<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/NCT02213900</url>
  </required_header>
  <id_info>
    <org_study_id>VFR-398-Khan</org_study_id>
    <nct_id>NCT02213900</nct_id>
  </id_info>
  <brief_title>Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy</brief_title>
  <acronym>PE-POD</acronym>
  <official_title>Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effectiveness of a preventative low-dose of&#xD;
      Haloperidol to prevent delirium in patients undergoing a esophagectomy, pneumonectomy or&#xD;
      thoracotomy.&#xD;
&#xD;
      Delirium is state of severe confusion and some symptoms include:&#xD;
&#xD;
        -  Cannot think clearly&#xD;
&#xD;
        -  Have trouble paying attention&#xD;
&#xD;
        -  Have a hard time understanding what is going on around them&#xD;
&#xD;
        -  May see or hear things that are not there. These things seem very real to them.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      50% of patients who undergo esophageal and/or lung resection suffer from acute brain&#xD;
      dysfunction or delirium postoperatively. Delirium is a state of brain failure characterized&#xD;
      by disturbance of consciousness with reduced ability to focus, sustain, or shift attention&#xD;
      that occurs over a short period of time and tends to fluctuate over the course of the day.&#xD;
      Presence of delirium in the post-operative phase is associated with a longer length of both&#xD;
      intensive care unit and hospital stay, increased health-care costs, long-term functional and&#xD;
      cognitive decline, and an increased risk of in-hospital and post-discharge mortality.&#xD;
&#xD;
      Haloperidol primarily acts by blocking dopamine (D2) receptors. This dopamine blockade in the&#xD;
      cerebral cortex improves cognition and reduces delirium. Along with the dopamine blockade,&#xD;
      haloperidol has anti-inflammatory properties. It inhibits production of lipopolysaccharide&#xD;
      induced pro-inflammatory cytokines, interleukin (IL-1) and tumor necrosis factor alpha&#xD;
      (TNF-α). Haloperidol also increases levels of Interleukin -1 receptor antagonist (IL-1RA), an&#xD;
      anti-inflammatory cytokine that blocks the action of other pro-inflammatory cytokines. If&#xD;
      unchecked, the inflammatory cytokines cause impaired concentration, sleep disturbances, and&#xD;
      agitation the cardinal symptoms of delirium; and induce a reduction in cholinergic activity.&#xD;
      Given the inhibitory effect of acetylcholine on certain cytokines such as interleukin-6, a&#xD;
      repetitive cycle of inadequate regulation of inflammation due to cholinergic depletion&#xD;
      ensues. Haloperidol with its anti-inflammatory properties seeks to mitigate this repetitive&#xD;
      vicious cycle.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of Low-dose Haloperidol in Reducing Days With Delirium</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay</measure>
    <time_frame>Date of hospital admission through date of hospital discharge, up to 3 weeks on average.</time_frame>
    <description>Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up</measure>
    <time_frame>Up to 3 months after hospital discharge on average.</time_frame>
    <description>Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Delirium</condition>
  <condition>Cognitive Impairment</condition>
  <condition>Post-traumatic Stress Disorder</condition>
  <condition>Depression</condition>
  <condition>Anxiety</condition>
  <arm_group>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol</intervention_name>
    <description>0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
    <arm_group_label>Haloperidol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. At least ≥ 18 years of age and older&#xD;
&#xD;
          2. Undergoing a possible or scheduled thoracotomy&#xD;
&#xD;
          3. English speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of Schizophrenia and Parkinson's disease&#xD;
&#xD;
          2. History of Severe Dementia&#xD;
&#xD;
          3. History of Alcohol Abuse&#xD;
&#xD;
          4. On Cholinesterase Inhibitors or Levodopa&#xD;
&#xD;
          5. Pregnant or Nursing&#xD;
&#xD;
          6. Corrected QT interval &gt; 550 milliseconds at the time of randomization&#xD;
&#xD;
          7. History of Neuroleptic Malignant Syndrome or Haloperidol Allergy&#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>Babar A Khan, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Regenstrief Institute, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kenneth A Kesler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IU School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>March 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <results_first_submitted>December 30, 2016</results_first_submitted>
  <results_first_submitted_qc>March 2, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2017</results_first_posted>
  <last_update_submitted>March 2, 2017</last_update_submitted>
  <last_update_submitted_qc>March 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Regenstrief Institute, Inc.</investigator_affiliation>
    <investigator_full_name>Babar Khan, MD, MS</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>delirium</keyword>
  <keyword>confusion</keyword>
  <keyword>surgery</keyword>
  <keyword>cognitive Impairment</keyword>
  <keyword>post-traumatic Stress disorder</keyword>
  <keyword>depression</keyword>
  <keyword>anxiety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Haloperidol</title>
          <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
                <participants group_id="P2" count="67"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
                <participants group_id="P2" count="67"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Haloperidol</title>
          <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="68"/>
            <count group_id="B2" value="67"/>
            <count group_id="B3" value="135"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" spread="12.4"/>
                    <measurement group_id="B2" value="59.6" spread="14.0"/>
                    <measurement group_id="B3" value="59.6" spread="13.2"/>
                  </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="22"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence</title>
        <description>Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
        <time_frame>Up to 30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol</title>
            <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence</title>
          <description>Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of Low-dose Haloperidol in Reducing Days With Delirium</title>
        <description>Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
        <time_frame>Up to 30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol</title>
            <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Low-dose Haloperidol in Reducing Days With Delirium</title>
          <description>Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.</description>
          <units>Days with Delirium</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="0.7"/>
                    <measurement group_id="O2" value="0.5" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay</title>
        <description>Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.</description>
        <time_frame>Date of hospital admission through date of hospital discharge, up to 3 weeks on average.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol</title>
            <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay</title>
          <description>Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.</description>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ICU Length of Stay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="2.2"/>
                    <measurement group_id="O2" value="2.8" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Length of Stay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.3" spread="3.5"/>
                    <measurement group_id="O2" value="10.2" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up</title>
        <description>Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.</description>
        <time_frame>Up to 3 months after hospital discharge on average.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol</title>
            <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up</title>
          <description>Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.</description>
          <units>Units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline RBANS Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.7" spread="27.6"/>
                    <measurement group_id="O2" value="30.1" spread="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 Month RBANS Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.8" spread="30.1"/>
                    <measurement group_id="O2" value="22.7" spread="23.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Haloperidol</title>
          <description>Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.&#xD;
Haloperidol: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="67"/>
              </event>
              <event>
                <sub_title>Life Threatening Episode</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="67"/>
              </event>
              <event>
                <sub_title>Inpatient or Prolonged Current Hospitalization</sub_title>
                <description>Could include significant incapacitation or an episode requiring intervention to prevent permanent impairment.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Babar Khan, MD</name_or_title>
      <organization>Indiana University</organization>
      <phone>317-274-9132</phone>
      <email>bakhan@iu.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02213900
org study id: VFR-398-Khan
nct id: NCT02213900
lead sponsor: 
has dmc: Yes
The purpose of this study is to investigate the effectiveness of a preventative low-dose of
      Haloperidol to prevent delirium in patients undergoing a esophagectomy, pneumonectomy or
      thoracotomy.

