PLUSS
Trial question
What is the role of early intratracheal budesonide in extremely preterm infants receiving surfactant for respiratory distress syndrome?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 1059
1059 patients (473 female, 586 male).
Inclusion criteria: infants born < 28 weeks and < 48 hours old, mechanically ventilated or receiving noninvasive respiratory support plus surfactant.
Key exclusion criteria: prior treatment with postnasal corticosteroids for prevention of lung disease; survival beyond the immediate postnatal period considered unlikely and/or active care not offered; major congenital anomaly likely to affect the respiratory status.
Interventions
N=524 budesonide and surfactant (intratracheal budesonide 0.25 mg/kg, mixed with poractant alfa).
N=535 surfactant only (identical doses of poractant alfa alone).
Primary outcome
Bronchopulmonary dysplasia-free survival at 36 weeks postmenstrual age
25.6%
22.6%
25.6 %
19.2 %
12.8 %
6.4 %
0.0 %
Budesonide and
surfactant
Surfactant
only
No significant
difference ↔
No significant difference in bronchopulmonary dysplasia-free survival at 36 weeks postmenstrual age (25.6% vs. 22.6%; AD 2.7%, 95% CI -2.1 to 7.4).
Secondary outcomes
No significant difference in survival at hospital discharge (81.5% vs. 78.7%; AD 2.8%, 95% CI -2.1 to 7.7).
No significant difference in survival at 36 weeks postmenstrual age (83.2% vs. 80.6%; AD 1.4%, 95% CI -2.9 to 5.7).
No significant difference in bronchopulmonary dysplasia in survivors (69.3% vs. 71.9%; ARD -2.7, 95% CI -8.4 to 3.1).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In infants born < 28 weeks and < 48 hours old, mechanically ventilated or receiving noninvasive respiratory support plus surfactant, budesonide and surfactant were not superior to surfactant only with respect to bronchopulmonary dysplasia-free survival at 36 weeks postmenstrual age.
Reference
Brett J Manley, C Omar F Kamlin, Susan M Donath et al. Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants: The PLUSS Randomized Clinical Trial. JAMA. 2024 Dec 10;332(22):1889-1899.
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