Lung UltrasouNd Guided Surfactant Therapy in Preterm Infants: an International Multicentric Randomized Control Trial (LUNG Study)

Background Management of neonatal respiratory distress syndrome (RDS) involves noninvasive respiratory supports, such as nasal continuous positive airway (nCPAP), and mechanical ventilation. On the other hand, exogenous surfactant administration is the other cornerstone for the treatment of RDS. Currently, the decision to administer surfactant in a non-invasively ventilated newborn is commonly based on cut-off values of inspired fraction of oxygen (FiO2). Nevertheless, the accuracy of this criterion might be weak because FiO2 values depend per se by the setting of respiratory support. Moreover, the American Academy of Pediatrics guidelines do not recommend any FiO2 threshold for surfactant administration. It has been shown that prompt administration of surfactant (within the first 3 hours of life) can reduce the risk of bronchopulmonary dysplasia (BPD). Unfortunately, criteria for surfactant treatment used, often leads to a delayed administration. The role of lung ultrasound (LU) as a semi-quantitative method for the decision to give exogenous surfactant has been studied in recent years. Researchers demonstrated that a LU score (LUS) of RDS severity is able to predict the need for surfactant therapy, as subsequently confirmed by subsequent studies. After these results, a first quality improvement study demonstrated that the use of a LUS cut-off for deciding surfactant treatment allowed a significant increase of early administration. This finding has been confirmed by a recent single-center randomized controlled trial. However, all these studies were single-center, and there are not multicenter randomized controlled trials which can support the wide use of LUS measurement as a standard method for surfactant replacement therapy.

This study, in addition to investigating the decision-making role of LUS in the administration of surfactant, also aims to evaluate the possibility of making treatment with surfactant earlier and more timely, having already been shown in the past that an early administration improves clinical outcomes.

Aim of the study The investigators hypothesized that the use of a LUS for measuring RDS severity and deciding surfactant treatment thresholds might decrease the incidence of early and late sequelae in the study group. Thus, a timely surfactant therapy would eventually improve short (e.g. Need of mechanical ventilation in the first 3 days) and more long-term outcomes, such as BPD or death.

To confirm this hypothesis, the investigators planned an international multicenter randomized controlled study in which preterm infants will be randomized into two groups: one will be managed deciding surfactant treatment of preterm infants with RDS on the basis of a cut-off value of FiO2 (CG), and one will be managed deciding surfactant treatment using a LUS cut-off and FiO2 (LUSG).

Study design The study will be a multicenter randomized open control trial carried out in Level III-IV neonatal intensive care units (NICUs). The financial outcome of the study is no profit. The design of the study is of superiority. The enrollment period will be 24 months (starting February 1, 2022).