<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/NCT03021486</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0687</org_study_id>
    <secondary_id>NCI-2017-01065</secondary_id>
    <secondary_id>2016-0687</secondary_id>
    <secondary_id>R21NR016736</secondary_id>
    <nct_id>NCT03021486</nct_id>
  </id_info>
  <brief_title>Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer</brief_title>
  <official_title>Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium in the Palliative Care Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This randomized phase II/III trial studies how well haloperidol with or without&#xD;
      chlorpromazine works in treating delirium in patients with cancer that has spread to other&#xD;
      parts of the body or has come back. Haloperidol and chlorpromazine may control the symptoms&#xD;
      of delirium (loss of contact with reality) in patients with cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Assess the within-arm effect of haloperidol dose escalation, rotation to chlorpromazine,&#xD;
      and combination therapy on agitation intensity (Richmond Agitation Sedation Scale [RASS])&#xD;
      over 24 hours in patients admitted to an acute palliative care unit (APCU) who did not&#xD;
      experience a response to low-dose haloperidol.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Obtain preliminary estimates of the effects of haloperidol dose escalation, rotation to&#xD;
      chlorpromazine, and combination therapy on (1) the proportion of patients with target RASS -2&#xD;
      to 0, (2) delirium-related distress in nurses and caregivers (delirium experience&#xD;
      questionnaire), (3) symptom expression (Edmonton Symptom Assessment Scale), (4) delirium&#xD;
      severity (Memorial Delirium Assessment Scale), (5) the need for neuroleptics, (6) delirium&#xD;
      recall (Delirium Recall Questionnaire), (7) adverse effects and (8) quality of end-of-life&#xD;
      (Quality of Death and Dying questionnaire) over time.&#xD;
&#xD;
      II. Obtain preliminary estimates of the between-arm effect size among haloperidol dose&#xD;
      escalation, rotation to chlorpromazine, and combination therapy in the first 24 hours.&#xD;
&#xD;
      III. To assess caregiver and nurse preferences regarding proxy sedation goals. IV. To examine&#xD;
      the feasibility of novel measures for the assessment of agitation with continuous video&#xD;
      monitoring.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 3 groups.&#xD;
&#xD;
      GROUP I: Patients receive haloperidol intravenously (IV) over 3-15 minutes every 4 hours in&#xD;
      the absence of unacceptable toxicity.&#xD;
&#xD;
      GROUP II: Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence&#xD;
      of unacceptable toxicity.&#xD;
&#xD;
      GROUP III: Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours&#xD;
      in the absence of unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 5, 2017</start_date>
  <completion_date type="Anticipated">June 5, 2023</completion_date>
  <primary_completion_date type="Actual">June 5, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Richmond Agitation Sedation Score (RASS) (0-24h)</measure>
    <time_frame>Time 0 or Baseline and 24 hours after study medication administration</time_frame>
    <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With RASS Score -2 to 0</measure>
    <time_frame>Time 0 or Baseline and 24 hours later.</time_frame>
    <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in RASS Score (0-30 Minutes)</measure>
    <time_frame>Time 0 or Baseline and 30 minutes later.</time_frame>
    <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With RASS Score of &gt;=1</measure>
    <time_frame>0 or Baseline and 24 hours later</time_frame>
    <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of &gt;=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pattern of Medication Use</measure>
    <time_frame>Baseline and 24 hours</time_frame>
    <description>Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived Comfort Level as Assessed by Caregiver</measure>
    <time_frame>Baseline and 24 hour</time_frame>
    <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived Comfort Level as Assessed by Nurse</measure>
    <time_frame>Baseline and 24 hour</time_frame>
    <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Delirium Experience Questionnaire</measure>
    <time_frame>Baseline and Day 3</time_frame>
    <description>This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Memorial Delirium Assessment Scale (MDAS)</measure>
    <time_frame>Baseline and 24 hours</time_frame>
    <description>The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Edmonton Expression Assessment System, ESAS</measure>
    <time_frame>Baseline and 24 hours</time_frame>
    <description>Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Udvalg for Kliniske Undersogelser, UKU</measure>
    <time_frame>Baseline and 3 days</time_frame>
    <description>We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Advanced Malignant Neoplasm</condition>
  <condition>Delirium</condition>
  <condition>Locally Advanced Malignant Neoplasm</condition>
  <condition>Metastatic Malignant Neoplasm</condition>
  <condition>Recurrent Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>Group I (haloperidol)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II (chlorpromazine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group III (haloperidol, chlorpromazine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorpromazine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Group II (chlorpromazine)</arm_group_label>
    <arm_group_label>Group III (haloperidol, chlorpromazine)</arm_group_label>
    <other_name>Chlor-PZ</other_name>
    <other_name>Thorazine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Group I (haloperidol)</arm_group_label>
    <arm_group_label>Group III (haloperidol, chlorpromazine)</arm_group_label>
    <other_name>Haldol</other_name>
