<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/NCT01690988</url>
  </required_header>
  <id_info>
    <org_study_id>201206071</org_study_id>
    <nct_id>NCT01690988</nct_id>
  </id_info>
  <brief_title>The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial</brief_title>
  <acronym>PODCAST</acronym>
  <official_title>The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Harvard Medical School (HMS and HSDM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Virginia Mason Hospital/Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Delirium is a medical term or condition that includes a temporary inability to focus&#xD;
      attention and to think clearly. Delirium occurs commonly (10% to 70%) in patients older than&#xD;
      60 undergoing large surgeries. The purpose of this study is to test rigorously whether a drug&#xD;
      called ketamine can decrease the chance that patients will experience delirium after their&#xD;
      surgery. The investigators are also testing whether ketamine decreases postoperative pain,&#xD;
      postoperative opioid consumption, postoperative nausea and vomiting, ICU and hospital length&#xD;
      of stay, and adverse outcomes (e.g. hallucinations and nightmares).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Postoperative delirium is one of the most common complications of major surgery, affecting&#xD;
      between 10% and 70% of all elderly surgical patients. Delirium manifests as poor attention&#xD;
      and inability to think logically, and is associated with longer intensive care unit and&#xD;
      hospital stay, long lasting cognitive deterioration, and increased mortality rate. Studies&#xD;
      have shown that a low sub-anesthetic dose of ketamine, an anesthetic drug, has the potential&#xD;
      to decrease several postoperative complications, including delirium, pain, opioid&#xD;
      consumption, and nausea and vomiting. Low dose ketamine would be particularly appealing as a&#xD;
      drug to prevent delirium and other postoperative complications, as it is inexpensive and&#xD;
      extremely safe. However, these proposed benefits of ketamine in the perioperative setting&#xD;
      have not yet been tested in a large clinical trial. The investigators are therefore proposing&#xD;
      a pragmatic, exploratory clinical trial to support or refute the contention that low dose&#xD;
      ketamine decreases the incidence of postoperative delirium, with the possibility of&#xD;
      conducting a larger randomized clinical trial pending the results of this study. At the time&#xD;
      of enrollment, patients will undergo the same delirium and pain evaluation that will be used&#xD;
      postoperatively. Additionally patients will be screened for functional dependence using the&#xD;
      Barthel Index of Activities of Daily Living, for depression using the Geriatric Depression&#xD;
      Scale - Short Form, and for obstructive sleep apnea using the STOP-Bang criteria. They will&#xD;
      also be asked about any falls they have experienced in the six months prior to surgery.&#xD;
      Comorbid conditions, including the components of the Charlson Comorbidity Index, will be&#xD;
      obtained by reviewing the patients' medical records. Any available preoperative lab results,&#xD;
      including electrolytes and blood counts, will also be recorded.&#xD;
&#xD;
      Patients will be randomized to receive low dose ketamine or placebo following induction of&#xD;
      anesthesia and prior to surgical incision. Blinded observers will assess delirium on the&#xD;
      afternoon/evening of postoperative day 0 (if feasible) and twice daily (morning and&#xD;
      afternoon/evening with at least six hours between assessments) on postoperative days 1-3&#xD;
      using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care&#xD;
      Unit. Acute pain will be assessed via the observer-based Behavioral Pain Scale or Behavioral&#xD;
      Pain Scale (Non-Intubated) with subsequent administration of the patient-reported Visual&#xD;
      Analog Scale from postoperative days 0-3. Postoperative opioid consumption will be assessed&#xD;
      from the patients' medical charts for postoperative days 0-3. Postoperative nausea and&#xD;
      vomiting will be assessed via a patient-reported section of the Behavioral Pain Scale or&#xD;
      Behavioral Pain Scale (Non-Intubated) for postoperative days 0-3. ICU and/or hospital length&#xD;
      of stay will be assessed from the patients' medical charts. Adverse outcomes (e.g.&#xD;
      hallucinations and nightmares) will be assessed via the Confusion Assessment Method or the&#xD;
      Confusion Assessment Method for Intensive Care Unit for postoperative days 0-3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2014</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">June 26, 2016</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3</measure>
    <time_frame>Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients</time_frame>
    <description>According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.&#xD;
To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS &lt;-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.&#xD;
The primary comparison will be between the combined ketamine groups and the placebo group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Daily Maximum Pain Recorded</measure>
    <time_frame>Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments</time_frame>
    <description>Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Opioid Consumption</measure>
    <time_frame>Postoperative days 0-3</time_frame>
    <description>Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively&#xD;
Opioid Drugs included:&#xD;
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Postoperative Nausea and Vomiting</measure>
    <time_frame>Postoperative days 1-3</time_frame>
    <description>Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they &quot;currently have nausea/vomiting&quot; AM &amp; PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3&#xD;
The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU and/or Hospital Length of Stay</measure>
    <time_frame>Postoperative period</time_frame>
