<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/NCT04462094</url>
  </required_header>
  <id_info>
    <org_study_id>UNUD-CTR-FK260620-002</org_study_id>
    <secondary_id>1143/UN14.2.2.VII.14/LT/2020</secondary_id>
    <nct_id>NCT04462094</nct_id>
  </id_info>
  <brief_title>Comparison of CRP Levels, Neutrophil Count, and Clinical Outcomes of Low Dose Ketamine Between at Anesthesia Induction and at the End of Surgery in Patients Undergo Elective Laparotomy</brief_title>
  <acronym>PRO-Ketamine</acronym>
  <official_title>Comparison of CRP Levels, Neutrophil Count, and Clinical Outcomes of Low Dose Ketamine Between at Anesthesia Induction and at the End of Surgery in Patients Undergo Elective Laparotomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Udayana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Udayana University</source>
  <oversight_info>
    <has_dmc>No</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>
      The effects of anesthesia and surgery can lead to stress responses that result in hormonal&#xD;
      and metabolic changes in the body. The immune system and the nervous system communicate both&#xD;
      ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory&#xD;
      role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major&#xD;
      surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The effects of anesthesia and surgery can lead to stress responses that result in hormonal&#xD;
      and metabolic changes in the body. The immune system and the nervous system communicate both&#xD;
      ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory&#xD;
      role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major&#xD;
      surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.&#xD;
&#xD;
      The acute analgesic effect of ketamine is generally believed to be mediated through the&#xD;
      blockade of the phencyclidine binding site of the N-methyl-d-aspartate (NMDA) receptor of&#xD;
      nociceptive neurons. Ketamine can reduce the inflammatory response marked by a decrease in&#xD;
      CRP levels to surgical trauma and can prevent secondary damage to tissues/organs that were&#xD;
      not initially affected by surgery by reducing inflammation. This also reduces postoperative&#xD;
      pain and analgesics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Actual">November 10, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</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>
    <intervention_model_description>This is a double-blind, randomized control trial. It provides a controlled care comparison between low-dose ketamine given at anesthesia induction and at the end-of-surgery.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Only care providers involved directly with the subjects in the operating room are not masked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Serum CRP level</measure>
    <time_frame>1-hour before surgery</time_frame>
    <description>Serum C-reactive protein level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum CRP level</measure>
    <time_frame>24-hours after surgery</time_frame>
    <description>Serum C-reactive protein level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>serum neutrophil-count</measure>
    <time_frame>1-hour before surgery</time_frame>
    <description>serum neutrophil-count (from a complete blood count test)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>serum neutrophil-count</measure>
    <time_frame>24-hours after surgery</time_frame>
    <description>serum neutrophil-count (from a complete blood count test)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>VAS (visual analog score)</measure>
    <time_frame>first 24 hours after the surgery</time_frame>
    <description>minimum=0; maximum=10; higher score corresponds to more severe pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>morphine consumption (mg)</measure>
    <time_frame>first 24 hours after the surgery</time_frame>
    <description>total morphine consumption in 24 hours after the surgery</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>General Anesthesia</condition>
  <condition>Laparotomy</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>End-of-surgery</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at the end of surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Induction</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at induction</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine 0.3 mg/kg at end-of-surgery</intervention_name>
    <description>Ketamine 0.3 mg/kg at end-of-surgery (intravenously)</description>
    <arm_group_label>End-of-surgery</arm_group_label>
    <arm_group_label>Induction</arm_group_label>
    <other_name>Group E</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine 0.3 mg/kg at anesthesia induction</intervention_name>
    <description>Ketamine 0.3 mg/kg at anesthesia induction (intravenously)</description>
    <arm_group_label>End-of-surgery</arm_group_label>
    <arm_group_label>Induction</arm_group_label>
    <other_name>Group I</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients undergoing elective laparotomy with general anesthesia at Sanglah Hospital&#xD;
             from July to September 2020.&#xD;
&#xD;
          2. Patients aged 18-65 years.&#xD;
&#xD;
          3. Patient physical status American American Society of Anesthesiologist (ASA) 1 and 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindication to ketamine.&#xD;
&#xD;
          2. Allergy to morphine&#xD;
&#xD;
          3. Presence of cardiorespiratory chronic diseases.&#xD;
&#xD;