    <other_name>McN-JR-1625</other_name>
    <other_name>R 1625</other_name>
    <other_name>R-1625</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (haloperidol)</arm_group_label>
    <arm_group_label>Group II (chlorpromazine)</arm_group_label>
    <arm_group_label>Group III (haloperidol, chlorpromazine)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (haloperidol)</arm_group_label>
    <arm_group_label>Group II (chlorpromazine)</arm_group_label>
    <arm_group_label>Group III (haloperidol, chlorpromazine)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion:&#xD;
&#xD;
          1. [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic&#xD;
             recurrent, or incurable disease)&#xD;
&#xD;
          2. [Patients] Admitted to the acute palliative care unit&#xD;
&#xD;
          3. [Patients] Delirium as per DSM-V criteria (The Diagnostic and Statistical Manual of&#xD;
             Mental Disorders, Fifth Edition (DSM-5))&#xD;
&#xD;
          4. [Patients] Hyperactive or mixed delirium with RASS &gt;/=1 in the past 24 h (RASS&gt;/=+1&#xD;
             indicates any degree of restlessness. In the electronic medical record nursing note,&#xD;
             this behavior would be indicated by any documentation of &quot;restless&quot;, &quot;agitated&quot;,&#xD;
             &quot;hyperactive&quot;, &quot;pulling on devices/IV&quot; or similar wording).&#xD;
&#xD;
          5. [Patients] On scheduled haloperidol for delirium (&lt;/=8 mg in the past 24 h) or rescue&#xD;
             haloperidol of &gt;/=4 mg for restlessness/agitation in the past 24 h&#xD;
&#xD;
          6. [Patients] Age 18 years or older&#xD;
&#xD;
          7. [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or&#xD;
             significant other (defined by the patient as a partner)&#xD;
&#xD;
          8. [Family Caregivers] Age 18 years or older&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. [Patients] History of myasthenia gravis or acute narrow angle glaucoma&#xD;
&#xD;
          2. [Patients] History of neuroleptic malignant syndrome or active seizure disorder (with&#xD;
             seizure episode within the past week)&#xD;
&#xD;
          3. [Patients] History of Parkinson's disease or Alzheimer's dementia&#xD;
&#xD;
          4. [Patients] History of prolonged QTc interval (&gt;500 ms) if documented by ECG within the&#xD;
             past month&#xD;
&#xD;
          5. [Patients] History of hypersensitivity to haloperidol or chlorpromazine&#xD;
&#xD;
          6. [Patients] On scheduled chlorpromazine within the past 48 h&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Hui</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <results_first_submitted>April 19, 2022</results_first_submitted>
  <results_first_submitted_qc>August 10, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 1, 2022</results_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Chlorpromazine</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 23, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03021486/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Adult participants (age&gt;18) with an active diagnosis of cancer were recruited between palliative and supportive Care unit at MD Anderson Cancer Center who met the inclusion and exclusion criteria.</recruitment_details>
      <pre_assignment_details>A total of 70 participants were consented, 2 were inevaluable and 68 were randomly assigned for interventions.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Escalation Group</title>
          <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>Rotation Group</title>
          <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
        </group>
        <group group_id="P3">
          <title>Combination Group</title>
          <description>Participants receive 1 mg of haloperidol and 12.5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</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="22"/>
                <participants group_id="P3" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not develop an RASS score of at least &gt;= 1</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Escalation Group</title>
          <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>Rotation Group</title>
          <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
        </group>
        <group group_id="B3">
          <title>Combination Group</title>
          <description>Participants receive 1 mg of haloperidol and 12.5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</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="15"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="14"/>
            <count group_id="B4" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65" lower_limit="61" upper_limit="75"/>
                    <measurement group_id="B2" value="63" lower_limit="59" upper_limit="70"/>
                    <measurement group_id="B3" value="60" lower_limit="57" upper_limit="74"/>
                    <measurement group_id="B4" value="64" lower_limit="58" upper_limit="72"/>
                  </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="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Some High school or less</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Completed High School</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Some College</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>College</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Advanced degree</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cancer Type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Breast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Genitourinary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gynecological</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematological</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Others</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Metastatic cancer or advanced stage disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Richmond Agitation Sedation Score (RASS) (0-24h)</title>