    <description>Assessed from patients' medical charts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Outcomes (Number of Patients With Hallucinations)</measure>
    <time_frame>Postoperative days 1-3</time_frame>
    <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Outcomes (Number of Patients With Nightmares)</measure>
    <time_frame>Postoperative days 1-3</time_frame>
    <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">746</enrollment>
  <condition>Delirium</condition>
  <arm_group>
    <arm_group_label>Ketamine (0.5 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal saline (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous normal saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine (1 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine (0.5 mg/kg)</intervention_name>
    <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
    <arm_group_label>Ketamine (0.5 mg/kg)</arm_group_label>
    <other_name>Ketalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline (placebo)</intervention_name>
    <description>Normal saline IV following induction of anesthesia or administration of sedative medications</description>
    <arm_group_label>Normal saline (placebo)</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine (1 mg/kg)</intervention_name>
    <description>Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
    <arm_group_label>Ketamine (1 mg/kg)</arm_group_label>
    <other_name>Ketalar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 60 and older&#xD;
&#xD;
          -  Competent to provide informed consent&#xD;
&#xD;
          -  Undergoing major surgery (e.g., open cardiac surgery, open or thoracoscopic thoracic&#xD;
             surgery, abdominal surgery, open urological surgery, open gynecological surgery, major&#xD;
             orthopedic surgery, major vascular surgery including endovascular procedures, major&#xD;
             ear, nose and throat surgery).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with an allergy to ketamine&#xD;
&#xD;
          -  Those in whom a significant elevation of blood pressure would constitute a serious&#xD;
             hazard (e.g., pheochromocytoma, aortic dissection)&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Patients with drug misuse history (e.g., ketamine, cocaine, heroin, amphetamine,&#xD;
             methamphetamine, MDMA, phencyclidine, lysergic acid, mescaline, psilocybin)&#xD;
&#xD;
          -  Patients taking anti-psychotic medications (e.g., chlorpromazine, clozapine,&#xD;
             olanzapine, risperidone, haloperidol, quetiapine, risperidone, paliperidone,&#xD;
             amisulpride, sertindole)&#xD;
&#xD;
          -  Patients with a weight outside the range 50 kg - 200 kg (110 lbs - 440 lbs)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George A Mashour, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniel A Emmert, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kane Pryor, MBBS</last_name>
    <role>Study Director</role>
    <affiliation>Cornell</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eric Jacobsohn, MB ChB</last_name>
    <role>Study Director</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Judith Hudetz, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hilary P Grocott, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael S Avidan, MBBCh</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sharon Inouye</last_name>
    <role>Study Director</role>
    <affiliation>Harvard Medical School (HMS and HSDM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Veselis</last_name>
    <role>Study Director</role>
    <affiliation>Memorial Sloan Kettering Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jayant Aveek</last_name>
    <role>Study Director</role>
    <affiliation>Postgraduate Institute of Medical Education and Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Heiko Kaiser</last_name>
    <role>Study Director</role>
    <affiliation>University of Bern</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephen Choi</last_name>
    <role>Study Chair</role>
    <affiliation>University of Toronto</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ryan Pong</last_name>
    <role>Study Chair</role>
    <affiliation>Virginia Mason Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gyujeong Noh</last_name>
    <role>Study Director</role>
    <affiliation>Asan Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Avidan MS, Fritz BA, Maybrier HR, Muench MR, Escallier KE, Chen Y, Ben Abdallah A, Veselis RA, Hudetz JA, Pagel PS, Noh G, Pryor K, Kaiser H, Arya VK, Pong R, Jacobsohn E, Grocott HP, Choi S, Downey RJ, Inouye SK, Mashour GA. The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial. BMJ Open. 2014 Sep 17;4(9):e005651. doi: 10.1136/bmjopen-2014-005651.</citation>
    <PMID>25231491</PMID>
  </reference>
  <results_reference>
    <citation>Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30. Erratum In: Lancet. 2017 Jul 15;390(10091):230.</citation>
    <PMID>28576285</PMID>
  </results_reference>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <results_first_submitted>September 15, 2017</results_first_submitted>
  <results_first_submitted_qc>March 30, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">May 2, 2018</results_first_posted>
  <last_update_submitted>May 2, 2018</last_update_submitted>
  <last_update_submitted_qc>May 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Michael Avidan</investigator_full_name>
    <investigator_title>Director, Institute of Quality Improvement, Research &amp; Informatics</investigator_title>
  </responsible_party>
  <keyword>Delirium</keyword>
  <keyword>ketamine</keyword>
  <keyword>surgery</keyword>
  <keyword>neurological complications</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>746 participants were consented to the study; however only 672 were randomly assigned as 74 participants were determined ineligible after consent. Reasons for ineligibility: operations were cancelled or patients withdrew from the study, etc.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ketamine (0.5 mg/kg)</title>
          <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
        </group>
        <group group_id="P2">
          <title>Normal Saline (Placebo)</title>
          <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
