Ramanathan Rangasamy, Biniwale Manoj, Sekar Krishnamurthy, Hanna Nazeeh, Golombek Sergio, Bhatia Jatinder, Naylor Martha, Fabbri Laura, Varoli Guido, Santoro Debora, Del Buono Dorothea, Piccinno Annalisa, Dammann Christiane E
Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Good Samaritan Hospital, Keck School of Medicine of USC, Los Angeles, CA.
Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Good Samaritan Hospital, Keck School of Medicine of USC, Los Angeles, CA.
J Pediatr. 2020 Oct;225:90-96.e1. doi: 10.1016/j.jpeds.2020.06.024. Epub 2020 Jun 14.
To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm.
Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO) ≥0.30 from 24 to 26 weeks and FiO ≥0.35 from 27 to 29 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO, respiratory severity score [FiO × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety.
Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected.
Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome.
ClinicalTrials.gov: NCT02452476.
比较一种富含表面活性蛋白、SP - B和SP - C肽类似物的新型合成表面活性剂CHF5633与猪肺表面活性剂（固尔苏）治疗早产儿呼吸窘迫综合征的疗效和安全性。
孕周24至26周时需要呼吸支持且吸入氧分数（FiO）≥0.30，孕周27至29周时FiO≥0.35以维持氧饱和度在88% - 95%的早产儿被随机分为两组，分别接受200mg/kg的CHF5633或固尔苏治疗。必要时，以100mg/kg的剂量重复给药。疗效终点指标为出生后24小时、7天、28天、出院时和/或孕龄36周时的氧需求（FiO、呼吸严重程度评分[FiO×平均气道压]）；孕龄28天和36周时的死亡率和支气管肺发育不良情况。监测不良事件和免疫原性以评估安全性。
123例随机分组的新生儿中，113例接受了治疗（CHF5633组和固尔苏组分别为56例和57例）。两组在所有时间点的FiO和呼吸严重程度评分均较基线下降（P < 0.001），组间无统计学显著差异。CHF5633组和固尔苏组使用抢救性表面活性剂的情况（分别为19例[33.9%]和17例[29.8%]）、支气管肺发育不良情况（分别为31例[55.4%]和32例[56.1%]）以及28天时的死亡率（分别为4例[7.1%]和3例[5.3%]）相似。CHF5633组和固尔苏组分别有2例（3.4%）和1例（1.7%）新生儿报告了药物不良反应。未检测到免疫原性。
对于患有中重度呼吸窘迫综合征的早产儿，CHF5633治疗显示出与固尔苏相似的疗效和安全性。
ClinicalTrials.gov：NCT02452476。
