<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/NCT01727505</url>
  </required_header>
  <id_info>
    <org_study_id>20120623</org_study_id>
    <nct_id>NCT01727505</nct_id>
  </id_info>
  <brief_title>Volume Guarantee Ventilation in Preterm Infants With Frequent Episodes of Hypoxemia</brief_title>
  <official_title>Volume Guarantee Ventilation in Preterm Infants With Frequent Episodes of Hypoxemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Preterm infants undergoing mechanical ventilation often present with respiratory instability&#xD;
      which leads to fluctuations in ventilation and oxygenation. In conventional modes of&#xD;
      mechanical ventilation used in these patients, the ventilator delivers breaths at a set rate&#xD;
      and a constant peak inspiratory pressure.&#xD;
&#xD;
      We have demonstrated that spontaneous episodes of hypoxemia in mechanically ventilated&#xD;
      preterm infants are frequently triggered by a loss in end-expiratory lung volume followed by&#xD;
      decrease in tidal volume. This is due to a reduction in respiratory system compliance and&#xD;
      increase in airway resistance.&#xD;
&#xD;
      Volume Guarantee ventilation is a mode of ventilation in which ventilator measures the&#xD;
      exhaled tidal volume of each ventilator breath and automatically adjusts the peak inspiratory&#xD;
      pressure to deliver the set tidal volume. We have previously shown that Volume Guarantee&#xD;
      reduced the severity and duration of hypoxemia episodes during a period of 2 hours in preterm&#xD;
      infants The study hypothesis is that Volume Guarantee ventilation will decrease the duration&#xD;
      of episodes of hypoxemia when compared to conventional mechanical ventilation during routine&#xD;
      clinical conditions and over longer periods of time.&#xD;
&#xD;
      The objective of the study is to evaluate the effects of Volume Guarantee on the duration,&#xD;
      severity and frequency of episodes of hypoxemia in mechanically ventilated preterm infants&#xD;
      who present with frequent hypoxemia episodes in comparison to conventional ventilation over&#xD;
      two periods of 24 hours each and under routine clinical conditions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Time Spent With Arterial Oxygen Saturation &lt; 75%</measure>
    <time_frame>24 hours</time_frame>
    <description>Percentage of time spent with arterial oxygen saturation &lt; 75%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Severe Hypoxemia Episodes</measure>
    <time_frame>24 hours</time_frame>
    <description>Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 &lt; 75% lasting for at least 20 seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Hypoxemia Episodes</measure>
    <time_frame>24 hours</time_frame>
    <description>Frequency of hypoxemia episodes defined as episodes with arterial saturation &lt; 85% for at least 20 seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hypoxemia Episodes</measure>
    <time_frame>24 hours</time_frame>
    <description>Duration of hypoxemia episodes of arterial saturation &lt; 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fraction of Inspired Oxygen (FiO2)</measure>
    <time_frame>24 hours</time_frame>
    <description>Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods.&#xD;
Reported as median and inter-quartile range of all subjects.</description>
  </other_outcome>
  <other_outcome>
    <measure>Tidal Volume</measure>
    <time_frame>24 hours</time_frame>
    <description>The mean exhaled tidal volume of mechanical breaths.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Episodic Hypoxemia in Mechanically Ventilated Preterm Infants</condition>
  <arm_group>
    <arm_group_label>Sequence A: Conventional-Volume Guarantee</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This is a crossover study. Infants will be assigned to one of two sequences. Sequence A consists of a 24-hour period during which the infant receives conventional mechanical ventilation followed by a second 24 hour period during which the infant receives volume guarantee ventilation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence B: Volume Guarantee-Conventional</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This is a crossover study. Infants will be assigned to one of two sequences. Sequence B consists of a 24-hour period during which the infant receives volume guarantee ventilation followed by a second 24 hour period during which the infant receives conventional mechanical ventilation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sequence A: Conventional-Volume Guarantee</intervention_name>
    <description>This is a crossover study. Infants will be randomly assigned to one of two sequences.&#xD;
In sequence A, the infant will undergo a 24-hour period of conventional mechanical ventilation followed by a 24 hour period of volume guarantee ventilation.&#xD;
Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA).&#xD;
During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team.&#xD;
During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.</description>
    <arm_group_label>Sequence A: Conventional-Volume Guarantee</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sequence B: Volume Guarantee-Conventional</intervention_name>
    <description>This is a crossover study. Infants will be randomly assigned to one of two sequences.&#xD;
In sequence B, the infant will undergo a 24-hour period of volume guarantee ventilation followed by a 24 hour period of conventional mechanical ventilation.&#xD;
Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA).&#xD;
During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team.&#xD;
During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.</description>
    <arm_group_label>Sequence B: Volume Guarantee-Conventional</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Born at less than 32 weeks of gestational age.&#xD;
