<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/NCT03821545</url>
  </required_header>
  <id_info>
    <org_study_id>Ostovic</org_study_id>
    <nct_id>NCT03821545</nct_id>
  </id_info>
  <brief_title>The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery</brief_title>
  <official_title>The Immunomodulatory Effects of Ketamine and Lidocaine in Abdominal Surgery: Double-Blind, Placebo-Controlled Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Dubrava</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Dubrava</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical studies have shown that IV administration of anesthetics, lidocaine and ketamine&#xD;
      with their anti-inflammatory properties, modulates the acute immune response associated with&#xD;
      surgical tissue injury, and in this manner they are able to reduce postoperative pain.&#xD;
      Lidocaine has anti-inflammatory effects on polymorphonuclear granulocytes, IL-6 and IL-8&#xD;
      cytokines, complement component C3a and IL-1ra in serum. Ketamine produces its&#xD;
      anti-inflammatory effects by reducing CRP and IL-6 in serum and by inhibiting NF-kB, which&#xD;
      regulates gene transcription responsible for the production of proinflammatory factors.&#xD;
&#xD;
      Perioperative combinend IV administration of lidocaine and ketamine could have a more&#xD;
      favorable anti-inflammatory effect compared to anesthetic given alone or with placebo.&#xD;
&#xD;
      To investigate the effects of lidocaine and ketamine in patients undergoing abdominal surgery&#xD;
      on: acute immune response following the level of proinflammatory factors in serum (CRP, IL-6,&#xD;
      IL-8); postoperative pain management; recovery of bowel function; administration of opioids;&#xD;
      reduction of total treatment costs; length of hospital stay (LOHS)&#xD;
&#xD;
      A double-blind, placebo-controlled study will include 100 patients undergoing open colorectal&#xD;
      surgery. Patients will be randomly assigned to one of four groups: lidocaine, ketamine,&#xD;
      lidocaine-ketamine, and placebo. Lidocaine will be administered at a dose of 1.5 mg/kg prior&#xD;
      to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of&#xD;
      surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical&#xD;
      incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.&#xD;
      Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same&#xD;
      dose as the aforementioned anesthetics until the end of the surgery.&#xD;
&#xD;
      Proinflammatory markers in serum (CRP, IL-6, IL-8) will be measured before induction of&#xD;
      anesthesia, then 12 hours and 36 hours following the completion of surgery. The intensity of&#xD;
      pain will be measured using the VAS score 2 hours and 4 hours following surgery and every 12&#xD;
      hours the following days. The investigators will measure also the consumption of opioids&#xD;
      during and after surgery, the length of stay in the ICU, where pain control and analgesics&#xD;
      use will be measured, as well as recovery of bowel function.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2019</start_date>
  <completion_date type="Actual">June 18, 2021</completion_date>
  <primary_completion_date type="Actual">June 12, 2021</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentration of inflammatory markers</measure>
    <time_frame>1-2 days</time_frame>
    <description>Measuring of inflammatory markers in serum (CRP, IL-6, IL-8) before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid consumption during anesthesia</measure>
    <time_frame>1 day</time_frame>
    <description>Measuring of total opioid consumption during intraoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAS- scores</measure>
    <time_frame>2 days</time_frame>
    <description>Measuring pain scores VAS scores 2 hours and 4 hours following surgery and every 12 hours the following 2 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analgesic consumption</measure>
    <time_frame>2 days</time_frame>
    <description>Measuring total analgesic consumption for 48 hours following the completion of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recovery of bowel function</measure>
    <time_frame>1-5 days</time_frame>
    <description>Measuring time to firs bowel movement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>1- 30 days</time_frame>
    <description>Follow-up patients until hospital discharge</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Lidocaine Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Lidocaine and Ketamine Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (0.9% NaCl) Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lidocaine</intervention_name>
    <description>Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery.</description>
    <arm_group_label>Lidocaine Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.</description>
    <arm_group_label>Ketamine Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lidocaine and Ketamine</intervention_name>
    <description>Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.</description>
    <arm_group_label>Lidocaine and Ketamine Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo (0.9% NaCl)</intervention_name>
    <description>Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same dose as the aforementioned anesthetics until the end of the surgery.</description>
    <arm_group_label>Placebo (0.9% NaCl) Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective Surgery&#xD;
&#xD;
          -  Expected duration of the operation &gt; 2 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients ≤ 18 years of age&#xD;
&#xD;
          -  Patients with history of allergy to local anesthetics&#xD;
&#xD;
          -  Chronic opioid analgesic&#xD;
&#xD;
          -  Patients who are unwilling or unable to participate&#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>The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery</name>
      <address>
        <city>Zagreb</city>
        <zip>10000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Croatia</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>January 27, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>May 14, 2022</last_update_submitted>
  <last_update_submitted_qc>May 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Dubrava</investigator_affiliation>
    <investigator_full_name>Helena Ostovic</investigator_full_name>
    <investigator_title>Helena Ostovic MD, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Anti-Inflammatory Effect</keyword>
  <keyword>Surgical Stress</keyword>
  <keyword>Lidocaine</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Abdominal Surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Ketamine</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/NCT03821545
org study id: Ostovic
nct id: NCT03821545
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Clinical studies have shown that IV administration of anesthetics, lidocaine and ketamine
      with their anti-inflammatory properties, modulates the acute immune response associated with
      surgical tissue injury, and in this manner they are able to reduce postoperative pain.
      Lidocaine has anti-inflammatory effects on polymorphonuclear granulocytes, IL-6 and IL-8
      cytokines, complement component C3a and IL-1ra in serum. Ketamine produces its
      anti-inflammatory effects by reducing CRP and IL-6 in serum and by inhibiting NF-kB, which
      regulates gene transcription responsible for the production of proinflammatory factors.

