Oral Ibuprofen versus Placebo for Management of Patent Ductus Arteriosus in Preterm infants: A Double Blinded, Randomized Controlled Trial

Abstract

Abstract Background A consensus on the management of patent ductus arteriosus (PDA) in premature neonates remains indefinable. Conservative PDA treatment is based on the premise that in most preterms PDAs spontaneously close before discharge. Ibuprofen has been used for treating PDA, however, no clear guidelines for management have been suggested. Aim of Work The aim of this work is to compare the effect of oral ibuprofen versus placebo on PDA closure in preterm infants less than 34 weeks’ gestation. Methodology This study was conducted on 80 preterm neonates with gestational age ≤ 34 weeks with a hemodynamically significant PDA. They were randomized into a medical treatment group (n = 40) and a placebo group (n = 40). Both groups received conservative PDA therapy in the form of fluid restriction, positive end-expiratory pressure, and/or diuretics. The medical treatment group received oral ibuprofen (at an initial dose of 10 mg/kg/day, followed by 5 mg/kg/day for the next 2 days) and the placebo group received an oral placebo. The open-label option and an extended oral ibuprofen therapy (an offered or a repeated course with the same dose) were only offered if there are concerns over a poor patient condition that was attributed to persistent PDA and only after meeting certain criteria like signs of pulmonary hyperperfusion and/or systemic hypoperfusion. Echocardiography was done on day 1 of recruitment (48-72 hours of age) and was followed up till discharge. The patients were followed up for adverse effects of ibuprofen by serum creatinine and total serum bilirubin after the first course of treatment. Results There was no significant difference in PDA closure rate following the first ibuprofen course (62.5% in the ibuprofen treated group vs 65% in the placebo group, p > 0.05). At discharge time (mean 13.5 days in the ibuprofen group, 14 days in the placebo group), a closure rate of 75% was achieved in both groups, respectively. There was no significant difference in initial serum creatinine levels between the two groups either on day 1 of recruitment or after the first course of the intervention, p > 0.05, respectively. Meanwhile, serum creatinine significantly decreased in both groups after treatment (p-value <0.001, respectively). Also, there was no difference between the two groups in serum bilirubin either on day 1 of recruitment or after the first course of treatment, p > 0.05, respectively. Conclusion Conservative treatment is not inferior to oral ibuprofen therapy in the management of PDA. Oral ibuprofen does not elevate serum creatinine levels or cause hyperbilirubinemia.