BACHb: Breathing Assistance in CHildren with bronchiolitis (BACHb): a group-sequential two stratum multicentre open-label randomised clinical trial of respiratory support in infants with acute bronchiolitis

BACKGROUND

The role of high-flow nasal cannula (HFNC) in the management of hospitalised infants with moderate and severe bronchiolitis is unclear.

RESEARCH QUESTIONS

1) In hospitalised infants with bronchiolitis not responding to low-flow nasal cannula oxygen (moderate bronchiolitis) [Population], is the use of HFNC [Intervention] superior to humidified standard oxygen

(HSO) [Comparator] in reducing time to hospital discharge [Outcome]?

2) In hospitalised infants with bronchiolitis and severe respiratory distress (severe bronchiolitis) [Population], is the use of HFNC [Intervention] superior to nasal continuous positive airway pressure

(CPAP) [Comparator] in reducing time to hospital discharge [Outcome]?

METHODS

DESIGN: Four-stage group-sequential design, two-stratum, multicentre, open-label, randomised clinical trial, with 6-month internal pilot phase and integrated health economic evaluation.

SETTING: Emergency departments, assessment units and paediatric wards in 50 UK National Health Service (NHS) hospitals.

INCLUSION CRITERIA: Hospitalised infant aged <12 months with a clinical diagnosis of acute bronchiolitis and clinically assessed at least twice 15 minutes apart to have EITHER:

(A) Severe respiratory distress and/or recurrent short apnoeas [Severe stratum], OR

(B) Lack of response to low-flow oxygen ≥2 L/min, with persistent hypoxia and/or moderate respiratory distress [Moderate stratum].

EXCLUSION CRITERIA: (1) Clinical decision that patient needs immediate intubation and ventilation; (2) Ongoing active air leak; (3) Received HSO, HFNC or CPAP for >2 hours in prior 24 hours; (4) On home ventilation; (5) Tracheostomy in place; (6) Nasal/midfacial anomalies or recent craniofacial surgery; (7) Previously recruited to BACHb trial.

HEALTH TECHNOLOGIES: Severe stratum: HFNC at a flow rate of 2 L/kg/minute compared with nasal CPAP at a set expiratory pressure of 6-8 cm H2O. Moderate stratum: HFNC at a flow rate of 2

L/kg/minute compared with HSO up to 15 L/minute.

CONSENT: Due to the emergency nature of the treatment, based on PPI feedback, we will defer written informed consent to after randomisation. Brief study information leaflets and posters will be available. All treatments are already used in clinical practice.

PRIMARY OUTCOME: Time from randomisation to hospital discharge.

SECONDARY OUTCOMES: Treatment failure; mortality; intubation and invasive ventilation; intensive care unit admission; sedation use; duration of oxygen therapy; time to adequate (75%) oral feeding; patient comfort; hospital readmission within 30 days; and health status at 30 and 90 days. Cost-effectiveness expressed in terms of incremental cost per quality-adjusted life year (QALY) gained.

SAMPLE SIZE: Severe stratum: A total of 584 patients (HFNC: 292, CPAP: 292) is necessary to detect a 25% decrease in median time to hospital discharge in HFNC group (HR=1.33). Moderate stratum: A

total of 924 patients (HFNC: 462, HSO: 462) is necessary to detect a 20% decrease in median time to discharge in HFNC group (HR=1.25). Both provide 90% power at 5% two-sided level of significance.