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

Trial Summary

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 drug Curosurf for treating neonatal respiratory distress syndrome?

Research shows that Curosurf, a surfactant therapy, can significantly reduce the risk of death in newborns with respiratory distress syndrome by 40% and increase the number of survivors without lung complications. Studies also indicate that many infants treated with Curosurf can avoid more invasive breathing support. ^{1 2 3 4 5}

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

MIST surfactant treatment, using poractant alfa (Curosurf), is unique because it can be administered noninvasively through nebulization, allowing for spontaneous breathing during treatment, which may reduce the need for mechanical ventilation and improve recovery outcomes. ^{2 3 4 5 6}

What is the purpose of this trial?

RESEARCH DESIGN Multicenter, randomized, controlled trial. RECRUITMENT Entry criteria Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome. Infants who are on NCPAP and FiO2 ≥0.30 will randomized to curosurf or infasurf via MIST. Exclusion criteria Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress. Babies who require emergent intubation will not be enrolled in the interventions. Parental Consent will be obtained prior to randomization.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland 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. [2018]

2. Norway pubmed.ncbi.nlm.nih.gov

[Surfactant treatment of premature infants with respiratory distress syndrome]. [2008]

3. Denmark 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]. [2013]

4. Switzerland 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. [2020]

5. 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]

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

Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome. [2018]