        <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
        <time_frame>Time 0 or Baseline and 24 hours after study medication administration</time_frame>
        <population>Analysis included 31 participants who completed 24 hours of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12.5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Richmond Agitation Sedation Score (RASS) (0-24h)</title>
          <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
          <population>Analysis included 31 participants who completed 24 hours of the study.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.6" lower_limit="-5.0" upper_limit="-2.2"/>
                    <measurement group_id="O2" value="-3.3" lower_limit="-4.4" upper_limit="-2.2"/>
                    <measurement group_id="O3" value="-3.0" lower_limit="-4.6" upper_limit="-1.4"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.71</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With RASS Score -2 to 0</title>
        <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
        <time_frame>Time 0 or Baseline and 24 hours later.</time_frame>
        <population>Analysis included 31 participants who completed 24 hours of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With RASS Score -2 to 0</title>
          <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
          <population>Analysis included 31 participants who completed 24 hours of the study.</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="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in RASS Score (0-30 Minutes)</title>
        <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
        <time_frame>Time 0 or Baseline and 30 minutes later.</time_frame>
        <population>Analysis included 45 participants who completed first 30 minutes of study</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in RASS Score (0-30 Minutes)</title>
          <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.</description>
          <population>Analysis included 45 participants who completed first 30 minutes of study</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" lower_limit="-3.6" upper_limit="-1.6"/>
                    <measurement group_id="O2" value="-2.4" lower_limit="-3.0" upper_limit="-1.8"/>
                    <measurement group_id="O3" value="-2.1" lower_limit="-3.0" upper_limit="-1.3"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.86</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With RASS Score of &gt;=1</title>
        <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of &gt;=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
        <time_frame>0 or Baseline and 24 hours later</time_frame>
        <population>Analysis included 45 participants who completed first 24 hours of study</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With RASS Score of &gt;=1</title>
          <description>RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of &gt;=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.</description>
          <population>Analysis included 45 participants who completed first 24 hours of study</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="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="9"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.12</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pattern of Medication Use</title>
        <description>Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.</description>
        <time_frame>Baseline and 24 hours</time_frame>
        <population>Analysis included 45 participants who were still on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Pattern of Medication Use</title>
          <description>Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.</description>
          <population>Analysis included 45 participants who were still on study.</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="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Need for study med dose escalation in first 24 hrs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Benzodiazepine use in first 24 hrs (scheduled)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Benzodiazepine use in first 24 hrs (as needed)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.007</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Perceived Comfort Level as Assessed by Caregiver</title>
        <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
        <time_frame>Baseline and 24 hour</time_frame>
        <population>Analysis included 37 participants who completed this questionnaire at that time point</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Perceived Comfort Level as Assessed by Caregiver</title>
          <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
          <population>Analysis included 37 participants who completed this questionnaire at that time point</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="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Perceived To Have A High Level of Comfort (More Comfortable)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Perceived To Have A Low Level of Agitation (Less Agitated)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="6"/>
                  </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>Perceived Comfort level as assessed by caregiver</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.83</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Perceived agitation level as assessed by caregiver</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.82</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Perceived Comfort Level as Assessed by Nurse</title>
        <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
        <time_frame>Baseline and 24 hour</time_frame>
        <population>Analysis included 37 participants who completed this questionnaire at that time point</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Perceived Comfort Level as Assessed by Nurse</title>
