<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/NCT04414228</url>
  </required_header>
  <id_info>
    <org_study_id>N202004045</org_study_id>
    <nct_id>NCT04414228</nct_id>
  </id_info>
  <brief_title>Anesthetic Guidance of Depth of Anesthesia and Indirect Cardiac Output Monitoring in Thoracic Surgery</brief_title>
  <official_title>An Investigation of the Impact of Anesthetic Guidance of Depth of Anesthesia and Indirect Cardiac Output Monitoring on the Clinical Outcomes of Patients Undergoing Thoracic Surgery: A Factorial Parallel Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taipei Medical University Shuang Ho Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taipei Medical University Shuang Ho 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>
      Patients undergoing thoracotomy in thoracic surgery are prone to have complications of&#xD;
      delayed recovery from general anesthesia and perioperative instable hemodynamics due to the&#xD;
      relatively invasive procedures and patient's underlying morbidity. Therefore, intraoperative&#xD;
      monitoring and corresponding management are of great importance to prevent relevant&#xD;
      complications in thoracic surgery. This study aims to investigate the clinical benefits of&#xD;
      two intraoperative monitoring techniques in patients undergoing thoracotomy surgery,&#xD;
      including depth of anesthesia and minimally invasive cardiac output monitoring. First,&#xD;
      M-Entropy system will be used to measure the depth of anesthesia and be evaluated regarding&#xD;
      the effect of spectral entropy guidance on postoperative recovery. Second, we will apply&#xD;
      ProAQT device in guiding goal-directed hemodynamic therapy and assess its impact on&#xD;
      occurrence of postoperative pulmonary complications and recovery. In this study, we will&#xD;
      conduct a factorial parallel randomized controlled trial and use the method of stratified&#xD;
      randomization to evaluate both two monitoring technologies in the same patient group. The&#xD;
      results of this study will provide important evidence and clinical implication for precision&#xD;
      anesthesia and enhanced recovery after surgery (ERAS) protocol in thoracic surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 19, 2020</start_date>
  <completion_date type="Actual">November 18, 2021</completion_date>
  <primary_completion_date type="Actual">November 18, 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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to spontaneous eye opening</measure>
    <time_frame>At the end of surgery</time_frame>
    <description>The interval from the cessation of anesthetics to spontaneous eye opening</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of in-hospital postoperative pulmonary complications</measure>
    <time_frame>Within 30 days after surgery</time_frame>
    <description>This includes atelectasis, pleural effusion, pneumonia, empyema, pulmonary embolism, re-operation, and respiratory failure. The diagnosis of atelectasis and pleural effusion will be made based on routinely performed chest radiographs on postoperative days 1 and 3. Pneumonia will be diagnosed if a patient presents with fever, leukocytosis and new infiltrates on chest radiography. Pleural empyema and pulmonary embolism will be confirmed by spiral computed tomography scan. Respiratory failure is defined as described in the protocol.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to tracheal extubation</measure>
    <time_frame>At the end of surgery</time_frame>
    <description>The interval from the cessation of anesthetics to tracheal extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to orientation in time and place</measure>
    <time_frame>At the end of surgery</time_frame>
    <description>The interval from the cessation of anesthetics to orientation in time and place</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to leave operating room</measure>
    <time_frame>At the end of surgery</time_frame>
    <description>The interval from the cessation of anesthetics to leave operating room</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of emergence agitation</measure>
    <time_frame>During the recovery from anesthesia</time_frame>
    <description>Richmond Agitation-Sedation Scale will be used to evaluate the level of agitation and sedation promptly after extubation. This is defined as +4 combative, +3 very agitated, +2 agitated, +1 restless, 0 alert and calm, -1 drowsy, -2 light sedation, -3 moderate sedation, -4 deep sedation, and -5 unarousable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of postoperative delirium</measure>
    <time_frame>30 minutes after tracheal extubation</time_frame>
    <description>Events of delirium will be evaluated using the Confusion Assessment Method at the postanesthetic care unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of intraoperative recall or awareness</measure>
    <time_frame>One day after surgery</time_frame>
    <description>As titled</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2)</measure>
    <time_frame>After induction of anesthesia and at the end of surgery</time_frame>
    <description>The relative change of PaO2/FiO2 values after induction of anesthesia and at the end of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of cardiac complications</measure>
    <time_frame>Within 30 days after surgery</time_frame>
    <description>Myocardial infarction diagnosed by electrocardiogram and troponin T serum concentration; newly developed atrial fibrillation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of hypotensive episodes</measure>
    <time_frame>Within 30 days after surgery</time_frame>
    <description>This is defined as a decrease in mean arterial pressure &gt; 20% for more than 15 min requiring vasopressors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of newly developed stroke</measure>
