Surfactant Therapy for Neonatal Respiratory Distress Syndrome

(Niftisurf Trial)

Overseen By Matthew Derrick

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: NorthShore University HealthSystem

Disqualifiers: Congenital anomaly, Emergent intubation, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 7 days

262 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different surfactant therapies (medications that help lungs function better) for newborns with respiratory distress syndrome. The researchers will compare Calfactant and Poractant alfa to determine which treatment better aids preterm babies in breathing more easily. The study seeks preterm infants born at 28 to 35 weeks, who are less than 48 hours old, diagnosed with respiratory distress syndrome, and receiving specific oxygen support. Babies with certain birth defects or other causes for their breathing issues are not eligible. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they benefit more patients.

Will I have to stop taking my current medications?

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

What is the safety track record for these treatments?

Earlier studies reviewed data from several clinical trials to assess the safety of Calfactant (Infasurf). These studies showed that Calfactant is generally safe for newborns with breathing problems and can reduce the need for more invasive procedures, such as intubation. Research also shows that Poractant alfa (Curosurf) is safe for infants with breathing issues and has been proven to lower the risk of death and lung problems. Both Calfactant and Poractant alfa are approved for treating this condition, indicating a strong safety record. Overall, both treatments have been used in many babies and are considered safe options. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for neonatal respiratory distress syndrome because of the innovative delivery method known as MIST (Minimally Invasive Surfactant Therapy). Unlike traditional methods that require intubation, MIST delivers surfactants directly into the lungs using a thin catheter while the baby continues to breathe on CPAP, which is much gentler. This approach uses two specific surfactants: Calfactant (Infasurf) and Poractant alfa (Curosurf). Both are designed to reduce the surface tension in the lungs, helping babies breathe more easily without the stress of invasive procedures. This could lead to fewer complications and a smoother recovery for newborns.

What evidence suggests that this trial's treatments could be effective for neonatal respiratory distress syndrome?

In this trial, calfactant, also known as Infasurf, is being studied for neonatal respiratory distress syndrome (RDS). Research has shown that calfactant can help treat breathing problems in newborns, potentially shortening hospital stays and lowering the risk of issues like a collapsed lung compared to some other treatments. Another treatment option in this trial is poractant alfa, also called Curosurf, which has been shown to quickly improve breathing and reduce the need for extra oxygen in babies with RDS. It might also reduce the need for repeated doses and lower death rates more effectively than some other options. Both treatments have proven effective in helping preterm infants with RDS breathe better. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for preterm infants between 28 and almost 36 weeks old, diagnosed with respiratory distress syndrome within their first 48 hours of life. They must be on nasal continuous positive airway pressure (NCPAP) with a certain level of oxygen need. Babies with congenital anomalies or other causes for respiratory distress, or those needing emergency intubation are not eligible.

Inclusion Criteria

My preterm infant has respiratory distress syndrome, confirmed by chest x-ray, needs NCPAP and FiO2 ≥0.30.

Exclusion Criteria

My infant does not require emergency breathing support.

My infant does not have a birth defect causing breathing problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Infants receive surfactant treatment via MIST with calfactant or poractant alfa, with potential for a second dose based on oxygen requirements

7 days

Post-Intervention Management

Management includes adherence to intubation criteria, CPAP titration, and early caffeine therapy

Up to 36 weeks corrected gestational age

Follow-up

Participants are monitored for safety and effectiveness after treatment, including duration of positive pressure support and supplemental oxygen

Up to 36 weeks corrected gestational age

What Are the Treatments Tested in This Trial?

Interventions

• MIST surfactant

Trial Overview The study is testing the effectiveness of administering surfactants through Minimally Invasive Surfactant Therapy (MIST) in treating neonatal respiratory distress syndrome. It's a multicenter trial where babies will randomly receive either curosuf or infasurf via MIST to see if one is not worse than the other.

How Is the Trial Designed?

Group I: Poractant alfa (Curosurf) Experimental Treatment 1 Intervention

Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP \> 30% oxygen will be given 2.5ml/kg of Poractant alfa.

Group II: Calfactant (Infasurf) Experimental Treatment 1 Intervention

Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP \> 30% oxygen will be given 3ml/kg of Calfacant

MIST surfactant is already approved in European Union, United States for the following indications:

Approved in European Union as CUROSURF for:

• Respiratory Distress Syndrome (RDS) in premature infants

Approved in United States as CUROSURF for:

• Respiratory Distress Syndrome (RDS) in premature infants

Who Is Running the Clinical Trial?

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

Published Research Related to This Trial

In a study of 924 very preterm infants with respiratory distress syndrome (RDS), treatment with the porcine-derived lung surfactant poractant alfa significantly impacted respiratory outcomes, with a mortality rate of 23.5% and survival without bronchopulmonary dysplasia (BPD) at 28 days and 36 weeks postmenstrual age being 38.9% and 54.0%, respectively.