&#xD;
          -  Requiring mechanical ventilation on a mandatory ventilator rate greater than or equal&#xD;
             to 20 per minute and receiving a mean tidal volume of at least 4 ml/kg.&#xD;
&#xD;
          -  Presenting with 4 or more episodes of hypoxemia, defined as oxygen saturation less&#xD;
             than 75%, in the 8 hours prior to the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major congenital anomalies.&#xD;
&#xD;
          -  Hemodynamic instability requiring inotropes within 72 hours prior to the study&#xD;
&#xD;
          -  Culture proven sepsis within 72 hours prior to the study.&#xD;
&#xD;
          -  Diagnosis of pulmonary interstitial emphysema or pneumothorax within the 72 hours&#xD;
             prior to the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nelson Claure, M.Sc., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eduardo Bancalari, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Newborn Intensitve Care Unit at Holtz Children's Hospital of Jackson Health System</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <results_first_submitted>August 29, 2016</results_first_submitted>
  <results_first_submitted_qc>January 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 1, 2017</results_first_posted>
  <last_update_submitted>January 10, 2017</last_update_submitted>
  <last_update_submitted_qc>January 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Nelson Claure</investigator_full_name>
    <investigator_title>Research Associate Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>hypoxemia</keyword>
  <keyword>desaturation</keyword>
  <keyword>mechanical ventilation</keyword>
  <keyword>preterm infants</keyword>
  <keyword>volume guarantee ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at the Project NewBorn Neonatal Intensive Care Unit of the Jackson Memorial Hospital/University of Miami Medical Center. Subjects were recruited into the study between December, 2012 and September, 2014.</recruitment_details>
      <pre_assignment_details>42 infants were screened. Of these, 9 declined participation and 3 did not meet inclusion criteria.&#xD;
30 infants were enrolled (consented). Of these, 4 infants became ineligible after consent and were not studied.&#xD;
26 enrolled infants were studied.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sequence A: Conventional-Volume Guarantee</title>
          <description>This is a crossover study. Each patient is randomly assigned to one of two sequences.&#xD;
Sequence A consisted of a 24-hour period during which the infant received conventional mechanical ventilation followed by a 24 hour period during which the infant received volume guarantee ventilation.</description>
        </group>
        <group group_id="P2">
          <title>Sequence B: Volume Guarantee-Conventional</title>
          <description>This is a crossover study. Each patient is randomly assigned to one of two sequences.&#xD;
Sequence B consisted of a 24-hour period during which the infant received volume guarantee ventilation followed by a 24 hour period during which the infant received conventional mechanical ventilation.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First 24 Hours</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second 24 Hours</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Missing data</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <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>Study Population</title>
          <description>This is a crossover study. Infants were randomly assigned to one of two sequences.&#xD;
Sequence A consisted of 24 hours of Conventional Mechanical Ventilation followed by 24 hours of Volume Guarantee Ventilation.&#xD;
Sequence B consisted of 24 hours of Volume Guarantee Ventilation followed by 24 hours of Conventional Mechanical Ventilation.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gestational age</title>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Birth weight</title>
          <units>grams</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="685" spread="216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ventilator mandatory rate</title>
          <units>breaths per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33" spread="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Peak inspiratory pressure</title>
          <units>cm H2O</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.4" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pressure support</title>
          <units>cm H2O</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.4" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Positive end expiratory pressure</title>
          <units>cm H2O</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.3" spread="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fraction of Inspired Oxygen</title>
          <units>fraction</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.38" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Time Spent With Arterial Oxygen Saturation &lt; 75%</title>
        <description>Percentage of time spent with arterial oxygen saturation &lt; 75%</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Time Spent With Arterial Oxygen Saturation &lt; 75%</title>
          <description>Percentage of time spent with arterial oxygen saturation &lt; 75%</description>
          <units>% of time</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="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="3.9" upper_limit="6.9"/>
                    <measurement group_id="O2" value="4.4" lower_limit="2.9" upper_limit="5"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.44</p_value>
            <method>Wilcoxon signed rank test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Severe Hypoxemia Episodes</title>
