Efficacy of ibuprofen versus acetaminophen and conservative management for closure of patent ductus arteriosus in preterm neonates: a randomized clinical trial

Abstract Background Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality in preterm neonates. This study aimed to compare the efficacy of ibuprofen with acetaminophen and conservative management in achieving PDA closure in preterm infants. Methods In this randomized clinical trial, 327 preterm neonates with a gestational age of less than 37 weeks and a birth weight under 2500 g were enrolled. Participants were randomly assigned to receive ibuprofen, acetaminophen, or conservative management without pharmacological treatment. Echocardiographic assessments were performed on the third postnatal day and repeated one day after completion of the treatment course to evaluate ductal closure. Statistical analyses were conducted using SPSS version 22. Results The 327 preterm neonates were evenly allocated to the acetaminophen, ibuprofen, and control groups. The PDA closure rate was significantly higher in both the acetaminophen (89.0%) and ibuprofen (94.5%) groups compared to the control group (71%) (p < 0.001 for both), with no significant difference between the two active drugs (p = 0.14). Similar patterns were observed for LA/Ao (left atrium-to-aortic root) ratio normalization. Subgroup analyses revealed that in infants born at ≥ 32 weeks of gestation, ibuprofen achieved a 100% closure rate, compared to 91.8% for acetaminophen (p = 0.05). Among infants weighing ≥ 1500 g, ibuprofen demonstrated significantly superior closure (98.6% vs. 91.1%, p = 0.04). However, in very low birth weight infants (<1500 g), neither active drug reached statistical significance over control. Conclusion Both pharmacologic agents were superior to conservative management, with ibuprofen showing enhanced efficacy over acetaminophen in more mature and heavier infants.