<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/NCT02992938</url>
  </required_header>
  <id_info>
    <org_study_id>803/16</org_study_id>
    <nct_id>NCT02992938</nct_id>
  </id_info>
  <brief_title>Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia</brief_title>
  <official_title>Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia: Randomize Double Blind Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chile</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chile</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Remifentanil is a potent opioid widely used during the administration of general anesthesia.&#xD;
      There is a lot of evidence that suggest that the used of remifentanil is associated with the&#xD;
      development of hyperalgesia (a reduction of nociceptive thresholds). However, the mechanism&#xD;
      of this hyperalgesia is not fully understood.&#xD;
&#xD;
      Recently, it was demonstrated that the disruption of the Cl- homeostasis could be involved.&#xD;
      Interestingly, this was prevented in a murine model with the administration of Acetazolamide,&#xD;
      a carbonic anhydrase inhibitor. In our clinical trial we will try to determine if the&#xD;
      preoperative administration of acetazolamide could prevent the hyperalgesia induced by&#xD;
      remifentanil in patients scheduled for thyroidectomy with general anesthesia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">September 28, 2018</completion_date>
  <primary_completion_date type="Actual">September 28, 2018</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the mechanical pain threshold in an area distant to the site of the injury</measure>
    <time_frame>12-18 hours after the end of the surgery</time_frame>
    <description>The threshold will be determine using von Frey monofilaments before the surgery and will be compared 12-18 hours after the end of the surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the mechanical pain threshold in an area distant to the site of the injury</measure>
    <time_frame>2 hours after the end of the surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain</measure>
    <time_frame>The first postoperative day</time_frame>
    <description>A visual analogue scale (VAS; 0, no pain; 100, worst poss- ible pain) will be used to assess pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morphine consumption</measure>
    <time_frame>The first postoperative day</time_frame>
    <description>Morphine consumption with a patient controlled analgesia (PCA) in mg</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Hyperalgesia</condition>
  <condition>Opioid-Related Disorders</condition>
  <arm_group>
    <arm_group_label>Acetazolamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>An oral tablet without active principle acetazolamide but with the same physical characteristics will be administered the day of the surgery 2 hours before anesthesia induction</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetazolamide</intervention_name>
    <arm_group_label>Acetazolamide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients scheduled for thyroidectomy with general anesthesia in the University of&#xD;
             Chile Clinical Hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients ASA III y IV&#xD;
&#xD;
          -  Chronic pain history&#xD;
&#xD;
          -  Drug and alcohol abuse&#xD;
&#xD;
          -  Chronic use of opioid and sedatives&#xD;
&#xD;
          -  Neuropsychiatric illness&#xD;
&#xD;
          -  NSAID and other analgesics used the 48 hours previous to the surgery&#xD;
&#xD;
          -  CMI &gt; 30&#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>Rodrigo Gutierrez, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anesthesia Department, University of Chile</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonello Penna, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anesthesia Department, University of Chile</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of Medicine, University of Chile</name>
      <address>
        <city>Santiago</city>
        <state>Metropolitana</state>
        <zip>7563215</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <results_reference>
    <citation>Ferrini F, Trang T, Mattioli TA, Laffray S, Del'Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci. 2013 Feb;16(2):183-92. doi: 10.1038/nn.3295. Epub 2013 Jan 6.</citation>
    <PMID>23292683</PMID>
  </results_reference>
  <results_reference>
    <citation>Echevarria G, Elgueta F, Fierro C, Bugedo D, Faba G, Iniguez-Cuadra R, Munoz HR, Cortinez LI. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth. 2011 Dec;107(6):959-65. doi: 10.1093/bja/aer323. Epub 2011 Sep 28.</citation>
    <PMID>21965050</PMID>
  </results_reference>
  <results_reference>
    <citation>Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8.</citation>
    <PMID>14581110</PMID>
  </results_reference>
  <results_reference>
    <citation>Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005 Jul;103(1):147-55. doi: 10.1097/00000542-200507000-00022.</citation>
    <PMID>15983467</PMID>
  </results_reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 11, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Chile</investigator_affiliation>
    <investigator_full_name>Rodrigo Gutiérrez</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Opioid hyperalgesia</keyword>
  <keyword>Acetazolamide</keyword>
  <keyword>Remifentanil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperalgesia</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetazolamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02992938
org study id: 803/16
nct id: NCT02992938
lead sponsor: 
has dmc: Yes
Remifentanil is a potent opioid widely used during the administration of general anesthesia.
      There is a lot of evidence that suggest that the used of remifentanil is associated with the
      development of hyperalgesia (a reduction of nociceptive thresholds). However, the mechanism
      of this hyperalgesia is not fully understood.

      Recently, it was demonstrated that the disruption of the Cl- homeostasis could be involved.
      Interestingly, this was prevented in a murine model with the administration of Acetazolamide,
      a carbonic anhydrase inhibitor. In our clinical trial we will try to determine if the
      preoperative administration of acetazolamide could prevent the hyperalgesia induced by
      remifentanil in patients scheduled for thyroidectomy with general anesthesia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in the mechanical pain threshold in an area distant to the site of the injury
time frame: 12-18 hours after the end of the surgery
description: The threshold will be determine using von Frey monofilaments before the surgery and will be compared 12-18 hours after the end of the surgery
measure: Change in the mechanical pain threshold in an area distant to the site of the injury
time frame: 2 hours after the end of the surgery
measure: Postoperative pain
time frame: The first postoperative day
description: A visual analogue scale (VAS; 0, no pain; 100, worst poss- ible pain) will be used to assess pain
measure: Morphine consumption
time frame: The first postoperative day
description: Morphine consumption with a patient controlled analgesia (PCA) in mg
arm group label: Acetazolamide
arm group type: Experimental
description: 250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction
arm group label: Placebo
arm group type: Placebo Comparator
description: An oral tablet without active principle acetazolamide but with the same physical characteristics will be administered the day of the surgery 2 hours before anesthesia induction
intervention type: Drug
intervention name: Acetazolamide
arm group label: Acetazolamide
intervention type: Drug
intervention name: Placebo Oral Tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rodrigo Gutierrez, MD
role: Principal Investigator
affiliation: Anesthesia Department, University of Chile
last name: Antonello Penna, MD PhD
role: Principal Investigator
affiliation: Anesthesia Department, University of Chile
facility: 
country: Chile
citation: Ferrini F, Trang T, Mattioli TA, Laffray S, Del'Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci. 2013 Feb;16(2):183-92. doi: 10.1038/nn.3295. Epub 2013 Jan 6.
PMID: 23292683
citation: Echevarria G, Elgueta F, Fierro C, Bugedo D, Faba G, Iniguez-Cuadra R, Munoz HR, Cortinez LI. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth. 2011 Dec;107(6):959-65. doi: 10.1093/bja/aer323. Epub 2011 Sep 28.
PMID: 21965050
citation: Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8.
PMID: 14581110
citation: Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005 Jul;103(1):147-55. doi: 10.1097/00000542-200507000-00022.
PMID: 15983467
responsible party type: Principal Investigator
investigator affiliation: University of Chile
investigator full name: Rodrigo Gutiérrez
investigator title: MD
mesh term: Hyperalgesia
mesh term: Opioid-Related Disorders
mesh term: Acetazolamide
sharing ipd: No