          <description>On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from &quot;strongly agree&quot;, &quot;agree&quot;, &quot;neutral&quot;, &quot;disagree&quot;, and &quot;strongly disagree&quot;. In this study, &quot;strongly agree&quot; and &quot;agree&quot; were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).</description>
          <population>Analysis included 37 participants who completed this questionnaire at that time point</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="14"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Perceived To Have A High Level of Comfort (More Comfortable)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Perceived To Have A Low Level of Agitation (Less Agitated)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="7"/>
                  </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>Perceived Comfort level as assessed by nurse</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.82</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Perceived agitation level as assessed by nurse</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.91</p_value>
            <method>Two-tailed Fisher's exact test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Delirium Experience Questionnaire</title>
        <description>This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3.</description>
        <time_frame>Baseline and Day 3</time_frame>
        <population>Analysis included 37 participants who completed this questionnaire at that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Delirium Experience Questionnaire</title>
          <description>This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3.</description>
          <population>Analysis included 37 participants who completed this questionnaire at that time point.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Nursing assessment, disorientation to time - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" lower_limit="-1.7" upper_limit="0.1"/>
                    <measurement group_id="O2" value="-0.8" lower_limit="-1.6" upper_limit="0.1"/>
                    <measurement group_id="O3" value="0.2" lower_limit="-0.8" upper_limit="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, disorientation to place - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" lower_limit="-1.7" upper_limit="-0.1"/>
                    <measurement group_id="O2" value="-0.8" lower_limit="-1.7" upper_limit="0.2"/>
                    <measurement group_id="O3" value="0.3" lower_limit="-0.7" upper_limit="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, visual hallucination - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1" lower_limit="-1.6" upper_limit="-0.5"/>
                    <measurement group_id="O2" value="0" lower_limit="-0.6" upper_limit="0.6"/>
                    <measurement group_id="O3" value="-0.7" lower_limit="-1.5" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, tactile hallucination - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" lower_limit="-1.1" upper_limit="0.3"/>
                    <measurement group_id="O2" value="0.1" lower_limit="-0.1" upper_limit="0.3"/>
                    <measurement group_id="O3" value="-0.9" lower_limit="-1.7" upper_limit="-0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, auditory hallucination - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" lower_limit="-0.5" upper_limit="0.2"/>
                    <measurement group_id="O2" value="0.1" lower_limit="-0.1" upper_limit="0.3"/>
                    <measurement group_id="O3" value="-0.4" lower_limit="-0.8" upper_limit="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, delusional thoughts - frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" lower_limit="-1.5" upper_limit="0"/>
                    <measurement group_id="O2" value="0" lower_limit="-0.3" upper_limit="0.3"/>
                    <measurement group_id="O3" value="0.2" lower_limit="-0.5" upper_limit="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, psychomotor agitation- frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" lower_limit="-1.9" upper_limit="-0.5"/>
                    <measurement group_id="O2" value="-0.8" lower_limit="-1.7" upper_limit="0"/>
                    <measurement group_id="O3" value="-0.4" lower_limit="-1" upper_limit="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, disorientation to time - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" lower_limit="-0.6" upper_limit="0.1"/>
                    <measurement group_id="O2" value="-0.3" lower_limit="-0.7" upper_limit="0.2"/>
                    <measurement group_id="O3" value="-0.5" lower_limit="-1.2" upper_limit="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, disorientation to place - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" lower_limit="-0.6" upper_limit="0.1"/>
                    <measurement group_id="O2" value="-0.3" lower_limit="-0.7" upper_limit="0.2"/>
                    <measurement group_id="O3" value="-0.4" lower_limit="-1.1" upper_limit="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, visual hallucination - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" lower_limit="-1.3" upper_limit="0"/>
                    <measurement group_id="O2" value="0.1" lower_limit="-0.1" upper_limit="0.3"/>
                    <measurement group_id="O3" value="-0.4" lower_limit="-0.9" upper_limit="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, tactile hallucination - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-1.1" upper_limit="0.1"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="-0.5" lower_limit="-1.1" upper_limit="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, auditory hallucination - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" lower_limit="-0.9" upper_limit="0.3"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="-0.2" lower_limit="-0.6" upper_limit="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, delusional thoughts - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" lower_limit="-1.4" upper_limit="0.1"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="-0.1" lower_limit="-0.6" upper_limit="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nursing assessment, psychomotor agitation - distress</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" lower_limit="-1.4" upper_limit="-0.2"/>