        </group>
        <group group_id="P3">
          <title>Ketamine (1 mg/kg)</title>
          <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="227"/>
                <participants group_id="P2" count="222"/>
                <participants group_id="P3" count="223"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="221"/>
                <participants group_id="P2" count="217"/>
                <participants group_id="P3" count="216"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Operation Cancelled</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Determined ineligible</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sedated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ketamine (0.5 mg/kg)</title>
          <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
        </group>
        <group group_id="B2">
          <title>Normal Saline (Placebo)</title>
          <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
        </group>
        <group group_id="B3">
          <title>Ketamine (1 mg/kg)</title>
          <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
        </group>
        <group group_id="B4">
          <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="227"/>
            <count group_id="B2" value="222"/>
            <count group_id="B3" value="223"/>
            <count group_id="B4" value="672"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="171"/>
                    <measurement group_id="B2" value="163"/>
                    <measurement group_id="B3" value="162"/>
                    <measurement group_id="B4" value="496"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="70" spread="7.2"/>
                    <measurement group_id="B2" value="70" spread="6.9"/>
                    <measurement group_id="B3" value="70" spread="7.3"/>
                    <measurement group_id="B4" value="70" spread="7.1"/>
                  </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="83"/>
                    <measurement group_id="B2" value="87"/>
                    <measurement group_id="B3" value="84"/>
                    <measurement group_id="B4" value="254"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                    <measurement group_id="B2" value="135"/>
                    <measurement group_id="B3" value="139"/>
                    <measurement group_id="B4" value="418"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="147"/>
                    <measurement group_id="B2" value="147"/>
                    <measurement group_id="B3" value="149"/>
                    <measurement group_id="B4" value="443"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="59"/>
                    <measurement group_id="B4" value="183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>India</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Korea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3</title>
        <description>According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.&#xD;
To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS &lt;-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.&#xD;
The primary comparison will be between the combined ketamine groups and the placebo group.</description>
        <time_frame>Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients</time_frame>
        <population>Of all 672 participants, data were analyzed AM and PM and post operative day 1 through day 3 for screened participants with a CAM. The overall incidence of delirium were compared, Ketamine 0.5 mg/kg and 1 mg/kg groups were combined as per-specified in the study protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg and 1 mg/kg)</title>
            <description>Both the 0.5 mg/kg and the 1mg/kg doses groups of Ketamine were combined for analysis)&#xD;
Low dose Ketamine (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3</title>
          <description>According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.&#xD;
To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS &lt;-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.&#xD;
The primary comparison will be between the combined ketamine groups and the placebo group.</description>
          <population>Of all 672 participants, data were analyzed AM and PM and post operative day 1 through day 3 for screened participants with a CAM. The overall incidence of delirium were compared, Ketamine 0.5 mg/kg and 1 mg/kg groups were combined as per-specified in the study protocol.</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="438"/>
                <count group_id="O2" value="217"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85"/>
                    <measurement group_id="O2" value="43"/>
                  </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>
            <groups_desc>The primary analysis was a comparison between the placebo control group and the combined ketamine groups</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Test of independence</non_inferiority_desc>
            <p_value>0.912</p_value>
            <method>Chi-squared</method>
            <param_type>Difference in Percentages</param_type>
            <param_value>0.36</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.301</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.07</ci_lower_limit>
            <ci_upper_limit>7.38</ci_upper_limit>
            <estimate_desc>Difference in delirium incidence between placebo control and combined ketamine groups.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Maximum Pain Recorded</title>
        <description>Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.</description>
        <time_frame>Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg )</title>
            <description>Low dose ketamine (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Maximum Pain Recorded</title>
          <description>Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.</description>
          <units>participants</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="227"/>
                <count group_id="O2" value="222"/>
                <count group_id="O3" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>VAS day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70" lower_limit="40" upper_limit="87"/>
