<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/NCT04435925</url>
  </required_header>
  <id_info>
    <org_study_id>UNUD-CTR-FK110620-001</org_study_id>
    <nct_id>NCT04435925</nct_id>
  </id_info>
  <brief_title>Inflammatory Effect Comparison Between Fentanyl and Remifentanil in Mastectomy Under General Anesthesia</brief_title>
  <official_title>Inflammatory Effect Comparison Between Fentanyl and Remifentanil in Mastectomy Under General Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Udayana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Udayana University</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>
      Mastectomy triggers stress and inflammation responses due to tissue trauma. Surgical stress&#xD;
      will increase levels of hormones (adrenocorticotropic hormone, cortisol, antidiuretic&#xD;
      hormone, epinephrine, norepinephrine, and dopamine) and inflammatory cytokines (Tumor&#xD;
      Necrotic Factor-α, interleukin-1, interleukin-2, and interleukin-6) in the body. This causes&#xD;
      insulin resistance, gluconeogenesis, and glycolysis, and impaired insulin secretion, which&#xD;
      results in hyperglycemia due to intraoperative stress. Intraoperative hyperglycemia increases&#xD;
      postoperative complications and mortality. Inhibition of hyperglycemia due to operative&#xD;
      stress and stress hormones with good anesthetic management in improving patient outcomes.&#xD;
&#xD;
      The choice of opioid type plays an important role in suppressing the perioperative stress and&#xD;
      inflammatory response. Opioids are an alternative, besides the use of regional anesthetic&#xD;
      techniques which have been proven to suppress the perioperative stress response. Fentanyl is&#xD;
      one of the phenylpiperidine synthetic opioids. Large doses of fentanyl can reduce stress&#xD;
      responses but also increase side effects, such as hemodynamic instability and decrease T-cell&#xD;
      function.&#xD;
&#xD;
      Remifentanil provides unique pharmacokinetic benefits through nonspecific esterase enzyme&#xD;
      metabolism, so it has a very fast onset and half-life. In addition, remifentanil also&#xD;
      provides benefits in reducing the production of interleukin 6 cytokines (IL-6) and tumor&#xD;
      necrosis factor α (TNF-α) and inhibits neutrophil migration through the endothelial layer.&#xD;
&#xD;
      The stress response to stress and inflammation is directly proportional to the dose of&#xD;
      remifentanil given. It is reported that remifentanil can suppress cortisol response according&#xD;
      to increasing dose.&#xD;
&#xD;
      Winterhalter et al. and Lee et al. reported that remifentanil is better at suppressing the&#xD;
      stress response than fentanyl. On the other hand, Bell et al. showed no difference in&#xD;
      cortisol and hemodynamic levels between the two groups.&#xD;
&#xD;
      The goal of this study is to see if remifentanil provides less increase in serum epinephrine&#xD;
      level, norepinephrine level, platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio&#xD;
      (LMR), and blood glucose level at one-hour and 24-hours postoperative in patients undergoing&#xD;
      mastectomy surgery under general anesthesia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 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 single-blind, randomized control trial. It provides a controlled treatment of general anesthesia with an opioid regimen between remifentanil and fentanyl.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The opioid selection disguised to the patient. Eligible subjects will be randomized so that each research subject has the same opportunity to be included in both groups.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Epinephrine</measure>
    <time_frame>1-hour (postoperative)</time_frame>
    <description>Serum epinephrine level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Epinephrine</measure>
    <time_frame>24-hours (postoperative)</time_frame>
    <description>Serum epinephrine level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Norepinephrine</measure>
    <time_frame>1-hour (postoperative)</time_frame>
    <description>Serum norepinephrine level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Norepinephrine</measure>
    <time_frame>24-hours (postoperative)</time_frame>
    <description>Serum norepinephrine level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PLR</measure>
    <time_frame>1-hour (postoperative)</time_frame>
    <description>platelet-to-lymphocyte ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PLR</measure>
    <time_frame>24-hours (postoperative)</time_frame>
    <description>platelet-to-lymphocyte ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LMR</measure>
    <time_frame>1-hour (postoperative)</time_frame>
    <description>lymphocyte-to-monocyte ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LMR</measure>
    <time_frame>24-hours (postoperative)</time_frame>
    <description>lymphocyte-to-monocyte ratio</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose</measure>
    <time_frame>1-hour (postoperative)</time_frame>
    <description>serum glucose level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose</measure>
    <time_frame>24-hours (postoperative)</time_frame>
    <description>serum glucose level</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Breast Disease</condition>
  <condition>Anesthesia</condition>
  <condition>Inflammatory Response</condition>
  <arm_group>
    <arm_group_label>Remifentanil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients assigned to this group will receive IV Remifentanil as an opioid for general anesthesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients assigned to this group will receive IV Fentanyl as an opioid for general anesthesia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>Loading dose: 0.5 mcg/kg Maintenance dose: 1 mcg/kg/minute</description>
    <arm_group_label>Remifentanil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>Loading dose: 2 mcg/kg Maintenance dose: 0.4 mcg/kg/30-minutes</description>
    <arm_group_label>Fentanyl</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients scheduled for a mastectomy under general anesthesia&#xD;
&#xD;
          -  Patients aged 30-65 years old&#xD;
&#xD;
          -  ASA physical status: I-II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to be included in the study&#xD;
&#xD;
          -  History of opioid allergies&#xD;
&#xD;
          -  Long-term use of steroids&#xD;
&#xD;
          -  Patients on β blockers medication&#xD;
&#xD;
          -  History of diabetes, autoimmune disease, or heart disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>I Gusti AG Hartawan</last_name>
    <role>Principal Investigator</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>May 2021</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>May 30, 2021</last_update_submitted>
  <last_update_submitted_qc>May 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2021</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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Remifentanil</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/NCT04435925
org study id: UNUD-CTR-FK110620-001
nct id: NCT04435925
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Mastectomy triggers stress and inflammation responses due to tissue trauma. Surgical stress
      will increase levels of hormones (adrenocorticotropic hormone, cortisol, antidiuretic
      hormone, epinephrine, norepinephrine, and dopamine) and inflammatory cytokines (Tumor
      Necrotic Factor-α, interleukin-1, interleukin-2, and interleukin-6) in the body. This causes
      insulin resistance, gluconeogenesis, and glycolysis, and impaired insulin secretion, which
      results in hyperglycemia due to intraoperative stress. Intraoperative hyperglycemia increases
      postoperative complications and mortality. Inhibition of hyperglycemia due to operative
      stress and stress hormones with good anesthetic management in improving patient outcomes.

