Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus

Topic overview

Another article you should know by Cecilia Gigena

"Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus" 

Authors: Tim Hundscheid, M.D., Wes Onland, M.D., Ph.D., Elisabeth M.W. Kooi, M.D., Ph.D., Daniel C. Vijlbrief, M.D., Ph.D., Willem B. de Vries, M.D., Ph.D., Koen P. Dijkman, M.D., Anton H. van Kaam, M.D., Ph.D., Eduardo Villamor, M.D., Ph.D., André A. Kroon, M.D., Ph.D., Remco Visser, M.D., Ph.D., Susanne M. Mulder-de Tollenaer, M.D., Barbara De Bisschop, M.D

Full article: nejm.org/doi/full/10.1056/NEJMoa2207418

BACKGROUND

Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.

METHODS

In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks’ gestational age) 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 noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points.

RESULTS

A total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 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 early-ibuprofen 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). Rates of other adverse outcomes were similar in the two groups.

CONCLUSIONS

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. 

Intended audience: Healthcare professionals and clinicians.