Duration of Surfactant administration and impact on Stabilisation of vital parameters in very preterm neonates: 1 minute versus 5 minutes – a prospective randomised-controlled phase IV trial

This clinical trial evaluates the impact of surfactant administration duration on physiological stability in extremely preterm neonates with neonatal respiratory distress syndrome. The primary objective is to assess differences in peripheral oxygen saturation (SpO2), heart rate (HR), and cerebral regional oxygen saturation (crSO2) during the first 72 hours after birth in preterm neonates less than 28 weeks of gestational age undergoing less invasive surfactant administration (LISA), comparing 1-minute versus 5-minute surfactant administration protocols. This objective addresses the clinical relevance of optimizing surfactant delivery techniques to improve cardiorespiratory and cerebral oxygenation parameters in this vulnerable population. The secondary objectives include: evaluation of differences in monitoring parameters (SpO2, HR, crSO2, mean arterial blood pressure) up to three hours post-LISA procedure between randomization groups; assessment of differences in supplemental oxygen requirements, duration of bradycardia and hypoxia (in minutes) up to three hours after surfactant administration; comparison of vital parameters until three hours after extubation, measured every five minutes; determination of differences in the need for a second surfactant dose during the first two days post-administration; evaluation of differences in the requirement for invasive ventilation during the first two days post-administration; and assessment of the influence of surfactant administration duration on short-term outcomes including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), periventricular hemorrhage (PVH), and periventricular leukomalacia (PVL) until discharge or term age, whichever occurs first.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of **preterm neonates** with a **gestational age** of less than 28 weeks (up to 27 weeks and 6 days) diagnosed with **neonatal respiratory distress syndrome**. Both male and female neonates were eligible for inclusion. Participants were selected based on the clinical indication for **surfactant** administration via the **LISA method** (less invasive surfactant administration) and a **postnatal age** of less than 72 hours at the time of enrollment. The trial involved a vulnerable population, specifically extremely premature infants requiring respiratory support during the early neonatal period.

This study is designed as a prospective **randomized-controlled phase IV trial** investigating the duration of **surfactant** administration and its impact on stabilization of vital parameters in very **preterm neonates**. The trial compares two different administration durations of **poractant alfa** delivered via the **LISA** (less invasive surfactant administration) method: a 1-minute administration versus a 5-minute administration. The investigational product is an **endotracheopulmonary instillation suspension** containing poractant alfa as the active substance, which is an authorized medicinal product used within current clinical guidelines. This is classified as a **low interventional trial** as the investigational product is used according to established guidelines and additional measures pose minimal risk to participants. The maximum daily dose is **400 mg/kg** with a maximum total dose of **800 mg/kg** administered via **endotracheopulmonary use** over a treatment period of 1 day.

The primary objective is to assess differences in **SpO2** (oxygen saturation), **HR** (heart rate), and **crSO2** (cerebral regional oxygen saturation) according to the randomized group assignment during the LISA procedure in preterm neonates less than 28 weeks of **gestational age** during the first 72 hours after birth. The **primary endpoint** evaluates vital parameters during surfactant administration, defined as maximum changes or drop from baseline starting with the beginning of surfactant administration after insertion of the thin catheter until 15 minutes after the LISA procedure. **Secondary endpoints** include vital parameters and **MABP** (mean arterial blood pressure) up to three hours after surfactant administration, need for supplemental oxygen, amount of **bradycardia** and **hypoxia**, vital parameters until three hours after extubation assessed every five minutes, need for a second or repetitive dose of surfactant, **invasive ventilation** during the first two days after initial surfactant administration, and short-term outcome including **morbidity** until discharge or term age, whichever occurs first.

The trial targets **neonatal respiratory distress syndrome** in a specific population with defined inclusion criteria. Principal inclusion criteria are: preterm neonate less than 28 weeks and 0 days of gestational age (up to 27 weeks and 6 days), indication of surfactant administration via the LISA method, and postnatal age less than 72 hours. The estimated recruitment start date is December 15, 2025, with an estimated end date of July 31, 2028, providing an overall trial duration of approximately 2.5 years. Participant involvement begins with screening and enrollment within the first 72 hours after birth, continues through the LISA procedure with randomization to either the 1-minute or 5-minute administration group, and includes monitoring of vital parameters for up to three hours post-administration with assessment of short-term outcomes until discharge or term age. Early termination from the study may occur based on clinical necessity, withdrawal of consent, or other conditions affecting participant safety or data integrity as determined by the investigator.

The experimental medication utilized in this clinical trial is **Curosurf®**, a **surfactant** preparation containing **poractant alfa** as the active substance. The investigational product is available in two formulations: Curosurf® 120 mg and Curosurf® 240 mg. Both formulations are presented as a **suspension for endotracheopulmonary instillation**. The active substance, poractant alfa, is classified as a natural phospholipid and belongs to the ATC code R07AA02.

The route of administration for both formulations is **endotracheopulmonary use**, delivered via the **LISA procedure** (Less Invasive Surfactant Administration) in preterm neonates with gestational age less than 28 weeks. The dosage is weight-based and expressed in **milligrams per kilogram** (mg/kg). The maximum daily dose amount is **400 mg/kg**, with a maximum total dose amount of **800 mg/kg** over the treatment period. The maximum treatment period is **1 day**.

A key aspect of this phase IV randomized controlled trial is the comparison of two different durations of surfactant administration during the LISA procedure. Participants are randomized to receive surfactant administration over either 1 minute or 5 minutes. This variation in administration duration constitutes the primary intervention being evaluated, with the objective of assessing differences in oxygen saturation (SpO2), heart rate (HR), and cerebral regional oxygen saturation (crSO2) during the first 72 hours after birth.

Efficacy will be assessed through evaluation of vital parameters during and after surfactant administration via the LISA procedure. The primary endpoint consists of vital parameters including SpO2, heart rate, and cerebral regional oxygen saturation during surfactant administration, defined as maximum changes or drop from baseline starting with the beginning of surfactant administration after insertion of the thin catheter until 15 minutes after the LISA procedure. Secondary endpoints include SpO2, heart rate, cerebral regional oxygen saturation, and mean arterial blood pressure up to three hours after surfactant administration, defined as maximum changes or drop from baseline starting with the beginning of surfactant administration after insertion of the thin catheter until three hours after the LISA procedure. Additional secondary endpoints encompass the need for supplemental oxygen and the amount of bradycardia and hypoxia measured in minutes up to three hours after surfactant administration, vital parameters assessed every five minutes until three hours after extubation, the need for a second or repetitive dose of surfactant, invasive ventilation during the first two days after initial surfactant administration, and short-term outcome including morbidity until discharge or term age, dependent on which occurs first.