Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial

Lancet. 2004;364(9449):1945-9. doi: 10.1016/S0140-6736(04)17477-1.

Abstract

Background: Ibuprofen is used for treatment and prevention of patent ductus arteriosus in low-birthweight infants. Its effects on regional circulations differ from those of indometacin. Because prophylactic indometacin reduces the frequency of severe intraventricular haemorrhage and patent ductus arteriosus, we aimed to study the efficacy of early ibuprofen in reducing these outcomes in a double-blind, multicentre trial.

Methods: Within 6 h after birth, 415 low-birthweight infants (gestational age <31 weeks) were randomly allocated ibuprofen-lysine (10 mg/kg then two doses of 5 mg/kg after 24 h and 48 h) or placebo intravenously. The primary outcome was occurrence of severe intraventricular haemorrhage; secondary outcomes were occurrence of patent ductus arteriosus and possible adverse effects of ibuprofen. Analysis was by intention to treat.

Findings: 17 (8%) of 205 infants assigned ibuprofen and 18 (9%) of 210 assigned placebo developed severe intraventricular haemorrhage (relative risk 0.97 [95% CI 0.51-1.82]). In 172 (84%) infants of the ibuprofen group, the ductus was closed on day 3 compared with 126 (60%) of the placebo group (relative risk 1.40 [1.23-1.59]). No important differences in other outcomes or side-effects were noted; however, urine production was significantly lower on day 1 and concentration of creatinine in serum was significantly higher on day 3 after ibuprofen.

Interpretation: Ibuprofen prophylaxis in preterm infants does not reduce the frequency of intraventricular haemorrhage, but does decrease occurrence of patent ductus arteriosus.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cerebral Hemorrhage / prevention & control*
  • Cerebral Ventricles
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Double-Blind Method
  • Ductus Arteriosus, Patent / prevention & control
  • Humans
  • Ibuprofen / adverse effects
  • Ibuprofen / analogs & derivatives*
  • Ibuprofen / therapeutic use*
  • Infant, Newborn
  • Infant, Premature, Diseases / prevention & control*
  • Lysine / adverse effects
  • Lysine / analogs & derivatives*
  • Lysine / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Lysine
  • solufenum
  • Ibuprofen