Calfactant vs Poractant Alfa Using a Less Invasive Technique in Preterm Infants With Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) remains one of the leading causes of respiratory failure in preterm infants. Surfactant replacement therapy is a cornerstone of RDS management; however, traditional administration through endotracheal intubation and mechanical ventilation may contribute to ventilator-induced lung injury and increase the risk of adverse pulmonary outcomes. With the widespread adoption of non-invasive respiratory support strategies, less-invasive approaches to surfactant administration have gained increasing attention.

Less Invasive Surfactant Administration (LISA) is a technique in which surfactant is delivered directly into the trachea via a thin catheter under direct laryngoscopic visualization. At the same time, the infant continues to breathe spontaneously on noninvasive respiratory support. This method avoids endotracheal intubation and mechanical ventilation and has been associated with reduced need for invasive ventilation and improved respiratory outcomes in preterm infants.

Several surfactant preparations are currently used in neonatal practice. Poractant alfa and calfactant are two commonly administered natural surfactants with differing biochemical composition and dosing characteristics. Although both agents are widely used for the treatment of RDS, data directly comparing their effectiveness when administered via the LISA technique are limited.

This multicenter, prospective, randomized study is designed to compare the clinical efficacy of poractant alfa and calfactant administered using the LISA technique in preterm infants with respiratory distress syndrome. Eligible participants will be preterm infants born at less than 30 weeks' gestation, diagnosed with RDS based on clinical and radiographic criteria, who are spontaneously breathing and receiving noninvasive respiratory support without prior endotracheal intubation.

After enrollment, infants will be randomly assigned to receive either poractant alfa or calfactant via the LISA method. In both groups, surfactant will be administered through a thin catheter inserted into the trachea under direct laryngoscopic visualization while maintaining spontaneous breathing and noninvasive respiratory support. Standard neonatal intensive care practices will be applied throughout the study period in all participating centers.

The primary focus of the study is to compare short-term respiratory outcomes between the two treatment groups. These include the need for endotracheal intubation, the requirement for repeat surfactant administration, and the level and duration of respiratory support within the first 72 hours of life. Secondary outcomes include longer-term clinical outcomes such as the development of bronchopulmonary dysplasia at 36 weeks' postmenstrual age, as well as other neonatal morbidities, including intraventricular hemorrhage, necrotizing enterocolitis, and overall survival to discharge.

By directly comparing poractant alfa and calfactant administered via the LISA technique in a randomized, multicenter setting, this study aims to provide evidence on the optimal surfactant choice for less invasive treatment of RDS in very preterm infants. The findings are expected to inform clinical practice and contribute to the improvement of respiratory management strategies.

• Need for Repeat Surfactant Administration [Time frame: Up to 72 hours after birth.]
• Adverse Events During Surfactant Administration [Time frame: During the surfactant administration and up to 72 hours after birth.]
• Bronchopulmonary dysplasia [Time frame: At 36 weeks' postmenstrual age or discharge, whichever occurred first.]
• Retinopathy of Prematurity [Time frame: From birth until discharge, assessed up to 44 weeks' postmenstrual age.]
• Patent Ductus Arteriosus [Time frame: From birth until the date of the first documented patent ductus arteriosus requiring medical or surgical treatment or the date of hospital discharge, whichever came first, assessed up to 36 weeks' postmenstrual age.]
• Air Leak Syndromes [Time frame: Up to 7 days after birth.]
• Duration of Respiratory Support [Time frame: From birth until discontinuation of respiratory support or discharge, whichever occurs first. (Through study completion, an average of 1 year.)]
• Length of Hospital Stay [Time frame: From birth until discharge. (Through study completion, an average of 1 year.)]
• Mortality [Time frame: From the date of randomization until the date of death from any cause or the date of discharge, whichever came first. (Through study completion, an average of 1 year.)]
• Intraventricular Hemorrhage [Time frame: Up to the 7th day after birth.]
• Necrotizing Enterocolitis [Time frame: From birth until the date of the first documented necrotizing enterocolitis or the date of discharge, whichever came first, assessed up to 36 weeks' postmenstrual age.]