                    <measurement group_id="O2" value="63.5" lower_limit="43" upper_limit="82"/>
                    <measurement group_id="O3" value="68" lower_limit="37.5" upper_limit="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56" lower_limit="30" upper_limit="80"/>
                    <measurement group_id="O2" value="59" lower_limit="31" upper_limit="80"/>
                    <measurement group_id="O3" value="57.5" lower_limit="27" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46" lower_limit="22.5" upper_limit="75"/>
                    <measurement group_id="O2" value="52.5" lower_limit="25.5" upper_limit="75"/>
                    <measurement group_id="O3" value="47" lower_limit="23" upper_limit="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BPS/BPS-NI day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3" upper_limit="5"/>
                    <measurement group_id="O2" value="4" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O3" value="4" lower_limit="3" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BPS/BPS-NI 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O3" value="3" lower_limit="3" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BPS/BPS-NI 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O3" value="3" lower_limit="3" 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>
            <groups_desc>We compared the combined average pain level (pain level at rest, taking a deep breath, and/or when moving) over the entire day (AM and PM).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.964</p_value>
            <method>ANOVA</method>
            <method_desc>one-way</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Opioid Consumption</title>
        <description>Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively&#xD;
Opioid Drugs included:&#xD;
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)</description>
        <time_frame>Postoperative days 0-3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg)</title>
            <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Opioid Consumption</title>
          <description>Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively&#xD;
Opioid Drugs included:&#xD;
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)</description>
          <units>mg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="222"/>
                <count group_id="O3" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.9" lower_limit="46.5" upper_limit="175.5"/>
                    <measurement group_id="O2" value="94.7" lower_limit="48" upper_limit="199"/>
                    <measurement group_id="O3" value="78.7" lower_limit="43.8" upper_limit="169"/>
                  </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>O3</group_id>
            </group_id_list>
            <groups_desc>All morphine equivalent drugs consumed by patients perioperatively&#xD;
Opioid Drugs included:&#xD;
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.476</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Postoperative Nausea and Vomiting</title>
        <description>Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they &quot;currently have nausea/vomiting&quot; AM &amp; PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3&#xD;
The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.</description>
        <time_frame>Postoperative days 1-3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg)</title>
            <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Postoperative Nausea and Vomiting</title>
          <description>Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they &quot;currently have nausea/vomiting&quot; AM &amp; PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3&#xD;
The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="222"/>
                <count group_id="O3" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72"/>
                    <measurement group_id="O2" value="73"/>
                    <measurement group_id="O3" value="64"/>
                  </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>
            <groups_desc>Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they &quot;currently have nausea/vomiting&quot; AM &amp; PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.572</p_value>
            <method>Chi-squared</method>
            <param_type>frequency-test</param_type>
            <param_value>0.572</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ICU and/or Hospital Length of Stay</title>
        <description>Assessed from patients' medical charts</description>
        <time_frame>Postoperative period</time_frame>
        <population>Outcome measure data were not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg)</title>
            <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>ICU and/or Hospital Length of Stay</title>
          <description>Assessed from patients' medical charts</description>
          <population>Outcome measure data were not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Outcomes (Number of Patients With Hallucinations)</title>
        <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit</description>
        <time_frame>Postoperative days 1-3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg)</title>
            <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Outcomes (Number of Patients With Hallucinations)</title>
          <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="222"/>
                <count group_id="O3" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="40"/>
                    <measurement group_id="O3" value="62"/>
                  </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>O3</group_id>
            </group_id_list>
            <groups_desc>Frequency of patients reporting hallucinations using the DSAQ instrument.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.01</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Outcomes (Number of Patients With Nightmares)</title>
        <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit</description>
        <time_frame>Postoperative days 1-3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine (0.5 mg/kg)</title>
