Surfactant Therapy for Neonatal Respiratory Distress Syndrome

Overseen By Jacob Kelner

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Connecticut Children's Medical Center

Disqualifiers: Congenital cardiac, lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate to 72 hours

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if bedside ultrasound can guide the timing of surfactant therapy for premature babies with breathing problems, potentially improving their short-term breathing outcomes. Surfactant therapy is crucial for babies with respiratory distress syndrome (RDS) as it enhances lung function. In this study, some babies will receive surfactant based on current guidelines, while others will receive it based on their lung ultrasound scores. The trial seeks premature infants diagnosed with RDS who require non-invasive breathing support and whose parents can provide consent. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance care for future premature infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What prior data suggests that this method is safe for neonatal respiratory distress syndrome?

Research has shown that surfactant therapy is generally safe for treating neonatal respiratory distress syndrome (RDS) in newborns. Surfactant keeps the lungs open and is already used for babies with these issues. Studies have demonstrated that using lung ultrasound, a type of imaging, to determine when to administer surfactant is both safe and effective. This method helps doctors choose the optimal time for treatment.

Reports indicate that ultrasound-guided surfactant therapy is well-tolerated by newborns and does not introduce significant risks. This approach aims to help doctors treat RDS more quickly and accurately. Overall, previous studies have found the treatment to be safe, providing reassurance for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for neonatal respiratory distress syndrome involve surfactant therapy administered based on clinical guidelines, often requiring specific oxygen levels. However, researchers are excited about the Echography-guided Surfactant THERapy (ESTHER) because it introduces a more personalized approach. Unlike standard methods, ESTHER uses lung ultrasound scores (LUS) to guide the timing of surfactant administration, potentially allowing for earlier and more precise intervention. This could improve outcomes by tailoring treatment to the baby's specific lung condition right from the start.

What evidence suggests that this ultrasound-guided surfactant therapy is effective for neonatal respiratory distress syndrome?

Research has shown that using lung ultrasound to guide treatment in premature babies with breathing problems can lead to earlier care. This early treatment, which helps keep the baby's lungs open, improves short-term breathing. Studies have found that lung ultrasound accurately predicts when this treatment is needed, allowing doctors to make quicker decisions. In this trial, one treatment arm tests the method called Echography-guided Surfactant THERapy (ESTHER) to see if it improves the survival and health of these babies. Overall, lung ultrasound might offer a faster and possibly more effective way to treat breathing issues in newborns. ^{1 3 4 6 7}

Who Is on the Research Team?

Jacob Kelner

Principal Investigator

Connecticut Children's

Are You a Good Fit for This Trial?

This trial is for premature infants with respiratory failure due to RDS, born between 27 and almost 37 weeks of gestation, who need non-invasive breathing support. Parents or guardians must understand and agree to the study by signing a consent form.

Inclusion Criteria

I was born between 27 and 36 weeks of pregnancy.

I have respiratory failure due to RDS and need a machine to help me breathe.

I am the parent/guardian and can sign the consent for my child's study participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive surfactant therapy guided by lung ultrasound scores or current guidelines

Immediate to 72 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Echography-guided Surfactant THERapy (ESTHER)

Trial Overview

The ESTHER trial uses bedside ultrasound (POCUS) to determine how severe an infant's respiratory distress syndrome (RDS) is and guides when to give surfactant therapy. It compares this new method with current guidelines on administering surfactant.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

The treatment group will receive surfactant therapy if the initial LUS at 1-2 hours of life is \> 9 or if they meet our unit's current surfactant therapy guidelines (irrespective of the LUS).

Group II: Control Active Control 1 Intervention

The control group will receive surfactant therapy based on our unit's current surfactant guidelines, including but not limited to a FiO2 requirement ≥ 0.3 on non-invasive positive pressure ventilation.

Echography-guided Surfactant THERapy (ESTHER) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Pulmonary surfactant for:

• Respiratory distress syndrome (RDS) in preterm infants
• Meconium aspiration syndrome
• Pneumonia/sepsis
• Pulmonary hemorrhage

Approved in United States as Pulmonary surfactant for:

• Respiratory distress syndrome (RDS) in preterm infants
• Meconium aspiration syndrome

Approved in Canada as Pulmonary surfactant for:

• Respiratory distress syndrome (RDS) in preterm infants
• Meconium aspiration syndrome

Who Is Running the Clinical Trial?

Connecticut Children's Medical Center

Lead Sponsor

Trials

76

Recruited

30,000+

Published Research Related to This Trial

In a case-control study involving 25 neonates treated with porcine surfactant (Curosurf) for severe respiratory distress syndrome, survival at discharge was significantly higher (76%) compared to 25 matched historical controls (48%), indicating the efficacy of surfactant treatment.

