The Budesonide in Babies (BiB) Trial

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

642 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-01

Study Completion Date

2026-12-17

Brief Summary

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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.

Detailed Description

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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

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Bronchopulmonary Dysplasia (BPD) Respiratory Distress Syndrome Prematurity; Extreme Neonatal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

The investigator, primary providers, primary data collectors, and participants will be masked to randomization arm assignment. Only research pharmacists and a designated respiratory therapist (or other qualified person) will be unmasked at the enrolling sites. The designated respiratory therapist (or other qualified person) must be unmasked to allow drug mixing at bedside for expeditious study drug administration; however, this person will not be the primary medical provider nor the primary data collector for that infant, and will not be otherwise involved in the research.

Study Groups

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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.

Group Type EXPERIMENTAL

budesonide (Pulmicort nebulizing suspension).

Intervention Type DRUG

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 alone

Infants randomized to the active control arm receive a dose of surfactant (poractant alfa; Curosurf).

Group Type ACTIVE_COMPARATOR

surfactant (poractant alfa;Curosurf)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Pulmicort nebulizing suspension. poractant alfa;Curosurf

Eligibility Criteria

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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

Maximum Eligible Age

48 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Namasivayam Ambalavanan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

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United States

References

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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.

Reference Type DERIVED

PMID: 41026481 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

The Budesonide in Babies (BiB) Trial

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

budesonide with surfactant

budesonide (Pulmicort nebulizing suspension).

surfactant alone

surfactant (poractant alfa;Curosurf)

Interventions

budesonide (Pulmicort nebulizing suspension).

surfactant (poractant alfa;Curosurf)

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NICHD Neonatal Research Network

Responsible Party

Principal Investigators

Namasivayam Ambalavanan, MD

Locations

University of Alabama

Stanford University

Sharp Mary Birch Hospital for Women & Newborns

Emory University

Northwestern Lurie Children's Hospital of Chicago

University of Iowa

University of Mississippi Medical Center - Children's of Mississippi

University of New Mexico

University of Rochester

RTI International

Duke University

Cincinnati Children's Medical Center

Case Western Reserve University, Rainbow Babies and Children's Hospital

Research Institute at Nationwide Children's Hospital

University of Pennsylvania

Brown University - Women and Infants Hospital of Rhode Island

University of Texas Southwestern Medical Center at Dallas

University of Texas Health Science Center at Houston

University of Utah

Countries

References

Provided Documents

Document Type: Study Protocol

Document Type: Statistical Analysis Plan

Other Identifiers

UG1HD034216

UG1HD027904

UG1HD021364

UG1HD027853

UG1HD040689

UG1HD040492

UG1HD027851

UG1HD087229

UG1HD053109

UG1HD068278

UG1HD068244

UG1HD068263

UG1HD027880

UG1HD053089

UG1HD087226

UG1HD112079

UG1HD112097

UG1HD112100

3U24HD095254-07

NICHD-NRN-0064