                    <measurement group_id="O2" value="-0.5" lower_limit="-0.9" upper_limit="-0.1"/>
                    <measurement group_id="O3" value="-0.8" lower_limit="-1.5" upper_limit="-0.1"/>
                  </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>Nursing assessment, disorientation to time - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.12</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, disorientation to place - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.07</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, visual hallucination - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.051</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, tactile hallucination - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.048</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, auditory hallucination - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.15</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, delusional thoughts - frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.10</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, psychomotor agitation- frequency</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.15</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, disorientation to time - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.98</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, disorientation to place - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.93</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, visual hallucination - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.08</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, tactile hallucination - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.28</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, auditory hallucination - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.83</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, delusional thoughts - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.22</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Nursing assessment, psychomotor agitation - distress</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.75</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Memorial Delirium Assessment Scale (MDAS)</title>
        <description>The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours.</description>
        <time_frame>Baseline and 24 hours</time_frame>
        <population>Analysis included 30 participants who completed this questionnaire at that time point</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12.5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Memorial Delirium Assessment Scale (MDAS)</title>
          <description>The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours.</description>
          <population>Analysis included 30 participants who completed this questionnaire at that time point</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" lower_limit="-6" upper_limit="0.7"/>
                    <measurement group_id="O2" value="1" lower_limit="-0.3" upper_limit="2.3"/>
                    <measurement group_id="O3" value="0.3" lower_limit="-2.9" upper_limit="3.5"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.09</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Edmonton Expression Assessment System, ESAS</title>
        <description>Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean.</description>
        <time_frame>Baseline and 24 hours</time_frame>
        <population>Analysis included 33 participants who completed this questionnaire at that time point. Note that 9 participants completed 'feeling of well being' question for Combination group, and 13 participants completed 'pain' and 'sleep' questions for Escalation group</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Edmonton Expression Assessment System, ESAS</title>
          <description>Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean.</description>
          <population>Analysis included 33 participants who completed this questionnaire at that time point. Note that 9 participants completed 'feeling of well being' question for Combination group, and 13 participants completed 'pain' and 'sleep' questions for Escalation group</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" lower_limit="-3.1" upper_limit="0.5"/>
                    <measurement group_id="O2" value="-4.1" lower_limit="-5.8" upper_limit="-2.4"/>
                    <measurement group_id="O3" value="-1.1" lower_limit="-2.3" upper_limit="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-2.6" upper_limit="1.6"/>
                    <measurement group_id="O2" value="-3" lower_limit="-5.9" upper_limit="-0.1"/>
                    <measurement group_id="O3" value="1" lower_limit="-0.8" upper_limit="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="-0.3" upper_limit="0.5"/>
                    <measurement group_id="O2" value="-1.8" lower_limit="-3.1" upper_limit="-0.5"/>
                    <measurement group_id="O3" value="-0.4" lower_limit="-1.1" upper_limit="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" lower_limit="-3.2" upper_limit="0.4"/>
                    <measurement group_id="O2" value="-1.2" lower_limit="-3.6" upper_limit="1.2"/>
                    <measurement group_id="O3" value="-0.8" lower_limit="-2.3" upper_limit="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" lower_limit="-3.7" upper_limit="0.7"/>
                    <measurement group_id="O2" value="-4.8" lower_limit="-6.6" upper_limit="-3.1"/>
