<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/NCT02983825</url>
  </required_header>
  <id_info>
    <org_study_id>17-013910</org_study_id>
    <secondary_id>825874</secondary_id>
    <nct_id>NCT02983825</nct_id>
  </id_info>
  <brief_title>Impact of CPAP Level on V/Q Mismatch in Premature Infants</brief_title>
  <official_title>Impact of Continuous Positive Airway Pressure Level on Ventilation/Perfusion Mismatch in Premature Infants: a Phase II Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Thrasher Research Fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Continuous positive airway pressure (CPAP) is used in premature infants to maintain lungs&#xD;
      open and facilitate gas exchange. When ventilation/perfusion (V/Q) mismatch is present, areas&#xD;
      of the lung that are open for gas exchange do not match up with the areas of the lung that&#xD;
      are receiving blood for gas exchange. This study measure the responsiveness of V/Q mismatch&#xD;
      to changes in the amount (or level) of CPAP.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">February 13, 2020</completion_date>
  <primary_completion_date type="Actual">July 8, 2019</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>Ventilation/Perfusion Mismatch</measure>
    <time_frame>variable; up to 2 hours</time_frame>
    <description>Measured by non-invasive computerized technique based on curvilinear characteristics generated by a best-fit curve connecting the fractional inspired oxygen and corresponding peripheral oxygen saturation pairs; measured as difference in degree of right-shift between baseline and &quot;best&quot; CPAP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best CPAP Level</measure>
    <time_frame>variable, up to 2 hours</time_frame>
    <description>Defined as the lowest CPAP level associated with an improvement greater than 5% in V/Q mismatch relative to the preceding CPAP level</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Infant, Premature, Diseases</condition>
  <condition>Respiratory Insufficiency Syndrome of Newborn</condition>
  <arm_group>
    <arm_group_label>Continuous positive airway pressure (CPAP) level changes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Continuous positive airway pressure (CPAP); level changes</intervention_name>
    <description>as per arm description</description>
    <arm_group_label>Continuous positive airway pressure (CPAP) level changes</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Born at 27-35 weeks gestational age (GA) by best obstetric estimate, determined by the&#xD;
             clinical obstetric team during antepartum admission.&#xD;
&#xD;
          2. Age limits: 24 hours of age - 35 weeks corrected gestational age.&#xD;
&#xD;
          3. On continuous CPAP support between 4-8 cm H2O for greater than 24 hours, as document&#xD;
             on the bedside infant flow sheet.&#xD;
&#xD;
          4. Supplemental oxygen requirement, with a fraction of inspired oxygen (FiO2) 0.25 for at&#xD;
             least 2 consecutive hours, as documented on the bedside infant flow sheet.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Congenital anomalies, as determined by the clinical supervising physician.&#xD;
&#xD;
          2. Current or prior air leak syndrome, as determined by the clinical supervising&#xD;
             physician.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>24 Hours</minimum_age>
    <maximum_age>35 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicolas Bamat, MD, MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pennsylvania Hosptital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <results_first_submitted>July 9, 2020</results_first_submitted>
  <results_first_submitted_qc>July 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2020</results_first_posted>
  <last_update_submitted>March 1, 2021</last_update_submitted>
  <last_update_submitted_qc>March 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CPAP</keyword>
  <keyword>Bronchopulmonary Dysplasia</keyword>
  <keyword>Ventilator Induced Lung Injury</keyword>
  <keyword>V/Q mismatch</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Infant, Premature, Diseases</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>February 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT02983825/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Continuous Positive Airway Pressure (CPAP) Level Changes</title>
          <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline&#xD;
Continuous positive airway pressure (CPAP); level changes: as per arm description</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12">Of 21 enrolled subjects, 9 became ineligible for between consent and intervention</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9">Of 12 subjects starting intervention, 3 met specified stopping critieria</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Continuous Positive Airway Pressure (CPAP) Level Changes</title>
          <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline&#xD;
Continuous positive airway pressure (CPAP); level changes: as per arm description</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19" lower_limit="16" upper_limit="39"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ventilation/Perfusion Mismatch</title>
