Paracetamol Versus Ibuprofen In Premature Infants With Patent Ductus Arteriosus: A Randomized Controlled Trial

Background: Patent Ductus Arteriosus is the most common disease inpremature infants. It has been showed that cyclooxygenases-inhibitor(COX-inhibitor), indometacin and ibuprofen, has a good effect on thesymptomatic patent ductus arteriosus (PDA) with many contraindications andpotential side-effects. Since there is no intravenous COX-inhibitor in China,which limits its clinical application, new drugs are needed to be explored. Inpast two years, oral paracetamol, an antipyretic and analgesic drug in neonates,was administrated in preterm infants with PDA in several case reports. Toevaluate efficiency and safety of oral paracetamol, a randomized, single-blind,parallel controlled and non-inferiority trial comparing oral paracetamol andibuprofen for PDA closure in premature infants was designed.Patients and Methods: One hundreds and sixty infants (gestational age≤34weeks) with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n=80) or ibuprofen (n=80). After the intialcourse in both groups, the need for a second course relyed onechocardiographic evaluation. The main outcome was rate of ductal closure;secondary outcomes were adverse effects and complications.Results: There were65(81.2%) infants of paracetamol group whoseductus was closed compared with63(78.8%) of ibuprofen group.95%confidence interval of difference between the groups was [-0.080,0.128],demonstrating that paracetamol group was non-inferior to ibuprofen group inthe efficiency rate. The incidence of hyperbilirubinemia or gastrointestinalbleeding in paracetamol group was significantly lower than ibuprofen group.No significantly differences in other side-effects or complications were noted inhospital.Conclusion: To explore the efficiency and safety of oral paracetamol inpremature infants with PDA, by comparing paracetamol and ibuprofen, wereveal that paracetamol was non-inferior to ibuprofen concerning the rate ofductal closure with decreasing the risk of hyperbilirubinemia or gastrointestinalbleeding. Paracetamol could be accepted as an first-line drug for PDA in preterm infants.