The Budesonide in Babies (BiB) Trial

NICHD Neonatal Research Network

Status and phase: Active, not recruiting; Phase 3

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

Treatments: Drug: budesonide (Pulmicort nebulizing suspension).; Drug: surfactant (poractant alfa;Curosurf)

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT04545866

UG1HD040689 (U.S. NIH Grant/Contract)

UG1HD021364 (U.S. NIH Grant/Contract)

UG1HD112097 (U.S. NIH Grant/Contract)

3U24HD095254-07 (U.S. NIH Grant/Contract)

UG1HD040492 (U.S. NIH Grant/Contract)

UG1HD027904 (U.S. NIH Grant/Contract)

UG1HD053089 (U.S. NIH Grant/Contract)

UG1HD112100 (U.S. NIH Grant/Contract)

UG1HD034216 (U.S. NIH Grant/Contract)

UG1HD068244 (U.S. NIH Grant/Contract)

UG1HD027851 (U.S. NIH Grant/Contract)

UG1HD027853 (U.S. NIH Grant/Contract)

UG1HD068278 (U.S. NIH Grant/Contract)

UG1HD087226 (U.S. NIH Grant/Contract)

UG1HD112079 (U.S. NIH Grant/Contract)

UG1HD027880 (U.S. NIH Grant/Contract)

UG1HD068263 (U.S. NIH Grant/Contract)

NICHD-NRN-0064

UG1HD087229 (U.S. NIH Grant/Contract)

UG1HD053109 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,160 estimated patients

Sex: All

Ages: Under 48 hours old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,160 participants in 2 patient groups

budesonide with surfactant

Experimental group

Description:

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.

Treatment:

Drug: budesonide (Pulmicort nebulizing suspension).

surfactant alone

Active Comparator group

Description:

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

Treatment:

Drug: surfactant (poractant alfa;Curosurf)