Objective: To examine the effects of early echocardiography-targeted ibuprofen treatment of large patent ductus arteriosus (PDA) on survival without cerebral palsy (CP) at 24 months corrected age.
Study design: We enrolled infants born at <28 weeks of gestation with a large PDA on echocardiography at 6-12 hours after birth to ibuprofen or placebo by 12 hours of age in a multicenter, double blind, randomized-controlled trial. Open-label ibuprofen was allowed for prespecified criteria of a hemodynamically significant PDA. The primary outcome was survival without CP at 24 months corrected age.
Results: Among 337 enrolled infants, 109 had a small or closed ductus and constituted a reference group; 228 had a large PDA and were randomized. The primary outcome was assessed at 2 years in 108/114 (94.7%) and 102/114 (89.5%) patients allocated to ibuprofen or placebo, respectively. Survival without CP occurred in 77/108 (71.3%) after ibuprofen, 73/102 (71.6%) after placebo (adjusted relative risk (aRR), 0.98, 95% confidence interval (CI) 0.83 to 1.16, P=.83), and 77/101 (76.2%) in reference group. Ibuprofen-treated infants had a lower incidence of PDA at day 3. Severe pulmonary hemorrhage during the first 3 days occurred in 2/114 (1.8%) ibuprofen and 9/114 (7.9%) placebo-treated infants (aRR, 0.22, 95% CI, 0.05 to 1.00, P=.05). Open-label rescue treatment with ibuprofen occurred in 62.3% placebo and 17.5% ibuprofen-treated infants (P<.001), at a median (IQR) age of 4 (3,5) and 4 (4,12) days, respectively.
Conclusion: Early echocardiography-targeted ibuprofen treatment of a large PDA did not change the rate of survival without CP.