<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/NCT02967562</url>
  </required_header>
  <id_info>
    <org_study_id>KCH16-155</org_study_id>
    <nct_id>NCT02967562</nct_id>
  </id_info>
  <brief_title>Neonatal Resuscitation - Sustained Inflations</brief_title>
  <official_title>Comparison of a Sustained Inflation to Shorter Inflation Breaths During Resuscitation at Delivery of Prematurely Born Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study compares a fifteen second sustained inflation (SI) to five repeated two - three&#xD;
      second 'inflation breaths' during resuscitation at delivery of infants born prematurely.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Around 10% of newborns will require some form of assistance after delivery, with babies born&#xD;
      more prematurely more likely to require resuscitation&#xD;
&#xD;
      Current UK guidelines advise initial resuscitation with the delivery of five 'inflation&#xD;
      breaths' lasting 2-3 seconds with peak inflation pressure of 30cmH2O (20-25cm H2O in&#xD;
      premature neonates). Previous studies have shown that despite resuscitation training,&#xD;
      clinicians in both simulated and real resuscitation scenarios do not deliver the recommended&#xD;
      duration of inflation breaths. This, combined with leaks around the facemask often being as&#xD;
      large as 50% or greater, contributes to low expired tidal volumes during resuscitation, thus&#xD;
      increasing the likelihood of hypoxia and delay in establishing effective respiration.&#xD;
&#xD;
      The use of sustained inflations (up to 15 seconds), rather than intermittent shorter&#xD;
      inflation breaths, has shown promising results, with reduction in the need for intubation,&#xD;
      and the need for and duration of mechanical ventilation. Around 30% of units in Germany use&#xD;
      sustained inflations as first line delivery room management, as do many other hospitals&#xD;
      around the world. Resuscitation guidelines from the USA, UK and Europe suggest that sustained&#xD;
      inflations should be researched further.&#xD;
&#xD;
      Several studies have shown that for several lengths of inflation breaths, the expired tidal&#xD;
      volume achieved is higher if the baby makes respiratory effort during the inflation (active&#xD;
      inflation) and that stimulation of spontaneous respiratory effort is a key part in&#xD;
      establishing an FRC, enabling spontaneous breathing, and increasing the likelihood of&#xD;
      successful resuscitation.&#xD;
&#xD;
      To date, there are no studies directly comparing whether prolonged inflations are more&#xD;
      successful at provoking an inspiration than other methods of resuscitation. We therefore aim&#xD;
      to compare a 15 second sustained inflation to repeated shorter inflations to determine which&#xD;
      is more effective.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">March 2018</primary_completion_date>
  <phase>N/A</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>Expiratory Tidal Volume</measure>
    <time_frame>one minute</time_frame>
    <description>Expiratory tidal volume during the first minute of resuscitation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>End Tidal Carbon Dioxide Level</measure>
    <time_frame>10 minutes</time_frame>
    <description>end tidal carbon dioxide level during resuscitation</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mechanical Ventilation</measure>
    <time_frame>48 hours</time_frame>
    <description>Duration of mechanical ventilation ini first 48 hours</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse Effects</measure>
    <time_frame>First week of life</time_frame>
    <description>Rates of intraventricular haemorrhage, significant patent ductus arteriosus, and pneumothorax</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Premature Birth</condition>
  <arm_group>
    <arm_group_label>Inflation Breaths</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Five 'inflation breaths' lasting two - three seconds</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sustained inflation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One fifteen second 'sustained inflation'</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Inflation Breaths</intervention_name>
    <arm_group_label>Inflation Breaths</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sustained Inflation</intervention_name>
    <arm_group_label>Sustained inflation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants born at less than 34 weeks gestation requiring resuscitation at delivery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major congenital abnormalities&#xD;
&#xD;
          -  Parents have previously expressed lack of consent for study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Minutes</minimum_age>
    <maximum_age>1 Hour</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Greenough, MD, FRCPCH</last_name>
    <role>Study Director</role>
    <affiliation>King's College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <zip>Se5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>January 20, 2020</results_first_submitted>
  <results_first_submitted_qc>October 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 10, 2020</results_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT02967562/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Inflation Breaths</title>
          <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
        </group>
        <group group_id="P2">
          <title>Sustained Inflation</title>
          <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</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 group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Consent not obtained</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>High leak precluding analysis</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Inflation Breaths</title>
          <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
        </group>
        <group group_id="B2">
          <title>Sustained Inflation</title>
          <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</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="30"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>post menstrual weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.7" lower_limit="23.1" upper_limit="33.6"/>
                    <measurement group_id="B2" value="30.6" lower_limit="24" upper_limit="33.7"/>
                    <measurement group_id="B3" value="30.3" lower_limit="23.3" upper_limit="33.7"/>
                  </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="30"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="34"/>
                  </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 group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Expiratory Tidal Volume</title>
        <description>Expiratory tidal volume during the first minute of resuscitation</description>
        <time_frame>one minute</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inflation Breaths</title>
            <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
          </group>
          <group group_id="O2">
            <title>Sustained Inflation</title>
            <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</description>
          </group>
        </group_list>
        <measure>
          <title>Expiratory Tidal Volume</title>
          <description>Expiratory tidal volume during the first minute of resuscitation</description>
          <units>ml/kg/min</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153" lower_limit="18" upper_limit="385"/>
                    <measurement group_id="O2" value="194" lower_limit="45" upper_limit="505"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>End Tidal Carbon Dioxide Level</title>
        <description>end tidal carbon dioxide level during resuscitation</description>
        <time_frame>10 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inflation Breaths</title>
            <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
          </group>
          <group group_id="O2">
            <title>Sustained Inflation</title>
            <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</description>
          </group>
        </group_list>
        <measure>
          <title>End Tidal Carbon Dioxide Level</title>
          <description>end tidal carbon dioxide level during resuscitation</description>
          <units>mmHg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="1.9" upper_limit="46"/>
                    <measurement group_id="O2" value="34.2" lower_limit="1.4" upper_limit="80.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mechanical Ventilation</title>
        <description>Duration of mechanical ventilation ini first 48 hours</description>
        <time_frame>48 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inflation Breaths</title>
            <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
          </group>
          <group group_id="O2">
            <title>Sustained Inflation</title>
            <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanical Ventilation</title>
          <description>Duration of mechanical ventilation ini first 48 hours</description>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" lower_limit="0" upper_limit="48"/>
                    <measurement group_id="O2" value="17" lower_limit="0" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Adverse Effects</title>
        <description>Rates of intraventricular haemorrhage, significant patent ductus arteriosus, and pneumothorax</description>
        <time_frame>First week of life</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until study completion, maximum of 6 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Inflation Breaths</title>
          <description>Five 'inflation breaths' lasting two - three seconds&#xD;
Inflation Breaths</description>
        </group>
        <group group_id="E2">
          <title>Sustained Inflation</title>
          <description>One fifteen second 'sustained inflation'&#xD;
Sustained Inflation</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="3" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </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"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </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>Professor Anne Greenough</name_or_title>
      <organization>King's College London</organization>
      <phone>02032999000</phone>
      <email>anne.greenough@kcl.ac.uk</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/NCT02967562
org study id: KCH16-155
nct id: NCT02967562
lead sponsor: 
collaborator: 
has dmc: No
This study compares a fifteen second sustained inflation (SI) to five repeated two - three
      second 'inflation breaths' during resuscitation at delivery of infants born prematurely.
Around 10% of newborns will require some form of assistance after delivery, with babies born
      more prematurely more likely to require resuscitation