      The choice of opioid type plays an important role in suppressing the perioperative stress and
      inflammatory response. Opioids are an alternative, besides the use of regional anesthetic
      techniques which have been proven to suppress the perioperative stress response. Fentanyl is
      one of the phenylpiperidine synthetic opioids. Large doses of fentanyl can reduce stress
      responses but also increase side effects, such as hemodynamic instability and decrease T-cell
      function.

      Remifentanil provides unique pharmacokinetic benefits through nonspecific esterase enzyme
      metabolism, so it has a very fast onset and half-life. In addition, remifentanil also
      provides benefits in reducing the production of interleukin 6 cytokines (IL-6) and tumor
      necrosis factor α (TNF-α) and inhibits neutrophil migration through the endothelial layer.

      The stress response to stress and inflammation is directly proportional to the dose of
      remifentanil given. It is reported that remifentanil can suppress cortisol response according
      to increasing dose.

      Winterhalter et al. and Lee et al. reported that remifentanil is better at suppressing the
      stress response than fentanyl. On the other hand, Bell et al. showed no difference in
      cortisol and hemodynamic levels between the two groups.

      The goal of this study is to see if remifentanil provides less increase in serum epinephrine
      level, norepinephrine level, platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio
      (LMR), and blood glucose level at one-hour and 24-hours postoperative in patients undergoing
      mastectomy surgery under general anesthesia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a single-blind, randomized control trial. It provides a controlled treatment of general anesthesia with an opioid regimen between remifentanil and fentanyl.
primary purpose: Supportive Care
masking: Single (Participant)
masking description: The opioid selection disguised to the patient. Eligible subjects will be randomized so that each research subject has the same opportunity to be included in both groups.
measure: Epinephrine
time frame: 1-hour (postoperative)
description: Serum epinephrine level
measure: Epinephrine
time frame: 24-hours (postoperative)
description: Serum epinephrine level
measure: Norepinephrine
time frame: 1-hour (postoperative)
description: Serum norepinephrine level
measure: Norepinephrine
time frame: 24-hours (postoperative)
description: Serum norepinephrine level
measure: PLR
time frame: 1-hour (postoperative)
description: platelet-to-lymphocyte ratio
measure: PLR
time frame: 24-hours (postoperative)
description: platelet-to-lymphocyte ratio
measure: LMR
time frame: 1-hour (postoperative)
description: lymphocyte-to-monocyte ratio
measure: LMR
time frame: 24-hours (postoperative)
description: lymphocyte-to-monocyte ratio
measure: Glucose
time frame: 1-hour (postoperative)
description: serum glucose level
measure: Glucose
time frame: 24-hours (postoperative)
description: serum glucose level
arm group label: Remifentanil
arm group type: Active Comparator
description: Patients assigned to this group will receive IV Remifentanil as an opioid for general anesthesia.
arm group label: Fentanyl
arm group type: Placebo Comparator
description: Patients assigned to this group will receive IV Fentanyl as an opioid for general anesthesia.
intervention type: Drug
intervention name: Remifentanil
description: Loading dose: 0.5 mcg/kg Maintenance dose: 1 mcg/kg/minute
arm group label: Remifentanil
intervention type: Drug
intervention name: Fentanyl
description: Loading dose: 2 mcg/kg Maintenance dose: 0.4 mcg/kg/30-minutes
arm group label: Fentanyl
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: No
last name: I Gusti AG Hartawan
role: Principal Investigator
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: Breast Diseases
mesh term: Fentanyl
mesh term: Remifentanil
sharing ipd: No