    <time_frame>Within 30 days after surgery</time_frame>
    <description>This will be based on the finding of imaging tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Within 30 days after surgery</time_frame>
    <description>As titled</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Anesthesia</condition>
  <condition>Hemodynamic Instability</condition>
  <condition>Postoperative Respiratory Complication</condition>
  <arm_group>
    <arm_group_label>M-Entropy guidance of anesthesia depth</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ProAQT in guiding goal-directed hemodynamic therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to the GDT group will be managed according to the ERAS algorithm utilizing ProAQT variables (mean arterial pressure, stroke volume variation and cardiac index) If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is &lt; 10%. If mean arterial pressure is &lt; 70 mmHg and/or cardiac index &lt; 2.5 l·min-1·m-2 despite the stroke volume variation of &lt; 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>M-Entropy guidance of anesthesia depth</intervention_name>
    <description>In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment.</description>
    <arm_group_label>M-Entropy guidance of anesthesia depth</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ProAQT in guiding goal-directed hemodynamic therapy</intervention_name>
    <description>If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is &lt; 10%. If mean arterial pressure is &lt; 70 mmHg and/or cardiac index &lt; 2.5 l·min-1·m-2 despite the stroke volume variation of &lt; 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered.</description>
    <arm_group_label>ProAQT in guiding goal-directed hemodynamic therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing video-assisted thoracotomy for lung resection at Shuang Ho&#xD;
             Hospital, Taipei Medical University, New Taipei City, Taiwan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 20 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  End-stage renal disease&#xD;
&#xD;
          -  Emergency surgery&#xD;
&#xD;
          -  Presence of circulatory shock needing vasoactive drugs before surgery&#xD;
&#xD;
          -  Any diagnosis of aortic diseases&#xD;
&#xD;
          -  Cerebral vascular diseases or trauma&#xD;
&#xD;
          -  High-degree cardiac arrythmia (e.g. atrial fibrillation)&#xD;
&#xD;
          -  Uses of cardiac pacemaker or automated implantable cardioverter defibrillator&#xD;
&#xD;
          -  New York Heart Association functional classification 4&#xD;
&#xD;
          -  Long-term use of psychiatric medications&#xD;
&#xD;
          -  Intraoperative blood loss &gt; 1 L&#xD;
&#xD;
          -  Intraoperative blood transfusion&#xD;
&#xD;
          -  Planned or unanticipated transferal to ICU for postoperative mechanical ventilation&#xD;
&#xD;
          -  Patient refusal to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ying-Hsuan Tai, M.D., M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shuang Ho Hospital, Taipei Medical University</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Taipei Medical University Shuang Ho Hospital</investigator_affiliation>
    <investigator_full_name>YingHsuanTai</investigator_full_name>
    <investigator_title>Department of Anesthesiology</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT04414228/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04414228
org study id: N202004045
nct id: NCT04414228
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Patients undergoing thoracotomy in thoracic surgery are prone to have complications of
      delayed recovery from general anesthesia and perioperative instable hemodynamics due to the
      relatively invasive procedures and patient's underlying morbidity. Therefore, intraoperative
      monitoring and corresponding management are of great importance to prevent relevant
      complications in thoracic surgery. This study aims to investigate the clinical benefits of
      two intraoperative monitoring techniques in patients undergoing thoracotomy surgery,
      including depth of anesthesia and minimally invasive cardiac output monitoring. First,
      M-Entropy system will be used to measure the depth of anesthesia and be evaluated regarding
      the effect of spectral entropy guidance on postoperative recovery. Second, we will apply
      ProAQT device in guiding goal-directed hemodynamic therapy and assess its impact on
      occurrence of postoperative pulmonary complications and recovery. In this study, we will
      conduct a factorial parallel randomized controlled trial and use the method of stratified
      randomization to evaluate both two monitoring technologies in the same patient group. The
      results of this study will provide important evidence and clinical implication for precision
      anesthesia and enhanced recovery after surgery (ERAS) protocol in thoracic surgery.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Time to spontaneous eye opening
time frame: At the end of surgery
description: The interval from the cessation of anesthetics to spontaneous eye opening
measure: Rate of in-hospital postoperative pulmonary complications
time frame: Within 30 days after surgery
description: This includes atelectasis, pleural effusion, pneumonia, empyema, pulmonary embolism, re-operation, and respiratory failure. The diagnosis of atelectasis and pleural effusion will be made based on routinely performed chest radiographs on postoperative days 1 and 3. Pneumonia will be diagnosed if a patient presents with fever, leukocytosis and new infiltrates on chest radiography. Pleural empyema and pulmonary embolism will be confirmed by spiral computed tomography scan. Respiratory failure is defined as described in the protocol.
