A Study To InvestigateThe Safety, Tolerability And Efficacy Of Nebulised Curosurf® In Preterm Neonates With Respiratory Distress Syndrome (RDS)

The study will be conducted in spontaneously breathing preterm neonates with mild to moderate RDS and will consist of two parts:

Part I, with the objective to assess the safety and tolerability of single ascending doses of nebulised Curosurf® ; Part II, with the objective to compare the efficacy of nebulised Curosurf®, administered at two selected doses from part I, during nCPAP, versus nCPAP alone in terms of incidence of respiratory failure in the first 72 hours of life.

• nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I) (Drug): Single ascending doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part I)
• nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II) (Drug): Two doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part II)
• nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I) (Other): Nasal continuous positive airway pressure alone
• nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II) (Other): nasal continuous positive airway pressure alone

Primary outcomes

• Percentage of neonates with respiratory failure [in the first 72 hours of life]: Respiratory failure defined as: need for endotracheal surfactant administration and/or mechanical ventilation
• Adverse Events [discharge or 36 weeks post menstrual age (PMA), whichever comes first]: Any untoward medical occurrence in a clinical trial neonate administered a medicinal product and which does not necessarily have a casual relationship with the treatment
• Adverse Drug Reactions [discharge or 36 weeks post menstrual age (PMA), whichever comes first]: Any untoward and unintended responses to an investigational product related to any dose administered

Sex: All, ages: 28 Weeks to 32 Weeks

Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
2. Inborn neonates from 28+0 to 32+6 weeks of gestational age (GA), spontaneously breathing and stabilised on nCPAP
3. Clinical course consistent with RDS.
4. Receiving CPAP pressure 5-8 centimeter of water (cm H2O) and fraction of inspired oxygen (FiO2) between 0.25 and 0.40 to maintain saturation of peripheral oxygen (SpO2) between 88% and 95% for at least 30 minutes. Randomization should occur between 60 minutes and 12 hours after birth.

Exclusion Criteria:

1. Early need for endotracheal intubation for cardiopulmonary resuscitation in delivery room or within 1 hour from birth because of severe RDS
2. Respiratory Distress not secondary to surfactant deficiency
3. Use of surfactant prior to study entry and need for endotracheal administration of any other treatment.
4. Major congenital anomalies.
5. Evidence of severe birth asphyxia
6. Mothers with prolonged rupture of the membranes
7. Presence of air leaks.
8. Presence of IVH (intraventricular hemorrhage ) ≥ III.
9. Hypotension or evidence of hemodynamic instability.
10. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk.
11. Participation in another clinical trial

• Results publication: Dani C, Talosi G, Piccinno A, Ginocchio VM, Balla G, Lavizzari A, Stranak Z, Gitto E, Martinelli S, Plavka R, Krolak-Olejnik B, Lista G, Spedicato F, Ciurlia G, Santoro D, Sweet D; CURONEB Study Group. A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome. J Pediatr. 2022 Jul;246:40-47.e5. doi: 10.1016/j.jpeds.2022.02.054. Epub 2022 Mar 5. PMID 35257740

• Carlo Dani, MD, Principal investigator, Careggi Hospital, Florence (Italy)

NIH grants: 2016