<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/NCT03041740</url>
  </required_header>
  <id_info>
    <org_study_id>12-008686</org_study_id>
    <nct_id>NCT03041740</nct_id>
  </id_info>
  <brief_title>Fluid Filled Lung Oxygenation Assistance Trial</brief_title>
  <acronym>FFLOAT</acronym>
  <official_title>A Pilot Study to Evaluate the Safety of Perflurooctylbromide (PFOB) Partial Liquid Ventilation (PLV) for Up to 10 Days in Neonates With Severe Bronchopulmonary Dysplasia (BPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Auto Dealers Caring for Kids Foundation</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary study objective is to assess the safety and feasibility of perfluorooctylbromide&#xD;
      (PFOB) partial liquid ventilation (PLV) in infants with severe Bronchopulmonary Dysplasia&#xD;
      (BPD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary study objective is to assess the safety and feasibility of perfluorooctylbromide&#xD;
      (PFOB) partial liquid ventilation for up to ten days in infants with severe BPD as evaluated&#xD;
      by: (1) no sustained oxygen desaturations (SpO2 ≤ 80%) for greater than ten minutes without&#xD;
      response to increased oxygen therapy, (2) no persistent hypotension without response to&#xD;
      volume expansion and/or inotropic therapy, (3) no major mucus plugging events (defined as&#xD;
      events that are unresolved after two bronchoscopes), (4) no pneumothoraces or pleural&#xD;
      effusion with PFOB, (5) and no evidence of increased carbon dioxide (CO2) retention, renal&#xD;
      insufficiency, hyperkalemia, or metabolic acidosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 27, 2017</start_date>
  <completion_date type="Actual">June 10, 2019</completion_date>
  <primary_completion_date type="Actual">June 10, 2019</primary_completion_date>
  <phase>Phase 1</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>Sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Incidence of sustained (greater than 10 minutes) oxygen desaturation events without response to increased oxygen therapy. These incidences will be measured by a continuous non-invasive percutaneous oxygen saturation monitor.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Persistent hypotension without response to volume expansion and/or inotropic therapy</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Incidence of persistent hypotension without response to volume expansion and/or inotropic therapy. Hypotension is a decrease in systolic blood pressure deemed significant by clinical staff. Measurement will be performed with a standard intensive care unit blood pressure cuff.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in number of major mucus plugging events</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Incidence of airway obstruction of the endotracheal tube, as indicated by decreased chest movement during mechanical ventilation, need for increased ventilator pressure, and/or elevation of carbon dioxide levels in the blood. Mucus plugs are confirmed by endotracheal suctioning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of pneumothorax or pleural effusion with PFOB</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Incidence of pneumothorax in the child will be measured by transillumination of the chest and confirmed by chest x-ray.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with sustained hypercapnia (elevated carbon dioxide in the blood, greater than 95 mmHg, for over four hours).</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Hypercapnia will be measured with blood tests and/or cutaneous carbon dioxide monitor.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in fraction of inspired oxygen (FiO2)</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Fraction of inspired oxygen is the percentage of oxygen that the patient is receiving for his or her lung disease. An FiO2 of 0.21 is room air oxygen and 1.00 is 100% oxygen. The higher the FiO2, the more severe the respiratory disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ventilator mean airway pressure (MAP)</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Mean airway pressure (MAP) is the average amount of airway pressure supplied to the lungs throughout a breath. Higher MAP indicates more severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Respiratory Severity Score (MAP x FiO2)</measure>
    <time_frame>Day 5, Day 10</time_frame>
    <description>Respiratory Severity Score (RSS) is a scale computed as the Mean Airway Pressure (MAP) multiplied by the Fraction of Inspired Oxygen (FiO2). Clinically, the scale range will often lie between 1 and 10, with higher numbers indicating more severe disease. The RSS can theoretically reach a score as high as 30-35.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Bronchopulmonary Dysplasia</condition>
  <arm_group>
    <arm_group_label>Usual Care (Control) Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control subjects will be treated as per standard of care for preterm infants with BPD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Perfluorooctylbromide (PFOB) Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in the PFOB group will be administered an initial PFOB treatment dose of 2.5 mL/kg and up to a total intra-pulmonary volume of 25 mL/kg for up to 10 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perfluorooctyl Bromide</intervention_name>
    <description>Subjects in the PFOB group will receive PFOB partial liquid ventilation instilled via side port of endotracheal tube (2.5 mL/kg/day) across 10 treatment days.</description>
    <arm_group_label>Perfluorooctylbromide (PFOB) Group</arm_group_label>
    <other_name>Perflubron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Neonates with severe BPD as defined by 36 weeks post conception age and require&#xD;
             positive pressure ventilation&#xD;
&#xD;
          2. Infants born at less than 32 weeks post conception age&#xD;
&#xD;
          3. Subjects may be up to 6 months corrected age&#xD;
&#xD;
          4. On conventional mechanical ventilation for chronic lung disease for at least two days&#xD;
             prior to enrollment&#xD;
&#xD;
          5. On conventional mechanical ventilation at the time of enrollment and anticipated to&#xD;
             continue for 14 days&#xD;
&#xD;
          6. Off systemic steroids for lung disease for 72 hours (3 days) prior to T=0&#xD;
&#xD;
          7. Hemoglobin value ≥8 g/dL: if less than 8 g/dL, transfusion is permitted. Clinical&#xD;
             blood transfusion should be administered prior to enrollment.&#xD;
&#xD;
          8. Parental/guardian permission (informed consent)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Mechanical ventilation for acute disease, such as for infection or for post-operative&#xD;
             complications&#xD;
&#xD;
          2. Severe Pulmonary Hypertension (PAH) (pulmonary pressure greater than 2/3 systemic) as&#xD;
             defined by either echocardiogram (ECHO), or cardiac catheterizations or a CT-Angiogram&#xD;
             consistent with PAH within the last 3 weeks.&#xD;
&#xD;
          3. Pneumothorax (active air leak) requiring chest tube within 72 hours of T=0&#xD;
&#xD;
          4. Active pulmonary hemorrhage within 72 hours of T=0&#xD;
&#xD;
          5. History of Grade III/IV interventricular hemorrhage without resolution or stability&#xD;
             within 3 weeks of verifying eligibility&#xD;
&#xD;
          6. Severe congenital heart disease compromising pulmonary circulation&#xD;
&#xD;
          7. Other major congenital malformation (including but not limited to CDH) or known&#xD;
             genetic syndromes at the discretion of the investigator&#xD;
&#xD;
          8. Use of an investigational drug within 7 days prior to confirmation of eligibility.&#xD;
&#xD;
          9. The clinical attending physician believes it is not in the subject's and/or&#xD;
             parents/guardians best interest to participate in the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William Fox, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital of Philadelphia</investigator_affiliation>
    <investigator_full_name>William Fox</investigator_full_name>
    <investigator_title>Attending Physician</investigator_title>
  </responsible_party>
  <keyword>Bronchopulmonary Dysplasia</keyword>
  <keyword>Neonates</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Perflubron</mesh_term>
    <mesh_term>Bromides</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03041740
org study id: 12-008686
nct id: NCT03041740
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary study objective is to assess the safety and feasibility of perfluorooctylbromide
      (PFOB) partial liquid ventilation (PLV) in infants with severe Bronchopulmonary Dysplasia
      (BPD).
The primary study objective is to assess the safety and feasibility of perfluorooctylbromide
      (PFOB) partial liquid ventilation for up to ten days in infants with severe BPD as evaluated
      by: (1) no sustained oxygen desaturations (SpO2 ≤ 80%) for greater than ten minutes without
      response to increased oxygen therapy, (2) no persistent hypotension without response to
      volume expansion and/or inotropic therapy, (3) no major mucus plugging events (defined as
      events that are unresolved after two bronchoscopes), (4) no pneumothoraces or pleural
      effusion with PFOB, (5) and no evidence of increased carbon dioxide (CO2) retention, renal
      insufficiency, hyperkalemia, or metabolic acidosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy
time frame: Day 5, Day 10
description: Incidence of sustained (greater than 10 minutes) oxygen desaturation events without response to increased oxygen therapy. These incidences will be measured by a continuous non-invasive percutaneous oxygen saturation monitor.
measure: Persistent hypotension without response to volume expansion and/or inotropic therapy
time frame: Day 5, Day 10
description: Incidence of persistent hypotension without response to volume expansion and/or inotropic therapy. Hypotension is a decrease in systolic blood pressure deemed significant by clinical staff. Measurement will be performed with a standard intensive care unit blood pressure cuff.
measure: Change in number of major mucus plugging events
time frame: Day 5, Day 10
description: Incidence of airway obstruction of the endotracheal tube, as indicated by decreased chest movement during mechanical ventilation, need for increased ventilator pressure, and/or elevation of carbon dioxide levels in the blood. Mucus plugs are confirmed by endotracheal suctioning.
measure: Incidence of pneumothorax or pleural effusion with PFOB
time frame: Day 5, Day 10
description: Incidence of pneumothorax in the child will be measured by transillumination of the chest and confirmed by chest x-ray.
measure: Number of participants with sustained hypercapnia (elevated carbon dioxide in the blood, greater than 95 mmHg, for over four hours).
time frame: Day 5, Day 10
description: Hypercapnia will be measured with blood tests and/or cutaneous carbon dioxide monitor.
measure: Change in fraction of inspired oxygen (FiO2)
time frame: Day 5, Day 10
description: Fraction of inspired oxygen is the percentage of oxygen that the patient is receiving for his or her lung disease. An FiO2 of 0.21 is room air oxygen and 1.00 is 100% oxygen. The higher the FiO2, the more severe the respiratory disease.
measure: Change in ventilator mean airway pressure (MAP)
time frame: Day 5, Day 10
description: Mean airway pressure (MAP) is the average amount of airway pressure supplied to the lungs throughout a breath. Higher MAP indicates more severe disease.
measure: Change in Respiratory Severity Score (MAP x FiO2)
time frame: Day 5, Day 10
description: Respiratory Severity Score (RSS) is a scale computed as the Mean Airway Pressure (MAP) multiplied by the Fraction of Inspired Oxygen (FiO2). Clinically, the scale range will often lie between 1 and 10, with higher numbers indicating more severe disease. The RSS can theoretically reach a score as high as 30-35.
arm group label: Usual Care (Control) Group
arm group type: No Intervention
description: Control subjects will be treated as per standard of care for preterm infants with BPD.
arm group label: Perfluorooctylbromide (PFOB) Group
arm group type: Active Comparator
description: Subjects in the PFOB group will be administered an initial PFOB treatment dose of 2.5 mL/kg and up to a total intra-pulmonary volume of 25 mL/kg for up to 10 days.
intervention type: Drug
intervention name: Perfluorooctyl Bromide
description: Subjects in the PFOB group will receive PFOB partial liquid ventilation instilled via side port of endotracheal tube (2.5 mL/kg/day) across 10 treatment days.
arm group label: Perfluorooctylbromide (PFOB) Group
other name: Perflubron
criteria: 
gender: All
minimum age: N/A
maximum age: 6 Months
healthy volunteers: No
last name: William Fox, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Philadelphia
investigator full name: William Fox
investigator title: Attending Physician
mesh term: Bronchopulmonary Dysplasia
mesh term: Perflubron
mesh term: Bromides
sharing ipd: No