biostudies-literatureAmbalavanan NNICHD NIH HHS1452-1462https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486137biostudies-literatureUnknown334(16)<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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).<h4>Interventions</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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]).<h4>Conclusions and relevance</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov Identifier: NCT04545866.JAMAEarly Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial.PMC12486137UG1 HD112097U10 HD027871UG1 HD040689U01 HD036790U24 HD095254UG1 HD027853UG1 HD112093U10 HD040689U10 HD034216Wright RKawamura MGrisby CSheffield MJTalbert JWilliams AMagana DKMcNamara PJSchibler KMasih RMoseley SScullin BGentle SAmbalavanan NWatterberg KLRussell DCotten CMLakshminrusimha SWalsh MCGoldberg RNDorner RBall MBBoylin ERowan MJohnson KJBell LMSalazar NJSnyder JWebbon MHMcKeown KKirker KMarchant TWalker JRBhatt AJPrelipcean ICosby SSGerday EBHogden LARamachandran SWard SMDonato JdeRegnier RAGreen GTurner SMMontoya JDominguez GHenry RMazur ASt Pierre LGhavam SKapadia VMontoya CBeauman SSCha CAliyev GKoo JBowman MFisher KAWoodbury KDThompson JPolin RACarlo WADeMauro SBPucio RBroadbent MTaylor NJMerhar SLFinkle JSmucny SDavis BGuilford SBahr TMBear KLi EVan Meurs KPBottcher DPak MLewis AHenning MMJones RFields LRadcliff LGuillet RSalas AAHiggins RDRecine BPMakhijani SReynolds AMCrisafulli MInes FRochez DZola KBremer AACrockett FPerez MJensen RYoder BAJackson WMJackson SKeszler MSauberan JMoore RHernandez RRutkowska LMancini TNewman NSPoindexter BBPatel RMReid CVan Muyden SLoertscher MCBabilonia-Rosa MBrion LPSiner BSKuan ESepulveda PEichenwald ECHibbs AMClark CBergstedt VSabaratnam PKakkilaya VColeman KGoeke CAZaterka-Baxter KMHunn JNowak KJConnor SPeterson CAleem SPrinzing DLaptook ARScorsone AMPetersen Rn Bsn BJDuran JKramer HLaursen JRysavy MANarendran VMcKenzie CChristensen SKim JPeirson AMoody SSJohnson SED'Angio CTBooth LArnell KSacilowski MFoshee KMKent ARoblyer LBell EFDavis ASPickett JWBenz RLPuopolo KMMeyer LROrme CWiener LEDavis RMWilson-Costello DECarlton DPBinion KParry DMKatheria AGambacorta MCWyckoff MHHess MGraber-Pels AHensman AMFamuyide MStephens EVoelker KGleason CALoggins YMorris KKBermick JRBaserga MMackie CChuck JEVieira ETravers CPBuie CLWade JSchmelzel MLOhls RKDhawan MAChock VYMoreland MRau CAWadkins HIMShukla VSRobinson DTGonzales SGiachelli CALaughon MMStone CMuthig GDellaValle NPorras KWeaver-Lewis KFloyd LHanda DAaron Hamvas AHKhan AMMozaffari AMaffett DHodges SBeiersdorfer TPerry KNational Institute of Child Health and Human Development Neonatal Research NetworkArcher SWKing CMcGrath KMMinton SDAuman JOElmont JOCatts CElenkiwich CDas AMickelsen HGFuller JOwen SEfalseEarly Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial.<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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).<h4>Interventions</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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]).<h4>Conclusions and relevance</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov Identifier: NCT04545866.2025-01-01T00:00:00Z2025 Oct2026-07-09T10:17:09.759Z2026-07-09T10:14:03.123ZS-EPMC124861374102648110.1001/jama.2025.16450