                    <measurement group_id="O3" value="-0.9" lower_limit="-3.4" upper_limit="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drowsiness</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" lower_limit="-1.9" upper_limit="1.6"/>
                    <measurement group_id="O2" value="-0.6" lower_limit="-2.2" upper_limit="1.1"/>
                    <measurement group_id="O3" value="0.7" lower_limit="-1.8" upper_limit="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" lower_limit="-2" upper_limit="6.2"/>
                    <measurement group_id="O2" value="-0.6" lower_limit="-4" upper_limit="2.9"/>
                    <measurement group_id="O3" value="0.1" lower_limit="-2.3" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Feeling of well being*</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="-2" upper_limit="2.3"/>
                    <measurement group_id="O2" value="-1.6" lower_limit="-4.7" upper_limit="1.6"/>
                    <measurement group_id="O3" value="0" lower_limit="-2.7" upper_limit="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Shortness of breath</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" lower_limit="0" upper_limit="1.6"/>
                    <measurement group_id="O2" value="-2.2" lower_limit="-5" upper_limit="0.6"/>
                    <measurement group_id="O3" value="0" lower_limit="-1.7" upper_limit="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" lower_limit="-4.7" upper_limit="-0.7"/>
                    <measurement group_id="O2" value="-5.1" lower_limit="-7.3" upper_limit="-2.9"/>
                    <measurement group_id="O3" value="-2.7" lower_limit="-4.5" upper_limit="-0.9"/>
                  </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>Mean change in pain.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Fatigue.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.10</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Nausea.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Depression.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.97</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Anxiety.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Drowsiness.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.68</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Appetite.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.80</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Feeling of well being.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.45</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Shortness of breath.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.16</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean change in Sleep.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.12</p_value>
            <method>Wilcoxon Rank Sum Test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Udvalg for Kliniske Undersogelser, UKU</title>
        <description>We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days.</description>
        <time_frame>Baseline and 3 days</time_frame>
        <population>Analysis included 25 participants who were still on study</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Group</title>
            <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Rotation Group</title>
            <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Combination Group</title>
            <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Udvalg for Kliniske Undersogelser, UKU</title>
          <description>We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days.</description>
          <population>Analysis included 25 participants who were still on study</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="7"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tremor (decreased)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Akathisia (decreased)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline and 24 hr.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Escalation Group (Haloperidol Dose Escalation Group)</title>
          <description>Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>Rotation Group</title>
          <description>Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</description>
        </group>
        <group group_id="E3">
          <title>Combination Group</title>
          <description>Participants receive 1 mg of haloperidol and 12·5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.</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="14" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.3)</default_vocab>
        <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="6" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Apnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </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>David Hui, MD- Associate Professor, Palliative Care Medicine</name_or_title>
      <organization>UT MD Anderson Cancer Center</organization>
      <phone>(713) 792-6258</phone>
      <email>dhui@mdanderson.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/NCT03021486
org study id: 2016-0687
secondary id: NCI-2017-01065
secondary id: 2016-0687
secondary id: R21NR016736
nct id: NCT03021486
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II/III trial studies how well haloperidol with or without
      chlorpromazine works in treating delirium in patients with cancer that has spread to other
      parts of the body or has come back. Haloperidol and chlorpromazine may control the symptoms
      of delirium (loss of contact with reality) in patients with cancer.
PRIMARY OBJECTIVES:

      I. Assess the within-arm effect of haloperidol dose escalation, rotation to chlorpromazine,
      and combination therapy on agitation intensity (Richmond Agitation Sedation Scale [RASS])
      over 24 hours in patients admitted to an acute palliative care unit (APCU) who did not
      experience a response to low-dose haloperidol.