      Perioperative combinend IV administration of lidocaine and ketamine could have a more
      favorable anti-inflammatory effect compared to anesthetic given alone or with placebo.

      To investigate the effects of lidocaine and ketamine in patients undergoing abdominal surgery
      on: acute immune response following the level of proinflammatory factors in serum (CRP, IL-6,
      IL-8); postoperative pain management; recovery of bowel function; administration of opioids;
      reduction of total treatment costs; length of hospital stay (LOHS)

      A double-blind, placebo-controlled study will include 100 patients undergoing open colorectal
      surgery. Patients will be randomly assigned to one of four groups: lidocaine, ketamine,
      lidocaine-ketamine, and placebo. Lidocaine will be administered at a dose of 1.5 mg/kg prior
      to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of
      surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical
      incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.
      Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same
      dose as the aforementioned anesthetics until the end of the surgery.

      Proinflammatory markers in serum (CRP, IL-6, IL-8) will be measured before induction of
      anesthesia, then 12 hours and 36 hours following the completion of surgery. The intensity of
      pain will be measured using the VAS score 2 hours and 4 hours following surgery and every 12
      hours the following days. The investigators will measure also the consumption of opioids
      during and after surgery, the length of stay in the ICU, where pain control and analgesics
      use will be measured, as well as recovery of bowel function.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Concentration of inflammatory markers
time frame: 1-2 days
description: Measuring of inflammatory markers in serum (CRP, IL-6, IL-8) before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery
measure: Opioid consumption during anesthesia
time frame: 1 day
description: Measuring of total opioid consumption during intraoperative period
measure: VAS- scores
time frame: 2 days
description: Measuring pain scores VAS scores 2 hours and 4 hours following surgery and every 12 hours the following 2 days.
measure: Analgesic consumption
time frame: 2 days
description: Measuring total analgesic consumption for 48 hours following the completion of surgery
measure: Recovery of bowel function
time frame: 1-5 days
description: Measuring time to firs bowel movement
measure: Length of hospital stay
time frame: 1- 30 days
description: Follow-up patients until hospital discharge
arm group label: Lidocaine Group
arm group type: Active Comparator
arm group label: Ketamine Group
arm group type: Active Comparator
arm group label: Lidocaine and Ketamine Group
arm group type: Active Comparator
arm group label: Placebo (0.9% NaCl) Group
arm group type: Placebo Comparator
intervention type: Other
intervention name: Lidocaine
description: Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery.
arm group label: Lidocaine Group
intervention type: Other
intervention name: Ketamine
description: Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.
arm group label: Ketamine Group
intervention type: Other
intervention name: Lidocaine and Ketamine
description: Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.
arm group label: Lidocaine and Ketamine Group
intervention type: Other
intervention name: Placebo (0.9% NaCl)
description: Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same dose as the aforementioned anesthetics until the end of the surgery.
arm group label: Placebo (0.9% NaCl) Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Croatia
responsible party type: Principal Investigator
investigator affiliation: University Hospital Dubrava
investigator full name: Helena Ostovic
investigator title: Helena Ostovic MD, Principal Investigator
mesh term: Colorectal Neoplasms
mesh term: Lidocaine
mesh term: Ketamine