Trial Finds No Harm in Leaving Preemies’ PDA Alone

Newborns with patent ductus arteriosus (PDA) had similar outcomes whether they received ibuprofen therapy or no intervention at all, a Korean randomized trial showed.

The incidence of bronchopulmonary dysplasia (BPD) or death was 44% without intervention versus 50% with oral ibuprofen (P=0.51), which met noninferiority criteria.

Findings were similar when analyzing BPD and morality separately, reported Won Soon Park, MD, PhD, of Samsung Medical Center and Sungkyunkwan University School of Medicine in Seoul, and colleagues. Their paper was published online in JAMA Pediatrics.

“[O]ur results suggest that most patients with hemodynamically significant PDA could eventually undergo spontaneous closure even with the nonintervention approach,” Park and colleagues concluded.

In the study, noninferiority of the nonintervention strategy could be attributed to the low efficacy of oral ibuprofen for closing PDA, Park’s group said.

“Although higher odds of PDA closure have been reported with oral ibuprofen than with intravenous ibuprofen or indomethacin, further studies using other NSAIDs [nonsteroidal anti-inflammatory drugs] are necessary to clarify whether there is a variation in the effectiveness of NSAIDs for closing PDA and thereby improving BPD or death,” the researchers said.

No NSAID has been found to improve mortality, long-term respiratory outcomes, or neurodevelopment in babies with persistent PDA.

Investigators identified preterm babies born at gestational age 23-30 weeks who were admitted to the neonatal intensive care unit at Samsung Medical Center. Newborns were eligible for the double-blind trial if they had a hemodynamically-significant PDA (ductal size larger than 1.5 mm plus respiratory support). All were enrolled in the study after the first postnatal week.

Congenital heart disease and life-threatening congenital anomalies were among the exclusion criteria of the study.

While 146 preterm babies were randomized to oral ibuprofen or placebo, 142 were included in the main per-protocol analysis after counting only those receiving complete ibuprofen cycles (first dose of 10 mg/kg followed by a 5-mg/kg dose after 24 hours, then a second 5-mg/kg dose after 48 hours).

The ibuprofen group had significantly more boys compared to controls.

One infant in the ibuprofen arm required backup treatment owing to cardiopulmonary compromise, and another received surgical ligation. None in the placebo group received backup treatment.

Ductal closure rates at 1 week after randomization significantly favored the oral ibuprofen group, but this advantage dissipated by the time of hospital discharge, Park and colleagues reported.

Another trial, PDA-TOLERATE, had already shown that early, routine pharmacologic treatment did not improve respiratory outcomes compared with conservative management.

“However, this study could have had a selection bias owing to the low enrollment rate of eligible infants, and the high rate of backup medical and surgical treatment of PDA might be another limitation,” the Korean group noted.

As for their own study, they acknowledged that the single-center study was limited by a relatively large noninferiority margin and the lack of long-term neurodevelopmental outcome data. Furthermore, the investigators noted the arbitrary definition of hemodynamically significant PDA used.