<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/NCT02989246</url>
  </required_header>
  <id_info>
    <org_study_id>CHLA-14-00473</org_study_id>
    <nct_id>NCT02989246</nct_id>
  </id_info>
  <brief_title>Effort of Breathing Guided Ventilator Protocol</brief_title>
  <acronym>EOBvent</acronym>
  <official_title>Effort of Breathing Guided Ventilator Management for Children Using Pressure Rate Product: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot study tests the feasibility of using a computerized ventilator management protocol&#xD;
      seeking to encourage lung protective ventilation during the acute phase of ventilation, and&#xD;
      esophageal manometry based titration of ventilator settings during the weaning phase of&#xD;
      ventilation, for children with acute respiratory failure. The investigators hypothesize that&#xD;
      such an approach will reduce time on mechanical ventilation, largely by preserving diaphragm&#xD;
      muscle function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives: This pilot study will help refine a computer based ventilator management protocol&#xD;
      which will be used in both acute and weaning phases of ventilation for children with acute&#xD;
      respiratory failure. The acute phase protocol is an adaptation of the Acute Respiratory&#xD;
      Distress Syndrome Network protocol for pediatrics, and the weaning phase involves an&#xD;
      esophageal manometry guided weaning protocol based on effort of breathing. The investigators&#xD;
      seek to test the safety and feasibility of the protocol recommendations and the software&#xD;
      system , and help determine the potential effect size of the intervention to determine&#xD;
      feasibility of a randomized controlled trial. They also seek to determine the feasibility and&#xD;
      reproducibility of serial diaphragm ultrasound measurements on mechanically ventilated&#xD;
      children.&#xD;
&#xD;
      Study Population: All children intubated and mechanically ventilated in the Children's&#xD;
      Hospital Los Angeles Pediatric ICU with an anticipated length of intubation &gt; 48 hours will&#xD;
      be eligible, with some exclusion criteria based on ability to perform the measurements.&#xD;
&#xD;
      Study methodology: After consent, an esophageal catheter will be placed. A software&#xD;
      management tool for ventilator management will be placed at the bedside for each enrolled&#xD;
      patient, and recommendations regarding changing ventilator support will be provided to the&#xD;
      clinicians every several hours during both acute and weaning phases. When ventilator support&#xD;
      is below a threshold, recommendations will be made to perform spontaneous breathing trials.&#xD;
      The clinicians will ultimately decide whether to accept or reject the recommendations, and&#xD;
      will evaluate the patient before each potential change to the ventilator. The acceptance or&#xD;
      rejection of recommendations will be tracked, and used to refine the intervention. Daily&#xD;
      diaphragm ultrasound measurements will also be obtained to monitor diaphragm thickness and&#xD;
      contractile activity.&#xD;
&#xD;
      Follow up: Clinical outcomes will be followed while in the ICU including re-intubation,&#xD;
      medications administered, and ICU length of stay. No follow up after ICU discharge is&#xD;
      planned.&#xD;
&#xD;
      Analysis plans: Data will be used to refine the intervention, test the acceptability of&#xD;
      protocol recommendations to bedside providers, and determine sample size estimates for a&#xD;
      follow up randomized controlled trial. These analyses will be descriptive. A pilot of 40&#xD;
      patients is anticipated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 1, 2015</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">October 18, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Protocol Recommendations Which Are Accepted by the Clinical Provider</measure>
    <time_frame>With each protocol recommendation, approximately every 4 hours during the course of mechanical ventilation (up to 28 days)</time_frame>
    <description>The investigators will track the percentage of recommendations which are accepted by providers, as well as the reasons why recommendations were not accepted</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Ventilators, Mechanical</condition>
  <condition>Work of Breathing</condition>
  <arm_group>
    <arm_group_label>Intervention Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ventilator management using the proposed protocol in both acute and weaning phases. Patients will be managed according the the Ventilator protocol using the esophageal catheter for the weaning phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ventilator protocol</intervention_name>
    <description>Open loop ventilator management by a computer based protocol</description>
    <arm_group_label>Intervention Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Esophageal Catheter</intervention_name>
    <description>Esophageal manometry measurements of patient effort of breathing will be used to guide the protocol recommendations</description>
    <arm_group_label>Intervention Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Intubated and mechanically ventilated patients in the Children's Hospital Los Angeles&#xD;
             Pediatric ICU&#xD;
&#xD;
          -  Anticipated length of intubation &gt; 48 hours.&#xD;
&#xD;
          -  The primary attending physician approves use of the protocol on the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Corrected gestational age less than 37 weeks&#xD;
&#xD;
          -  Contraindications to nasoesophageal catheter placement (nasopharyngeal or esophageal&#xD;
             abnormalities) or Respiratory Inductance Plethysmography bands (abdominal wall defects&#xD;
             such as omphalocele).&#xD;
&#xD;
          -  Significant lower airway obstruction (asthma or bronchiolitis), confirmed by&#xD;
             ventilator spirometry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>37 Weeks</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robinder Khemani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <results_first_submitted>March 2, 2021</results_first_submitted>
  <results_first_submitted_qc>October 21, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 22, 2021</results_first_posted>
  <last_update_submitted>October 21, 2021</last_update_submitted>
  <last_update_submitted_qc>October 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pediatrics</keyword>
  <keyword>ventilator weaning</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT02989246/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>No exclusion of patients prior to assignment to the intervention.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intervention Arm</title>
          <description>Ventilator management using the proposed protocol in both acute and weaning phases. Patients were managed according the the Ventilator protocol using the esophageal catheter&#xD;
Ventilator protocol: Open loop ventilator management by a computer based protocol&#xD;
Esophageal Catheter: Esophageal manometry measurements of patient effort of breathing were used to guide the protocol recommendations</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intervention Arm</title>
          <description>Ventilator management using the proposed protocol in both acute and weaning phases. Patients will be managed according the the Ventilator protocol using the esophageal catheter for the weaning phase&#xD;
Ventilator protocol: Open loop ventilator management by a computer based protocol&#xD;
Esophageal Catheter: Esophageal manometry measurements of patient effort of breathing will be used to guide the protocol recommendations</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="100.7" lower_limit="30.7" upper_limit="150.4"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Protocol Recommendations Which Are Accepted by the Clinical Provider</title>
        <description>The investigators will track the percentage of recommendations which are accepted by providers, as well as the reasons why recommendations were not accepted</description>
        <time_frame>With each protocol recommendation, approximately every 4 hours during the course of mechanical ventilation (up to 28 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Arm</title>
            <description>Ventilator management using the proposed protocol in both acute and weaning phases. Patients were managed according the the Ventilator protocol using the esophageal catheter&#xD;
Ventilator protocol: Open loop ventilator management by a computer based protocol&#xD;
Esophageal Catheter: Esophageal manometry measurements of patient effort of breathing were used to guide the protocol recommendations</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Protocol Recommendations Which Are Accepted by the Clinical Provider</title>
          <description>The investigators will track the percentage of recommendations which are accepted by providers, as well as the reasons why recommendations were not accepted</description>
          <units>percentage adherant</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="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76" lower_limit="74.8" upper_limit="77.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During ICU admission</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intervention Arm</title>
          <description>Ventilator management using the proposed protocol in both acute and weaning phases. Patients were managed according the the Ventilator protocol using the esophageal catheter&#xD;
Ventilator protocol: Open loop ventilator management by a computer based protocol&#xD;
Esophageal Catheter: Esophageal manometry measurements of patient effort of breathing were used to guide the protocol recommendations</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="7" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
              </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="32"/>
              </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 Robinder Khemani, Associate Director of Research ACCM</name_or_title>
      <organization>Children's Hospital Los Angeles</organization>
      <phone>323-361-2376</phone>
      <email>rkhemani@chla.usc.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/NCT02989246
org study id: CHLA-14-00473
nct id: NCT02989246
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This pilot study tests the feasibility of using a computerized ventilator management protocol
      seeking to encourage lung protective ventilation during the acute phase of ventilation, and
      esophageal manometry based titration of ventilator settings during the weaning phase of
      ventilation, for children with acute respiratory failure. The investigators hypothesize that
      such an approach will reduce time on mechanical ventilation, largely by preserving diaphragm
      muscle function.
Objectives: This pilot study will help refine a computer based ventilator management protocol
      which will be used in both acute and weaning phases of ventilation for children with acute
      respiratory failure. The acute phase protocol is an adaptation of the Acute Respiratory
      Distress Syndrome Network protocol for pediatrics, and the weaning phase involves an
      esophageal manometry guided weaning protocol based on effort of breathing. The investigators
      seek to test the safety and feasibility of the protocol recommendations and the software
      system , and help determine the potential effect size of the intervention to determine
      feasibility of a randomized controlled trial. They also seek to determine the feasibility and
      reproducibility of serial diaphragm ultrasound measurements on mechanically ventilated
      children.

