No mortality benefit of early ibuprofen in preterm infants with arteriosus

DENVER — A randomized controlled trial found that early targeted treatment with ibuprofen did not reduce mortality among 72-hour-old extremely preterm infants with a large patent ductus arteriosus, researchers reported here.

There also was no benefit on moderate or severe bronchopulmonary dysplasia (BPD), although treatment was beneficial in other ways, according to data presented at the Pediatric Academic Societies Meeting.

The Baby-OSCAR trial examined infants born before 28 weeks of gestation to evaluate whether early targeted treatment of a large PDA with ibuprofen within 72 hours of birth improves short-term health outcomes at 36 weeks post-menstrual age.

Samir Gupta, MD, professor of neonatology in the department of engineering at Durham University in the United Kingdom, said patent ductus arteriosus (PDA) has puzzled practitioners.

“PDA is a condition that is caused by a blood vessel called the ductus arteriosus staying open after a baby’s birth,” Gupta said in a release “During pregnancy, the ductus arteriosus allows blood from the baby’s heart to flow to the mother’s placenta to get oxygen, bypassing the baby’s lungs. Soon after birth, the ductus should close to allow blood to flow to the baby’s own lungs to get oxygen. However, in extreme preterm babies, the ductus often takes a long time to close on its own, and this can lead to a variety of complications.

“Clinicians are unsure if early treatment should be offered to extreme preterm babies to close the patent ductus arteriosus and reduce the risks of complications, or whether it would be better to wait and see if the ductus will close on its own.”

Gupta told Healio in an interview that the best way to manage these infants has long been elusive until the last decade.

“In the last decade, there have been advances in terms of the expertise available on the neonatal units, and one of them is availability of the bedside echocardiography that is done by the neonatologist,” Gupta said. “So, what we decided to look at was that if we identify the babies using echocardiography, before this PDA is symptomatic, and try to treat them, will it make differences in their debt or long-term outcome?”

The trial included 646 infants: 324 allocated to ibuprofen and 322 to placebo. There were 44 (13.6%) deaths by 36 weeks in the ibuprofen group and 33 (10.3%) in the placebo arm in the same time (unadjusted risk ratio = 1.33; 95% CI, 0.87-2.02), with the remaining subjects in both groups surviving to 36 weeks.

Evidence suggested that early targeted treatment with ibuprofen within 72 hours increased the chance of closed or significant PDA (< 1.5 mm) at 3 weeks post-menstrual age and reduced the risk for surgical treatment for a symptomatic PDA.

“The results of the trial suggest that giving the [ibuprofen] treatment very early did not benefit babies in terms of the primary outcome of PDA, or death,” Gupta said.
And hence, this will dissuade the clinicians [from using ibuprofen], which was gaining popularity in terms of treating these babies early after identification [because] the treatment does not confer any benefits. We remain open with the question of selecting the babies in a more appropriate way before we decide to give the treatment and which could be a symptomatic treatment or a newer modality that needs to be tested in the future trials.”

References:

Gupta S, et al. Does selective early treatment of patent ductus arteriosus (PDA) reduce death or bronchopulmonary dysplasia(BPD) at 36 weeks in extreme preterm babies? A randomized controlled trial (Baby-OSCAR Trial). Presented at: Pediatric Academic Societies Meeting; April 21-25, 2022.