Endotracheal surfactant for infants with life-threatening bronchiolitis (BESS): a randomised, blinded, sham-controlled, phase 2 trial.

Endotracheal administration of exogenous surfactant has been shown in small studies to improve gas exchange in critically ill infants with bronchiolitis.

小规模研究显示，经气管给予外源性表面活性剂可以改善重症支气管炎婴儿的气体交换。

We aimed to investigate the safety and efficacy of endotracheal poractant alfa for treating critical bronchiolitis compared with a sham procedure.

我们旨在研究气管内注射猪肺磷脂α治疗重症细支气管炎的安全性和有效性，与安慰剂程序进行比较。

Methods

BESS was a multicentre, blinded, randomised, sham-controlled, parallel-group, phase 2, superiority trial with exploratory mechanism evaluation studies.

BESS是一项多中心、双盲、随机、安慰剂对照、平行组、2期、优效性试验，同时进行探索性机制评估研究。

The trial was done in 15 paediatric intensive care units in the devolved National Health Service (NHS) of England, Scotland, and Northern Ireland.

该试验在英格兰、苏格兰和北爱尔兰的15个儿科重症监护病房进行，这些病房属于地方国家卫生服务（NHS）系统。

Preterm and term-born infants younger than 26 weeks of gestationally corrected age admitted to hospitals with bronchiolitis requiring invasive mechanical ventilation (IMV) were randomly assigned (1:1) to receive up to three doses of endotracheal poractant alfa (Curosurf) or sham intervention, allocated through web-based randomisation.

胎龄小于26周的早产儿和足月儿，因支气管炎需要侵入性机械通气（IMV）而被收入医院的，按照1:1的比例随机分配接受最多三次气管内注射猪肺磷脂alfa（Curosurf）或安慰剂干预，通过基于网络的随机化程序进行分配。

Randomisation was stratified by duration of IMV before randomisation (<24 h and ≥24 h) and by site.

随机分组按随机化前的有创机械通气时间(<24小时和≥24小时)和地点进行分层。

The infants and their families, clinical care staff, Liverpool Clinical Trial Centre staff, and members of the site research teams were masked to treatment allocations.

婴儿及其家人、临床护理人员、利物浦临床试验中心工作人员以及现场研究团队成员对治疗分配情况进行了盲法处理。

Endotracheal poractant alfa was given initially at 200 mg/kg, followed by 100 mg/kg at 12 h intervals.

最初给予气管内注射猪肺磷脂α 200 mg/kg，随后每12小时给予100 mg/kg。

The primary endpoint was the duration of IMV from randomisation to final successful extubation.

主要终点是随机化至最终成功撤机的有创机械通气(IMV)持续时间。

All infants who were successfully extubated were included in the intention-to-treatanalysis.

所有成功撤机的婴儿都被纳入意向治疗分析。

Safety outcomes were analysed in infants who had received at least one trial intervention.

在至少接受过一次试验性干预的婴儿中分析了安全性结果。

This trial was registered prospectively with ISRCTN (ISRCTN11746266) and EudraCT (2018-001169-18), and is completed.

该试验已前瞻性地在ISRCTN (ISRCTN11746266)和EudraCT (2018-001169-18)进行注册，并已完成。

Results

The trial was completed after six recruitment seasons.

该试验在六个招募季节后完成。

Between Dec 18, 2018, to March 31, 2024, 1009 infants were assessed for eligibility, 232 of whom were randomly assigned to receive either endotracheal poractant alfa (n=115) or a sham intervention (n=117). 130 (56%) of 232 infants were male and 102 (44%) were female.

在2018年12月18日至2024年3月31日期间，共有1009名婴儿被评估符合纳入标准，其中232名随机分配接受气管内注射猪源性肺表面活性剂alfa（n=115）或假性干预（n=117）。232名婴儿中，130名（56%）为男性，102名（44%）为女性。

Three infants were withdrawn from the study.

有三名婴儿被从研究中撤回。

None were lost to follow-up.

随访期间无失访病例。

The median duration of IMV was 64·9 h (IQR 43·2-92·1) in the endotracheal poractant alfa group and 62·0 h (39·3-95·1) in the sham intervention group.

气管内注射猪肺磷脂α组的间歇性机械通气中位持续时间为64.9小时（四分位数间距43.2-92.1小时），而假干预组为62.0小时（四分位数间距39.3-95.1小时）。

The geometric mean ratio was 1·02 (95% CI 0·84-1·24; t-test p=0·86).

几何平均比率是1.02（95%置信区间0.84-1.24；t检验p=0.86）。

No clinically significant safety issues were associated with endotracheal poractant alfa and there were no deaths.

与气管内注射猪肺磷脂α相关的安全性问题在临床上没有显著性，且无死亡病例。

interpretation

Poractant alfa, administered endotracheally to infants with early critical bronchiolitis, although safe, did not reduce the duration of IMV compared with the sham intervention.

尽管安全，但通过气管内给予早发性重症细支气管炎婴儿Poractant alfa，并没有比安慰剂干预减少有创机械通气（IMV）的持续时间。

Therefore, our findings suggest that it should not be used for this indication at this dose and administration method.

因此，我们的研究结果表明，在这种剂量和给药方法下，不应将其用于此适应症。

funding

UK National Institute for Health and Care Research, UK Research and Innovation Medical Research Council, Chief Scientist Office Scotland, Health and Social Care Research and Development Division Northern Ireland, and Chiesi Farmaceutici, Italy.

英国国家卫生与护理研究院、英国研究与创新医学研究委员会、苏格兰首席科学家办公室、北爱尔兰卫生与社会保健研究与发展部以及意大利Chiesi制药公司。