Randomized Noninferiority Trial of Expectant Management versus Early Treatment of Patent Ductus Arteriosus in Preterm Infants

Abstract

Objective: The study aimed to investigate, whether expectant management is noninferior to early patent ductus arteriosus (PDA) treatment with regard to the composite of mortality and/or incidence of bronchopulmonary dysplasia (BPD) in very preterm infants.

Study design: A total of 208 very preterm infants of the gestational age <32 weeks, birth weight <1,500 g, chronological age <72 hours, and PDA >1.5 mm were randomized between the treatment or expectant management groups. Both, the intention-to-treat and per-protocol analyses were performed.

Results: A total of 104 (50%) patients received rectal ibuprofen (n = 52) or intravenous acetaminophen (n = 52) within first 72 hours of life. In 104 (50%) infants, expectant management was used. Eight of them (8%) received rescue treatment at the median age of 7 (range: 6-13) days. PDA closure rates by the 10th day of life were 81% (n = 84) in the treatment arm, and 58% (n = 60) in the expectant management arm (p < 0.01). The median age at the time of ductus closure was 5 (range: 5-6) days in the treatment arm and 8 (range: 6-11) days in the expectant management arm (p < 0.01). At the time of discharge, ductus was closed in 83% of treated infants and in 78% of patients who were managed expectantly (p > 0.05). No significant difference between the groups was found for the primary clinical outcomes, BPD/death, or the secondary outcomes at a postmenstrual age of 36 weeks or discharge.

Conclusion: Expectant management is noninferior to early PDA treatment for reducing the incidence of death/BPD. Compared with the expectant management, early pharmacological treatment provides more frequent and faster PDA closure in preterm infants with gestational age <32 weeks, but it neither reduces morbidity nor improves survival rates.

Key points: · PDA persistence in very preterm infants is associated with an increased risk of BPD/death.. · PDA treatment accelerates ductus closure, but does not improve survival or reduce severe neonatal morbidity.. · Expectant management is not associated with a higher risk of BPD/death..