545 Does selective early treatment of Patent Ductus Arteriosus (PDA) with ibuprofen reduce death or Bronchopulmonary Dysplasia (BPD) at 36 weeks in extreme preterm babies? A Randomised Controlled Trial (Baby-OSCAR Trial)

Abstract

<h3>Aims</h3> The management of PDA continues to be a clinical conundrum in extremely low gestational age newborns (ELGANS). Presence of a PDA at 72 hours after birth in ELGANS is associated with an increased risk of death and complications of prematurity. Functional echocardiography (fEcho) is increasingly used to assess the haemodynamic impact of PDA and can be used in the first 3 days after birth to identify babies with a large pre-symptomatic PDA. The objective of this study was to evaluate whether early targeted treatment of a large PDA (diagnosed by fEcho) in extreme preterm babies with ibuprofen within 72 hours of birth improves short term health outcomes of death or moderate to severe BPD at 36 weeks post-menstrual age (PMA). <h3>Methods</h3> Baby-OSCAR is a UK multi-centre placebo-controlled masked randomised clinical trial in babies between 23⁺⁰and 28⁺⁶weeks’ gestation. With parental consent, eligible babies admitted to tertiary NICU were screened using fEcho. Babies with a large PDA on fEcho, (diameter &gt;1.5mm and with a pulsatile or growing pulse wave Doppler ductal flow pattern), were randomised within the first 72 hours after birth. A central secure web-based randomisation system using a probabilistic minimisation algorithm was used to allocate treatments. Babies received either i.v. ibuprofen at dose 10-5-5 mg/kg 24 hours apart or matched placebo (0.9% normal saline). The primary outcome was a composite of death or moderate to severe BPD at 36 weeks PMA. The trial was funded by the UK National Institute for Health Research. Ethics approval was obtained from East Midlands Research Ethics Committee. Statistical analysis by intention-to-treat was performed using Stata 17®. <h3>Results</h3> A total of 3848 babies were screened with fEcho from 32 tertiary NICU in the UK from July 2015–December 2020. Of these, 653 infants were randomised: 326 to ibuprofen and 327 to placebo. Infant baseline characteristics were broadly similar between the study groups (table 1). The median size of the PDA was 2.2mm in both groups. The primary outcome event rate in the ibuprofen and control groups was 220/318 (69.2%) and 202/318 (63.5%) respectively; adjusted risk ratio 1.09 (95% CI 0.98 to 1.20); p=0.104. There was no evidence of differences in secondary outcomes, except reduced need for surgical ligation (2.8% vs 9.6%; p&lt;0.001) and a higher proportion of closed/non-significant PDA at ~3 weeks age (55.5% vs 37%; p&lt;0.001) in ibuprofen compared to placebo respectively (table 2). <h3>Conclusion</h3> We found no evidence of a reduction in death or moderate to severe BPD with early selective treatment of a large PDA with ibuprofen within 72 hours of birth in extreme preterm infants.