      Study Population: All children intubated and mechanically ventilated in the Children's
      Hospital Los Angeles Pediatric ICU with an anticipated length of intubation > 48 hours will
      be eligible, with some exclusion criteria based on ability to perform the measurements.

      Study methodology: After consent, an esophageal catheter will be placed. A software
      management tool for ventilator management will be placed at the bedside for each enrolled
      patient, and recommendations regarding changing ventilator support will be provided to the
      clinicians every several hours during both acute and weaning phases. When ventilator support
      is below a threshold, recommendations will be made to perform spontaneous breathing trials.
      The clinicians will ultimately decide whether to accept or reject the recommendations, and
      will evaluate the patient before each potential change to the ventilator. The acceptance or
      rejection of recommendations will be tracked, and used to refine the intervention. Daily
      diaphragm ultrasound measurements will also be obtained to monitor diaphragm thickness and
      contractile activity.

      Follow up: Clinical outcomes will be followed while in the ICU including re-intubation,
      medications administered, and ICU length of stay. No follow up after ICU discharge is
      planned.

      Analysis plans: Data will be used to refine the intervention, test the acceptability of
      protocol recommendations to bedside providers, and determine sample size estimates for a
      follow up randomized controlled trial. These analyses will be descriptive. A pilot of 40
      patients is anticipated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Protocol Recommendations Which Are Accepted by the Clinical Provider
time frame: With each protocol recommendation, approximately every 4 hours during the course of mechanical ventilation (up to 28 days)
description: The investigators will track the percentage of recommendations which are accepted by providers, as well as the reasons why recommendations were not accepted
arm group label: Intervention Arm
arm group type: Experimental
description: Ventilator management using the proposed protocol in both acute and weaning phases. Patients will be managed according the the Ventilator protocol using the esophageal catheter for the weaning phase
intervention type: Other
intervention name: Ventilator protocol
description: Open loop ventilator management by a computer based protocol
arm group label: Intervention Arm
intervention type: Device
intervention name: Esophageal Catheter
description: Esophageal manometry measurements of patient effort of breathing will be used to guide the protocol recommendations
arm group label: Intervention Arm
criteria: 
gender: All
minimum age: 37 Weeks
maximum age: 18 Years
healthy volunteers: No
last name: Robinder Khemani, MD
role: Principal Investigator
affiliation: Children's Hospital Los Angeles
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Aspiration
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 