            <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline (Placebo)</title>
            <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
          </group>
          <group group_id="O3">
            <title>Ketamine (1 mg/kg)</title>
            <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Outcomes (Number of Patients With Nightmares)</title>
          <description>Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="222"/>
                <count group_id="O3" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="34"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <p_value_desc>Patients where asked whether &quot;Following their surgery they had bad dreams or nightmares the response choices: Yes/No question The incidence of hallucination and nightmares were assessed separately and compared across the three study group.</p_value_desc>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessed up to 3 days (POD 0-3).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ketamine (0.5 mg/kg)</title>
          <description>Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</description>
        </group>
        <group group_id="E2">
          <title>Normal Saline (Placebo)</title>
          <description>Intravenous normal saline&#xD;
Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications</description>
        </group>
        <group group_id="E3">
          <title>Ketamine (1 mg/kg)</title>
          <description>High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.&#xD;
Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.</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="227"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="227"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="90" subjects_at_risk="227"/>
                <counts group_id="E2" subjects_affected="82" subjects_at_risk="222"/>
                <counts group_id="E3" subjects_affected="86" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia/Bleeding</sub_title>
                <counts group_id="E1" events="19" subjects_affected="19" subjects_at_risk="227"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="222"/>
                <counts group_id="E3" events="20" subjects_affected="20" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="227"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="222"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="227"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="222"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="16" subjects_affected="16" subjects_at_risk="227"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="222"/>
                <counts group_id="E3" events="15" subjects_affected="15" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibriliation</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="227"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="222"/>
                <counts group_id="E3" events="15" subjects_affected="15" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="227"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="222"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="227"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="222"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="227"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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. Michael Avidan</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-747-4155</phone>
      <email>avidanm@wustl.edu</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/NCT01690988
org study id: 201206071
nct id: NCT01690988
lead sponsor: 
collaborator: 
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has dmc: Yes
Delirium is a medical term or condition that includes a temporary inability to focus
      attention and to think clearly. Delirium occurs commonly (10% to 70%) in patients older than
      60 undergoing large surgeries. The purpose of this study is to test rigorously whether a drug
      called ketamine can decrease the chance that patients will experience delirium after their
      surgery. The investigators are also testing whether ketamine decreases postoperative pain,
      postoperative opioid consumption, postoperative nausea and vomiting, ICU and hospital length
      of stay, and adverse outcomes (e.g. hallucinations and nightmares).
Postoperative delirium is one of the most common complications of major surgery, affecting
      between 10% and 70% of all elderly surgical patients. Delirium manifests as poor attention
      and inability to think logically, and is associated with longer intensive care unit and
      hospital stay, long lasting cognitive deterioration, and increased mortality rate. Studies
      have shown that a low sub-anesthetic dose of ketamine, an anesthetic drug, has the potential
      to decrease several postoperative complications, including delirium, pain, opioid
      consumption, and nausea and vomiting. Low dose ketamine would be particularly appealing as a
      drug to prevent delirium and other postoperative complications, as it is inexpensive and
      extremely safe. However, these proposed benefits of ketamine in the perioperative setting
      have not yet been tested in a large clinical trial. The investigators are therefore proposing
      a pragmatic, exploratory clinical trial to support or refute the contention that low dose
      ketamine decreases the incidence of postoperative delirium, with the possibility of
      conducting a larger randomized clinical trial pending the results of this study. At the time
      of enrollment, patients will undergo the same delirium and pain evaluation that will be used
      postoperatively. Additionally patients will be screened for functional dependence using the
      Barthel Index of Activities of Daily Living, for depression using the Geriatric Depression
      Scale - Short Form, and for obstructive sleep apnea using the STOP-Bang criteria. They will
      also be asked about any falls they have experienced in the six months prior to surgery.
      Comorbid conditions, including the components of the Charlson Comorbidity Index, will be
      obtained by reviewing the patients' medical records. Any available preoperative lab results,
      including electrolytes and blood counts, will also be recorded.

