<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/NCT03019835</url>
  </required_header>
  <id_info>
    <org_study_id>B406201629996</org_study_id>
    <secondary_id>U1111-1190-7993</secondary_id>
    <nct_id>NCT03019835</nct_id>
  </id_info>
  <brief_title>Can we Antagonize Mivacurium With Neostigmine ?</brief_title>
  <official_title>Can we Antagonize Mivacurium With Neostigmine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université Libre de Bruxelles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Université Libre de Bruxelles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The antagonism of neuromuscular blocking agents (NMBA) (or curares), as well as the&#xD;
      antagonism of other drugs used in anesthesia, is a major challenge for the speciality.&#xD;
&#xD;
      Residual paralysis is indeed a risk factor for post-operative morbidity and mortality and&#xD;
      antagonization of curares at the end of the procedure is associated with a reduction in&#xD;
      mortality .&#xD;
&#xD;
      Its use should be as large as possible and its contraindications are extremely rare.&#xD;
&#xD;
      The antagonism of the NMBA reduces the duration of the neuromuscular block and the&#xD;
      complications that are associated .&#xD;
&#xD;
      In this study, the investigators use mivacurium (or Mivacron) as non-depolarizing curare and&#xD;
      neostigmine as an antagonist.&#xD;
&#xD;
      Neostigmine reduces the duration of the neuromuscular block induced by mivacurium, By&#xD;
      reducing the breakdown of acetylcholine, neostigmine induces an increase in acetylcholine in&#xD;
      the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular&#xD;
      blocking agents, and reverses the neuromuscular blockade.&#xD;
&#xD;
      But the use of neostigmine in current practice is not very widespread in this clinical&#xD;
      situation.&#xD;
&#xD;
      The reduction in the duration of the block is significant in comparison with a spontaneous&#xD;
      recovery .&#xD;
&#xD;
      Moreover, spontaneous recovery is not always complete and sometimes very long.&#xD;
&#xD;
      Nevertheless, its action is effective and this study could support this use but also specify&#xD;
      the duration and the quality of the return to normal of the neuromuscular transmission.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">April 22, 2017</completion_date>
  <primary_completion_date type="Actual">April 22, 2017</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in TOF ( Train Of Four) measure</measure>
    <time_frame>for each patient, measure of Train Of Four at 3, 6, 9, 12, 15 minutes</time_frame>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Mivacurium</condition>
  <condition>Neostigmine</condition>
  <condition>Residual Paralysis</condition>
  <arm_group>
    <arm_group_label>GROUP 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 1 response of 4 in TOF mode (Train Of Four)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GROUP 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 2 response of 4 in TOF mode (Train Of Four)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GROUP 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 3 response of 4 in TOF mode (Train Of Four)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GROUP 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 4 response of 4 in TOF mode (Train Of Four)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CONTROL</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A control group : not receiving an antagonist (spontaneous recovery)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neostigmine (40 mcg / kg) at different time of neuromuscular block's recovery</intervention_name>
    <arm_group_label>GROUP 1</arm_group_label>
    <arm_group_label>GROUP 2</arm_group_label>
    <arm_group_label>GROUP 3</arm_group_label>
    <arm_group_label>GROUP 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Spontaneous recovery</intervention_name>
    <description>just measuring the Train Of Four at 3 6 9 12 and 15 minutes and measure the Train Of Four Ratio</description>
    <arm_group_label>CONTROL</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients American Society of Anesthesiologists (ASA) 1 to 3&#xD;
&#xD;
          -  Absence of neuromuscular disease, renal and hepatic insufficiency&#xD;
&#xD;
          -  Absence of medication that could interfere with the mediators of the neuromuscular&#xD;
             junction&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bronchial asthma&#xD;
&#xD;
          -  Parkinson disease&#xD;
&#xD;
          -  BMI&gt; 35&#xD;
&#xD;
          -  Known hypersensitivity to neostigmine or to any of the excipients of Neostigmine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Michel Baurain</name>
      <address>
        <city>Bruxelles Capitale</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <results_reference>
    <citation>Baurain MJ, Dernovoi BS, d'Hollander AA, Hennart DA. Comparison of neostigmine-induced recovery with spontaneous recovery from mivacurium-induced neuromuscular block. Br J Anaesth. 1994 Dec;73(6):791-4. doi: 10.1093/bja/73.6.791.</citation>
    <PMID>7880668</PMID>
  </results_reference>
  <results_reference>
    <citation>Baillard C, Clec'h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM. Postoperative residual neuromuscular block: a survey of management. Br J Anaesth. 2005 Nov;95(5):622-6. doi: 10.1093/bja/aei240. Epub 2005 Sep 23.</citation>
    <PMID>16183681</PMID>
  </results_reference>
  <results_reference>
    <citation>Szenohradszky J, Fogarty D, Kirkegaard-Nielsen H, Brown R, Sharma ML, Fisher DM. Effect of edrophonium and neostigmine on the pharmacokinetics and neuromuscular effects of mivacurium. Anesthesiology. 2000 Mar;92(3):708-14. doi: 10.1097/00000542-200003000-00015.</citation>
    <PMID>10719950</PMID>
  </results_reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>May 17, 2017</last_update_submitted>
  <last_update_submitted_qc>May 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Université Libre de Bruxelles</investigator_affiliation>
    <investigator_full_name>JOHN NICOLARDOT</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>mivacurium</keyword>
  <keyword>neostigmine</keyword>
  <keyword>antagonism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neostigmine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.ncbi.nlm.nih.gov/pubmed/7880668</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03019835
org study id: B406201629996
secondary id: U1111-1190-7993
nct id: NCT03019835
lead sponsor: 
has dmc: No
The antagonism of neuromuscular blocking agents (NMBA) (or curares), as well as the
      antagonism of other drugs used in anesthesia, is a major challenge for the speciality.

