Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: study protocol for a randomized control trial

Abstract

BackgroundPatent ductus arteriosus (PDA) is one of most common complications in preterm infants. Although ibuprofen represents the first choice for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. The successful closure of the PDA with paracetamol has been recently reported in several preterm infants, and the safety of paracetamol for this use has been suggested by the available data.Methods/designWe present the design of a randomized, multicenter, controlled study, whose aim is to assess the effectiveness and safety of intravenous paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in preterm infants. A total of 110 infants born at 25+0 to 31+6 weeks of gestational age will be enrolled and randomized to receive paracetamol or ibuprofen (55 patients per group) starting at 24–72 h of life. The primary endpoint of the study is the comparison of the PDA closing rate observed after a 3-day course with paracetamol or ibuprofen. The secondary endpoints include the closure rate of PDA after the second course of treatment with ibuprofen, the re-opening rate of the PDA, the incidence of surgical ligation, and the occurrence of adverse effects.DiscussionThe results of this study will provide new information about the possible use of paracetamol in the treatment of PDA. Paracetamol could offer several important therapeutic advantages over current treatment options, and it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile.Trial registrationClinicaltrials.gov NCT02422966.Eudract no. 2013-003883-30.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1294-4) contains supplementary material, which is available to authorized users.

Oral ibuprofen is superior to oral paracetamol for patent ductus arteriosus in very low and extremely low birth weight infants

“…[11] Some studies demonstrated a lower PDA closure rate with paracetamol compared to ibuprofen. [12,13] Almost all studies had very small sample sizes, with less than 30 VLBW subjects in each group and even fewer subjects with extremely low birth weight (ELBW). Therefore, the true efficacy of paracetamol in VLBW infants is difficult to determine.…”

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation

“…Indomethacin and ibuprofen inhibit cyclooxygenase (COX3) in a no selective manner. How paracetamol acts for closing PDA still remains unclear, but it is known that it inhibits prostaglandin synthetase ( 5 ). Alternatively, paracetamol has been proposed to selectively inhibit a central isoform of COX3, but the existence of a functional human COX3 has been questioned ( 6 ).…”

“…Hammerman et al reported for the first time the use of paracetamol for closing PDA ( 4 ). Since then, many studies have reported similar efficiency of paracetamol to COX-inhibitors for closing PDA and less adverse events ( 5 ).…”

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

“…More recently, oral or iv administration of paracetamol (acetaminophen) gained attention in PDA treatment; the first case report on this topic has been published by Hammerman et al on 2011 [ 82 , 83 ]. Successively, this drug has been evaluated through many trials as safe and effective compared to traditional NSAIDs in PDA closure, with fewer side effects [ 2 , 18 , 84 – 86 ].…”