The Budesonide in Babies (BiB) Trial

NCT04545866 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 20 other identifiers: NICHD-NRN-0064UG1HD034216UG1HD027904UG1HD021364UG1HD027853UG1HD040689UG1HD040492UG1HD027851UG1HD087229UG1HD053109UG1HD068278UG1HD068244UG1HD068263UG1HD027880UG1HD053089UG1HD087226UG1HD112079UG1HD112097UG1HD1121003U24HD095254-07
• Study Type: interventional
• Target: 642
• Locations: 1 country
• Sites: 19

Brief 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' post-menstrual age in extremely preterm infants.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Death by 36 Weeks PMA

  Randomization to 36 weeks PMA

• Physiologic BPD

  At 36 weeks PMA

• Grade of BPD Severity

  At 36 weeks PMA

• Severe BPD

  At 36 weeks PMA

• Use of Additional Postnatal Steroids

  7 days post last dose of study drug through 36 weeks PMA

Study Arms (2)

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.

Drug: budesonide (Pulmicort nebulizing suspension).

surfactant alone

ACTIVE COMPARATOR

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

Drug: surfactant (poractant alfa;Curosurf)

Interventions

budesonide (Pulmicort nebulizing suspension). 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.

Also known as: Pulmicort nebulizing suspension.

budesonide with surfactant

surfactant (poractant alfa;Curosurf) 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.

Also known as: poractant alfa;Curosurf

surfactant alone

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (19)

University of Alabama

Birmingham, Alabama, 35249-7335, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Northwestern Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Mississippi Medical Center - Children's of Mississippi

Jackson, Mississippi, 39216, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University - Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• 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.

  PMID: 41026481 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Respiratory Distress Syndrome; Premature Birth

Interventions

Budesonide; Surface-Active Agents; poractant alfa

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiration Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Namasivayam Ambalavanan MD
• Organization: University of Alabama at Birmingham

nambalav@uabmc.edu

2059344680

Study Officials

• Namasivayam Ambalavanan, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 11, 2020
• Study Start: April 1, 2021
• Primary Completion: September 5, 2024
• Study Completion (Estimated): December 17, 2026
• Last Updated: April 15, 2026
• Results First Posted: November 10, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (19)