      Residual paralysis is indeed a risk factor for post-operative morbidity and mortality and
      antagonization of curares at the end of the procedure is associated with a reduction in
      mortality .

      Its use should be as large as possible and its contraindications are extremely rare.

      The antagonism of the NMBA reduces the duration of the neuromuscular block and the
      complications that are associated .

      In this study, the investigators use mivacurium (or Mivacron) as non-depolarizing curare and
      neostigmine as an antagonist.

      Neostigmine reduces the duration of the neuromuscular block induced by mivacurium, By
      reducing the breakdown of acetylcholine, neostigmine induces an increase in acetylcholine in
      the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular
      blocking agents, and reverses the neuromuscular blockade.

      But the use of neostigmine in current practice is not very widespread in this clinical
      situation.

      The reduction in the duration of the block is significant in comparison with a spontaneous
      recovery .

      Moreover, spontaneous recovery is not always complete and sometimes very long.

      Nevertheless, its action is effective and this study could support this use but also specify
      the duration and the quality of the return to normal of the neuromuscular transmission.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
measure: Change in TOF ( Train Of Four) measure
time frame: for each patient, measure of Train Of Four at 3, 6, 9, 12, 15 minutes
arm group label: GROUP 1
arm group type: Active Comparator
description: A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 1 response of 4 in TOF mode (Train Of Four)
arm group label: GROUP 2
arm group type: Active Comparator
description: A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 2 response of 4 in TOF mode (Train Of Four)
arm group label: GROUP 3
arm group type: Active Comparator
description: A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 3 response of 4 in TOF mode (Train Of Four)
arm group label: GROUP 4
arm group type: Active Comparator
description: A group receiving neostigmine (40 mcg / kg) when the block Neuromuscular block's recovery measured by acceleromyography is 4 response of 4 in TOF mode (Train Of Four)
arm group label: CONTROL
arm group type: Active Comparator
description: A control group : not receiving an antagonist (spontaneous recovery)
intervention type: Drug
intervention name: Neostigmine (40 mcg / kg) at different time of neuromuscular block's recovery
arm group label: GROUP 1
arm group label: GROUP 2
arm group label: GROUP 3
arm group label: GROUP 4
intervention type: Other
intervention name: Spontaneous recovery
description: just measuring the Train Of Four at 3 6 9 12 and 15 minutes and measure the Train Of Four Ratio
arm group label: CONTROL
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Belgium
citation: Baurain MJ, Dernovoi BS, d'Hollander AA, Hennart DA. Comparison of neostigmine-induced recovery with spontaneous recovery from mivacurium-induced neuromuscular block. Br J Anaesth. 1994 Dec;73(6):791-4. doi: 10.1093/bja/73.6.791.
PMID: 7880668
citation: Baillard C, Clec'h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM. Postoperative residual neuromuscular block: a survey of management. Br J Anaesth. 2005 Nov;95(5):622-6. doi: 10.1093/bja/aei240. Epub 2005 Sep 23.
PMID: 16183681
citation: Szenohradszky J, Fogarty D, Kirkegaard-Nielsen H, Brown R, Sharma ML, Fisher DM. Effect of edrophonium and neostigmine on the pharmacokinetics and neuromuscular effects of mivacurium. Anesthesiology. 2000 Mar;92(3):708-14. doi: 10.1097/00000542-200003000-00015.
PMID: 10719950
responsible party type: Principal Investigator
investigator affiliation: Université Libre de Bruxelles
investigator full name: JOHN NICOLARDOT
investigator title: MD
mesh term: Paralysis
mesh term: Neostigmine
sharing ipd: Yes
study doc: 