      Current UK guidelines advise initial resuscitation with the delivery of five 'inflation
      breaths' lasting 2-3 seconds with peak inflation pressure of 30cmH2O (20-25cm H2O in
      premature neonates). Previous studies have shown that despite resuscitation training,
      clinicians in both simulated and real resuscitation scenarios do not deliver the recommended
      duration of inflation breaths. This, combined with leaks around the facemask often being as
      large as 50% or greater, contributes to low expired tidal volumes during resuscitation, thus
      increasing the likelihood of hypoxia and delay in establishing effective respiration.

      The use of sustained inflations (up to 15 seconds), rather than intermittent shorter
      inflation breaths, has shown promising results, with reduction in the need for intubation,
      and the need for and duration of mechanical ventilation. Around 30% of units in Germany use
      sustained inflations as first line delivery room management, as do many other hospitals
      around the world. Resuscitation guidelines from the USA, UK and Europe suggest that sustained
      inflations should be researched further.

      Several studies have shown that for several lengths of inflation breaths, the expired tidal
      volume achieved is higher if the baby makes respiratory effort during the inflation (active
      inflation) and that stimulation of spontaneous respiratory effort is a key part in
      establishing an FRC, enabling spontaneous breathing, and increasing the likelihood of
      successful resuscitation.

      To date, there are no studies directly comparing whether prolonged inflations are more
      successful at provoking an inspiration than other methods of resuscitation. We therefore aim
      to compare a 15 second sustained inflation to repeated shorter inflations to determine which
      is more effective.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Expiratory Tidal Volume
time frame: one minute
description: Expiratory tidal volume during the first minute of resuscitation
measure: End Tidal Carbon Dioxide Level
time frame: 10 minutes
description: end tidal carbon dioxide level during resuscitation
measure: Mechanical Ventilation
time frame: 48 hours
description: Duration of mechanical ventilation ini first 48 hours
measure: Adverse Effects
time frame: First week of life
description: Rates of intraventricular haemorrhage, significant patent ductus arteriosus, and pneumothorax
arm group label: Inflation Breaths
arm group type: Active Comparator
description: Five 'inflation breaths' lasting two - three seconds
arm group label: Sustained inflation
arm group type: Experimental
description: One fifteen second 'sustained inflation'
intervention type: Other
intervention name: Inflation Breaths
arm group label: Inflation Breaths
intervention type: Other
intervention name: Sustained Inflation
arm group label: Sustained inflation
criteria: 
gender: All
minimum age: 0 Minutes
maximum age: 1 Hour
healthy volunteers: No
last name: Anne Greenough, MD, FRCPCH
role: Study Director
affiliation: King's College London
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Premature Birth
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 