Clinical trial NCT04545866: The Budesonide in Babies (BiB) Trial
Official title: Randomized Controlled Trial of Budesonide + Surfactant Versus Surfactant Alone in Extremely Preterm Infants ("The Budesonide in Babies (BiB) Trial")
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia (BPD)
Respiratory Distress Syndrome
Prematurity; Extreme
Neonatal
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2020-09-11
Enrollment: 1160
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants with Physiologic BPD or death
timeFrame: Randomization to 36 weeks' post-menstrual age
Secondary outcomes:
measure: Number of Participants with Death by 36 weeks' post-menstrual age
timeFrame: Randomization to 36 weeks' post-menstrual age
measure: Number of Participants with Physiologic BPD
timeFrame: 36 weeks' post-menstrual age
measure: Grade of BPD Severity
timeFrame: 36 weeks' post-menstrual age
measure: Number of Participants with Grade 3 BPD
timeFrame: 36 weeks' post-menstrual age
measure: Number of Participants with Use of Additional Postnatal Steroids
timeFrame: 7 days post final dose of study drug through 36 weeks' post-menstrual age
measure: Number of Participants with Severe Neurodevelopmental Impairment (NDI)
timeFrame: 22-26 months corrected age
measure: Number of Participants with Death by 2 years
timeFrame: Randomization to 22-26 months corrected age
measure: Number of Participants with Severe NDI or death
timeFrame: Randomization to 22-26 months corrected age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Jackson
country: United States
facility: University of Mississippi Medical Center - Children's of Mississippi
state: Mississippi
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University - Women and Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: Namasivayam Ambalavanan, MD
role: PRINCIPAL_INVESTIGATOR
References: