Dargaville Peter A, Kamlin Camille Omar F, De Paoli Antonio G, Carlin John B, Orsini Francesca, Soll Roger F, Davis Peter G
Department of Paediatrics, Royal Hobart Hospital and University of Tasmania, Liverpool Street, Hobart TAS 7000, Australia.
BMC Pediatr. 2014 Aug 27;14:213. doi: 10.1186/1471-2431-14-213.
It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.
METHODS/DESIGN: This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.
Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation.
Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.
目前已认识到，对于妊娠≤28周的早产儿，从一开始就可通过鼻持续气道正压通气得到有效支持。然而，这种呼吸治疗方式可能无法充分支持那些存在严重表面活性物质缺乏的婴儿，结果就需要进行插管及延迟表面活性物质治疗。已知走这条治疗路径的婴儿出现不良结局的风险更高，包括死亡、支气管肺发育不良及其他疾病。为了规避这一问题，已开发出微创表面活性物质治疗技术，即给自主呼吸的婴儿给予外源性表面活性物质，然后该婴儿可继续接受持续气道正压通气。一种使用半刚性表面活性物质滴注导管短暂插入气管的表面活性物质给药方法（“霍巴特方法”）已被证明是可行且可能有效的，现在需要在一项随机对照试验中进行评估。
方法/设计：这是一项针对妊娠25 - 28周早产儿的多中心、随机、盲法、对照试验。如果婴儿在未预先插管的情况下接受持续气道正压通气管理，且在≤6小时龄时需要FiO₂≥0.30，则符合入选标准。随机分组将接受通过霍巴特方法给予外源性表面活性物质（200mg/kg猪肺磷脂）或假治疗。此后，两组婴儿将继续接受持续气道正压通气，除非达到插管标准（FiO₂≥0.45、持续呼吸暂停或持续酸中毒）。主要结局是死亡或生理性支气管肺发育不良的复合结局，次要结局包括死亡率；主要新生儿疾病；所有呼吸支持模式及住院时间；霍巴特方法的安全性；以及2岁时的结局。总共将纳入606名婴儿。该试验将在全球30多个中心进行，预计于2017年底完成。
微创表面活性物质治疗有可能减轻早产儿呼吸疾病的负担。该试验将为这种方法在治疗妊娠25 - 28周出生的早产儿中的有效性提供确凿证据。
澳大利亚和新西兰临床试验注册中心：ACTRN12611000916943；美国国立医学图书馆临床试验注册中心：NCT02140580。
