<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/NCT03831854</url>
  </required_header>
  <id_info>
    <org_study_id>18-952</org_study_id>
    <nct_id>NCT03831854</nct_id>
  </id_info>
  <brief_title>Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine</brief_title>
  <official_title>The Role of Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine Use</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches&#xD;
      peak level 1-4 hours after oral administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1:1 randomization without stratification use web-based software (Redcap) before surgery.&#xD;
      Allocation will be concealed from the patient, the nurse, the operating room team. Both&#xD;
      patient and the operating room team will be blinded to the treatment allocation (double&#xD;
      blind).&#xD;
&#xD;
      Standard preoperative care as per anesthesia care team. Patient will receive lamotrigine vs.&#xD;
      placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral&#xD;
      administration. Single dose lamotrigine is safe and is not associated with rash.&#xD;
&#xD;
      Standard intraoperative care as per the anesthesia care team. All patients will receive&#xD;
      Ketamine 1 mg/kg at induction. Ketamine 5mcg/kg/min will be started at induction and stopped&#xD;
      at the end of surgery.&#xD;
&#xD;
      Standard postoperative care as per PACU team. The psychologic side-effects will be measured&#xD;
      using Brief Psychiatric Rating Scale (BPRS) using an online tool.&#xD;
&#xD;
      Research fellow will receive standardized training in administering BPRS from Dr. Amit Anand&#xD;
      using structured material. Dr. Anand has used this training for other current research&#xD;
      projects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 24, 2019</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>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>
    <intervention_model_description>randomization without stratification</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The Pharmacy will know the treatment</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Psychologic Side-effects</measure>
    <time_frame>in PACU (up to 90 minutes after ketamine infusion)</time_frame>
    <description>The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients With Psychologic Disturbances-</measure>
    <time_frame>Up to 90 minutes of PACU arrival</time_frame>
    <description>The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of &gt; 4 (having any symptoms present) were determined as having psychologic disturbance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Opioid Consumption in PACU (mg)</measure>
    <time_frame>from entry to PACU to leaving PACU, up to 4 hours</time_frame>
    <description>Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Score in PACU</measure>
    <time_frame>from entry to PACU to leaving PACU</time_frame>
    <description>Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Had PONV (Postoperative Nausea Vomiting)</measure>
    <time_frame>after surgery up to discharge</time_frame>
    <description>PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Daily Average Opioid Use During Hospital Stay</measure>
    <time_frame>from admission up to discharge</time_frame>
    <description>The average daily opioid use (mg) during the hospital stay.</description>
  </other_outcome>
  <other_outcome>
    <measure>Opioid Related Side-effects (ORSDS)-POD1</measure>
    <time_frame>postoperative day 1</time_frame>
    <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Opioid Related Side-effects (ORSDS)-POD2</measure>
    <time_frame>postoperative day 2</time_frame>
    <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.</description>
  </other_outcome>
  <other_outcome>
    <measure>PACU Length of Stay, Hours</measure>
    <time_frame>in PACU</time_frame>
    <description>Hours spent in PACU (Postanesthesia Care Unit).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Reducing Psychological Side Effects of Ketamine</condition>
  <arm_group>
    <arm_group_label>lamotrigine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lamotrigine 300 MG</intervention_name>
    <description>300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P&lt;.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P&lt;.05).</description>
    <arm_group_label>lamotrigine</arm_group_label>
    <other_name>Lamictal 300 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>300 mg of oral Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>lamotrigine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 -65 Years of age&#xD;
&#xD;
          -  Planned overnight hospital stay&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and planning to become pregnant&#xD;
&#xD;
          -  No known History of seizure&#xD;
&#xD;
          -  No known History of Schizophrenia&#xD;
&#xD;
          -  No known History of unstable angina&#xD;
&#xD;
          -  Patients taking Antiepileptic medications&#xD;
&#xD;
          -  Known history of Lamotrigine intake in past.&#xD;
&#xD;
          -  Any history of allergic reaction to lamotrigine in the past.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <results_first_submitted>March 15, 2021</results_first_submitted>
  <results_first_submitted_qc>May 12, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2021</results_first_posted>
  <last_update_submitted>May 12, 2021</last_update_submitted>
  <last_update_submitted_qc>May 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2021</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>Lamotrigine</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to make subjects data available to outside researchers</ipd_description>
  </patient_data>
  <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>January 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03831854/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lamotrigine</title>
          <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lamotrigine</title>
          <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="46"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44" spread="13"/>
                    <measurement group_id="B2" value="42" spread="12"/>
                    <measurement group_id="B3" value="43" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA status, No (%)</title>
          <description>The ASA Physical Status Classification System is to assess and communicate a patient's pre-anesthesia medical co-morbidities. ASA scores included I, II, III, IV, V, and VI where I means normal status (best) and VI means a declared brain-dead patient whose organs are being removed for donor purposes (worst).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of alcoholism</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Surgery duration (hours)</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" lower_limit="3" upper_limit="5"/>
