PLUSS (Preventing Chronic Lung Disease in Extremely Preterm Infants Using Surfactant + Steroid)-HEARTS (Haemodynamic Echocardiogram Assessment after Receiving Therapy with Steroids) in extremely preterm infants

Abstract

Patency of the ductus arteriosus in preterm infants is dictated primarily by Prostaglandin E2 (PGE2) and the non-steroidal anti-inflammatory medications that have long been used to promote ductal closure act by reducing prostaglandin production through cyclooxygenase enzyme inhibition. There is evidence that corticosteroids may also promote ductal closure through at least two mechanisms that impact PGE2 levels. This includes increasing phospholipase A2 inhibitor production with resultant decreased PGE2 synthesis and inhibition of 15-PGHD with resultant increased PGE2 break-down. More importantly, the vast majority of randomised controlled trials evaluating administration of early systemic, inhaled, or intra-tracheal corticosteroids to very preterm infants have found decreased rates of patent ductus arteriosus (PDA) diagnosis, medical treatment of PDA and/or surgical ductal ligation in exposed infants, suggesting a possible effect on early ductus arteriosus closure. What remains unclear is whether the mechanism behind decreased rates of PDA diagnosis and treatment is a direct effect due to corticosteroids promoting early ductus arteriosus closure, or an indirect effect of corticosteroids providing a respiratory benefit that results in clinicians being less inclined to pursue or treat a PDA.

The PLUSS Trial is a multicentre, two-arm, parallel, double-blind randomised clinical trial designed to evaluate the effect of early intra-tracheal budesonide (a corticosteroid) mixed with surfactant on survival without BPD in extremely preterm infants born <28 weeks’ gestation (n = 1060). The PLUSS-HEARTS sub-study will utilise the double-blind randomised methodology of PLUSS in select participating sites to measure rates of early ductus arteriosus closure following exposure to intra-tracheal corticosteroids, compared with no exposure. This will hopefully shed light on the true effect of intratracheal corticosteroids on PDA diagnosis or treatment in this high-risk patient population.