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. 2025 Sep 30:e2516450.
doi: 10.1001/jama.2025.16450. Online ahead of print.

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

Namasivayam Ambalavanan  1 , Waldemar A Carlo  1 , Kayla J Nowak  2 , Laura Elizabeth Wiener  2 , Shirley S Cosby  1 , Abhay J Bhatt  3 , Kristi L Watterberg  4 , Brenda B Poindexter  5 , Martin Keszler  6 , Carl T D'Angio  7 , Luc P Brion  8 , Vivek Narendran  9 , Carrie A Rau  10 , C Michael Cotten  11 , Matthew M Laughon  12 , Abhik Das  13 , Matthew A Rysavy  14 , Anna Maria Hibbs  15 , Janell Fuller  4 , Karen M Puopolo  16 , Anup Katheria  17 , Ravi M Patel  5 , Jennifer R Bermick  18 , Abbot R Laptook  6 , Irina Prelipcean  7 , Myra H Wyckoff  19 , Ryan Moore  20 , Stephanie L Merhar  21 , Robin K Ohls  10 , Bradley A Yoder  10 , Marta Perez  22 , Sarvin Ghavam  23 , Lauritz R Meyer  24 , Valerie Y Chock  25 , Sara B DeMauro  16 , Wesley M Jackson  12 , Deepali Handa  26 , Michele C Walsh  27 ; National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations

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

Namasivayam Ambalavanan et al. JAMA. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ambalavanan reported serving on the data and safety monitoring board for OakHill Bio; serving as medical advisor to ResBiotic; and owning stock in AlveolusBio outside the submitted work. Dr D’Angio reported receiving grants from NIH outside the submitted work. Dr Cotten reported serving on the advisory board for ReALTA Life Sciences outside the submitted work. Dr Laughon reported receiving grants from NIH outside the submitted work. Dr Hibbs reported receiving grants from the National Heart, Lung, and Blood Institute outside the submitted work. Dr DeMauro reported receiving grants from NIH outside the submitted work. Dr Walsh reported being employed by the NICHD outside the submitted work. No other disclosures were reported.

References

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