Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen
Samir Gupta1, Nimish V Subhedar1, Jennifer L Bell1
1From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.
Insights
Early ibuprofen treatment for large patent ductus arteriosus (PDA) in preterm infants did not significantly reduce the risk of death or bronchopulmonary dysplasia. This study found no improved short-term outcomes with early ibuprofen intervention for PDA in extremely preterm infants.
Area of Science:
- Neonatalogy
- Pharmacology
- Pediatric Critical Care
Background:
- Patent ductus arteriosus (PDA) is a common condition in preterm infants.
- Ibuprofen, a cyclooxygenase inhibitor, is used to treat PDA.
- The efficacy of early, selective treatment of large PDAs with ibuprofen in extremely preterm infants remains unclear.
Purpose of the Study:
- To evaluate the effect of early ibuprofen treatment on short-term outcomes in extremely preterm infants with large PDAs.
- To determine if selective early treatment improves the composite outcome of death or moderate/severe bronchopulmonary dysplasia.
Main Methods:
- A multicenter, randomized, double-blind, placebo-controlled trial was conducted.
- Infants born between 23 and 28 weeks' gestation with large PDAs (≥1.5 mm diameter) received early ibuprofen (≤72 hours) or placebo.
- The primary outcome was a composite of death or moderate/severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age.
Main Results:
- The primary outcome occurred in 69.2% of the ibuprofen group and 63.5% of the placebo group (adjusted risk ratio 1.09; P=0.10).
- Mortality rates were 13.6% with ibuprofen and 10.3% with placebo (adjusted risk ratio 1.32).
- Moderate or severe bronchopulmonary dysplasia occurred in 64.2% of the ibuprofen group and 59.3% of the placebo group among survivors.
Conclusions:
- Early treatment with ibuprofen did not significantly lower the risk of death or moderate/severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age.
- The study found no significant short-term benefit of early ibuprofen for large PDAs in extremely preterm infants.
- Two serious adverse events possibly related to ibuprofen were reported.
Background:
The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known.
Methods:
We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age.
Results:
A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen.
Conclusions:
The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).
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