Prophylactic Surfactant for Neonatal Respiratory Distress Syndrome

(PreProMISe Trial)

Overseen By Matthew Derrick, MBBS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: NorthShore University HealthSystem

Disqualifiers: Congenital anomalies, alternate respiratory distress

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

200 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

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

What data supports the effectiveness of the drug Poractant Alfa (Curosurf) for treating neonatal respiratory distress syndrome?

Research shows that Poractant Alfa (Curosurf) significantly reduces neonatal mortality by 40% and increases the percentage of survivors without severe lung problems in preterm infants with respiratory distress syndrome. Additionally, higher doses of Curosurf are more effective in treating severe cases, leading to better outcomes and lower costs. ^{1 2 3 4 5}

Is Poractant Alfa (Curosurf) safe for humans?

Poractant Alfa (Curosurf) has been used safely in preterm infants with respiratory distress syndrome, and studies have shown it to be effective with manageable complication rates. It has been compared to other treatments and used in various doses, showing a good safety profile in these contexts. ^{1 2 4 5 6}

How is the drug Poractant Alfa (Curosurf) unique in treating neonatal respiratory distress syndrome?

Poractant Alfa (Curosurf) is unique because it is a porcine-derived surfactant that can be administered in different doses, with higher doses showing better outcomes in severe cases of neonatal respiratory distress syndrome. It has been shown to significantly reduce neonatal mortality and improve survival without bronchopulmonary dysplasia (a chronic lung disease) compared to other treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to explore the question: Does prophylactic administration of exogenous surfactant in the delivery room, using a minimally-invasive technique, improve outcome in preterm infants 22-29 weeks' gestation compared to rescue treatment using the same technique?

Research Team

Matthew Derrick, MBBS

Principal Investigator

Northshore Univ Healthsystem

Eligibility Criteria

This trial is for premature infants born at 22-29 weeks' gestation. To participate, parents must give consent before birth. Infants with congenital anomalies or another cause of respiratory distress cannot join.

Inclusion Criteria

Antenatal consent from Parent

You are less than 30 weeks pregnant.

Exclusion Criteria

Birth defects

My breathing problems are caused by something other than my current condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants receive prophylactic or rescue surfactant treatment using the MIST technique shortly after birth

7 days

Continuous monitoring in NICU

Post-Intervention Management

Infants are managed with CPAP or HFNC, with criteria for intubation and potential additional surfactant doses

First week of life

Follow-up

Participants are monitored for respiratory and non-respiratory outcomes until discharge and followed up at 2 years

Until discharge and 2-year follow-up

Treatment Details

Interventions

• Poractant Alfa

Trial Overview The study tests if giving a substance called Poractant Alfa right after birth improves health outcomes compared to waiting until the baby shows signs of breathing trouble (rescue treatment).

Participant Groups

Group I: Prophylactic Surfactant via Minimally Invasive Technique Experimental Treatment 1 Intervention

Infants randomized to prophylactic surfactant treatment will receive a dose of poractant alfa (Curosurf) administered under direct laryngoscopy using a surfactant instillation catheter (MIST) 16G Angiocath (Becton Dickinson, Sandy, UT, USA), at a dosage of 200 mg/kg as soon as possible after delivery (within 15 minutes).

Group II: Rescue Surfactant via Minimally Invasive Technique Active Control 1 Intervention

The control group will be given surfactant will receive a dose of poractant alfa (Curosurf) administered under direct laryngoscopy using a surfactant instillation catheter (MIST) 16G Angiocath (Becton Dickinson, Sandy, UT, USA), at a dosage of 200 mg/kg if their fiO2 reaches a threshold of ≥30% within the first 48 hours of life.

Poractant Alfa is already approved in European Union, United States, Canada 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

Approved in Canada 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+

Chiesi USA, Inc.

Industry Sponsor

Trials

9

Recruited

6,100+

Findings from Research

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]

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 study of 54 neonates with acute respiratory distress syndrome, a high dose of Poractant alfa (Curosurf®) significantly reduced the duration of oxygen therapy and mechanical ventilation compared to a low dose, particularly in severe cases.

Despite the differences in treatment duration and costs, both high and low doses showed similar cure rates, indicating that higher doses are more effective without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome. Wang, N., Wang, L.[2021]

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]

In a study of 293 preterm infants with respiratory distress syndrome (RDS), treatment with 200 mg/kg of poractant alfa resulted in a faster reduction in the need for supplemental oxygen compared to beractant, indicating its efficacy in managing RDS.

Infants born at or below 32 weeks gestation who received 200 mg/kg of poractant alfa had significantly lower mortality rates (3%) compared to those treated with beractant (11%) or 100 mg/kg of poractant alfa, highlighting its potential safety and effectiveness in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. Ramanathan, R., Rasmussen, MR., Gerstmann, DR., et al.[2022]

References

1. 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]

2. 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]

3. Norway pubmed.ncbi.nlm.nih.gov

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

4. Pakistan pubmed.ncbi.nlm.nih.gov

Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome. [2021]

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

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

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

A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. [2022]