The Budesonide in Babies (BiB) Trial (BiB)

Randomized Controlled Trial of Budesonide + Surfactant Versus Surfactant Alone in Extremely Preterm Infants ("The Budesonide in Babies (BiB) Trial")

This is a Phase 3, randomized, masked, active-controlled, multicenter trial designed to determine whether early intratracheal administration of a combination of budesonide with surfactant, as compared to surfactant alone, will reduce the incidence of physiologic bronchopulmonary dysplasia (BPD) or death by 36 weeks' post-menstrual age in extremely preterm infants.

Study Overview

• Status: Active, not recruiting
• Conditions: Respiratory Distress Syndrome; Bronchopulmonary Dysplasia (BPD); Prematurity; Extreme; Neonatal
• Intervention / Treatment: Drug: budesonide (Pulmicort nebulizing suspension).; Drug: surfactant (poractant alfa;Curosurf)

Detailed Description

From a study of 9575 extremely preterm (22-28 weeks gestational age and 401-1500g birth weight) infants born between 2003 and 2007 and enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), it is anticipated that 93% of extremely preterm infants will develop respiratory distress syndrome, 68% will develop bronchopulmonary dysplasia (BPD), 16% will develop severe intraventricular hemorrhage, and 36% will develop late-onset sepsis (PMID: 20732945). Furthermore, in 2014 20% of the infants enrolled in the NRN Generic Database (GDB) died (8% by less than 12 hours, 12% between 12 hours and 120 days, and 1% after 120 days) and 47% of infants who survived to 36 weeks' post-menstrual age (PMA) developed physiologic BPD (NRN GDB data). BPD is therefore one of the most common morbidities in extremely preterm infants. Death is a competing outcome for BPD, as infants who die before ascertainment of BPD at 36 weeks' PMA cannot be diagnosed with BPD even though they may have been at the highest risk. As children get older, BPD has been shown to be associated with worse cognitive outcomes in school age and with abnormal pulmonary function in adolescence and adulthood (PMID: 14595077; 15499947; 2247118).

Recent randomized trials have indicated a lower incidence of BPD/death with the use of a combination of budesonide with surfactant (budesonide + surfactant) compared to surfactant alone when administered soon after birth. Therefore, after obtaining informed consent and confirming eligibility for the trial, infants are randomized in a 1:1 allocation ratio to either the budesonide + surfactant arm or the surfactant alone arm within 48 hours of birth.

• Study Type: Interventional
• Enrollment (Actual): 642
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249-7335
      • University of Alabama
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women & Newborns
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center - Children's of Mississippi
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University - Women and Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Liveborn infants 22 0/7 - 28 6/7 weeks gestation or 401 - 1000 grams (inclusive) birth weight
• Clinical decision to give surfactant
• Less than or equal to 48 hours postnatal age

Exclusion Criteria:

