<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/NCT03231683</url>
  </required_header>
  <id_info>
    <org_study_id>EC 200801014</org_study_id>
    <nct_id>NCT03231683</nct_id>
  </id_info>
  <brief_title>Use of S+Ketamine During Target-Controlled Intravenous Anaesthesia After Abdominal Hysterectomy</brief_title>
  <official_title>The Use of S+Ketamine Versus Placebo During Target-Controlled Intravenous Anaesthesia to Reduce Morphine Consumption and Side Effects After Abdominal Hysterectomy: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>KK Women's and Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>KK Women's and Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators want to investigate the effect of low dose S+ ketamine compared to placebo&#xD;
      on cumulative morphine consumption at 24 hours in 90 women undergoing open abdominal&#xD;
      hysterectomy with remifentanil-propofol target controlled infusion (TCI) in KK Women's and&#xD;
      Children's Hospital. The secondary aims are to investigate the use of low dose S+ ketamine on&#xD;
      the incidence of nausea, vomiting, pruritus (opioid side effect), sedation score and psycho&#xD;
      mimetic assessment compared to placebo group. The investigators propose to conduct a double&#xD;
      blinded, randomized controlled study in women undergoing open abdominal hysterectomy with&#xD;
      remifentanil-propofol TCI. (1) Treatment Group: intravenous ketamine 0.5 mg/kg at the&#xD;
      beginning and 0.5 mg/kg 20 minutes before extubation. (2) Control Group: intravenous normal&#xD;
      saline (as placebo) at the beginning and 20 minutes before extubation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A number of 90 American Society of Anesthesiologists (ASA) I and II patients undergoing&#xD;
      elective open abdominal hysterectomies will be randomly distributed in two groups of 45&#xD;
      patient's each and assigned to receive one of the of the following:&#xD;
&#xD;
        1. Treatment Group: intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and&#xD;
           0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according&#xD;
           to Minto model and propofol infusion according to Marsh model through target control&#xD;
           infusion pump.&#xD;
&#xD;
        2. Control Group: intravenous normal saline (as placebo, with similar volume) at the&#xD;
           beginning and 20 minutes before extubation along with remifentanil according to Minto&#xD;
           model and propofol according to Schnider model through target control infusion pump.&#xD;
&#xD;
      Randomization procedure is performed by the unblinded study team investigator. Patients will&#xD;
      be randomized to either the treatment or control groups with a 1:1 allocation ratio. Sequence&#xD;
      generation will be performed using a computerized random number generator, employing a&#xD;
      permuted block randomization scheme. Allocation concealment will be maintained by having the&#xD;
      random numbers pre-generated by an off-site statistician who will not be involved in subject&#xD;
      recruitment. Implementation will be via serially numbered opaque sealed envelopes.&#xD;
&#xD;
      Throughout the study period, blinded study members will perform drug administration and data&#xD;
      collection, while unblinded study members will be in charge for the investigational drug&#xD;
      storage, dispensing and preparation. Any premature unblinding (e.g. accidental unblinding,&#xD;
      unblinding due a serious adverse event) of the investigational product will be promptly&#xD;
      documented and explained. In the case of adverse effect or severe adverse effect requiring&#xD;
      information on the study treatment to manage a patient, the treatment code of the patient&#xD;
      will be unblinded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-operative Cumulative morphine consumption at 24 hours</measure>
    <time_frame>1 day</time_frame>
    <description>Post-operative Cumulative morphine consumption at 24 hours will be measured in the S-ketamine group compared to the placebo group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of nausea</measure>
    <time_frame>1 day</time_frame>
    <description>The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of vomiting</measure>
    <time_frame>1 day</time_frame>
    <description>The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of pruritus</measure>
    <time_frame>1 day</time_frame>
    <description>The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Ketamine</condition>
  <condition>Anesthesia</condition>
  <condition>Morphine</condition>
  <condition>Hysterectomy</condition>
  <arm_group>
    <arm_group_label>Esketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Esketamine and remifentanil to be given alongside with propofol through target control infusion pump.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline and remifentanil to be given alongside with propofol through target control infusion pump.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and 0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Marsh model</description>
    <arm_group_label>Esketamine</arm_group_label>
    <other_name>S+ ketamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>intravenous normal saline (as placebo, with similar volume) at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Sodium chloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Esketamine</arm_group_label>
    <other_name>Ultiva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Esketamine</arm_group_label>
    <other_name>Diprivan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female ASA I/II patients above age of 21 years old scheduled gynecological open&#xD;
             surgery for benign condition (fibroids, adenomyosis), who are willing and able to give&#xD;
             written informed consent for participation in this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to the use of S+ ketamine, as listed in the product label e.g.&#xD;
             untreated or insufficiently treated thyroid hyperfunction, unstable angina pectoris or&#xD;
             myocardial infarction within the last 6 months, diseases of the central nervous&#xD;
             system, increased intraocular pressure and perforating ocular injuries, surgical&#xD;
             procedures in the upper respiratory tract;&#xD;
&#xD;
          -  History of drug or alcohol abuse;&#xD;
&#xD;
          -  Regular use of analgesics, or use of opioids within 12 hours of surgery;&#xD;
&#xD;
          -  Chronic use of benzodiazepine or neuroleptics;&#xD;
&#xD;
          -  Thyroid replacement hormone;&#xD;
&#xD;
          -  History of ischaemic heart disease, hypertension, psychiatric disorder;&#xD;
&#xD;
          -  BMI&gt; 30kg/m2;&#xD;
&#xD;
          -  Laparoscopic surgery converted to open surgery;&#xD;
&#xD;
          -  Pregnant or breast feeding females.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Farida Ithnin, MBBCh</last_name>
    <role>Principal Investigator</role>
    <affiliation>KK Women's and Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kk Women'S and Children'S Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>229899</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 3, 2015</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>July 24, 2017</last_update_submitted>
  <last_update_submitted_qc>July 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Esketamine</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/NCT03231683
org study id: EC 200801014
nct id: NCT03231683
lead sponsor: 
has dmc: No
The investigators want to investigate the effect of low dose S+ ketamine compared to placebo
      on cumulative morphine consumption at 24 hours in 90 women undergoing open abdominal
      hysterectomy with remifentanil-propofol target controlled infusion (TCI) in KK Women's and
      Children's Hospital. The secondary aims are to investigate the use of low dose S+ ketamine on
      the incidence of nausea, vomiting, pruritus (opioid side effect), sedation score and psycho
      mimetic assessment compared to placebo group. The investigators propose to conduct a double
      blinded, randomized controlled study in women undergoing open abdominal hysterectomy with
      remifentanil-propofol TCI. (1) Treatment Group: intravenous ketamine 0.5 mg/kg at the
      beginning and 0.5 mg/kg 20 minutes before extubation. (2) Control Group: intravenous normal
      saline (as placebo) at the beginning and 20 minutes before extubation.
A number of 90 American Society of Anesthesiologists (ASA) I and II patients undergoing
      elective open abdominal hysterectomies will be randomly distributed in two groups of 45
      patient's each and assigned to receive one of the of the following:

