<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/NCT03793075</url>
  </required_header>
  <id_info>
    <org_study_id>R/18.09.287</org_study_id>
    <nct_id>NCT03793075</nct_id>
  </id_info>
  <brief_title>Ketamine Versus Propofol Effect on the Immune-mediatory Response for Abdominal Surgery</brief_title>
  <official_title>Immune-mediatory Response of Intravenous Ketamine Versus Propofol for Major Abdominal Surgeries: a Prospective Randomized Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Host systemic responses to vigorous stimuli as trauma, surgical tissue injury, anesthesia and&#xD;
      post-operative pain, leads to release a variety of pro-inflammatory cytokines including&#xD;
      interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages Thus, the&#xD;
      rise of IL-6 is regarded as an early marker of tissue damage and its rise proportional to the&#xD;
      degree of tissue damage .&#xD;
&#xD;
      It has been demonstrated that systemic responses to stress may be modified by the anesthetic&#xD;
      technique used . Total intravenous anesthesia (TIVA) especially propofol based greatly&#xD;
      suppresses the stress response induced by surgery when compared to inhalation by lowering&#xD;
      cortisol levels.&#xD;
&#xD;
      Ketamine has the ability to modulate (modify) inflammation . Even the sub-anesthetic doses of&#xD;
      ketamine in animal models were even provided to have an effect on the inflammatory response&#xD;
      system in the central nervous system&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The release a variety of pro-inflammatory cytokines including tumor necrosis factor-α&#xD;
      (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages&#xD;
      due to surgical trauma or anesthesia .&#xD;
&#xD;
      IL-6 is constantly found in the peripheral blood and rapidly within few minutes unlike other&#xD;
      pro inflammatory mediators. Thus, the rise of IL-6 is regarded as an early marker of tissue&#xD;
      damage and IL-6 levels are proportional to the degree of tissue damage . The two major&#xD;
      actions of IL-6 are having a key role in regulating stress responses by activating the&#xD;
      hypothalamic-pituitary- adrenal (HPA) axis and synthesizing fibrinogen (which is necessary&#xD;
      for the acute-phase response) serving as a growth factor for activated B-cells .&#xD;
&#xD;
      While appropriate inflammatory reactions are advantageous and essential for wound healing and&#xD;
      host defense against microorganisms, excessive immune responses can be detrimental. The&#xD;
      released mediators prompt systemic endocrine, immunological and metabolic responses result in&#xD;
      increased pain sensitivity, altered metabolism, hyperthermia and greater secretion of liver&#xD;
      acute phase proteins and stress hormones, so yields unstable patient's hemodynamic status&#xD;
&#xD;
      Propofol was documented to have an advantage in terms of inflammatory and immunomodulatory&#xD;
      effects through significant effect on TNF-α, IL-6 and IL-10 release .&#xD;
&#xD;
      Ketamine has the ability to modulate (modify) inflammation and this is why it is recommended&#xD;
      in patients with sepsis undergoing surgery . This may be possibly related with the variations&#xD;
      in TNF-α and nuclear factor-κB expression . Even the sub-anesthetic doses of ketamine in&#xD;
      animal models were even provided to have an effect on the inflammatory response system in the&#xD;
      central nervous system which is involved in its therapeutic effect on depression (Yang-2 et&#xD;
      al., 2013).&#xD;
&#xD;
      This study will be conducted to compare between the intravenous infusion of ketamine against&#xD;
      the intravenous infusion of propofol during general anesthesia in patients undergoing major&#xD;
      abdominal surgeries.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 10, 2019</start_date>
  <completion_date type="Anticipated">August 15, 2019</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2019</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>Participating subject will be divided equally and randomly into two groups.The first group is propofol group while the second is the ketamine group</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>Double -blinded ( masking of both participant and care provider)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Serum level of interleukin 6 (IL-6)</measure>
    <time_frame>The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>picogram/milliliter using ELISA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum level of interleukin IL-1β (IL-1β)</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>picogram/milliliter using ELSA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute neutrophil count</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>Number multiplied by 1000/micro liter,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total leukocyte count</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>Number multiplied by 1000/micro liter ,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutrophil-lymphocyte ratio (N/L ratio)</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Cortisol level</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>micro-gram /deciliter by immunoassays techniques.measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein serum level</measure>
    <time_frame>The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative</time_frame>
    <description>milgram/liter using ELISA technique. measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Major Abdominal Surgery</condition>
  <arm_group>
    <arm_group_label>Propofol group (P)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of propofol 17 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine group ((K)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of ketamine 5 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>ketamine 5 mcg/kg/min will be used as intravenous anesthetic infusion</description>
    <arm_group_label>Ketamine group ((K)</arm_group_label>
    <other_name>ketalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>propofol 17 mcg /kg/min</description>
    <arm_group_label>Propofol group (P)</arm_group_label>
    <other_name>diprivan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective major abdominal surgeries with median incision with right or left extension.&#xD;
&#xD;
          -  ASA -physical status I -II&#xD;
&#xD;
          -  aged from 18 till 70 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  body mass index more than 35 kg/m2,&#xD;
&#xD;
          -  Patients having severe cardiovascular, respiratory, hepatic, renal, Endocrinol&#xD;
             disorders, malignant&#xD;
&#xD;
          -  Patients having chronic inflammatory diseases&#xD;
&#xD;
          -  Patients received suppressant drugs in the 6 weeks before surgery.&#xD;
&#xD;
          -  Any known allergy or any contraindications to anesthetic drugs;&#xD;
&#xD;
          -  patient refusal,&#xD;
&#xD;
          -  The usage of anti- emetic drug 24 hours before operation&#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>Reem Abdelraouf, lecturer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mansoura University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Reem Abdelraouf, lecturer</last_name>
    <phone>01006151100</phone>
    <email>reemraouf64@gmail.com</email>
  </overall_contact>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 30, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>January 3, 2019</last_update_submitted>
  <last_update_submitted_qc>January 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University Hospital</investigator_affiliation>
    <investigator_full_name>Abdelraouf Elsharkawy</investigator_full_name>
    <investigator_title>Lecturer of anesthesia and surgical intensive care</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Propofol</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/NCT03793075
org study id: R/18.09.287
nct id: NCT03793075
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Host systemic responses to vigorous stimuli as trauma, surgical tissue injury, anesthesia and
      post-operative pain, leads to release a variety of pro-inflammatory cytokines including
      interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages Thus, the
      rise of IL-6 is regarded as an early marker of tissue damage and its rise proportional to the
      degree of tissue damage .