• Terminal illness (heart rate < 100 beats per minute, unresponsiveness to resuscitation) or unlikely to survive as judged by the clinician
• Decision to redirect or limit support
• Use of surfactant before enrollment (first dose of surfactant must be study drug)
• Infant received systemic steroids prior to enrollment
• Use of indomethacin, either received by the mother within 24 hours prior to delivery,received by the infant prior to enrollment, or intent to administer to the infant for IVH prophylaxis or PDA management from enrollment up to 7 days of final dose of study drug
• Serious chromosomal abnormalities or major malformations
• Known congenital infections including, but not limited to, confirmed sepsis, congenital CMV, etc.
• Infants with a permanent neuromuscular condition that affects respiration
• Enrollment in a conflicting clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: budesonide with surfactant; Infants randomized to the intervention arm receive a dose of surfactant (poractant alfa; Curosurf) mixed with budesonide (Pulmicort nebulizing suspension) within 50 hours of birth and administered via endotracheal tube.	Drug: budesonide (Pulmicort nebulizing suspension).; The first dose of budesonide is 0.25 mg/kg in a volume of 1 ml/kg, for a total volume of 2.5 ml/kg of Curosurf + 1 ml/kg of budesonide. If the infant is to receive a second dose of study drug within 50 hours of birth, the dosage of Curosurf is 1.25 ml/kg for the second dose and 1 ml/kg of budesonide.; Other Names: Pulmicort nebulizing suspension.
Active Comparator: surfactant alone; Infants randomized to the active control arm receive a dose of surfactant (poractant alfa; Curosurf).	Drug: surfactant (poractant alfa;Curosurf); The first dose of surfactant (poractant alfa; Curosurf) is 2.5 ml/kg. If the infant is to receive a second dose of study drug within 50 hours of birth, the dosage of Curosurf is 1.25 ml/kg for the second dose.; Other Names: poractant alfa;Curosurf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiologic BPD or Death by 36 Weeks PMA	A composite outcome for infants who were diagnosed with physiologic BPD or died by 36 weeks PMA. Physiologic BPD is determined using existing NRN GDB criteria at 36 weeks' PMA. Infants alive an in hospital are classified based on respiratory status at 36 week's PMA or by a room air weaning challenge performed between 36 and 37 weeks' PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks' PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks' PMA.	Randomization to 36 weeks PMA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death by 36 Weeks PMA	Died (all-cause) after randomization and by 36 weeks PMA	Randomization to 36 weeks PMA
Physiologic BPD	Diagnosed with physiologic BPD at 36 weeks PMA. Physiologic BPD is determined using existing NRN GDB criteria at 36 weeks' PMA. Infants alive an in hospital are classified based on respiratory status at 36 week's PMA or by a room air weaning challenge performed between 36 and 37 weeks' PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks' PMA are not assessed for BPD.	At 36 weeks PMA
Grade of BPD Severity	BPD Severity Grade at 36 weeks PMA according to the Jensen et al. (2019; PMID: 30995069) definition, also known as pragmatic BPD. Infants are assess based on the mode of support at 36 weeks' postmenstrual age regardless of prior duration or current level of oxygen therapy.	At 36 weeks PMA
Severe BPD	Diagnosed with Severe (Grade 3) BPD at 36 weeks PMA according to the Jensen et al. (2019; PMID: 30995069) definition. This outcome is a dichotomy of the pragmatic BPD severity grades (Grade 3 vs. Grade 2, 1, or 0).	At 36 weeks PMA
Use of Additional Postnatal Steroids	Use of any postnatal steroids for treatment of evolving chronic lung disease (separate from study drug) between 7 days after the final dose of study drug and 36 weeks PMA. Note: Infants were permitted up to two doses of study drug within 50 hours postnatal age, so this outcome spans 7-10 days postnatal age through 36 weeks postmenstrual age.	7 days post last dose of study drug through 36 weeks PMA

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Namasivayam Ambalavanan, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Ambalavanan N, Carlo WA, Nowak KJ, Wiener LE, Cosby SS, Bhatt AJ, Watterberg KL, Poindexter BB, Keszler M, D'Angio CT, Brion LP, Narendran V, Rau CA, Cotten CM, Laughon MM, Das A, Rysavy MA, Hibbs AM, Fuller J, Puopolo KM, Katheria A, Patel RM, Bermick JR, Laptook AR, Prelipcean I, Wyckoff MH, Moore R, Merhar SL, Ohls RK, Yoder BA, Perez M, Ghavam S, Meyer LR, Chock VY, DeMauro SB, Jackson WM, Handa D, Walsh MC; National Institute of Child Health and Human Development Neonatal Research Network. Early Intratracheal Budesonide to Reduce Bronchopulmonary Dysplasia in Extremely Preterm Infants: The Budesonide in Babies (BiB) Randomized Clinical Trial. JAMA. 2025 Oct 28;334(16):1452-1462. doi: 10.1001/jama.2025.16450.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): September 5, 2024
• Study Completion (Estimated): December 17, 2026

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Respiratory Distress Syndrome; Bronchopulmonary Dysplasia; Chemical Actions and Uses; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Specialty Uses of Chemicals; Pregnenediones; Pregnenes; Budesonide; Surface-Active Agents; poractant alfa
• Other Study ID Numbers: NICHD-NRN-0064; UG1HD034216 (U.S. NIH Grant/Contract); UG1HD027904 (U.S. NIH Grant/Contract); UG1HD021364 (U.S. NIH Grant/Contract); UG1HD027853 (U.S. NIH Grant/Contract); UG1HD040689 (U.S. NIH Grant/Contract); UG1HD040492 (U.S. NIH Grant/Contract); UG1HD027851 (U.S. NIH Grant/Contract); UG1HD087229 (U.S. NIH Grant/Contract); UG1HD053109 (U.S. NIH Grant/Contract); UG1HD068278 (U.S. NIH Grant/Contract); UG1HD068244 (U.S. NIH Grant/Contract); UG1HD068263 (U.S. NIH Grant/Contract); UG1HD027880 (U.S. NIH Grant/Contract); UG1HD053089 (U.S. NIH Grant/Contract); UG1HD087226 (U.S. NIH Grant/Contract); UG1HD112079 (U.S. NIH Grant/Contract); UG1HD112097 (U.S. NIH Grant/Contract); UG1HD112100 (U.S. NIH Grant/Contract); 3U24HD095254-07 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No