        1. Treatment Group: intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and
           0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according
           to Minto model and propofol infusion according to Marsh model through target control
           infusion pump.

        2. Control Group: intravenous normal saline (as placebo, with similar volume) at the
           beginning and 20 minutes before extubation along with remifentanil according to Minto
           model and propofol according to Schnider model through target control infusion pump.

      Randomization procedure is performed by the unblinded study team investigator. Patients will
      be randomized to either the treatment or control groups with a 1:1 allocation ratio. Sequence
      generation will be performed using a computerized random number generator, employing a
      permuted block randomization scheme. Allocation concealment will be maintained by having the
      random numbers pre-generated by an off-site statistician who will not be involved in subject
      recruitment. Implementation will be via serially numbered opaque sealed envelopes.

      Throughout the study period, blinded study members will perform drug administration and data
      collection, while unblinded study members will be in charge for the investigational drug
      storage, dispensing and preparation. Any premature unblinding (e.g. accidental unblinding,
      unblinding due a serious adverse event) of the investigational product will be promptly
      documented and explained. In the case of adverse effect or severe adverse effect requiring
      information on the study treatment to manage a patient, the treatment code of the patient
      will be unblinded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Post-operative Cumulative morphine consumption at 24 hours
time frame: 1 day
description: Post-operative Cumulative morphine consumption at 24 hours will be measured in the S-ketamine group compared to the placebo group
measure: Incidence of nausea
time frame: 1 day
description: The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.
measure: Incidence of vomiting
time frame: 1 day
description: The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.
measure: Incidence of pruritus
time frame: 1 day
description: The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.
arm group label: Esketamine
arm group type: Active Comparator
description: Esketamine and remifentanil to be given alongside with propofol through target control infusion pump.
arm group label: Control
arm group type: Placebo Comparator
description: Saline and remifentanil to be given alongside with propofol through target control infusion pump.
intervention type: Drug
intervention name: Esketamine
description: intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and 0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Marsh model
arm group label: Esketamine
other name: S+ ketamine
intervention type: Drug
intervention name: Saline
description: intravenous normal saline (as placebo, with similar volume) at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model
arm group label: Control
other name: Sodium chloride
intervention type: Drug
intervention name: Remifentanil
description: Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model
arm group label: Control
arm group label: Esketamine
other name: Ultiva
intervention type: Drug
intervention name: Propofol
description: Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model
arm group label: Control
arm group label: Esketamine
other name: Diprivan
criteria: 
gender: Female
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Farida Ithnin, MBBCh
role: Principal Investigator
affiliation: KK Women's and Children's Hospital
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Ketamine
mesh term: Remifentanil
mesh term: Propofol
mesh term: Esketamine
sharing ipd: No