FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care

Padmanabhan Ramnarayan, Paula Lister, Troy Dominguez, Parviz Habibi, Naomi Edmonds, Ruth R Canter, Jerome Wulff, David A Harrison, Paul M Mouncey, Mark J Peters, United Kingdom Paediatric Intensive Care Society Study Group (PICS-SG), Padmanabhan Ramnarayan, Paula Lister, Troy Dominguez, Parviz Habibi, Naomi Edmonds, Ruth R Canter, Jerome Wulff, David A Harrison, Paul M Mouncey, Mark J Peters, United Kingdom Paediatric Intensive Care Society Study Group (PICS-SG)

Abstract

Background: Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care.

Methods: In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT.

Results: Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2).

Conclusions: Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients.

Trial registration: clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

Keywords: Continuous positive airway pressure; High-flow nasal cannula therapy; Non-invasive respiratory support; Paediatric critical care.

Conflict of interest statement

Ethics approval

Ethical approval for the study was provided by the National Research Ethics Committee (NRES) North East – Tyne and Wear South (ref. 15/NE/0296). Management approvals were obtained from all study sites.

Competing interests

PR received travel support from Fisher and Paykel Healthcare to attend an international research symposium in November 2017. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram. CPAP continuous positive airway pressure, HFNC high-flow nasal cannula, PICU paediatric intensive care unit
Fig. 2
Fig. 2
High-flow nasal cannula (HFNC) gas flow rates and continuous positive airway pressure (CPAP) measurements for study participants. a HFNC gas flow rate for patients weighing < 10 kg; b HFNC gas flow rate for patients weighing > 10 kg; c CPAP pressure for all patients

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