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The Budesonide in Babies (BiB) Trial (BiB)

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ClinicalTrials.gov Identifier: NCT04545866
Recruitment Status : Recruiting
First Posted : September 11, 2020
Last Update Posted : March 25, 2021
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

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.

Condition or disease Intervention/treatment Phase
Bronchopulmonary Dysplasia (BPD) Respiratory Distress Syndrome Prematurity; Extreme Neonatal Drug: budesonide (Pulmicort nebulizing suspension). Drug: surfactant (poractant alfa;Curosurf) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Budesonide + Surfactant Versus Surfactant Alone in Extremely Preterm Infants ("The Budesonide in Babies (BiB) Trial")
Actual Study Start Date : March 15, 2021
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : September 2025


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 Name: 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 Name: poractant alfa;Curosurf




Primary Outcome Measures :
  1. Number of Participants with Physiologic BPD or death [ Time Frame: Randomization to 36 weeks' post-menstrual age ]
    Physiologic BPD or death by 36 weeks' PMA. Physiologic BPD is determined using existing NRN GDB criteria at 36 weeks' PMA.


Secondary Outcome Measures :
  1. Number of Participants with Death by 36 weeks' post-menstrual age [ Time Frame: Randomization to 36 weeks' post-menstrual age ]
    Death by 36 weeks' PMA

  2. Number of Participants with Physiologic BPD [ Time Frame: 36 weeks' post-menstrual age ]
    Physiologic BPD as determined by existing NRN GDB criteria at 36 weeks' PMA.

  3. Grade of BPD Severity [ Time Frame: 36 weeks' post-menstrual age ]

    BPD severity is defined as in Jensen et al. (2019; PMID: 30995069) at 36 weeks' PMA according to treatment with the following respiratory support:

    1. No BPD: room air;
    2. Grade 1: nasal cannula at flow rates ≤ 2 L/min;
    3. Grade 2: nasal cannula at flow rates > 2 L/min or noninvasive positive airway pressure;
    4. Grade 3: invasive mechanical ventilation.

  4. Number of Participants with Grade 3 BPD [ Time Frame: 36 weeks' post-menstrual age ]
    Grade 3 BPD at 36 weeks' PMA according to the Jensen et al. (2019 PMID: 30995069) definition.

  5. Number of Participants with Use of Additional Postnatal Steroids [ Time Frame: 7 days post final dose of study drug through 36 weeks' post-menstrual age ]
    Use of postnatal steroids for treatment of evolving chronic lung disease (separate from study drug) from 7 days after the final dose of study drug through 36 weeks' PMA.

  6. Number of Participants with Severe Neurodevelopmental Impairment (NDI) [ Time Frame: 22-26 months corrected age ]

    Severe NDI is assessed at the 2-year follow-up (22-26 months corrected age). In light of the upcoming transition to BSID IV, severe NDI assessment will be based on the agreed upon definition at the time of the first participant's follow-up assessment. An example of such a definition could be presence of any of the following:

    1. Cognitive composite score on the BSID IV < 70,
    2. GMFCS level 3-5,
    3. Severe hearing impairment (no functional hearing despite amplification), or
    4. Bilateral severe visual impairment (bilateral blindness despite correction).

  7. Number of Participants with Death by 2 years [ Time Frame: Randomization to 22-26 months corrected age ]
    Death by 2-year follow-up (22-26 months corrected age)

  8. Number of Participants with Severe NDI or death [ Time Frame: Randomization to 22-26 months corrected age ]
    Severe NDI or death as assessed at 2-year follow-up (22-26 months corrected age)



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Ages Eligible for Study:   up to 48 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04545866


Contacts
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Contact: Namasivayam Ambalavanan, MD (205) 934 4680 ambal@uab.edu
Contact: Abhik Das, PhD 301-230-4640 adas@rti.org

Locations
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United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35249-7335
Contact: Namasivayam A. Ambalavanan, MD         
Principal Investigator: Waldemar Carlo, MD         
United States, California
Stanford University Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P Van Meurs, MD         
Principal Investigator: Krisa P Van Meurs, MD         
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30303
Contact: Ravi Patel, MD         
Sub-Investigator: Brenda Poindexter, MD         
Principal Investigator: Ravi Patel, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F Bell, MD         
Principal Investigator: Edward F Bell, MD         
United States, New Mexico
University of New Mexico Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L Watterberg, MD         
Principal Investigator: Kristi L Watterberg, MD         
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD         
Principal Investigator: Carl T D'Angio, MD         
United States, North Carolina
RTI International Active, not recruiting
Durham, North Carolina, United States, 27705
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: C. Michael Cotten, MD         
Principal Investigator: C. Michael Cotten, MD MHS         
United States, Ohio
Cincinnati Children's Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Stephanie Merhar, MD MS         
Sub-Investigator: Vivek Narendran, MD, MBA         
Principal Investigator: Stephanie Merhar, MD MS         
Case Western Reserve University, Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: Anna Maria C. Hibbs, MD, MSCE         
Sub-Investigator: Deanne C. Wilson, MD         
Principal Investigator: Anna Maria C. Hibbs, MD, MSCE         
Research Institute at Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Pablo Sanchez, MD         
Principal Investigator: Pablo Sanchez, MD         
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eric Eichenwald, MD         
Principal Investigator: Eric Eichenwald, MD         
United States, Rhode Island
Brown University - Women and Infants Hospital of Rhode Island Not yet recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD         
Principal Investigator: Abbot R Laptook, MD         
United States, Texas
University of Texas Southwestern Medical Center at Dallas Recruiting
Dallas, Texas, United States, 75235
Contact: Myra Wyckoff, MD         
Principal Investigator: Myra Wyckoff, MD         
University of Texas Health Science Center at Houston Not yet recruiting
Houston, Texas, United States, 77030
Contact: Jon E Tyson, MD MPH         
Principal Investigator: Jon E. Tyson, MD MPH         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Robin Ohls, MD         
Principal Investigator: Robin Ohls, MD         
Sponsors and Collaborators
NICHD Neonatal Research Network
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Namasivayam Ambalavanan, MD University of Alabama at Birmingham
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Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT04545866    
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 )
U10HD036790 ( U.S. NIH Grant/Contract )
First Posted: September 11, 2020    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Bronchopulmonary Dysplasia
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Ventilator-Induced Lung Injury
Lung Injury
Budesonide
Poractant alfa
Pulmonary Surfactants
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists