<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/NCT02203019</url>
  </required_header>
  <id_info>
    <org_study_id>L14-136</org_study_id>
    <nct_id>NCT02203019</nct_id>
  </id_info>
  <brief_title>Study of Sedative Medications in Patients With Severe Infection and Respiratory Failure</brief_title>
  <acronym>PRO-DEFENSE</acronym>
  <official_title>PRO-DEFENSE: Propofol Versus Dexmedetomidine for Sedation in Mechanically Ventilated Patients With Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Tech University Health Sciences Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas Tech University Health Sciences Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with infections in their blood often become very sick. These patients are usually&#xD;
      put in an intensive care unit for careful observation and treatment. These patients may&#xD;
      develop a low blood pressure, lung failure, and kidney failure. When these problems develop,&#xD;
      care becomes quite complicated. Patients with lung failure often need help with a breathing&#xD;
      machine to make certain that the breathing is adequate. The machine helps keep the oxygen&#xD;
      level high enough for healthy tissues. When patients are placed on the machine for breathing&#xD;
      they require a tube to be placed into lungs. This can be quite uncomfortable. These patients&#xD;
      need sedation to help them tolerate the uncomfortable breathing tube and other parts of their&#xD;
      routine necessary care. This study will compare two drugs (dexmedetomidine and propofol)&#xD;
      which are frequently used for sedation in intensive care patients. Clinical studies suggest&#xD;
      that these drugs are both effective and safe. The main question is whether or not one of the&#xD;
      drugs is better in a patient with a blood infection. This study will try to determine that.&#xD;
      Our main goal is to see whether or not patients on one particular drug come off the breathing&#xD;
      machine faster than patients on the other drug. These drugs are not experimental drugs and&#xD;
      are approved by the Food and Drug Administration. There is no placebo drug being used in this&#xD;
      study. All patients in this study will receive the best possible care based on their medical&#xD;
      condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients admitted to the MICU with acute respiratory care and possible sepsis will be&#xD;
      evaluated and managed by the internal medicine MICU team. This team includes faculty members,&#xD;
      pulmonary fellows, and internal medicine residents. These physicians will make all the&#xD;
      decisions regarding the initial management of the patient. The admitting team will be&#xD;
      approached by the study investigators to solicit their support for the recruitment of the&#xD;
      patient into the study. During some periods of time the study investigators will be directly&#xD;
      involved in the patient care.&#xD;
&#xD;
      The general approach to managing patients with sepsis includes blood cultures, serum lactate&#xD;
      levels, and empiric antibiotics. Other cultures from the respiratory tract, urinary tract,&#xD;
      and other sites are also obtained as indicated. Empiric antibiotic choices will be based on&#xD;
      the most likely source of infection. Patient will receive fluid administration and&#xD;
      vasopressors to maintain mean arterial pressure blood pressures greater than or equal to 60&#xD;
      mmHg.&#xD;
&#xD;
      Mechanical ventilation support will follow ARDS network guidelines. In general patients will&#xD;
      be on an assist-control mode, a low tidal volume (6 mm/kg ideal body weight), and a FiO2&#xD;
      adequate to maintain O2 saturations greater than equal to 90%. PEEP levels will be based on&#xD;
      the FiO2 using ARDS network recommendations. The ventilator management goal is to have the&#xD;
      lowest possible plateau pressure and lowest FiO2 possible to maintain adequate ventilation&#xD;
      and oxygenation.&#xD;
&#xD;
      Fentanyl will be routinely ordered for analgesia. Per current UMC policy, initial fentanyl&#xD;
      boluses will be given at 50mcg IV every 2 hours as needed to keep pain level less than 4/10.&#xD;
      At the discretion of the provider, a fentanyl drip may be administered if intermittent&#xD;
      fentanyl does not achieve adequate analgesia. If a fentanyl drip is initiated, the drip will&#xD;
      have a range of 25-200 mcg/hour to achieve a pain level of less than 4/10. If an allergy to&#xD;
      fentanyl is documented, the patient will be excluded from the study.&#xD;
&#xD;
      Once a mechanically ventilated patient with sepsis is selected for enrollment, the patient&#xD;
      will be randomized (via a computer-generated randomization program) to one of two sedation&#xD;
      arms: 1) propofol, or 2) dexmedetomidine.&#xD;
&#xD;
      Per current UMC policy, propofol will be initiated at 5 mcg/kg/minute (0.3mg/kg/hour) and&#xD;
      titrated every 5 minutes by 5mcg/kg/minute to RASS (Richmond Agitation and Sedation Scale)&#xD;
      goal -1 to +1. The maximum dose of propofol will be 80 mcg/kg/minute.&#xD;
&#xD;
      Dexmedetomidine will be initiated at 0.2 mcg/kg/hour and will be titrated every 5 minutes by&#xD;
      0.1mcg/kg/hour to a maximum dose of 1.4 mcg/kg/hour to a RASS goal of -1 to +1. Although&#xD;
      dexmedetomidine has only been approved in the United States for short-term sedation of ICU&#xD;
      patients (&lt; 24 hrs) at a maximal dose of 0.7 μg/kg/hr (up to 1.0 μg/kg/h for procedural&#xD;
      sedation), several studies demonstrate the safety and efficacy of dexmedetomidine infusions&#xD;
      administered for greater than 24 hrs (up to 28 days) and at higher doses (up to 1.5&#xD;
      μg/kg/hr).&#xD;
&#xD;
      Daily sedation stops will be performed in both study arms per MICU weaning policy. Patients&#xD;
      will be allowed to return to a RASS of 0 to +1, and the physician will be alerted for&#xD;
      assessment. If the physician determines sedation needs to be re-started, it will be at 50% of&#xD;
      the dose prior to the sedation stop. This dose will then be titrated to a RASS goal of -1 to&#xD;
      +1.&#xD;
&#xD;
      Patients with inadequate sedation scores on their assigned drug will receive supplemental&#xD;
      sedation with midazolam or lorazepam using IV boluses as needed based on nursing and&#xD;
      physician assessment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">September 22, 2016</completion_date>
  <primary_completion_date type="Actual">September 22, 2016</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of Mechanical Ventilation</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Number of days patient requires mechanical ventilation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of MICU Stay</measure>
    <time_frame>Up to 28 Days</time_frame>
    <description>Number of days patient stays in the MICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Vasopressor Support</measure>
    <time_frame>Up to 28 Days</time_frame>
    <description>Number of days the patient requires intravenous vasopressors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Up to 28 Days</time_frame>
    <description>Number of patients who die within 28 days after randomization</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Sepsis</condition>
  <condition>Respiratory Failure</condition>
  <condition>Agitation</condition>
  <arm_group>
    <arm_group_label>Propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Propofol will be administered for sedation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexmedetomidine will be administered for sedation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol will be administered for sedation in mechanically ventilated patients with sepsis.</description>
    <arm_group_label>Propofol</arm_group_label>
    <other_name>Diprivan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis.</description>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <other_name>Precedex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <arm_group_label>Propofol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women 18-89 years old&#xD;
&#xD;
          -  with the diagnosis of sepsis (as specified below) within the previous 24 hours&#xD;
&#xD;
          -  who require mechanical ventilation, and&#xD;
&#xD;
          -  provide informed consent either personally or by an authorized representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with documented allergies to propofol, dexmedetomidine, fentanyl, eggs or egg&#xD;
             products, or soy or soy products.&#xD;
&#xD;
          -  A heart rate less than 50 beats/minute or grade 2 or 3 AV heart block&#xD;
&#xD;
          -  Mean arterial pressure less than 55 mmHg despite appropriate fluid resuscitation and&#xD;
             vasopressor support.&#xD;
&#xD;
          -  Current triglyceride level &gt; 400 mg/dl&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kenneth Nugent, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Texas Tech University Health Sciences Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Carson SS, Kress JP, Rodgers JE, Vinayak A, Campbell-Bright S, Levitt J, Bourdet S, Ivanova A, Henderson AG, Pohlman A, Chang L, Rich PB, Hall J. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med. 2006 May;34(5):1326-32. doi: 10.1097/01.CCM.0000215513.63207.7F.</citation>
    <PMID>16540958</PMID>
  </reference>
  <reference>
    <citation>Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007 Dec 12;298(22):2644-53. doi: 10.1001/jama.298.22.2644.</citation>
    <PMID>18073360</PMID>
  </reference>
  <reference>
    <citation>Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16. Erratum In: Crit Care. 2011;15(1):402.</citation>
    <PMID>20233428</PMID>
  </reference>
  <reference>
    <citation>Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.</citation>
    <PMID>22436955</PMID>
  </reference>
  <reference>
    <citation>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74.</citation>
    <PMID>1597042</PMID>
  </reference>
  <results_reference>
    <citation>Sigler MB, Islam EA, Nugent K. Comparison of dexmedetomidine and propofol in mechanically ventilated patients with sepsis: a pilot study. The Southwest Respiratory and Critical Care Chronicles 2018;6(22):10-15.</citation>
  </results_reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <results_first_submitted>February 19, 2020</results_first_submitted>
  <results_first_submitted_qc>February 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2020</results_first_posted>
  <last_update_submitted>February 19, 2020</last_update_submitted>
  <last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dexmedetomidine</keyword>
  <keyword>Propofol</keyword>
  <keyword>Sepsis</keyword>
  <keyword>Mechanical Ventilation</keyword>
  <keyword>Respiratory Failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Dexmedetomidine</mesh_term>
    <mesh_term>Propofol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Propofol</title>
          <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
        </group>
        <group group_id="P2">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="17"/>
              </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>Propofol</title>
          <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
        </group>
        <group group_id="B2">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</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="19"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="36"/>
          </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="59.0" spread="15.4"/>
                    <measurement group_id="B2" value="62.5" spread="9.6"/>
                    <measurement group_id="B3" value="60.75" spread="NA">The person who managed this study has left the school and the raw data are not available.</measurement>
                  </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="10"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="22"/>
                  </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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </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_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="19"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.1" spread="6.5"/>
                    <measurement group_id="B2" value="29.7" spread="8.2"/>
                    <measurement group_id="B3" value="29.9" spread="NA">The person who managed this study has left the school and the raw data are not available</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Duration of Mechanical Ventilation</title>
        <description>Number of days patient requires mechanical ventilation</description>
        <time_frame>Up to 28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Propofol</title>
            <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
          <group group_id="O2">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Mechanical Ventilation</title>
          <description>Number of days patient requires mechanical ventilation</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="3" upper_limit="13"/>
                    <measurement group_id="O2" value="3" lower_limit="2.75" upper_limit="5.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Outcome comparison used the Mann Whitney U test</non_inferiority_desc>
            <p_value>0.107</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of MICU Stay</title>
        <description>Number of days patient stays in the MICU</description>
        <time_frame>Up to 28 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Propofol</title>
            <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
          <group group_id="O2">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of MICU Stay</title>
          <description>Number of days patient stays in the MICU</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="4" upper_limit="14"/>
                    <measurement group_id="O2" value="5" lower_limit="3" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Outcomes were compared using a Mann Whitney U test.</non_inferiority_desc>
            <p_value>0.260</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Vasopressor Support</title>
        <description>Number of days the patient requires intravenous vasopressors</description>
        <time_frame>Up to 28 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Propofol</title>
            <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
          <group group_id="O2">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Vasopressor Support</title>
          <description>Number of days the patient requires intravenous vasopressors</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="3.3"/>
                    <measurement group_id="O2" value="2" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Outcomes were compared using a Mann Whitney U test.</non_inferiority_desc>
            <p_value>0.376</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mortality</title>
        <description>Number of patients who die within 28 days after randomization</description>
        <time_frame>Up to 28 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Propofol</title>
            <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
          <group group_id="O2">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
          </group>
        </group_list>
        <measure>
          <title>Mortality</title>
          <description>Number of patients who die within 28 days after randomization</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="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" 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_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Outcomes were compared using a Chi square test.</non_inferiority_desc>
            <p_value>0.739</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 28 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Propofol</title>
          <description>Propofol will be administered for sedation.&#xD;
Propofol: Propofol will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</description>
        </group>
        <group group_id="E2">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered for sedation&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis using a titration based on level of agitation.&#xD;
Fentanyl: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention &quot;of interest&quot;.</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="8" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Kenneth Nugent</name_or_title>
      <organization>Texas Tech University</organization>
      <phone>18067436847</phone>
      <email>kenneth.nugent@ttuhsc.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/NCT02203019
org study id: L14-136
nct id: NCT02203019
lead sponsor: 
has dmc: Yes
Patients with infections in their blood often become very sick. These patients are usually
      put in an intensive care unit for careful observation and treatment. These patients may
      develop a low blood pressure, lung failure, and kidney failure. When these problems develop,
      care becomes quite complicated. Patients with lung failure often need help with a breathing
      machine to make certain that the breathing is adequate. The machine helps keep the oxygen
      level high enough for healthy tissues. When patients are placed on the machine for breathing
      they require a tube to be placed into lungs. This can be quite uncomfortable. These patients
      need sedation to help them tolerate the uncomfortable breathing tube and other parts of their
      routine necessary care. This study will compare two drugs (dexmedetomidine and propofol)
      which are frequently used for sedation in intensive care patients. Clinical studies suggest
      that these drugs are both effective and safe. The main question is whether or not one of the
      drugs is better in a patient with a blood infection. This study will try to determine that.
      Our main goal is to see whether or not patients on one particular drug come off the breathing
      machine faster than patients on the other drug. These drugs are not experimental drugs and
      are approved by the Food and Drug Administration. There is no placebo drug being used in this
      study. All patients in this study will receive the best possible care based on their medical
      condition.
Patients admitted to the MICU with acute respiratory care and possible sepsis will be
      evaluated and managed by the internal medicine MICU team. This team includes faculty members,
      pulmonary fellows, and internal medicine residents. These physicians will make all the
      decisions regarding the initial management of the patient. The admitting team will be
      approached by the study investigators to solicit their support for the recruitment of the
      patient into the study. During some periods of time the study investigators will be directly
      involved in the patient care.

      The general approach to managing patients with sepsis includes blood cultures, serum lactate
      levels, and empiric antibiotics. Other cultures from the respiratory tract, urinary tract,
      and other sites are also obtained as indicated. Empiric antibiotic choices will be based on
      the most likely source of infection. Patient will receive fluid administration and
      vasopressors to maintain mean arterial pressure blood pressures greater than or equal to 60
      mmHg.

      Mechanical ventilation support will follow ARDS network guidelines. In general patients will
      be on an assist-control mode, a low tidal volume (6 mm/kg ideal body weight), and a FiO2
      adequate to maintain O2 saturations greater than equal to 90%. PEEP levels will be based on
      the FiO2 using ARDS network recommendations. The ventilator management goal is to have the
      lowest possible plateau pressure and lowest FiO2 possible to maintain adequate ventilation
      and oxygenation.

      Fentanyl will be routinely ordered for analgesia. Per current UMC policy, initial fentanyl
      boluses will be given at 50mcg IV every 2 hours as needed to keep pain level less than 4/10.
      At the discretion of the provider, a fentanyl drip may be administered if intermittent
      fentanyl does not achieve adequate analgesia. If a fentanyl drip is initiated, the drip will
      have a range of 25-200 mcg/hour to achieve a pain level of less than 4/10. If an allergy to
      fentanyl is documented, the patient will be excluded from the study.

      Once a mechanically ventilated patient with sepsis is selected for enrollment, the patient
      will be randomized (via a computer-generated randomization program) to one of two sedation
      arms: 1) propofol, or 2) dexmedetomidine.

      Per current UMC policy, propofol will be initiated at 5 mcg/kg/minute (0.3mg/kg/hour) and
      titrated every 5 minutes by 5mcg/kg/minute to RASS (Richmond Agitation and Sedation Scale)
      goal -1 to +1. The maximum dose of propofol will be 80 mcg/kg/minute.

      Dexmedetomidine will be initiated at 0.2 mcg/kg/hour and will be titrated every 5 minutes by
      0.1mcg/kg/hour to a maximum dose of 1.4 mcg/kg/hour to a RASS goal of -1 to +1. Although
      dexmedetomidine has only been approved in the United States for short-term sedation of ICU
      patients (< 24 hrs) at a maximal dose of 0.7 μg/kg/hr (up to 1.0 μg/kg/h for procedural
      sedation), several studies demonstrate the safety and efficacy of dexmedetomidine infusions
      administered for greater than 24 hrs (up to 28 days) and at higher doses (up to 1.5
      μg/kg/hr).

      Daily sedation stops will be performed in both study arms per MICU weaning policy. Patients
      will be allowed to return to a RASS of 0 to +1, and the physician will be alerted for
      assessment. If the physician determines sedation needs to be re-started, it will be at 50% of
      the dose prior to the sedation stop. This dose will then be titrated to a RASS goal of -1 to
      +1.

      Patients with inadequate sedation scores on their assigned drug will receive supplemental
      sedation with midazolam or lorazepam using IV boluses as needed based on nursing and
      physician assessment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of Mechanical Ventilation
time frame: Up to 28 days
description: Number of days patient requires mechanical ventilation
measure: Duration of MICU Stay
time frame: Up to 28 Days
description: Number of days patient stays in the MICU
measure: Duration of Vasopressor Support
time frame: Up to 28 Days
description: Number of days the patient requires intravenous vasopressors
measure: Mortality
time frame: Up to 28 Days
description: Number of patients who die within 28 days after randomization
arm group label: Propofol
arm group type: Active Comparator
description: Propofol will be administered for sedation.
arm group label: Dexmedetomidine
arm group type: Active Comparator
description: Dexmedetomidine will be administered for sedation
intervention type: Drug
intervention name: Propofol
description: Propofol will be administered for sedation in mechanically ventilated patients with sepsis.
arm group label: Propofol
other name: Diprivan
intervention type: Drug
intervention name: Dexmedetomidine
description: Dexmedetomidine will be administered for sedation in mechanically ventilated patients with sepsis.
arm group label: Dexmedetomidine
other name: Precedex
intervention type: Drug
intervention name: Fentanyl
description: Fentanyl will be administered for analgesia in mechanically ventilated patients with sepsis. The use of Fentanyl is not an intervention "of interest".
arm group label: Dexmedetomidine
arm group label: Propofol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Kenneth Nugent, MD
role: Principal Investigator
affiliation: Texas Tech University Health Sciences Center
facility: 
country: United States
citation: Carson SS, Kress JP, Rodgers JE, Vinayak A, Campbell-Bright S, Levitt J, Bourdet S, Ivanova A, Henderson AG, Pohlman A, Chang L, Rich PB, Hall J. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med. 2006 May;34(5):1326-32. doi: 10.1097/01.CCM.0000215513.63207.7F.
PMID: 16540958
citation: Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007 Dec 12;298(22):2644-53. doi: 10.1001/jama.298.22.2644.
PMID: 18073360
citation: Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16. Erratum In: Crit Care. 2011;15(1):402.
PMID: 20233428
citation: Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.
PMID: 22436955
citation: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74.
PMID: 1597042
citation: Sigler MB, Islam EA, Nugent K. Comparison of dexmedetomidine and propofol in mechanically ventilated patients with sepsis: a pilot study. The Southwest Respiratory and Critical Care Chronicles 2018;6(22):10-15.
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Respiratory Insufficiency
mesh term: Fentanyl
mesh term: Dexmedetomidine
mesh term: Propofol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 