      Delirium is state of severe confusion and some symptoms include:

        -  Cannot think clearly

        -  Have trouble paying attention

        -  Have a hard time understanding what is going on around them

        -  May see or hear things that are not there. These things seem very real to them.
50% of patients who undergo esophageal and/or lung resection suffer from acute brain
      dysfunction or delirium postoperatively. Delirium is a state of brain failure characterized
      by disturbance of consciousness with reduced ability to focus, sustain, or shift attention
      that occurs over a short period of time and tends to fluctuate over the course of the day.
      Presence of delirium in the post-operative phase is associated with a longer length of both
      intensive care unit and hospital stay, increased health-care costs, long-term functional and
      cognitive decline, and an increased risk of in-hospital and post-discharge mortality.

      Haloperidol primarily acts by blocking dopamine (D2) receptors. This dopamine blockade in the
      cerebral cortex improves cognition and reduces delirium. Along with the dopamine blockade,
      haloperidol has anti-inflammatory properties. It inhibits production of lipopolysaccharide
      induced pro-inflammatory cytokines, interleukin (IL-1) and tumor necrosis factor alpha
      (TNF-α). Haloperidol also increases levels of Interleukin -1 receptor antagonist (IL-1RA), an
      anti-inflammatory cytokine that blocks the action of other pro-inflammatory cytokines. If
      unchecked, the inflammatory cytokines cause impaired concentration, sleep disturbances, and
      agitation the cardinal symptoms of delirium; and induce a reduction in cholinergic activity.
      Given the inhibitory effect of acetylcholine on certain cytokines such as interleukin-6, a
      repetitive cycle of inadequate regulation of inflammation due to cholinergic depletion
      ensues. Haloperidol with its anti-inflammatory properties seeks to mitigate this repetitive
      vicious cycle.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence
time frame: Up to 30 days
description: Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.
measure: Efficacy of Low-dose Haloperidol in Reducing Days With Delirium
time frame: Up to 30 days
description: Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo.
measure: Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay
time frame: Date of hospital admission through date of hospital discharge, up to 3 weeks on average.
description: Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo.
measure: Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up
time frame: Up to 3 months after hospital discharge on average.
description: Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment.
arm group label: Haloperidol
arm group type: Experimental
description: Randomized patients will receive 0.5mg Haloperidol immediately after surgery and Q8H following the initial dose for a total of 4 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Randomized patients will receive a placebo solution immediately after surgery and Q8H following for a total of 4 days.
intervention type: Drug
intervention name: Haloperidol
description: 0.5mg IV Push immediately after surgery and Q8H following for a total of 4 days
arm group label: Haloperidol
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Babar A Khan, MD, MS
role: Principal Investigator
affiliation: Regenstrief Institute, Inc.
last name: Kenneth A Kesler, MD
role: Principal Investigator
affiliation: IU School of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Regenstrief Institute, Inc.
investigator full name: Babar Khan, MD, MS
investigator title: Principle Investigator
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Depression
mesh term: Cognitive Dysfunction
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
mesh term: Haloperidol
mesh term: Haloperidol decanoate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 