A Study in Preterm Neonates With Respiratory Distress Syndrome (RDS) Comparing CUROSURF® Administration Through Less Invasive Surfactant Administration (LISA) and Conventional Administration

An Open-Label, Multicenter, Randomized, Controlled Study in Spontaneously Breathing Preterm Neonates With Respiratory Distress Syndrome to Compare Two Procedures for Porcine Surfactant (Poractant Alfa, CUROSURF®) Administration: A Less Invasive Method (LISA) During Non-invasive Ventilation (NIV) and the Conventional Administration During Brief Invasive Ventilation.

This study compared the administration of porcine surfactant (poractant alfa, Curosurf®) through a less invasive method (LISA), using a thin catheter, CHF 6440 (LISACATH®), during non-invasive ventilation (CPAP, NIPPV, BiPAP) with an approved conventional surfactant administration during invasive ventilation followed by rapid extubation in terms of short term and mid-term safety and efficacy in spontaneously breathing preterm neonates who have clinical signs of respiratory distress syndrome (RDS).

This study was an open-label, multicentre, randomized, controlled study of spontaneously breathing neonates with RDS. Neonates were evaluated according to the selection criteria and then randomized to surfactant treatment via LISA or standard administration procedure. The enrolment was staggered: the gestational age was restricted to 27+0 weeks up to 28+6 weeks for the first 15 neonates. Provided no safety concerns were raised, the enrolment was planned to be extended to the whole population (i.e. 25+0 weeks up to 28+6 weeks). Enrolled neonates were evaluated in a main phase of the trial until discharge or 40 weeks post-menstrual age (PMA), whichever came first. Their clinical status and neurodevelopment was to be assessed at 24-month corrected age as a separate stand-alone visit.

The Sponsor decided to terminate the study early, due to uncertain sufficient availability of the CHF 6440 catheter.

Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
2. Preterm neonates of either sex aged ≥30 minutes and <24 hours, spontaneously breathing and stabilized on non-invasive ventilation (NIV).
3. Gestational age of 25+0 weeks up to 28+6 completed weeks, except for the first 15 enrolled neonates in which the gestational age will be restricted to 27+0 weeks up to 28+6 weeks.
4. Clinical course consistent with RDS.
5. Fraction of inspired oxygen (FiO2) ≥0.30 to maintain preductal oxygen saturation (SpO2) between 88-95%.

Exclusion Criteria:

1. Need for immediate endotracheal intubation for cardiopulmonary resuscitation or insufficient respiratory drive
2. Use of nasal high frequency oscillatory ventilation (nHFOV) prior to study entry
3. Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
4. Known genetic or chromosomal disorders, major congenital anomalies (congenital heart diseases, myelomeningocele etc)
5. Mothers with prolonged rupture of the membranes (> 21 days duration)
6. Presence of air leaks if identified and known prior to study entry
7. Evidence of severe birth asphyxia (e.g. continued need for resuscitation at 10 minutes after birth, altered neurological state, or neonatal encephalopathy)
8. Neonatal seizures prior to study entry
9. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
10. Participation in another clinical trial of any medicinal product, placebo, experimental medical device, or biological substance conducted under the provisions of a protocol on the same therapeutic target.