Is Expectant Management Noninferior to Early Ibuprofen for Patent Ductus Arteriosus?

In this multicentre non-inferiority trial, 273 infants with echocardiographically confirmed PDA (diameter >1.5 mm) who were extremely preterm (<28 weeks gestational age) underwent randomization to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The median gestational age was 26 weeks, with a median birth weight of 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], 7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the earlyibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). The authors concluded that expectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age.

Automated summary

In this multicentre trial, extremely preterm infants with echocardiographically confirmed PDA were randomly assigned to expectant management or early ibuprofen treatment. The primary outcome was a composite measure of necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The study found that expectant management was noninferior to early ibuprofen treatment in terms of reducing the occurrence of the primary outcome.