Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants: The PLUSS Randomized Clinical Trial
Importance
Bronchopulmonary dysplasia (BPD) is a significant adverse outcome in extremely preterm infants born at less than 28 weeks' gestation. While systemic corticosteroids are effective against BPD, they may carry risks of adverse outcomes. Delivering corticosteroids directly into the lungs could be a safer alternative.
Objective
This study aimed to assess the effectiveness of early intratracheal corticosteroid administration on survival free of BPD in extremely preterm infants.
Design, Setting, and Participants
A double-blind randomized clinical trial was conducted across 21 neonatal units in Australia, New Zealand, Canada, and Singapore. Eligible infants were born at less than 28 weeks' gestation, were less than 48 hours old, and were either mechanically ventilated or receiving noninvasive respiratory support with a clinical decision to administer surfactant. Recruitment took place between January 2018 and March 2023, with the last participant discharged in August 2023.
Interventions
Infants were randomly assigned (1:1) to receive either:
Budesonide (0.25 mg/kg) mixed with surfactant (poractant alfa) administered via an endotracheal tube or thin catheter.
Surfactant alone (control group).
Main Outcomes and Measures
The primary outcome was survival free of BPD at 36 weeks' postmenstrual age. Additionally, 15 secondary outcomes were examined, including the components of the primary outcome (survival at 36 weeks and BPD among survivors), as well as 9 predefined safety outcomes (adverse events).
Results
The primary analysis included 1059 infants: 524 in the budesonide and surfactant group and 535 in the surfactant-only group. The key findings include:
Mean gestational age: 25.6 weeks (SD, 1.3 weeks)
Mean birth weight: 775 g (SD, 197 g)
Male infants: 586 (55.3%)
Survival free of BPD occurred in 134 infants (25.6%) in the budesonide and surfactant group and 121 infants (22.6%) in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, -2.1% to 7.4%]).
At 36 weeks' postmenstrual age, 83.2% of infants in the budesonide and surfactant group were alive compared to 80.6% in the surfactant-only group.
Among survivors, 69.3% in the budesonide and surfactant group and 71.9% in the surfactant-only group were diagnosed with BPD.
Conclusions and Relevance
Early intratracheal budesonide administration in extremely preterm infants receiving surfactant for respiratory distress syndrome appears to have little to no effect on survival free of BPD. Further research may be needed to determine the potential benefits and risks of this approach.
Trial Registration: anzctr.org.au Identifier: ACTRN12617000322336.
Comentários