        <description>Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 &lt; 75% lasting for at least 20 seconds.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Severe Hypoxemia Episodes</title>
          <description>Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 &lt; 75% lasting for at least 20 seconds.</description>
          <units>severe hypoxemia episodes per hour</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="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="1.3" upper_limit="2.6"/>
                    <measurement group_id="O2" value="1.9" lower_limit="1.1" upper_limit="2.5"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>.75</p_value>
            <method>Wilcoxon signed rank test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Hypoxemia Episodes</title>
        <description>Frequency of hypoxemia episodes defined as episodes with arterial saturation &lt; 85% for at least 20 seconds</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Hypoxemia Episodes</title>
          <description>Frequency of hypoxemia episodes defined as episodes with arterial saturation &lt; 85% for at least 20 seconds</description>
          <units>hypoxemia episodes per hour</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="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" lower_limit="4.6" upper_limit="7.9"/>
                    <measurement group_id="O2" value="6.5" lower_limit="5.6" upper_limit="8.9"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.2</p_value>
            <method>Wilcoxon signed rank test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hypoxemia Episodes</title>
        <description>Duration of hypoxemia episodes of arterial saturation &lt; 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hypoxemia Episodes</title>
          <description>Duration of hypoxemia episodes of arterial saturation &lt; 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects.</description>
          <units>seconds</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="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76" lower_limit="70" upper_limit="92"/>
                    <measurement group_id="O2" value="73" lower_limit="65" upper_limit="81"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Wilcoxon signed rank test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Fraction of Inspired Oxygen (FiO2)</title>
        <description>Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods.&#xD;
Reported as median and inter-quartile range of all subjects.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Fraction of Inspired Oxygen (FiO2)</title>
          <description>Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods.&#xD;
Reported as median and inter-quartile range of all subjects.</description>
          <units>fraction</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="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".42" lower_limit=".37" upper_limit=".53"/>
                    <measurement group_id="O2" value=".41" lower_limit=".36" upper_limit=".46"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>.049</p_value>
            <method>Wilcoxon signed rank test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Tidal Volume</title>
        <description>The mean exhaled tidal volume of mechanical breaths.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conventional Mechanical Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
          <group group_id="O2">
            <title>Volume Guarantee Ventilation Period</title>
            <description>This is a crossover study that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
The sequence of conventional and volume guarantee ventilation were assigned at random.</description>
          </group>
        </group_list>
        <measure>
          <title>Tidal Volume</title>
          <description>The mean exhaled tidal volume of mechanical breaths.</description>
          <units>ml/Kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" spread="1.6"/>
                    <measurement group_id="O2" value="5.6" spread="0.7"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.006</p_value>
            <method>Paired t-test</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Conventional Mechanical Ventilation Period</title>
          <description>This is a crossover study. Infants were randomly assigned to one of two sequences that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
These data represent the 24 hours of Conventional Mechanical Ventilation.</description>
        </group>
        <group group_id="E2">
          <title>Volume Guarantee Ventilation Period</title>
          <description>This is a crossover study. Infants were randomly assigned to one of two sequences that consisted of a 24-hour period during which the infant received conventional mechanical ventilation and another 24 hour period during which the infant received volume guarantee ventilation.&#xD;
These data represent the 24 hours of Volume Guarantee Ventilation.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Increased PaCO2 requiring high frequency ventilation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Nelson Claure, MSc, PhD, Director Neonatal Pulmonary Research Lab</name_or_title>
      <organization>University of Miami School of Medicine, Dept. of Pediatrics - Div. of Neonatology</organization>
      <phone>305 585 6408</phone>
      <email>nclaure@miami.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/NCT01727505
org study id: 20120623
nct id: NCT01727505
lead sponsor: 
has dmc: No
Preterm infants undergoing mechanical ventilation often present with respiratory instability
      which leads to fluctuations in ventilation and oxygenation. In conventional modes of
      mechanical ventilation used in these patients, the ventilator delivers breaths at a set rate
      and a constant peak inspiratory pressure.