                    <measurement group_id="B2" value="3" lower_limit="2" upper_limit="5"/>
                    <measurement group_id="B3" value="3.5" lower_limit="3" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Surgery type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Orthopedic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypertension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Chronic pulmonary disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Renal failure</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Psychoses</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Depression</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Other neurological disorders</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BPRS(Brief Psychiatric Rating Scale) baseline score</title>
          <description>Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score based on four key items of BPRS will be between 4 (best score) and 28 (worst score).</description>
          <units>scores</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25" lower_limit="25" upper_limit="27"/>
                    <measurement group_id="B2" value="25" lower_limit="24" upper_limit="27"/>
                    <measurement group_id="B3" value="25" lower_limit="24" upper_limit="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Positive symptoms of schizophrenia based on four key items of BPRS (Brief Psychiatric Rati)-baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total dose of Ketamine, mg</title>
          <units>mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="143" spread="48"/>
                    <measurement group_id="B2" value="142" spread="54"/>
                    <measurement group_id="B3" value="143" spread="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Psychologic Side-effects</title>
        <description>The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score).</description>
        <time_frame>in PACU (up to 90 minutes after ketamine infusion)</time_frame>
        <population>46 patients were analyzed but 3 people were missing on the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Psychologic Side-effects</title>
          <description>The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score).</description>
          <population>46 patients were analyzed but 3 people were missing on the primary outcome.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="4" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.08</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Psychologic Disturbances-</title>
        <description>The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of &gt; 4 (having any symptoms present) were determined as having psychologic disturbance.</description>
        <time_frame>Up to 90 minutes of PACU arrival</time_frame>
        <population>A total of 3 people were missing on this outcome</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Psychologic Disturbances-</title>
          <description>The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of &gt; 4 (having any symptoms present) were determined as having psychologic disturbance.</description>
          <population>A total of 3 people were missing on this outcome</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.11</p_value>
            <method>Fisher Exact</method>
            <method_desc>The relative risk could not be assessed due to zero incidence in the treatment group</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Opioid Consumption in PACU (mg)</title>
        <description>Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)</description>
        <time_frame>from entry to PACU to leaving PACU, up to 4 hours</time_frame>
        <population>The final study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Opioid Consumption in PACU (mg)</title>
          <description>Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)</description>
          <population>The final study population.</population>
          <units>mg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="0" upper_limit="15"/>
                    <measurement group_id="O2" value="10" lower_limit="0" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.63</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-2.3</param_value>
            <ci_percent>98.5</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.5</ci_lower_limit>
            <ci_upper_limit>5.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Score in PACU</title>
        <description>Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.</description>
        <time_frame>from entry to PACU to leaving PACU</time_frame>
        <population>The final study population</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Score in PACU</title>
          <description>Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.</description>
          <population>The final study population</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="3.1"/>
                    <measurement group_id="O2" value="4.4" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.58</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.5</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.7</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Had PONV (Postoperative Nausea Vomiting)</title>
        <description>PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV.</description>
        <time_frame>after surgery up to discharge</time_frame>
        <population>Two patients were missing on this outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Had PONV (Postoperative Nausea Vomiting)</title>
          <description>PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV.</description>
          <population>Two patients were missing on this outcome.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0</p_value>
            <method>Chi-squared</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3</ci_lower_limit>
            <ci_upper_limit>3.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Daily Average Opioid Use During Hospital Stay</title>
        <description>The average daily opioid use (mg) during the hospital stay.</description>
        <time_frame>from admission up to discharge</time_frame>
        <population>The final study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Average Opioid Use During Hospital Stay</title>
          <description>The average daily opioid use (mg) during the hospital stay.</description>
          <population>The final study population.</population>
          <units>mg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24" lower_limit="15" upper_limit="69"/>