Other outcome parameters did not show significant differences between the surfactant-treated group and the controls, suggesting that while surfactant improves survival, it may not impact other health measures in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of curosurf for severe respiratory distress syndrome: a case-control study. Valls-i-Soler, A., Lizarraga, M., López de Heredia, J., et al.[2018]

Nebulizing surfactant (Poractant alfa) in humidified air for 3 hours significantly improved oxygenation and lung function in preterm lambs, indicating its efficacy in treating neonatal respiratory distress.

The study found that the distribution of surfactant was better in the lower lung lobes when administered in humidified air, suggesting that both treatment duration and air humidity are crucial for optimal surfactant delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulization of Poractant alfa via a vibrating membrane nebulizer in spontaneously breathing preterm lambs with binasal continuous positive pressure ventilation. Hütten, MC., Kuypers, E., Ophelders, DR., et al.[2018]

In a study involving 617 newborns with respiratory distress syndrome, there was no significant difference in the rates of death or bronchopulmonary dysplasia between those treated with Exosurf Neonatal and those treated with Survanta, indicating similar safety and efficacy for both surfactants.

However, infants receiving Survanta required a lower average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment, suggesting a more favorable initial response to Survanta compared to Exosurf.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. National Institute of Child Health and Human Development Neonatal Research Network. Horbar, JD., Wright, LL., Soll, RF., et al.[2019]

Curosurf, a porcine surfactant developed in the 1980s, has been shown to significantly reduce pulmonary air leaks and neonatal mortality in preterm infants with severe respiratory distress syndrome (RDS), based on multiple clinical trials.

Recent advancements in surfactant therapy, including new-generation synthetic surfactants like CHF5633, hold the potential to provide safe and effective treatment for preterm infants, possibly revolutionizing care due to their ability to be produced in large quantities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A unique story in neonatal research: the development of a porcine surfactant. Curstedt, T., Halliday, HL., Speer, CP.[2015]

In a study of 871 premature infants, Infasurf significantly reduced the incidence of neonatal respiratory distress syndrome (RDS) by 62% and RDS-related deaths by 70% compared to Exosurf Neonatal, indicating its superior efficacy in preventing RDS.

While Infasurf was more effective, it was associated with a higher overall risk of total intraventricular hemorrhage (IVH), although severe IVH rates were similar between the two treatments, highlighting a safety consideration in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome. Hudak, ML., Martin, DJ., Egan, EA., et al.[2019]

Surfactant replacement therapy is effective for treating preterm neonates with respiratory distress syndrome and may also be beneficial for other conditions like meconium aspiration syndrome, although more evidence is needed for widespread clinical use.

Current research shows limited support for surfactant therapy in conditions such as pneumonia, pulmonary hemorrhage, and bronchopulmonary dysplasia, highlighting the need for large multicenter randomized trials to better understand its efficacy in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surfactant Replacement Therapy Beyond Respiratory Distress Syndrome in Neonates. Jasani, B., Kabra, N., Nanavati, R.[2019]

Surfactant therapy is a promising treatment for neonatal respiratory distress syndrome (RDS) in premature infants, as it helps improve lung function by reducing surface tension and stabilizing alveoli, which can decrease the work of breathing.

Clinical trials have shown that surfactant therapy can reduce mortality and improve gas exchange in infants with RDS, although results are inconsistent and it does not significantly reduce the risk of bronchopulmonary dysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of surfactant in the prevention and treatment of neonatal respiratory distress syndrome. Reynolds, MS., Wallander, KA.[2005]

In a study involving 49 neonates with respiratory distress syndrome, treatment with the synthetic surfactant Exosurf led to a significant reduction in the severity of the condition compared to untreated neonates.

While the improvement in radiologic severity was slightly delayed compared to those treated with human surfactant, Exosurf showed similar safety profiles, with no significant differences in complications like pneumothorax or bronchopulmonary dysplasia, suggesting it is a viable alternative to biological surfactants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic vs human surfactants in the treatment of respiratory distress syndrome: radiographic findings. Levine, D., Edwards, DK., Merritt, TA.[2018]

In a study of 203 premature infants with respiratory distress syndrome (RDS), Survanta surfactant showed a significantly greater improvement in respiratory function compared to Exosurf from 12 to 48 hours after treatment.

Both Survanta and Exosurf were effective in treating RDS, but Survanta provided a faster response, while Exosurf was associated with a higher rate of retinopathy of prematurity in older infants (28 to 32 weeks).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity. Modanlou, HD., Beharry, K., Padilla, G., et al.[2018]

In a randomized controlled trial involving 218 premature infants, the use of Exosurf Neonatal, a synthetic surfactant, resulted in a 69% reduction in mortality at 28 days compared to control infants treated with air (4 deaths in the Exosurf group vs. 14 in the air group).

Exosurf also improved survival without bronchopulmonary dysplasia by 15% at 28 days, indicating its efficacy in enhancing outcomes for high-risk premature infants without increasing the risk of other serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced mortality in small premature infants treated at birth with a single dose of synthetic surfactant. Corbet, AJ., Long, WA., Murphy, DJ., et al.[2019]

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