      We have demonstrated that spontaneous episodes of hypoxemia in mechanically ventilated
      preterm infants are frequently triggered by a loss in end-expiratory lung volume followed by
      decrease in tidal volume. This is due to a reduction in respiratory system compliance and
      increase in airway resistance.

      Volume Guarantee ventilation is a mode of ventilation in which ventilator measures the
      exhaled tidal volume of each ventilator breath and automatically adjusts the peak inspiratory
      pressure to deliver the set tidal volume. We have previously shown that Volume Guarantee
      reduced the severity and duration of hypoxemia episodes during a period of 2 hours in preterm
      infants The study hypothesis is that Volume Guarantee ventilation will decrease the duration
      of episodes of hypoxemia when compared to conventional mechanical ventilation during routine
      clinical conditions and over longer periods of time.

      The objective of the study is to evaluate the effects of Volume Guarantee on the duration,
      severity and frequency of episodes of hypoxemia in mechanically ventilated preterm infants
      who present with frequent hypoxemia episodes in comparison to conventional ventilation over
      two periods of 24 hours each and under routine clinical conditions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Time Spent With Arterial Oxygen Saturation < 75%
time frame: 24 hours
description: Percentage of time spent with arterial oxygen saturation < 75%
measure: Frequency of Severe Hypoxemia Episodes
time frame: 24 hours
description: Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 < 75% lasting for at least 20 seconds.
measure: Frequency of Hypoxemia Episodes
time frame: 24 hours
description: Frequency of hypoxemia episodes defined as episodes with arterial saturation < 85% for at least 20 seconds
measure: Duration of Hypoxemia Episodes
time frame: 24 hours
description: Duration of hypoxemia episodes of arterial saturation < 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects.
measure: Fraction of Inspired Oxygen (FiO2)
time frame: 24 hours
description: Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods.
Reported as median and inter-quartile range of all subjects.
measure: Tidal Volume
time frame: 24 hours
description: The mean exhaled tidal volume of mechanical breaths.
arm group label: Sequence A: Conventional-Volume Guarantee
arm group type: Active Comparator
description: This is a crossover study. Infants will be assigned to one of two sequences. Sequence A consists of a 24-hour period during which the infant receives conventional mechanical ventilation followed by a second 24 hour period during which the infant receives volume guarantee ventilation.
arm group label: Sequence B: Volume Guarantee-Conventional
arm group type: Active Comparator
description: This is a crossover study. Infants will be assigned to one of two sequences. Sequence B consists of a 24-hour period during which the infant receives volume guarantee ventilation followed by a second 24 hour period during which the infant receives conventional mechanical ventilation.
intervention type: Device
intervention name: Sequence A: Conventional-Volume Guarantee
description: This is a crossover study. Infants will be randomly assigned to one of two sequences.
In sequence A, the infant will undergo a 24-hour period of conventional mechanical ventilation followed by a 24 hour period of volume guarantee ventilation.
Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA).
During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team.
During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.
arm group label: Sequence A: Conventional-Volume Guarantee
intervention type: Device
intervention name: Sequence B: Volume Guarantee-Conventional
description: This is a crossover study. Infants will be randomly assigned to one of two sequences.
In sequence B, the infant will undergo a 24-hour period of volume guarantee ventilation followed by a 24 hour period of conventional mechanical ventilation.
Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA).
During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team.
During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.
arm group label: Sequence B: Volume Guarantee-Conventional
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Nelson Claure, M.Sc., Ph.D.
role: Principal Investigator
affiliation: University of Miami
last name: Eduardo Bancalari, M.D.
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: Nelson Claure
investigator title: Research Associate Professor of Pediatrics
mesh term: Premature Birth
mesh term: Hypoxia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 