                    <measurement group_id="O2" value="24" lower_limit="15" upper_limit="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Opioid Related Side-effects (ORSDS)-POD1</title>
        <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1</description>
        <time_frame>postoperative day 1</time_frame>
        <population>The final study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Related Side-effects (ORSDS)-POD1</title>
          <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1</description>
          <population>The final study population.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.38" lower_limit="0" upper_limit="0.58"/>
                    <measurement group_id="O2" value="0.57" lower_limit="0" upper_limit="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Opioid Related Side-effects (ORSDS)-POD2</title>
        <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.</description>
        <time_frame>postoperative day 2</time_frame>
        <population>the final study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Related Side-effects (ORSDS)-POD2</title>
          <description>ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.</description>
          <population>the final study population.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" lower_limit="0" upper_limit="3.5"/>
                    <measurement group_id="O2" value="0.26" lower_limit="0.16" upper_limit="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>PACU Length of Stay, Hours</title>
        <description>Hours spent in PACU (Postanesthesia Care Unit).</description>
        <time_frame>in PACU</time_frame>
        <population>the final study population</population>
        <group_list>
          <group group_id="O1">
            <title>Lamotrigine</title>
            <description>Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.</description>
          </group>
        </group_list>
        <measure>
          <title>PACU Length of Stay, Hours</title>
          <description>Hours spent in PACU (Postanesthesia Care Unit).</description>
          <population>the final study population</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="1"/>
                    <measurement group_id="O2" value="2" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>from the beginning of the study to discharge, up to 10 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lamotrigine</title>
          <description>Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.&#xD;
Lamotrigine 300 MG: 300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P&lt;.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P&lt;.05).&#xD;
Ketamine: 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.&#xD;
Placebo: 300 mg of oral Placebo&#xD;
Ketamine: 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Kamal Maheshwari</name_or_title>
      <organization>Cleveland Clinic</organization>
      <phone>216-318-7235</phone>
      <email>maheshk@ccf.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03831854
org study id: 18-952
nct id: NCT03831854
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches
      peak level 1-4 hours after oral administration.
1:1 randomization without stratification use web-based software (Redcap) before surgery.
      Allocation will be concealed from the patient, the nurse, the operating room team. Both
      patient and the operating room team will be blinded to the treatment allocation (double
      blind).

      Standard preoperative care as per anesthesia care team. Patient will receive lamotrigine vs.
      placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral
      administration. Single dose lamotrigine is safe and is not associated with rash.

      Standard intraoperative care as per the anesthesia care team. All patients will receive
      Ketamine 1 mg/kg at induction. Ketamine 5mcg/kg/min will be started at induction and stopped
      at the end of surgery.

      Standard postoperative care as per PACU team. The psychologic side-effects will be measured
      using Brief Psychiatric Rating Scale (BPRS) using an online tool.

      Research fellow will receive standardized training in administering BPRS from Dr. Amit Anand
      using structured material. Dr. Anand has used this training for other current research
      projects.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomization without stratification
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
masking description: The Pharmacy will know the treatment
measure: Psychologic Side-effects
time frame: in PACU (up to 90 minutes after ketamine infusion)
description: The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score).
measure: Number of Patients With Psychologic Disturbances-
time frame: Up to 90 minutes of PACU arrival
description: The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of > 4 (having any symptoms present) were determined as having psychologic disturbance.
measure: Total Opioid Consumption in PACU (mg)
time frame: from entry to PACU to leaving PACU, up to 4 hours
description: Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)
measure: Pain Score in PACU
time frame: from entry to PACU to leaving PACU
description: Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.
measure: Number of Patients Who Had PONV (Postoperative Nausea Vomiting)
time frame: after surgery up to discharge
description: PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV.
measure: Daily Average Opioid Use During Hospital Stay
time frame: from admission up to discharge
description: The average daily opioid use (mg) during the hospital stay.
measure: Opioid Related Side-effects (ORSDS)-POD1
time frame: postoperative day 1
description: ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1
measure: Opioid Related Side-effects (ORSDS)-POD2
time frame: postoperative day 2
description: ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.
measure: PACU Length of Stay, Hours
time frame: in PACU
description: Hours spent in PACU (Postanesthesia Care Unit).
arm group label: lamotrigine
arm group type: Active Comparator
description: Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use.
intervention type: Drug
intervention name: Lamotrigine 300 MG
description: 300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05).
arm group label: lamotrigine
other name: Lamictal 300 mg
intervention type: Drug
intervention name: Placebo
description: 300 mg of oral Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Ketamine
description: 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery
arm group label: Placebo
arm group label: lamotrigine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lamotrigine
mesh term: Ketamine
sharing ipd: No
ipd description: There is no plan to make subjects data available to outside researchers
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 