<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/NCT04425473</url>
  </required_header>
  <id_info>
    <org_study_id>Z191100006619067</org_study_id>
    <nct_id>NCT04425473</nct_id>
  </id_info>
  <brief_title>Esketamine and Perioperative Depressive Symptoms</brief_title>
  <official_title>Effect of Esketamine on Perioperative Depressive Symptoms in Patients Undergoing Major Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Tiantan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Tiantan Hospital</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>
      Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this&#xD;
      would be sharpened especially for complicated, high-risk major surgery. However, None of&#xD;
      treatments could resolve this clinical problem during limited perioperative period. The&#xD;
      remarkable effects of ketamine on treatment resistant depression have been verified by&#xD;
      several clinical trials and the enantiomer S-ketamine (esketamine) showed similar&#xD;
      antidepressant efficacy with better safety in recent studies. The efficacy and safety of&#xD;
      esketamine administrated intra-operatively for PDS will be verified in this study. Other&#xD;
      secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 19, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Depressive symptoms remission</measure>
    <time_frame>Postoperative 3-day</time_frame>
    <description>Remission is defined as MADRS total score no more than 10</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MADRS scores</measure>
    <time_frame>Postoperative 3-day</time_frame>
    <description>The differences in MADRS scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depressive symptoms response</measure>
    <time_frame>Postoperative 3-day</time_frame>
    <description>The rates of patients achieving a response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe pain</measure>
    <time_frame>postoperative 3-day</time_frame>
    <description>The rate of severe pain after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side-effects and Adverse events</measure>
    <time_frame>During surgery or up to 7 days after surgery</time_frame>
    <description>All drug-related adverse events during surgery or before discharge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">564</enrollment>
  <condition>Depressive Symptoms</condition>
  <condition>Esketamine</condition>
  <condition>Perioperative Complication</condition>
  <condition>Major Surgery</condition>
  <arm_group>
    <arm_group_label>Esketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>Esketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes.</description>
    <arm_group_label>Esketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>Equivalent amount of normal saline will be administrated intravenously suturing incision.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient undergoing elective major surgery&#xD;
&#xD;
          -  Ages between 18 and 65 years old&#xD;
&#xD;
          -  Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores&#xD;
             equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to&#xD;
             or more than 22 )&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients combined with aphasia or other conditions leads that patients inability to&#xD;
             cooperate with the metal assessments;&#xD;
&#xD;
          -  Tumor related injury of the 9th, 10th, 11th, 12th cranial nerve or patients need&#xD;
             keeping intubation after surgery;&#xD;
&#xD;
          -  Medical history of psychotic or bipolar disorder;&#xD;
&#xD;
          -  Laboratory evidence of hormone levels disorder due to primary diseases;&#xD;
&#xD;
          -  Body Mass Index more than 30 kg/㎡;&#xD;
&#xD;
          -  Child-Pugh grade B or C;&#xD;
&#xD;
          -  Major depressive disorder with antidepressant therapy in the past 2 weeks before&#xD;
             screening;&#xD;
&#xD;
          -  History of adverse events to ketamine or esketamine;&#xD;
&#xD;
          -  Patients with repeated suicide attempts (QIDS-SR 12-item more than or equal to 3);&#xD;
&#xD;
          -  History of drug abused;&#xD;
&#xD;
          -  Pregnant or breastfeeding woman.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ruquan Han, M.D., Ph D.</last_name>
    <role>Study Chair</role>
    <affiliation>Beijing Tiantan Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ruquan Han, M.D., Ph D.</last_name>
    <phone>8610-59976660</phone>
    <email>ruquan.han@ccmu.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Tiantan Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <zip>100070</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruquan Han, M.D., Ph.D</last_name>
      <phone>8610-59976660</phone>
      <email>ruquan.han@ccmu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Tiantan Hospital</investigator_affiliation>
    <investigator_full_name>Ruquan Han</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>After the publication of the study results.</ipd_time_frame>
    <ipd_access_criteria>Publication in peer reviewed journal</ipd_access_criteria>
  </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/NCT04425473
org study id: Z191100006619067
nct id: NCT04425473
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this
      would be sharpened especially for complicated, high-risk major surgery. However, None of
      treatments could resolve this clinical problem during limited perioperative period. The
      remarkable effects of ketamine on treatment resistant depression have been verified by
      several clinical trials and the enantiomer S-ketamine (esketamine) showed similar
      antidepressant efficacy with better safety in recent studies. The efficacy and safety of
      esketamine administrated intra-operatively for PDS will be verified in this study. Other
      secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be
      investigated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Depressive symptoms remission
time frame: Postoperative 3-day
description: Remission is defined as MADRS total score no more than 10
measure: MADRS scores
time frame: Postoperative 3-day
description: The differences in MADRS scores
measure: Depressive symptoms response
time frame: Postoperative 3-day
description: The rates of patients achieving a response
measure: Severe pain
time frame: postoperative 3-day
description: The rate of severe pain after surgery
measure: Side-effects and Adverse events
time frame: During surgery or up to 7 days after surgery
description: All drug-related adverse events during surgery or before discharge
arm group label: Esketamine
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Esketamine
description: Esketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes.
arm group label: Esketamine
intervention type: Drug
intervention name: Normal saline
description: Equivalent amount of normal saline will be administrated intravenously suturing incision.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ruquan Han, M.D., Ph D.
role: Study Chair
affiliation: Beijing Tiantan Hospital
last name: Ruquan Han, M.D., Ph D.
phone: 8610-59976660
email: ruquan.han@ccmu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Tiantan Hospital
investigator full name: Ruquan Han
investigator title: Professor
mesh term: Depression
mesh term: Esketamine
sharing ipd: Yes
ipd description: The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After the publication of the study results.
ipd access criteria: Publication in peer reviewed journal