measure: Time to tracheal extubation
time frame: At the end of surgery
description: The interval from the cessation of anesthetics to tracheal extubation
measure: Time to orientation in time and place
time frame: At the end of surgery
description: The interval from the cessation of anesthetics to orientation in time and place
measure: Time to leave operating room
time frame: At the end of surgery
description: The interval from the cessation of anesthetics to leave operating room
measure: Rate of emergence agitation
time frame: During the recovery from anesthesia
description: Richmond Agitation-Sedation Scale will be used to evaluate the level of agitation and sedation promptly after extubation. This is defined as +4 combative, +3 very agitated, +2 agitated, +1 restless, 0 alert and calm, -1 drowsy, -2 light sedation, -3 moderate sedation, -4 deep sedation, and -5 unarousable.
measure: Rate of postoperative delirium
time frame: 30 minutes after tracheal extubation
description: Events of delirium will be evaluated using the Confusion Assessment Method at the postanesthetic care unit.
measure: Rate of intraoperative recall or awareness
time frame: One day after surgery
description: As titled
measure: Arterial partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2)
time frame: After induction of anesthesia and at the end of surgery
description: The relative change of PaO2/FiO2 values after induction of anesthesia and at the end of surgery
measure: Rate of cardiac complications
time frame: Within 30 days after surgery
description: Myocardial infarction diagnosed by electrocardiogram and troponin T serum concentration; newly developed atrial fibrillation.
measure: Rate of hypotensive episodes
time frame: Within 30 days after surgery
description: This is defined as a decrease in mean arterial pressure > 20% for more than 15 min requiring vasopressors.
measure: Rate of newly developed stroke
time frame: Within 30 days after surgery
description: This will be based on the finding of imaging tests.
measure: Length of hospital stay
time frame: Within 30 days after surgery
description: As titled
arm group label: M-Entropy guidance of anesthesia depth
arm group type: Active Comparator
description: In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment.
arm group label: ProAQT in guiding goal-directed hemodynamic therapy
arm group type: Active Comparator
description: Subjects randomized to the GDT group will be managed according to the ERAS algorithm utilizing ProAQT variables (mean arterial pressure, stroke volume variation and cardiac index) If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is < 10%. If mean arterial pressure is < 70 mmHg and/or cardiac index < 2.5 l·min-1·m-2 despite the stroke volume variation of < 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered.
intervention type: Device
intervention name: M-Entropy guidance of anesthesia depth
description: In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment.
arm group label: M-Entropy guidance of anesthesia depth
intervention type: Device
intervention name: ProAQT in guiding goal-directed hemodynamic therapy
description: If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is < 10%. If mean arterial pressure is < 70 mmHg and/or cardiac index < 2.5 l·min-1·m-2 despite the stroke volume variation of < 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered.
arm group label: ProAQT in guiding goal-directed hemodynamic therapy
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ying-Hsuan Tai, M.D., M.Sc.
role: Principal Investigator
affiliation: Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Taipei Medical University Shuang Ho Hospital
investigator full name: YingHsuanTai
investigator title: Department of Anesthesiology
mesh term: Anesthetics
provided document: 