Paracetamol Versus Ibuprofen In Very Low Birth Weight Infants With Patent Ductus Arteriosus:A Randomized Controlled Trial

Background:Patent ductus arteriosus(PDA)is the most common disease and the major risk factorfor mortality and morbidity in premature infants.A PDA can be treated surgically,interventional therapy or medically with one of prostaglandin inhibitors.The traditional prostaglandin inhibitors,including indomethacin and ibuprofen,has demonstrated good effects on patent ductus arteriosus(PDA)but with potential adverse effects,for example,gastrointestinal hemorrhage,renal impairmentandhyperbilirubinemia.Nowadays many studies have shown that oral paracetamolis both safe and effective in treatingPDA.Theaim of our study is to compare the efficacy and safety profiles of enteral paracetamol andibuprofen for closure of patent ductus arteriosus(PDA)in very low birth weight infants.Population and Methods:We collected 240 preterm infants with birth weight< 1500 g in the first three days of life with hs-PDA diagnosedwith ECHO and randomly assigned them to receive either oral paracetamol(n = 120)or ibuprofen(n = 120).The primary outcome was the rate ofductal closure,and secondary outcomes were adverse effects and complications including gastrointestinalbleeding,necrotizing enterocolitis(NEC),renalimpairment and the like.Results:A total of 227 infants finished trial,including 117 cases in enteral paracetamol group and 110 cases in enteral ibuprofen group.According intention to treat analysis,the ductus was closed in 99 infants(82.5%)of the paracetamolgroup compared with 97(80.8%)of the ibuprofen group,andthere was no significant difference between the two treatments(P =0.74).Meanwhile,the 95% CI for the difference between thetwo groups was [-0.081,0.115].In addition,According per-protocol analysis,PDA closure rate was 84.6%(99/117)in enteral paracetamol group as compared to 88.2%(97/110)in enteral ibuprofen group,andthere was no significant difference between the two treatments(P =0.43).Meanwhile,the 95% CI for the difference between thetwo groups was [-0.125,0.053].Thus,the efficacy of paracetamolwas non-inferior to the ibuprofen group.The early complications were similar between the two groups.However,the incidence of gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen within 1 week after medication(P =0.02).No significantdifferences in other early and late complications were noted.Conclusion:1?The efficacy of enteral paracetamol for closure of patent ductus arteriosus(PDA)in very low birth weight infants was not inferior to that of ibuprofen.2?This comparison of drug safety profiles in very low birth weight infants with PDA revealed that oralparacetamol showed a decreased risk ofgastrointestinal bleeding.