Key risk factors for developing severe BPD included low gestational age, low birthweight, and complications such as interstitial emphysema and pulmonary infections, highlighting the importance of early intervention and monitoring in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term outcome of a large cohort of very preterm infants treated with poractant alfa (Curosurf) for respiratory distress syndrome. A postmarketing phase IV study. Lamboley-Gilmert, G., Lacaze-Masmonteil, T.[2018]

In two animal models of respiratory distress, Poractant alfa (100 and 200 mg/kg) demonstrated a significantly better acute pulmonary response compared to Bovactant (50 mg/kg), achieving rapid and sustained recovery in respiratory function.

At equivalent phospholipid doses, Poractant alfa resulted in superior arterial oxygenation and lung gas volumes compared to Bovactant, indicating its greater efficacy in treating neonatal respiratory distress syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Evaluation of the Acute Pulmonary Response to Poractant Alfa and Bovactant Treatments in Lung-Lavaged Adult Rabbits and in Preterm Lambs with Respiratory Distress Syndrome. Ricci, F., Salomone, F., Kuypers, E., et al.[2020]

Treatment with porcine surfactant (Curosurf) significantly reduced neonatal mortality by 40% in preterm babies with respiratory distress syndrome, highlighting its efficacy.

In addition to lowering mortality, the use of Curosurf resulted in more than double the percentage of survivors without bronchopulmonary dysplasia compared to the control group, indicating improved safety and outcomes for treated infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surfactant treatment of premature infants with respiratory distress syndrome]. Saugstad, OD., Gloppestad, K.[2008]

In a pilot study involving 34 patients with respiratory distress syndrome, the administration of Curosurf (200 mg/kg) showed that 18 patients could be maintained on nasal-CPAP therapy after treatment, indicating potential efficacy in reducing the need for more invasive ventilation.

However, 16 patients required artificial ventilation and experienced a higher rate of complications, suggesting that while Curosurf may help some patients, it does not eliminate the risk of severe outcomes, warranting further investigation in a randomized trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. Verder, H., Agertoft, L., Albertsen, P., et al.[2013]

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 20 preterm lambs with respiratory distress syndrome, atomized poractant alfa (Curosurf) delivered via a novel atomizer showed similar efficacy in improving lung function and oxygenation as traditional bolus surfactant administration.

Both atomized and bolus surfactant groups exhibited better lung mechanics and more uniform regional lung compliance compared to the control group, suggesting that atomization could be a viable noninvasive alternative for surfactant delivery in similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome. Milesi, I., Tingay, DG., Zannin, E., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10937453/

a review of its use in neonatal respiratory distress syndrome As rescue treatment, calfactant 100 or 105 mg/kg reduced RDS severity, but not mortality rates, significantly more than colfosceril palmitate 67.5 mg/kg or ...

2. publications.aap.org publications.aap.org/pediatrics/article/146/5/e20193967/75345/Aerosolized-Calfactant-for-Newborns-With

Aerosolized Calfactant for Newborns With Respiratory ... This is the largest clinical trial evaluating the efficacy of aerosolized surfactant for preterm infants with respiratory distress syndrome.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/ppul.26149

Comparative effectiveness of calfactant and beractant in ... Calfactant significantly lowered the duration of hospital stay, risk of pneumothorax and air leak syndrome whereas beractant users had lower ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/020521s038lbl.pdf

INFASURF® (calfactant) intratracheal suspension While efficacy cannot be established from uncontrolled trials, there were four uncontrolled trials that included 15,500 preterm neonates who were treated with ...

5. archivesofmedicalscience.com archivesofmedicalscience.com/Comparative-efficacy-of-pulmonary-surfactant-in-respiratory-distress-syndrome-in,124153,0,2.html

Comparative efficacy of pulmonary surfactant in respiratory ... Compared with beractant, other pulmonary surfactants are more effective to reduce the mortality of respiratory distress syndrome in preterm infants.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8290378/

Comparative efficacy and safety of late surfactant ... Characterize the use, efficacy, and safety of poractant alfa and calfactant surfactants compared to beractant in preterm infants receiving late surfactant.

7. infasurf.com infasurf.com/prescribing-information/

Prescribing Information Infasurf is indicated for the prevention of Respiratory Distress Syndrome (RDS) in premature infants at high risk for RDS and for the treatment (“rescue”) of ...

8. bmcpulmmed.biomedcentral.com bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-025-03728-4

Safety and efficacy of pulmonary surfactant therapy for acute ... PS treatment was associated with a reduction in the mortality rate and incidence of adverse events in critically ill children with ARDS.