessment will be done at the baseline using a
      validated numeric rating scale (NRS).

      The primary outcome will be the proportion of patients with a pain score less than or equal
      to 3 after 20 minutes. The secondary outcomes will be in between-group comparison of: the
      treatment safety, pain score every 5 minutes during 30 minutes and the total morphine dose
      required until obtaining a pain score less than or equal to 3.
Patient will be included in pre-hospital setting. They must have an acute pain NRS greater
      than or equal to 6 from a traumatic origin. The participation of the study for each patient
      will be the time of the pre-hospital setting. The study will stop when the patient arrives at
      the hospital.

      Patient will be randomized after obtaining an informed consent. Then, the nurse will
      administered intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg or intravenous morphine
      0.10 mg/kg and placebo.

      Only the nurse will be aware of the treatment received by the patient. Every 5 minutes, life
      constants and pain score will be recorded on the case report form.

      Assessment will be done at the baseline using a validated numeric rating scale. The primary
      outcome will be the proportion of patients with a pain score less than or equal to 3 after 20
      minutes. The secondary outcomes will be in between-group comparison of: the treatment safety,
      pain score every 5 minutes during 30 minutes and the total morphine dose required until
      obtaining a pain score less than or equal to 3.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Pain score
time frame: 20 minutes
description: The primary outcome was the proportion of patients with a pain score less than or equal to 3 after 20 minutes
measure: pain evolution
time frame: every 5 minutes and at the end of the study
description: The secondary outcomes were in between-group comparison of:
- pain score every 5 minutes during 30 minutes
measure: Safety
time frame: during all the study
description: The secondary outcomes were in between-group comparison of:
- The treatment safety
measure: Morphine total dose
time frame: During all the study
description: The secondary outcomes were in between-group comparison of:
- The total morphine dose required until obtaining pain score less than or equal to 3
arm group label: Midazolam
arm group type: Experimental
description: Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).
intervention type: Drug
intervention name: Midazolam
description: Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).
arm group label: Midazolam
other name: Midazolam (hypnovel)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yannick AUFFRET, Dr
role: Principal Investigator
affiliation: Centre Hospitalier intercommunal de Cornouaille
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Acute Pain
mesh term: Midazolam