Endotracheal surfactant for infants with life-threatening bronchiolitis (BESS): a randomised, blinded, sham-controlled, phase 2 trial.
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All Authors
Semple, MG.
Donohue, C.
Price, L.
Cooper, R.
Vaughan, C.
Moitt, T.
Finnetty, L.
Ritson, PC.
Osaghae, B.
Allen, E.
LTHT Author
Sundararajan, Santosh
LTHT Department
Leeds Children's Hospital
Paediatric Intensive Care Unit
Paediatric Intensive Care Unit
Non Medic
Publication Date
2026
Item Type
Journal Article
Language
Subject
Subject Headings
Abstract
BACKGROUND: Bronchiolitis is a common viral respiratory disease of infants, with severity ranging from mild symptoms, such as coryza and feeding difficulties, to fulminant respiratory failure. Endotracheal administration of exogenous surfactant has been shown in small studies to improve gas exchange in critically ill infants with bronchiolitis. We aimed to investigate the safety and efficacy of endotracheal poractant alfa for treating critical bronchiolitis compared with a sham procedure.
METHODS: BESS was a multicentre, blinded, randomised, sham-controlled, parallel-group, phase 2, superiority trial with exploratory mechanism evaluation studies. The trial was done in 15 paediatric intensive care units in the devolved National Health Service (NHS) of England, Scotland, and Northern Ireland. 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. Randomisation was stratified by duration of IMV before randomisation (<24 h and >=24 h) and by site. 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. Endotracheal poractant alfa was given initially at 200 mg/kg, followed by 100 mg/kg at 12 h intervals. The primary endpoint was the duration of IMV from randomisation to final successful extubation. All infants who were successfully extubated were included in the intention-to-treat analysis. Safety outcomes were analysed in infants who had received at least one trial intervention. This trial was registered prospectively with ISRCTN (ISRCTN11746266) and EudraCT (2018-001169-18), and is completed.
FINDINGS: The trial was completed after six recruitment seasons. 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. Three infants were withdrawn from the study. None were lost to follow-up. 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. The geometric mean ratio was 1.02 (95% CI 0.84-1.24; t-test p=0.86). No clinically significant safety issues were associated with endotracheal poractant alfa and there were no deaths.
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. Therefore, our findings suggest that it should not be used for this indication at this dose and administration method.
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.
Journal
The Lancet Respiratory Medicine