Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen

Background: The cyclooxygenase inhibitor ibuprofen may be used to treat a patent ductus arteriosus (PDA) in preterm infants. We hypothesized that selective early treatment of large PDAs with ibuprofen would improve short-term outcomes. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial evaluating early (up to 72 hours) treatment with ibuprofen for a large PDA (diameter ≥ 1.5 mm and pulsatile flow) in extreme preterm infants (born between 23 weeks+0 days and 28 weeks+6 days' gestation), we randomly assigned 326 infants to receive ibuprofen and 327 to receive placebo. The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age. Results: The primary outcome occurred in 220 of 318 infants (69.2%) assigned to ibuprofen and 202 of 318 infants (63.5%) assigned to placebo (adjusted risk ratio [aRR], 1.09; 95% confidence interval (CI), 0.98 to 1.20; p=0.10). Death occurred in 44 of 323 infants (13.6%) assigned to ibuprofen and 33 of 321 infants (10.3%) assigned to placebo (aRR, 1.32; 95% CI, 0.92 to 1.90). Among infants that survived to 36 weeks' post-menstrual age, moderate or severe BPD occurred in 176 of 274 infants (64.2%) assigned to ibuprofen and 169 of 285 infants (59.3%) assigned to placebo (aRR 1.09, 95% CI 0.96 to 1.23). There were two severe adverse events that were possibly related to ibuprofen. Conclusions: Early treatment with ibuprofen was not associated with an improvement in the composite outcome of death or moderate or severe BPD at 36 weeks' post-menstrual age compared to placebo. (Funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977)

Samir Gupta, Nimish V. Subhedar, Jennifer L. Bell, David Field, Ursula Bowler, Elizabeth Hutchison, Sam Johnson, Wilf Kelsall, Justine Pepperell, Tracy Roberts, Sunil Sinha, Kayleigh Stanbury, Jonathan Wyllie, Pollyanna Hardy, Edmund Juszczak