<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/NCT03772054</url>
  </required_header>
  <id_info>
    <org_study_id>903/17</org_study_id>
    <nct_id>NCT03772054</nct_id>
  </id_info>
  <brief_title>Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.</brief_title>
  <official_title>Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled 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>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>
      Endothelial damage has been reported after ischemia-reperfusion events. This can be&#xD;
      characterized by measurements of glycocalyx and endothelial components that are released to&#xD;
      blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have&#xD;
      shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery&#xD;
      with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state&#xD;
      after the tourniquet is released. This research aims to compare the effect of sevoflurane and&#xD;
      propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical&#xD;
      scenario.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion&#xD;
      (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial&#xD;
      comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial&#xD;
      glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell&#xD;
      damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal&#xD;
      anesthesia.&#xD;
&#xD;
      After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled&#xD;
      for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of&#xD;
      the study. All patients will enter the operating room and after standard ASA monitorization&#xD;
      and placement of an intravenous line (IV), a spinal anesthesia will be performed under&#xD;
      midazolam sedation. After analgesia and motor block establishment, an intravenous or&#xD;
      inhalation hypnosis induction will be performed (according to the study arm allocation). The&#xD;
      airway will be secured by a laryngeal mask placement and the surgery will be started. A&#xD;
      femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over&#xD;
      patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will&#xD;
      be taken in five different moments to follow concentration changes before and after the IR&#xD;
      insult. Fluid and drugs administration will be standardized.&#xD;
&#xD;
      Venous blood samples will be collected at the moment of IV placement (baseline values),&#xD;
      during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After&#xD;
      obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured&#xD;
      by a researcher blinded to patient allocation using commercial available Elisa kits. The&#xD;
      concentration of each biomarker at each sample time will be compared.&#xD;
&#xD;
      A sample size calculation was performed based on a few clinical reports to detect a 25%&#xD;
      reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of&#xD;
      0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a&#xD;
      two-sides test analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Actual">December 11, 2019</completion_date>
  <primary_completion_date type="Actual">December 11, 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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Blood samples will be codified by the principal investigator. Laboratory team will receive all samples for biomarkers measures. Results will be analyzed by the principal investigator.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Syndecan-1 levels</measure>
    <time_frame>At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR</time_frame>
    <description>Differences in the concentration of syndecan-1 in blood serum during and after surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heparan sulfate levels</measure>
    <time_frame>At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR</time_frame>
    <description>Differences in the concentration of heparan sulfate in blood serum during and after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombomodulin</measure>
    <time_frame>At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR</time_frame>
    <description>Differences in the concentration of thrombomodulin in blood serum during and after surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Ischemia Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>Propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sevoflurane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevoflurane</intervention_name>
    <description>Inhalation anesthetic agent</description>
    <arm_group_label>Sevoflurane</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Intravenous anesthetic agent</description>
    <arm_group_label>Propofol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists Classification (ASA Class) I and II&#xD;
&#xD;
          -  Elective knee ligament surgery&#xD;
&#xD;
          -  Use of a femoral tourniquet&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergies to egg or soya&#xD;
&#xD;
          -  Previous history of critical events during surgery and perioperative period&#xD;
&#xD;
          -  Patients at risk of hyperthermia malignant&#xD;
&#xD;
          -  Patients with 3 or more predictor of difficult airway management&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Felipe Maldonado, M.D., M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Clìnico de la Universidad de Chile.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Clínico de la Universidad de Chile</name>
      <address>
        <city>Independencia</city>
        <state>Santiago</state>
        <zip>8380456</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 9, 2018</study_first_submitted>
  <study_first_submitted_qc>December 9, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>December 11, 2019</last_update_submitted>
  <last_update_submitted_qc>December 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Chile</investigator_affiliation>
    <investigator_full_name>Felipe Andrés Maldonado Caniulao</investigator_full_name>
    <investigator_title>Instructor</investigator_title>
  </responsible_party>
  <keyword>Syndecan-1</keyword>
  <keyword>Heparan sulfate</keyword>
  <keyword>Thrombomodulin</keyword>
  <keyword>Ischemia Reperfusion</keyword>
  <keyword>Anesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Sevoflurane</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/NCT03772054
org study id: 903/17
nct id: NCT03772054
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Endothelial damage has been reported after ischemia-reperfusion events. This can be
      characterized by measurements of glycocalyx and endothelial components that are released to
      blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have
      shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery
      with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state
      after the tourniquet is released. This research aims to compare the effect of sevoflurane and
      propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical
      scenario.
To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion
      (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial
      comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial
      glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell
      damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal
      anesthesia.

      After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled
      for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of
      the study. All patients will enter the operating room and after standard ASA monitorization
      and placement of an intravenous line (IV), a spinal anesthesia will be performed under
      midazolam sedation. After analgesia and motor block establishment, an intravenous or
      inhalation hypnosis induction will be performed (according to the study arm allocation). The
      airway will be secured by a laryngeal mask placement and the surgery will be started. A
      femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over
      patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will
      be taken in five different moments to follow concentration changes before and after the IR
      insult. Fluid and drugs administration will be standardized.

      Venous blood samples will be collected at the moment of IV placement (baseline values),
      during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After
      obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured
      by a researcher blinded to patient allocation using commercial available Elisa kits. The
      concentration of each biomarker at each sample time will be compared.

      A sample size calculation was performed based on a few clinical reports to detect a 25%
      reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of
      0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a
      two-sides test analysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
masking description: Blood samples will be codified by the principal investigator. Laboratory team will receive all samples for biomarkers measures. Results will be analyzed by the principal investigator.
measure: Syndecan-1 levels
time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
description: Differences in the concentration of syndecan-1 in blood serum during and after surgery
measure: Heparan sulfate levels
time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
description: Differences in the concentration of heparan sulfate in blood serum during and after surgery
measure: Thrombomodulin
time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
description: Differences in the concentration of thrombomodulin in blood serum during and after surgery
arm group label: Propofol
arm group type: Active Comparator
description: After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery.
arm group label: Sevoflurane
arm group type: Experimental
description: After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery.
intervention type: Drug
intervention name: Sevoflurane
description: Inhalation anesthetic agent
arm group label: Sevoflurane
intervention type: Drug
intervention name: Propofol
description: Intravenous anesthetic agent
arm group label: Propofol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Felipe Maldonado, M.D., M.Sc.
role: Principal Investigator
affiliation: Hospital Clìnico de la Universidad de Chile.
facility: 
country: Chile
responsible party type: Principal Investigator
investigator affiliation: University of Chile
investigator full name: Felipe Andrés Maldonado Caniulao
investigator title: Instructor
mesh term: Reperfusion Injury
mesh term: Ischemia
mesh term: Propofol
mesh term: Sevoflurane
sharing ipd: No