          4. Presence of autoimmune diseases.&#xD;
&#xD;
          5. History of the central nervous system or psychiatric disorders.&#xD;
&#xD;
          6. BMI &lt;18.5 kg/m2 or ≥30 kg/m2.&#xD;
&#xD;
          7. A history of chronic pain killer medications (such as opioid or non-steroidal anti-&#xD;
             inflammatory drugs)&#xD;
&#xD;
        Drop Out Criteria&#xD;
&#xD;
          1. Patients with class 3 bleeding during the surgery&#xD;
&#xD;
          2. Patients with more than 5-hours duration of surgery&#xD;
&#xD;
          3. Patients need mechanical ventilation after the surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tjokorda GA Senapathi, Dr</last_name>
    <role>Study Chair</role>
    <affiliation>Udayana University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christopher Ryalino, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Udayana University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Made SP Adi, Dr</last_name>
    <role>Study Director</role>
    <affiliation>Udayana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sanglah General Hospital</name>
      <address>
        <city>Denpasar</city>
        <state>Bali</state>
        <zip>80114</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>November 9, 2020</last_update_submitted>
  <last_update_submitted_qc>November 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Udayana University</investigator_affiliation>
    <investigator_full_name>Christopher Ryalino</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>stress response</keyword>
  <keyword>infammation</keyword>
  <keyword>general anesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</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/NCT04462094
org study id: UNUD-CTR-FK260620-002
secondary id: 1143/UN14.2.2.VII.14/LT/2020
nct id: NCT04462094
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The effects of anesthesia and surgery can lead to stress responses that result in hormonal
      and metabolic changes in the body. The immune system and the nervous system communicate both
      ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory
      role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major
      surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.
The effects of anesthesia and surgery can lead to stress responses that result in hormonal
      and metabolic changes in the body. The immune system and the nervous system communicate both
      ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory
      role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major
      surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.

      The acute analgesic effect of ketamine is generally believed to be mediated through the
      blockade of the phencyclidine binding site of the N-methyl-d-aspartate (NMDA) receptor of
      nociceptive neurons. Ketamine can reduce the inflammatory response marked by a decrease in
      CRP levels to surgical trauma and can prevent secondary damage to tissues/organs that were
      not initially affected by surgery by reducing inflammation. This also reduces postoperative
      pain and analgesics.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a double-blind, randomized control trial. It provides a controlled care comparison between low-dose ketamine given at anesthesia induction and at the end-of-surgery.
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Only care providers involved directly with the subjects in the operating room are not masked.
measure: Serum CRP level
time frame: 1-hour before surgery
description: Serum C-reactive protein level
measure: Serum CRP level
time frame: 24-hours after surgery
description: Serum C-reactive protein level
measure: serum neutrophil-count
time frame: 1-hour before surgery
description: serum neutrophil-count (from a complete blood count test)
measure: serum neutrophil-count
time frame: 24-hours after surgery
description: serum neutrophil-count (from a complete blood count test)
measure: VAS (visual analog score)
time frame: first 24 hours after the surgery
description: minimum=0; maximum=10; higher score corresponds to more severe pain
measure: morphine consumption (mg)
time frame: first 24 hours after the surgery
description: total morphine consumption in 24 hours after the surgery
arm group label: End-of-surgery
arm group type: Active Comparator
description: Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at the end of surgery
arm group label: Induction
arm group type: Placebo Comparator
description: Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at induction
intervention type: Drug
intervention name: Ketamine 0.3 mg/kg at end-of-surgery
description: Ketamine 0.3 mg/kg at end-of-surgery (intravenously)
arm group label: End-of-surgery
arm group label: Induction
other name: Group E
intervention type: Drug
intervention name: Ketamine 0.3 mg/kg at anesthesia induction
description: Ketamine 0.3 mg/kg at anesthesia induction (intravenously)
arm group label: End-of-surgery
arm group label: Induction
other name: Group I
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Tjokorda GA Senapathi, Dr
role: Study Chair
affiliation: Udayana University
last name: Christopher Ryalino, Dr
role: Principal Investigator
affiliation: Udayana University
last name: Made SP Adi, Dr
role: Study Director
affiliation: Udayana University
facility: 
country: Indonesia
responsible party type: Principal Investigator
investigator affiliation: Udayana University
investigator full name: Christopher Ryalino
investigator title: Principal Investigator
mesh term: Inflammation
mesh term: Ketamine
sharing ipd: No