      It has been demonstrated that systemic responses to stress may be modified by the anesthetic
      technique used . Total intravenous anesthesia (TIVA) especially propofol based greatly
      suppresses the stress response induced by surgery when compared to inhalation by lowering
      cortisol levels.

      Ketamine has the ability to modulate (modify) inflammation . Even the sub-anesthetic doses of
      ketamine in animal models were even provided to have an effect on the inflammatory response
      system in the central nervous system
The release a variety of pro-inflammatory cytokines including tumor necrosis factor-α
      (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages
      due to surgical trauma or anesthesia .

      IL-6 is constantly found in the peripheral blood and rapidly within few minutes unlike other
      pro inflammatory mediators. Thus, the rise of IL-6 is regarded as an early marker of tissue
      damage and IL-6 levels are proportional to the degree of tissue damage . The two major
      actions of IL-6 are having a key role in regulating stress responses by activating the
      hypothalamic-pituitary- adrenal (HPA) axis and synthesizing fibrinogen (which is necessary
      for the acute-phase response) serving as a growth factor for activated B-cells .

      While appropriate inflammatory reactions are advantageous and essential for wound healing and
      host defense against microorganisms, excessive immune responses can be detrimental. The
      released mediators prompt systemic endocrine, immunological and metabolic responses result in
      increased pain sensitivity, altered metabolism, hyperthermia and greater secretion of liver
      acute phase proteins and stress hormones, so yields unstable patient's hemodynamic status

      Propofol was documented to have an advantage in terms of inflammatory and immunomodulatory
      effects through significant effect on TNF-α, IL-6 and IL-10 release .

      Ketamine has the ability to modulate (modify) inflammation and this is why it is recommended
      in patients with sepsis undergoing surgery . This may be possibly related with the variations
      in TNF-α and nuclear factor-κB expression . Even the sub-anesthetic doses of ketamine in
      animal models were even provided to have an effect on the inflammatory response system in the
      central nervous system which is involved in its therapeutic effect on depression (Yang-2 et
      al., 2013).

      This study will be conducted to compare between the intravenous infusion of ketamine against
      the intravenous infusion of propofol during general anesthesia in patients undergoing major
      abdominal surgeries.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participating subject will be divided equally and randomly into two groups.The first group is propofol group while the second is the ketamine group
primary purpose: Supportive Care
masking: Double (Participant, Care Provider)
masking description: Double -blinded ( masking of both participant and care provider)
measure: Serum level of interleukin 6 (IL-6)
time frame: The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative
description: picogram/milliliter using ELISA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: Serum level of interleukin IL-1β (IL-1β)
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: picogram/milliliter using ELSA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: Absolute neutrophil count
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: Number multiplied by 1000/micro liter,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: Total leukocyte count
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: Number multiplied by 1000/micro liter ,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: Neutrophil-lymphocyte ratio (N/L ratio)
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: Serum Cortisol level
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: micro-gram /deciliter by immunoassays techniques.measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
measure: C-reactive protein serum level
time frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
description: milgram/liter using ELISA technique. measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
arm group label: Propofol group (P)
arm group type: Placebo Comparator
description: The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of propofol 17 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings
arm group label: Ketamine group ((K)
arm group type: Active Comparator
description: The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of ketamine 5 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings
intervention type: Drug
intervention name: Ketamine
description: ketamine 5 mcg/kg/min will be used as intravenous anesthetic infusion
arm group label: Ketamine group ((K)
other name: ketalar
intervention type: Drug
intervention name: Propofol
description: propofol 17 mcg /kg/min
arm group label: Propofol group (P)
other name: diprivan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Reem Abdelraouf, lecturer
role: Principal Investigator
affiliation: Mansoura University
last name: Reem Abdelraouf, lecturer
phone: 01006151100
email: reemraouf64@gmail.com
responsible party type: Principal Investigator
investigator affiliation: Mansoura University Hospital
investigator full name: Abdelraouf Elsharkawy
investigator title: Lecturer of anesthesia and surgical intensive care
mesh term: Ketamine
mesh term: Propofol