Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE)
Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE)
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DOI：
10.1038/s41390-020-0792-y
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发表时间：
2020-02-01
影响因子：
3.6
通讯作者：
Ballard, Roberta A.
中科院分区：
文献类型：
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作者：
McEvoy, Cindy T.;Ballard, Philip L.;Ballard, Roberta A.
肺靶向布地奈德（0.25 mg/kg）在表面活性剂中预防早产儿支气管肺发育不良（BPD）的初步试验显示了益处;然而，最佳安全剂量尚不清楚。方法在需要插管的极低胎龄新生儿（ELGAN）中进行布地奈德（0.025、0.05、0.10 mg/kg）在钙化剂中的剂量递增研究。测量气管抽吸物（TA）细胞因子、血液布地奈德浓度和非靶向血液代谢组学。将结果与晚期表面活性剂试验（TOLSURF）中接受表面活性剂的匹配婴儿进行比较。结果24例平均胎龄25.0周、出生体重743 g、需要机械通气的婴儿，平均年龄6 d。在所有婴儿的血液中检测到布地奈德，半衰期为3.4小时。在基线时TA细胞因子水平升高的11例婴儿中，治疗与所有三个剂量水平的持续降低（平均65%）相关。血液皮质醇浓度和血液总代谢物的变化存在时间和剂量依赖性降低。呼吸结局与历史对照无差异。结论布地奈德/表面活性剂在任何剂量水平下对插管ELGAN均无临床呼吸益处。以前试验中使用的剂量的十分之一具有最小的全身代谢作用，并且似乎对肺部靶向抗炎作用有效。
Background Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. Methods Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). Results Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. Conclusions Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action.