      SECONDARY OBJECTIVES:

      I. Obtain preliminary estimates of the effects of haloperidol dose escalation, rotation to
      chlorpromazine, and combination therapy on (1) the proportion of patients with target RASS -2
      to 0, (2) delirium-related distress in nurses and caregivers (delirium experience
      questionnaire), (3) symptom expression (Edmonton Symptom Assessment Scale), (4) delirium
      severity (Memorial Delirium Assessment Scale), (5) the need for neuroleptics, (6) delirium
      recall (Delirium Recall Questionnaire), (7) adverse effects and (8) quality of end-of-life
      (Quality of Death and Dying questionnaire) over time.

      II. Obtain preliminary estimates of the between-arm effect size among haloperidol dose
      escalation, rotation to chlorpromazine, and combination therapy in the first 24 hours.

      III. To assess caregiver and nurse preferences regarding proxy sedation goals. IV. To examine
      the feasibility of novel measures for the assessment of agitation with continuous video
      monitoring.

      OUTLINE: Patients are randomized to 1 of 3 groups.

      GROUP I: Patients receive haloperidol intravenously (IV) over 3-15 minutes every 4 hours in
      the absence of unacceptable toxicity.

      GROUP II: Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence
      of unacceptable toxicity.

      GROUP III: Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours
      in the absence of unacceptable toxicity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Richmond Agitation Sedation Score (RASS) (0-24h)
time frame: Time 0 or Baseline and 24 hours after study medication administration
description: RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.
measure: Percentage of Participants With RASS Score -2 to 0
time frame: Time 0 or Baseline and 24 hours later.
description: RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.
measure: Change in RASS Score (0-30 Minutes)
time frame: Time 0 or Baseline and 30 minutes later.
description: RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.
measure: Number of Participants With RASS Score of >=1
time frame: 0 or Baseline and 24 hours later
description: RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of >=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.
measure: Pattern of Medication Use
time frame: Baseline and 24 hours
description: Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.
measure: Perceived Comfort Level as Assessed by Caregiver
time frame: Baseline and 24 hour
description: On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from "strongly agree", "agree", "neutral", "disagree", and "strongly disagree". In this study, "strongly agree" and "agree" were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).
measure: Perceived Comfort Level as Assessed by Nurse
time frame: Baseline and 24 hour
description: On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from "strongly agree", "agree", "neutral", "disagree", and "strongly disagree". In this study, "strongly agree" and "agree" were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).
measure: Change in Delirium Experience Questionnaire
time frame: Baseline and Day 3
description: This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3.
measure: Memorial Delirium Assessment Scale (MDAS)
time frame: Baseline and 24 hours
description: The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours.
measure: Edmonton Expression Assessment System, ESAS
time frame: Baseline and 24 hours
description: Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean.
measure: Udvalg for Kliniske Undersogelser, UKU
time frame: Baseline and 3 days
description: We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days.
arm group label: Group I (haloperidol)
arm group type: Experimental
description: Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
arm group label: Group II (chlorpromazine)
arm group type: Experimental
description: Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
arm group label: Group III (haloperidol, chlorpromazine)
arm group type: Experimental
description: Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
intervention type: Drug
intervention name: Chlorpromazine
description: Given IV
arm group label: Group II (chlorpromazine)
arm group label: Group III (haloperidol, chlorpromazine)
other name: Chlor-PZ
other name: Thorazine
intervention type: Drug
intervention name: Haloperidol
description: Given IV
arm group label: Group I (haloperidol)
arm group label: Group III (haloperidol, chlorpromazine)
other name: Haldol
other name: McN-JR-1625
other name: R 1625
other name: R-1625
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Group I (haloperidol)
arm group label: Group II (chlorpromazine)
arm group label: Group III (haloperidol, chlorpromazine)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Group I (haloperidol)
arm group label: Group II (chlorpromazine)
arm group label: Group III (haloperidol, chlorpromazine)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Hui
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Delirium
mesh term: Recurrence
mesh term: Haloperidol
mesh term: Chlorpromazine
mesh term: Haloperidol decanoate
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 