        <description>Measured by non-invasive computerized technique based on curvilinear characteristics generated by a best-fit curve connecting the fractional inspired oxygen and corresponding peripheral oxygen saturation pairs; measured as difference in degree of right-shift between baseline and &quot;best&quot; CPAP</description>
        <time_frame>variable; up to 2 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Positive Airway Pressure (CPAP) Level Changes</title>
            <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline&#xD;
Continuous positive airway pressure (CPAP); level changes: as per arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilation/Perfusion Mismatch</title>
          <description>Measured by non-invasive computerized technique based on curvilinear characteristics generated by a best-fit curve connecting the fractional inspired oxygen and corresponding peripheral oxygen saturation pairs; measured as difference in degree of right-shift between baseline and &quot;best&quot; CPAP</description>
          <units>difference in right shift (kPa)</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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0" upper_limit="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Within subject repeat analysis; V/Q mismatch (measured as degree of right shift in kPa) baseline vs &quot;best&quot; CPAP</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Wilcoxon signed-rank test for nonparametric matched-pairs</non_inferiority_desc>
            <p_value>0.02</p_value>
            <method>Sign test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best CPAP Level</title>
        <description>Defined as the lowest CPAP level associated with an improvement greater than 5% in V/Q mismatch relative to the preceding CPAP level</description>
        <time_frame>variable, up to 2 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Positive Airway Pressure (CPAP) Level Changes</title>
            <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline&#xD;
Continuous positive airway pressure (CPAP); level changes: as per arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Best CPAP Level</title>
          <description>Defined as the lowest CPAP level associated with an improvement greater than 5% in V/Q mismatch relative to the preceding CPAP level</description>
          <units>cm H2O</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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="7" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>48 hours after intervention</time_frame>
      <desc>Adverse event monitoring limited to air leak syndromes (pneumothorax, pulmonary interstitial emphysema, pneumomediastinum; as determined by the clinical supervising physician during routine clinical care) and respiratory deterioration, defined as an increase in baseline FiO2 greater than 0.10 in the 48 hour following the study intervention,</desc>
      <group_list>
        <group group_id="E1">
          <title>Continuous Positive Airway Pressure (CPAP) Level Changes</title>
          <description>Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline&#xD;
Continuous positive airway pressure (CPAP); level changes: as per arm description</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </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="12"/>
              </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>Nicolas Bamat, MD MSCE</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>2155904010</phone>
      <email>bamatn@email.chop.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/NCT02983825
org study id: 17-013910
secondary id: 825874
nct id: NCT02983825
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
Continuous positive airway pressure (CPAP) is used in premature infants to maintain lungs
      open and facilitate gas exchange. When ventilation/perfusion (V/Q) mismatch is present, areas
      of the lung that are open for gas exchange do not match up with the areas of the lung that
      are receiving blood for gas exchange. This study measure the responsiveness of V/Q mismatch
      to changes in the amount (or level) of CPAP.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ventilation/Perfusion Mismatch
time frame: variable; up to 2 hours
description: Measured by non-invasive computerized technique based on curvilinear characteristics generated by a best-fit curve connecting the fractional inspired oxygen and corresponding peripheral oxygen saturation pairs; measured as difference in degree of right-shift between baseline and "best" CPAP
measure: Best CPAP Level
time frame: variable, up to 2 hours
description: Defined as the lowest CPAP level associated with an improvement greater than 5% in V/Q mismatch relative to the preceding CPAP level
arm group label: Continuous positive airway pressure (CPAP) level changes
arm group type: Experimental
description: Protocol guided changes in CPAP level from clinical baseline, with responsiveness in V/Q mismatch guiding subsequent changes; limited to a range of -2 to +3 cm H2O from baseline
intervention type: Device
intervention name: Continuous positive airway pressure (CPAP); level changes
description: as per arm description
arm group label: Continuous positive airway pressure (CPAP) level changes
criteria: 
gender: All
minimum age: 24 Hours
maximum age: 35 Weeks
healthy volunteers: No
last name: Nicolas Bamat, MD, MSCE
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
mesh term: Premature Birth
mesh term: Infant, Premature, Diseases
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 