Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT)

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)

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).

Study Overview

• Status: Completed
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: Perfluorooctyl Bromide

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
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 Names: Perflubron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained oxygen desaturations for greater than ten minutes without response to increased oxygen therapy	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.	Day 5, Day 10
Persistent hypotension without response to volume expansion and/or inotropic therapy	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.	Day 5, Day 10
Change in number of major mucus plugging events	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.	Day 5, Day 10
Incidence of pneumothorax or pleural effusion with PFOB	Incidence of pneumothorax in the child will be measured by transillumination of the chest and confirmed by chest x-ray.	Day 5, Day 10
Number of participants with sustained hypercapnia (elevated carbon dioxide in the blood, greater than 95 mmHg, for over four hours).	Hypercapnia will be measured with blood tests and/or cutaneous carbon dioxide monitor.	Day 5, Day 10

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Auto Dealers Caring for Kids Foundation
• Investigators: Principal Investigator: William Fox, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2017
• Primary Completion (ACTUAL): June 10, 2019
• Study Completion (ACTUAL): June 10, 2019

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (ESTIMATE): February 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Neonates; Bronchopulmonary Dysplasia
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Anticonvulsants; Anti-Obesity Agents; Bromides; Perflubron
• Other Study ID Numbers: 12-008686

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No