Original Investigation 

Early Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial

Namasivayam Ambalavanan, Waldemar A. Carlo, Kayla J. Nowak, et al

JAMA Published Online: September 30, 2025

doi: 10.1001/jama.2025.16450

Key Points

Question  Does intratracheal administration of budesonide mixed with surfactant, compared with surfactant alone, reduce bronchopulmonary dysplasia or death by 36 weeks’ postmenstrual age in preterm infants less than 29 weeks’ gestation?

Findings  In this multicenter randomized trial, after recruiting 641 infants, recruitment was stopped early when prespecified futility criteria were satisfied. There was no difference in bronchopulmonary dysplasia or death between infants receiving budesonide with surfactant (68.5%) vs those receiving surfactant alone (67.9%; adjusted relative risk 1.00 [95% CI, 0.90-1.11]).

Meaning  In extremely preterm infants, mixing budesonide with surfactant did not reduce bronchopulmonary dysplasia or death.

Abstract

Importance  Extremely preterm infants are at high risk for bronchopulmonary dysplasia (BPD) and death. Multiple small randomized clinical trials showed that a combination of budesonide with surfactant compared with surfactant alone reduced BPD or death.

Objective  To determine if early intratracheal administration of a combination of budesonide (0.25 mg/kg) mixed with surfactant, compared with surfactant alone, reduces physiologic BPD or death by 36 weeks’ postmenstrual age in extremely preterm infants.

Design, Setting, and Participants  This double-masked randomized clinical trial was conducted from April 2021 to June 2024 in the 17 centers of the United States Neonatal Research Network. Infants 22 to 28 weeks’ gestation or 401 to 1000 g birth weight were enrolled after clinical decision to give surfactant, with the first dose of surfactant being study drug (prior surfactant was an exclusion criterion).

Interventions  Infants were randomly allocated 1:1 to receive 1 to 2 doses of budesonide + surfactant (poractant alfa) or surfactant alone via endotracheal tube within 50 hours of birth.

Main Outcomes and Measures  The primary outcome was physiologic BPD or death by 36 weeks’ postmenstrual age. There were 5 prespecified secondary outcomes and multiple prespecified exploratory and safety outcomes.

Results  The trial was stopped with 641 infants enrolled (55.3% of 1160 planned; mean birth weight, 810 g [SD, 256 g]; gestational age, 25.9 weeks [SD, 1.9 weeks]), because interim analysis at 50% enrollment reached the prespecified futility threshold. The incidence of BPD or death was 68.5% in the budesonide + surfactant group and 67.9% in the surfactant-alone group (adjusted relative risk [RR], 1.00 [95% CI, 0.90-1.11]). No differences were noted in mortality (15.3% vs 13.2%; adjusted RR, 1.13 [95% CI, 0.78-1.64]) or BPD among survivors to 36 weeks’ postmenstrual age (62.9% vs 63.0%; adjusted RR, 0.99 [95% CI, 0.87-1.12]). More infants who received budesonide + surfactant compared with surfactant alone had hyperglycemia (66.7% vs 49.8%; adjusted RR, 1.33 [95% CI, 1.17-1.51]).

Conclusions and Relevance  In this large multicenter trial, the combination of budesonide with surfactant did not reduce the risk of BPD or death at 36 weeks’ postmenstrual age in extremely preterm infants.

Trial Registration  ClinicalTrials.gov Identifier: NCT04545866