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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether administering Poractant Alfa (also known as Curosurf, a type of surfactant) immediately after birth can improve breathing in preterm babies (born between 22-29 weeks) compared to waiting until they exhibit breathing problems. Preterm babies often struggle with breathing due to underdeveloped lungs. The trial compares two groups: one receives the medicine immediately after birth, and the other only if needed within the first two days. Newborns born before 30 weeks with parental consent may qualify if they do not have other health issues, such as birth defects. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Poractant Alfa?

Research shows that poractant alfa, also known as Curosurf, is generally safe for premature babies with respiratory distress syndrome (RDS). Studies have found that this treatment is usually well-tolerated and can help reduce the severity of RDS.

Previous studies reported some common side effects, such as a slow heart rate and low blood pressure, but these are usually manageable. Poractant alfa is already FDA-approved for treating RDS in premature babies, indicating a strong safety record.

Overall, evidence supports poractant alfa as a reliable and safe option for managing breathing issues in newborns. However, healthcare providers should be consulted to understand the specific risks and benefits for each case. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the trial of poractant alfa for neonatal respiratory distress syndrome because it explores the timing and method of surfactant administration. Unlike standard treatments that typically administer surfactant reactively once infants show significant respiratory distress, this approach includes a prophylactic strategy, delivering the surfactant within 15 minutes of birth. This early intervention, using a minimally invasive technique (MIST), could reduce the severity of respiratory issues and improve outcomes by providing surfactant before distress occurs. Additionally, the use of MIST offers a less invasive alternative compared to traditional methods, potentially reducing complications and improving the overall experience for these vulnerable infants.

What is the effectiveness track record for Poractant Alfa in treating neonatal respiratory distress syndrome?

Research has shown that Poractant Alfa, also known as Curosurf, effectively treats breathing problems in premature babies. It reduces the risk of death by 40% and increases the number of babies who survive without serious lung issues. In this trial, participants will be randomized into two groups: one receiving prophylactic surfactant treatment with Poractant Alfa shortly after birth, and the other receiving rescue surfactant treatment if needed. Studies have found that Curosurf improves oxygen levels in the blood within 5 minutes and quickly reduces the need for extra oxygen. This treatment is as good as or better than other options for improving conditions like broncho-pulmonary dysplasia (a lung problem) and retinopathy of prematurity (an eye problem). Overall, Poractant Alfa is a well-established treatment with strong evidence of effectiveness for babies at risk of breathing problems. ^{1 4 6 7 8}

Who Is on the Research Team?

Matthew Derrick, MBBS

Principal Investigator

Northshore Univ Healthsystem

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK538371/

Curosurf (poractant alfa) for the Treatment of Infants At Risk ... Overall, poractant alfa was found to be similarly or more clinically effective for outcomes such as broncho-pulmonary dysplasia, and retinopathy of prematurity.

2. curosurf.com curosurf.com/clinical-data/

Clinical Data | CUROSURF® (poractant alfa) | HCP Website CUROSURF improves oxygenation within 5 minutes and rapidly reduces FiO2 requirements over the initial treatment period—delivering better short-term efficacy.1,2.

3. nature.com nature.com/articles/s41372-020-0603-7

Beractant and poractant alfa in premature neonates with ... Comparison of efficacy between beractant and poractant alfa in respiratory distress syndrome among preterm infants (28–33 weeks ...

4. withpower.com withpower.com/trial/phase-4-respiratory-distress-syndrome-8-2023-5b9d3

Prophylactic Surfactant for Neonatal Respiratory Distress ... Research shows that Poractant Alfa (Curosurf) significantly reduces neonatal mortality by 40% and increases the percentage of survivors without severe lung ...

5. gynecology.su gynecology.su/jour/article/view/1802

Effect of same dose varying concentration poractant alfa on ... Results. It was found that development of pulmonary hemorrhages in LC and SC groups was significantly less common in infants who received PA at concentration of ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/020744s028lbl.pdf

CUROSURF (poractant alfa) intratracheal suspension Adverse Reactions in Studies in Premature Infants with Respiratory Distress Syndrome. The safety data described below reflect exposure to CUROSURF at a ...

7. curosurf.com curosurf.com/

CUROSURF® (poractant alfa) | Official HCP Website Explore Curosurf (poractant alfa) for respiratory distress syndrome (RDS), including clinical data, dosing and resources. See Full Prescribing and Important ...

8. go.drugbank.com go.drugbank.com/drugs/DB09113

Poractant alfa: Uses, Interactions, Mechanism of Action Poractant alfa is a pulmonary surfactant used for the treatment of Respiratory Distress Syndrome (RDS) in premature infants.