Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT)

• ClinicalTrials.gov Identifier: NCT03041740
• Recruitment Status: Active, not recruiting
• First Posted: February 3, 2017
• Last Update Posted: April 8, 2021
• Sponsor: Children's Hospital of Philadelphia
• Collaborator: Auto Dealers Caring for Kids Foundation
• Information provided by (Responsible Party): William Fox, Children's Hospital of Philadelphia

Tracking Information

• First Submitted Date: January 30, 2017
• First Posted Date: February 3, 2017
• Last Update Posted Date: April 8, 2021
• Actual Study Start Date: June 27, 2017
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2019)

• Sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy [ Time Frame: Day 5, Day 10 ]
  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.
• Persistent hypotension without response to volume expansion and/or inotropic therapy [ Time Frame: Day 5, Day 10 ]
  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.
• Change in number of major mucus plugging events [ Time Frame: Day 5, Day 10 ]
  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.
• Incidence of pneumothorax or pleural effusion with PFOB [ Time Frame: Day 5, Day 10 ]
  Incidence of pneumothorax in the child will be measured by transillumination of the chest and confirmed by chest x-ray.
• 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 ]
  Hypercapnia will be measured with blood tests and/or cutaneous carbon dioxide monitor.

Original Primary Outcome Measures (submitted: February 1, 2017)

Number of PFOB participants with no treatment-related adverse events as assessed by CTCAE v4.03 toxicity Scale. [ Time Frame: Up to 10 days ]

(1) No sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy, (2) persistent hypotension (as defined by ≥ 20% decrease in blood pressure) requiring volume expansion and/or inotropic therapy, (3) no major mucus plugging events (defined as events that are unresolved after two bronchoscopes), (4) no increase in mechanical ventilator settings predictive of ventilator induced lung injury, and (5) no pneumothoraces.

Current Secondary Outcome Measures (submitted: September 27, 2019)

• Change in fraction of inspired oxygen (FiO2) [ Time Frame: Day 5, Day 10 ]
  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.
• Change in ventilator mean airway pressure (MAP) [ Time Frame: Day 5, Day 10 ]
  Mean airway pressure (MAP) is the average amount of airway pressure supplied to the lungs throughout a breath. Higher MAP indicates more severe disease.
• Change in Respiratory Severity Score (MAP x FiO2) [ Time Frame: Day 5, Day 10 ]
  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.

Original Secondary Outcome Measures (submitted: February 1, 2017)

Pulmonary Artery Pressure Response to PFOB [ Time Frame: Up to 10 days ]

The effect of PFOB-PLV on pulmonary artery pressure will also be evaluated by obtaining an echocardiogram prior and post instillation.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fluid Filled Lung Oxygenation Assistance Trial
• 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)
• Brief Summary: 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).
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bronchopulmonary Dysplasia

Intervention

Drug: Perfluorooctyl Bromide

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.

Other Name: Perflubron

Study Arms

• No Intervention: Usual Care (Control) Group
  Control subjects will be treated as per standard of care for preterm infants with BPD.
• Active Comparator: Perfluorooctylbromide (PFOB) Group
  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: Drug: Perfluorooctyl Bromide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 1, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2022
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

1. Neonates with severe BPD as defined by 36 weeks post conception age and require positive pressure ventilation
2. Infants born at less than 32 weeks post conception age
3. Subjects may be up to 6 months corrected age
4. On conventional mechanical ventilation for chronic lung disease for at least two days prior to enrollment
5. On conventional mechanical ventilation at the time of enrollment and anticipated to continue for 14 days
6. Off systemic steroids for lung disease for 72 hours (3 days) prior to T=0
7. Hemoglobin value ≥8 g/dL: if less than 8 g/dL, transfusion is permitted. Clinical blood transfusion should be administered prior to enrollment.
8. Parental/guardian permission (informed consent)

Exclusion Criteria

1. Mechanical ventilation for acute disease, such as for infection or for post-operative complications
2. Severe Pulmonary Hypertension (PAH) (pulmonary pressure greater than 2/3 systemic) as defined by either echocardiogram (ECHO), or cardiac catheterizations or a CT-Angiogram consistent with PAH within the last 3 weeks.
3. Pneumothorax (active air leak) requiring chest tube within 72 hours of T=0
4. Active pulmonary hemorrhage within 72 hours of T=0
5. History of Grade III/IV interventricular hemorrhage without resolution or stability within 3 weeks of verifying eligibility
6. Severe congenital heart disease compromising pulmonary circulation
7. Other major congenital malformation (including but not limited to CDH) or known genetic syndromes at the discretion of the investigator
8. Use of an investigational drug within 7 days prior to confirmation of eligibility.
9. The clinical attending physician believes it is not in the subject's and/or parents/guardians best interest to participate in the trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 6 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03041740
• Other Study ID Numbers: 12-008686
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: William Fox, Children's Hospital of Philadelphia
• Study Sponsor: Children's Hospital of Philadelphia
• Collaborators: Auto Dealers Caring for Kids Foundation

Investigators

• Principal Investigator: William Fox, MD; Children's Hospital of Philadelphia

• PRS Account: Children's Hospital of Philadelphia
• Verification Date: April 2021