Clinical Trial: High-dose Ibuprofen for Patent Ductus Arteriosus (PDA) in Preterm Infant

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: High-dose Ibuprofen for Patent Ductus Arteriosus in Extremely Preterm Infants: a Randomized Controlled Study

Brief Summary: The investigators hypothesized that the early treatment of PDA with ibuprofen doses higher than those actually recommended might increase the closure rate in preterm infants with gestational age <29 weeks without increasing the occurrence of associated adverse effects. To assess this hypothesis the investigators planned a multicenter randomized controlled study to compare the effectiveness of the current ibuprofen regimen to that of a high-dose regimen in closing PDA.

Detailed Summary:

The patency of ductus arteriosus (PDA) is a frequent complication in preterm infants suffering from respiratory distress syndrome (RDS), and 60% to 70% of preterm infants of <28 weeks' gestation receive medical or surgical therapy for a PDA [1]. Neonates with a left-to-right shunt through the ductus complicating their RDS have higher respiratory failure, lower survival rate, and increased risk of intracranial haemorrhage (ICH), bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) [2]. Therefore, closure of PDA is indicated before a significant left-to-right shunting occurs.

Patent ductus arteriosus can be treated effectively with intravenous indomethacin and ibuprofen, leading to permanent ductal closure in 60% to 80% of infants [3-5]. However, preterm infants treated with ibuprofen experience lower serum creatinine values, higher urine output, and less undesirable decreased organ blood flow and vasoconstrictive adverse effects than indomethacin-treated patients [4].

Recently, Sperandio et al. reported that high-doses of indomethacin (1 mg/kg: fivefold the usual dose) were safe and effective in closing PDA in 98.5% of infants with gestational age < 33 weeks, and demonstrated that the closure rate of PDA was related to the cumulative dose of given indomethacin [6]. Moreover, Desfrere et al. demonstrated that the currently recommended dose regimen of ibuprofen (10-5-5 mg/kg/day) is associated with a low estimated probability (30.6%) of closing PDA in infants while a high-dose regimen (20-10-10 mg/kg/day) might be associated with a greater, although unsatisfactory, probability (54.8%) of closing PDA, without relevant side affects [7]. Furthermore, Hirt et al., based on pharmacokinetic findings, proposed increasing the dose regimen of ibuprofen during the postnatal period from 10-5-5 mg/kg/day in preterm
Sponsor: University of Florence

Current Primary Outcome: Successful rate in closing PDA of ibuprofen administered at high or standard dose. [ Time Frame: Between 84 and 96 hours of life ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Effectiveness of a second high dose ibuprofen course; correlation between peak plasma level of ibuprofen and PDA closure; mortality or BPD among survivors, incidence of ICH, PVL, ROP, NEC, sepsis, and length of stay in hospital. [ Time Frame: Hospital discharge ]

Original Secondary Outcome: Same as current

Information By: University of Florence

Dates:
Date Received: November 17, 2010
Date Started: June 2008
Date Completion:
Last Updated: November 18, 2010
Last Verified: July 2010