Surfactant Therapy for Neonatal Respiratory Distress Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Jacob Kelner

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Connecticut Children's Medical Center

Disqualifiers: Congenital cardiac, lung disease, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Point-of-care ultrasound (POCUS) is the use of ultrasound by the bedside provider in real time to answer a specific question and guide medical management. POCUS can be used to diagnose the severity of neonatal respiratory distress syndrome (RDS) through a lung ultrasound score. Lung ultrasound scores have also been shown to predict if an infant is treated with an initial dose of surfactant. Therefore, using lung ultrasound scores to guide surfactant therapy for RDS will likely lead to earlier surfactant therapy and may improve short-term respiratory outcomes. This study will test this theory by comparing lung ultrasound score-guided surfactant therapy for premature infants with RDS with our current surfactant administration guidelines.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Echography-guided Surfactant THERapy (ESTHER) for neonatal respiratory distress syndrome?

Research shows that surfactant therapy, including treatments like Curosurf, is effective in improving survival rates in newborns with severe respiratory distress syndrome. Studies have demonstrated that surfactants can reduce lung complications and improve outcomes in preterm infants. ^{1 2 3 4 5}

Is surfactant therapy safe for humans?

Research shows that surfactant therapy, including products like Exosurf and Survanta, is generally safe for treating neonatal respiratory distress syndrome. Studies found no significant increase in complications like infections or lung issues, and it may even reduce mortality in high-risk premature infants. ^{1 2 6 7 8}

How is the ESTHER treatment different from other treatments for neonatal respiratory distress syndrome?

The ESTHER treatment is unique because it uses echography (ultrasound) guidance to administer surfactant therapy, which may improve precision and effectiveness compared to traditional methods. This approach could potentially enhance the delivery of surfactant directly to the lungs, optimizing its benefits in treating neonatal respiratory distress syndrome. ^{1 3 4 9 10}

Research Team

Jacob Kelner

Principal Investigator

Connecticut Children's

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Echography-guided Surfactant THERapy (ESTHER) (Surfactant)

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.

Participant Groups

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 Canada for the following indications:

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+

James E. Shmerling

Connecticut Children's Medical Center

Chief Executive Officer since 2015

Bachelor of Science in Health Education from the University of Tennessee, Master of Science in Hospital and Health Administration from the University of Alabama at Birmingham, MBA from Samford University, Doctorate of Health Administration from the Medical University of South Carolina

Dorothy A. Levine

Connecticut Children's Medical Center

Chief Medical Officer since 2022

MD

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity. [2018]

3. United States 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. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A unique story in neonatal research: the development of a porcine surfactant. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of curosurf for severe respiratory distress syndrome: a case-control study. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

Reduced mortality in small premature infants treated at birth with a single dose of synthetic surfactant. [2019]

7. United States 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Synthetic vs human surfactants in the treatment of respiratory distress syndrome: radiographic findings. [2018]

9. India pubmed.ncbi.nlm.nih.gov

Surfactant Replacement Therapy Beyond Respiratory Distress Syndrome in Neonates. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Use of surfactant in the prevention and treatment of neonatal respiratory distress syndrome. [2005]