Large Trial Shows Budesonide-Surfactant Mix Fails to Prevent Lung Disease in Preemies
Major study of 641 extremely premature infants finds no benefit from adding steroid to surfactant treatment for preventing chronic lung disease.
Summary
A large randomized trial tested whether adding the steroid budesonide to surfactant treatment could prevent bronchopulmonary dysplasia (BPD), a serious chronic lung disease, in extremely premature babies. The study enrolled 641 infants born at 22-28 weeks gestation across 17 US medical centers. Results showed no difference in BPD or death rates between babies receiving budesonide plus surfactant (68.5%) versus surfactant alone (67.9%). The trial was stopped early when interim analysis showed the treatment was unlikely to be beneficial. This contradicts smaller previous studies that suggested the combination might help.
Detailed Summary
Bronchopulmonary dysplasia (BPD) is a devastating chronic lung disease affecting extremely premature infants, leading to long-term breathing problems and increased mortality. Previous smaller studies suggested that combining the anti-inflammatory steroid budesonide with surfactant might reduce BPD risk compared to surfactant alone.
This major randomized controlled trial, conducted across 17 centers in the US Neonatal Research Network, tested whether early intratracheal administration of budesonide (0.25 mg/kg) mixed with surfactant could prevent BPD or death by 36 weeks postmenstrual age in extremely preterm infants. The study enrolled babies born at 22-28 weeks gestation or weighing 401-1000 grams who required surfactant treatment within 50 hours of birth.
The trial was designed to enroll 1,160 infants but was stopped early after recruiting 641 babies (55% of planned enrollment) when interim analysis reached prespecified futility criteria. The primary outcome - BPD or death by 36 weeks - occurred in 68.5% of infants receiving budesonide plus surfactant versus 67.9% receiving surfactant alone, showing no meaningful difference (adjusted relative risk 1.00, 95% CI 0.90-1.11).
Secondary analyses revealed no differences in mortality rates (15.3% vs 13.2%) or BPD among survivors (62.9% vs 63.0%). However, infants receiving budesonide experienced significantly more hyperglycemia (66.7% vs 49.8%), a concerning side effect that could impact brain development and other outcomes.
These findings contradict several smaller previous trials and highlight the importance of large, well-powered studies before adopting new treatments. The results suggest that this particular approach to preventing BPD in extremely premature infants is not effective and may cause harm through increased blood sugar levels.
Key Findings
- No reduction in bronchopulmonary dysplasia or death with budesonide-surfactant combination (68.5% vs 67.9%)
- Trial stopped early after enrolling 641 of planned 1,160 infants due to futility
- Significantly increased hyperglycemia risk in budesonide group (66.7% vs 49.8%)
- No differences in mortality or BPD rates among survivors at 36 weeks
- Results contradict smaller previous studies suggesting benefit from steroid-surfactant combination
Methodology
Double-masked randomized controlled trial across 17 US Neonatal Research Network centers from April 2021 to June 2024. Infants 22-28 weeks gestation received either budesonide (0.25 mg/kg) mixed with surfactant or surfactant alone via endotracheal tube within 50 hours of birth.
Study Limitations
Trial was stopped early at 55% enrollment which may limit generalizability. The study used a specific budesonide dose and timing that may not reflect all possible treatment protocols. Long-term neurodevelopmental outcomes were not assessed in this analysis.
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