A study of partial liquid ventilation in premature infants with severe chronic lung disease

Despite advances in neonatal care, severe chronic lung disease (CLD) — or bronchopulmonary dysplasia (BPD) — remains a major cause of life-long illness, or even death, for infants with extremely low birth weight.

Currently, there is no effective treatment for BPD, and it is the leading cause of death in premature infants older than 120 days. Survivors of  BPD are often chronically ill from their lung disease and many other problems related to BPD and prematurity.

The Newborn and Infant Chronic Lung Disease Program specializes in the care of infants with severe BPD, and has cared for more than 400 patients in the past eight years. Our team of investigators is seeking potential ways of treating this disease. We are now studying if partial liquid ventilation with perfluorooctyl bromide (PFOB-PLV) can be safely used in infants with severe BPD. Find more information below about the Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT).

What is partial liquid ventilation?

Partial liquid ventilation (PLV) is a technique of mechanical ventilation that includes filling the lungs with a special liquid. Traditional mechanical ventilation refers to the use of a ventilator to push oxygen-containing gas into the lungs to help a patient breathe.

In PLV, lungs are filled with perflubron, also known as perfluorooctyl bromide (PFOB). Perflubron has been previously approved by the FDA for diagnostic imaging. PFOB has also been tried in the past, with success, in critically ill neonates with respiratory failure due to the three characteristics of PFOB:

1. PFOB decreases the pressure on the surface of the air sacs in the lung, making these breathing units more stable
2. Gas diffuses through the liquid very rapidly
3. The liquid carries 9 times as much oxygen as blood

FFLOAT: Fluid Filled Lung Oxygenation Assistance Trial

In 2017, Children’s Hospital of Philadelphia launched the Fluid Filled Lung Oxygenation Assistance Trial (FFLOAT). FFLOAT is a randomized controlled pilot study designed to evaluate the safety and feasibility of PFOB partial liquid ventilation (PLV) in infants with severe BPD.

This study is being conducted by the chronic lung disease team at CHOP:

Principle investigator: William Fox, MD
Investigative team: Kevin Dysart, MD; David Munson, MD; Huayan Zhang, MD; Kathy Maschhoff, MD; Erik Jensen, MD; Kristin McKenna, MD; Iyalla Peterside, MD; Natalie Napolitano, RRT

Study background and goals

This study is the result of a 25-year effort by William Fox, MD, attending neonatologist and Director of CHOP’s Infant Breathing Disorder Center — with the goal to establish liquid ventilation as a potential treatment for infants with severe lung disease.

In the 1990’s, initial infant trials studying PFOB-PLV in newborns with acute lung injury showed promising results. Dr. Fox and his team saw improvement in lung function and oxygenation in infants with severe lung disease, and no significant adverse events or side effects were observed. However, before partial liquid ventilation can be considered as a potential therapy for infants with severe CLD, we must confirm the safety of PLV-PFOB in this population.

The main goal of this study is to see if PFOB can be used safely as a liquid breathing medium for up to ten days in infants with severe BPD

Study design

For the FFLOAT study, eligible infants will be randomized to one of two treatment groups: PFOB group or control standard of care group. A total of 20 infants will be enrolled in the first phase of the safety trial, which will be broken into two parts:

• Part 1: up to 5 days
• Part 2: up to 10 days

How does PFOB-PLV work?

No special equipment is needed to place the PFOB in the lungs of mechanically ventilated infants. PFOB is administered into the breathing tube using a syringe through the side port of the tube.

The first dose of the liquid is administered by a team of neonatologists and respiratory therapists while the infant remains on a ventilator. Ventilation settings, heart rate and blood pressure are documented before and after each dose. The infant’s clinical status and laboratory values will be monitored closely. Based on how well the infant tolerates each treatment dose, the study team will determine when and if additional doses should be given.

Filling the lungs with PFOB allows oxygen to be delivered to the tiniest air sacs with increased efficiency. It may also help to clear mucous plugs in the lung and make the lungs less inflamed, which is commonly seen in infants with severe BPD. The hope is that these factors may help the lungs work more efficiently and lessen lung damage.

After infants are on PLV-PFOB for up to 5 or 10 days, they will resume standard BPD care. The PFOB will slowly evaporate from the lungs. The infants will be carefully monitored until hospital discharge and then followed at the CHOP BPD follow-up clinic, directed by Sara DeMauro, MD. Their lung function will be tested at 1 year of age.

Additional study details, including inclusion and exclusion criteria, can be found on ClinicalTrials.gov. Study details »

What’s next?

This first study will allow us to take the first steps in understanding how BPD responds to PFOB-PLV. Our goal is to advance care for infants with severe chronic lung disease. Once this trial establish safety of PFOB-PLV in infants with severe CLD, we hope to expand to efficacy studies at multiple institutions and for other pulmonary diseases.

We believe this has the potential to change the clinical course and outlook for infants with severe CLD and potentially other diagnoses beyond BPD. Ultimately, the aim is to identify new therapies that can help infants with severe chronic lung disease and other breathing problems.