      Patients will be randomized to receive low dose ketamine or placebo following induction of
      anesthesia and prior to surgical incision. Blinded observers will assess delirium on the
      afternoon/evening of postoperative day 0 (if feasible) and twice daily (morning and
      afternoon/evening with at least six hours between assessments) on postoperative days 1-3
      using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care
      Unit. Acute pain will be assessed via the observer-based Behavioral Pain Scale or Behavioral
      Pain Scale (Non-Intubated) with subsequent administration of the patient-reported Visual
      Analog Scale from postoperative days 0-3. Postoperative opioid consumption will be assessed
      from the patients' medical charts for postoperative days 0-3. Postoperative nausea and
      vomiting will be assessed via a patient-reported section of the Behavioral Pain Scale or
      Behavioral Pain Scale (Non-Intubated) for postoperative days 0-3. ICU and/or hospital length
      of stay will be assessed from the patients' medical charts. Adverse outcomes (e.g.
      hallucinations and nightmares) will be assessed via the Confusion Assessment Method or the
      Confusion Assessment Method for Intensive Care Unit for postoperative days 0-3.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3
time frame: Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients
description: According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.
To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS <-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.
The primary comparison will be between the combined ketamine groups and the placebo group.
measure: Daily Maximum Pain Recorded
time frame: Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments
description: Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.
measure: Median Opioid Consumption
time frame: Postoperative days 0-3
description: Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively
Opioid Drugs included:
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)
measure: Number of Patients With Postoperative Nausea and Vomiting
time frame: Postoperative days 1-3
description: Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they "currently have nausea/vomiting" AM & PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3
The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.
measure: ICU and/or Hospital Length of Stay
time frame: Postoperative period
description: Assessed from patients' medical charts
measure: Adverse Outcomes (Number of Patients With Hallucinations)
time frame: Postoperative days 1-3
description: Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit
measure: Adverse Outcomes (Number of Patients With Nightmares)
time frame: Postoperative days 1-3
description: Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit
arm group label: Ketamine (0.5 mg/kg)
arm group type: Experimental
description: Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
arm group label: Normal saline (placebo)
arm group type: Placebo Comparator
description: Intravenous normal saline
arm group label: Ketamine (1 mg/kg)
arm group type: Experimental
description: Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
intervention type: Drug
intervention name: Ketamine (0.5 mg/kg)
description: Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
arm group label: Ketamine (0.5 mg/kg)
other name: Ketalar
intervention type: Drug
intervention name: Normal Saline (placebo)
description: Normal saline IV following induction of anesthesia or administration of sedative medications
arm group label: Normal saline (placebo)
other name: Normal saline
intervention type: Drug
intervention name: Ketamine (1 mg/kg)
description: Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
arm group label: Ketamine (1 mg/kg)
other name: Ketalar
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: George A Mashour, MD PhD
role: Principal Investigator
affiliation: University of Michigan
last name: Daniel A Emmert, MD PhD
role: Study Director
affiliation: Washington University School of Medicine
last name: Kane Pryor, MBBS
role: Study Director
affiliation: Cornell
last name: Eric Jacobsohn, MB ChB
role: Study Director
affiliation: University of Manitoba
last name: Judith Hudetz, PhD
role: Study Director
affiliation: Medical College of Wisconsin
last name: Hilary P Grocott, MD
role: Study Chair
affiliation: University of Manitoba
last name: Michael S Avidan, MBBCh
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Sharon Inouye
role: Study Director
affiliation: Harvard Medical School (HMS and HSDM)
last name: Robert Veselis
role: Study Director
affiliation: Memorial Sloan Kettering Medical Center
last name: Jayant Aveek
role: Study Director
affiliation: Postgraduate Institute of Medical Education and Research
last name: Heiko Kaiser
role: Study Director
affiliation: University of Bern
last name: Stephen Choi
role: Study Chair
affiliation: University of Toronto
last name: Ryan Pong
role: Study Chair
affiliation: Virginia Mason Medical Center
last name: Gyujeong Noh
role: Study Director
affiliation: Asan Medical Center
facility: 
country: United States
citation: Avidan MS, Fritz BA, Maybrier HR, Muench MR, Escallier KE, Chen Y, Ben Abdallah A, Veselis RA, Hudetz JA, Pagel PS, Noh G, Pryor K, Kaiser H, Arya VK, Pong R, Jacobsohn E, Grocott HP, Choi S, Downey RJ, Inouye SK, Mashour GA. The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial. BMJ Open. 2014 Sep 17;4(9):e005651. doi: 10.1136/bmjopen-2014-005651.
PMID: 25231491
citation: Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30. Erratum In: Lancet. 2017 Jul 15;390(10091):230.
PMID: 28576285
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Michael Avidan
investigator title: Director, Institute of Quality Improvement, Research & Informatics
mesh term: Delirium
mesh term: Ketamine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 