Journal article
Early Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial
JAMA : the journal of the American Medical Association, Vol.334(16), pp.1452-1462
10/28/2025
DOI: 10.1001/jama.2025.16450
PMCID: PMC12486137
PMID: 41026481
Abstract
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.
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.
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).
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.
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.
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]).
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.
ClinicalTrials.gov Identifier: NCT04545866.
Details
- Title: Subtitle
- Early Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial
- Creators
- Namasivayam Ambalavanan - University of Alabama at BirminghamWaldemar A Carlo - University of Alabama at BirminghamKayla J Nowak - RTI InternationalLaura Elizabeth Wiener - RTI InternationalShirley S Cosby - University of Alabama at BirminghamAbhay J Bhatt - University of Mississippi Medical CenterKristi L Watterberg - University of New MexicoBrenda B Poindexter - Emory UniversityMartin Keszler - Brown UniversityCarl T D'Angio - University of RochesterLuc P Brion - The University of Texas Southwestern Medical CenterVivek Narendran - University of CincinnatiCarrie A Rau - University of UtahC Michael Cotten - Duke UniversityMatthew M Laughon - University of North Carolina at Chapel HillAbhik Das - RTI InternationalMatthew A Rysavy - The University of Texas Health Science Center at HoustonAnna Maria Hibbs - Case Western Reserve UniversityJanell Fuller - University of New MexicoKaren M Puopolo - University of PennsylvaniaAnup Katheria - Sharp Mary Birch Hospital for Women & NewbornsRavi M Patel - Emory UniversityJennifer R Bermick - University of IowaAbbot R Laptook - Brown UniversityIrina Prelipcean - University of RochesterMyra H Wyckoff - William P. Clements Jr. University HospitalRyan Moore - East Carolina UniversityStephanie L Merhar - Legacy Good Samaritan Medical CenterRobin K Ohls - University of UtahBradley A Yoder - University of UtahMarta Perez - Lurie Children's HospitalSarvin Ghavam - Virtua Voorhees HospitalLauritz R Meyer - Sanford HealthValerie Y Chock - Lucile Packard Children's HospitalSara B DeMauro - University of PennsylvaniaWesley M Jackson - University of North Carolina at Chapel HillDeepali Handa - University at Buffalo, State University of New YorkMichele C Walsh - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.334(16), pp.1452-1462
- DOI
- 10.1001/jama.2025.16450
- PMID
- 41026481
- PMCID
- PMC12486137
- NLM abbreviation
- JAMA
- ISSN
- 1538-3598
- eISSN
- 1538-3598
- Publisher
- AMER MEDICAL ASSOC
- Grant note
- National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD27871, U10 HD53119, UG1 HD21364, UG1 HD21373, UG1 HD21385, UG1 HD27851, UG1 HD27853, UG1 HD27856, UG1 HD27880, UG1 HD27904, UG1 HD34216, UG1 HD36790, UG1 HD40492, UG1 HD40689, UG1 HD53089, UG1 HD53109, UG1 HD68244, UG1 HD68270, UG1 HD68278, UG1 HD68263, UG1 HD68284, UG1 HD87226, UG1 HD87229 National Center for Advancing Translational Sciences (NCATS): UL1 TR6, UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR442, UL1 TR454, UL1 TR1117
The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (U10 HD27871, U10 HD53119, UG1 HD21364, UG1 HD21373, UG1 HD21385, UG1 HD27851, UG1 HD27853, UG1 HD27856, UG1 HD27880,UG1 HD27904, UG1 HD34216, UG1 HD36790, UG1 HD40492, UG1 HD40689, UG1 HD53089, UG1 HD53109, UG1 HD68244, UG1 HD68270, UG1 HD68278, UG1 HD68263, UG1 HD68284, UG1 HD87226, UG1 HD87229) and the National Center for Advancing Translational Sciences (NCATS) (UL1 TR6, UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR442, UL1 TR454, UL1 TR1117) provided grant support through cooperative agreements for the Neonatal Research Network.
- Language
- English
- Electronic publication date
- 09/30/2025
- Date published
- 10/28/2025
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984969238202771
Metrics
44 Record Views