Bronchopulmonary Dysplasia (BPD)Phase 3BiBNCT04545866
The Budesonide in Babies (BiB) Trial
A Phase 3 study testing budesonide (Pulmicort nebulizing suspension). and surfactant (poractant alfa;Curosurf) in people with Bronchopulmonary Dysplasia (BPD) and Respiratory Distress Syndrome, run by NICHD Neonatal Research Network at 19 sites in United States.
Trial summary
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'… Read more about this study
- Who is it for?
- Ages Up to 48 hours
- Conditions the study is for
- Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome, Prematurity; Extreme
- What is being tested?
- budesonide (Pulmicort nebulizing suspension). and surfactant (poractant alfa;Curosurf)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 642 participants
- Where
- 19 sitesUnited States
- Study dates
- 1 Apr 2021to 17 Dec 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama
Birmingham, Alabama, 35249-7335
Northwestern Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Mississippi Medical Center - Children's of Mississippi
Jackson, Mississippi, 39216
Stanford University
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University - Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
About this study
Official title: 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.
Read the 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.
- Conditions
- Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome, Prematurity; Extreme, Neonatal
- Being tested
- budesonide (Pulmicort nebulizing suspension)., surfactant (poractant alfa;Curosurf)
- Medical subject headings
- Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
budesonide (Pulmicort nebulizing suspension).Drug
Also called 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.
surfactant (poractant alfa;Curosurf)Drug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| budesonide with surfactant | Experimental | 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. Receives: Drug: budesonide (Pulmicort nebulizing suspension). |
| surfactant alone | Active comparator | Infants randomized to the active control arm receive a dose of surfactant (poractant alfa; Curosurf). Receives: Drug: surfactant (poractant alfa;Curosurf) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Randomization to 36 weeks PMA
Secondary outcomes (5)
Death by 36 Weeks PMA
Died (all-cause) after randomization and by 36 weeks PMA
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 7 days post last dose of study drug through 36 weeks PMA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2020
- Study start1 Apr 2021
- Primary completion5 Sep 2024
- Study completion17 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary Dysplasia (BPD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 642 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Namasivayam Ambalavanan, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04545866
- Sponsor's protocol ID
- NICHD-NRN-0064
- Other IDs
- UG1HD034216, UG1HD027904, UG1HD021364, UG1HD027853, UG1HD040689, UG1HD040492, UG1HD027851, UG1HD087229
- Acronym
- BiB
- Status last verified
- Apr 2026
- First submitted
- 4 Sep 2020
- Last updated
- 15 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
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.
PubMed 41026481