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. 2017 May 30;2017(5):CD010172. doi: 10.1002/14651858.CD010172.pub2

Azoulay 2018.

Study characteristics
Methods RCT, parallel‐group design. Multicentre study
Participants Total number of randomized participants: 778
Setting: 32 ICUs; France
Inclusion criteria: ICU admission; ≥ 18 years of age; AHRF with PaO2 < 60 mmHg or SpO2 < 90% on room air, or tachypnoea > 30 breaths/min or laboured breathing or respiratory distress; need for oxygen flow of ≥ 6 L/min; known immunosuppression; written informed consent
Exclusion criteria: people with AIDS; imminent death; refusal to participate in study; anatomical factors precluding use of nasal cannula; hypercapnia indicting NIV; isolated cardiogenic pulmonary oedema indicating NIV; pregnancy or breastfeeding; absence of health insurance coverage; surgery within the last 6 days
Baseline characteristics:
Intervention group (HFNC):

  • Age, median (IQR): 64 (55 to 70) years

  • Gender, M/F: 270/118

  • BMI, mean (SD): not reported

  • SOFA, median (IQR) : 6 (4 to 8)

  • SAPS II, median (IQR): 36 (28 to 46)

  • PaCO2, mean (SD): not reported

  • PaO2/FiO2, median (IQR): 136 (96 to 187) mmHg

  • Respiratory rate, median (IQR): 33 (28 to 39) breaths/min


Control group (standard oxygen therapy):

  • Age, median (IQR): 63 (56 to 71) years

  • Gender, M/F: 247/141

  • BMI, mean (SD): not reported

  • SOFA, median (IQR): 6 (4 to 8)

  • SAPS II, median (IQR): 37 (28 to 48)

  • PaCO2, mean (SD): not reported

  • PaO2/FiO2, median (IQR): 128 (92 to 164) mmHg

  • Respiratory rate, median (IQR): 32 (27 to 38) breaths/min
Interventions Intervention group:

  • Randomized, n = 389; losses, n = 1 (withdrew consent), 13 did not receive intervention as randomized; analysed, n = 388

  • Details: started within 15 minutes of randomization, and for whole duration of ICU stay. Flow initiated at 50 L/min and 100% FiO2, then subsequent flow to achieve SpO2 ≥ 95% up to ≥ 50 L/min within the first 3 days then up to 60 L/min as needed. If participants needed MV, HFNC was used during laryngoscopy and immediately after extubation. Standard oxygen therapy was only used if significant nasal discomfort or skin breakdown.


Control group (standard oxygen):

  • Randomized, n = 389 ; losses, n = 1 (withdrew consent), 31 did not receive intervention as randomized, 30 received HFNC; analysed, n = 388

  • Details: started within 15 minutes of randomization, and for whole duration of ICU stay. Oxygen given by any device or combination of devices (nasal prongs or mask with or without reservoir bag and with or without Venturi system). Flow to achieve target SpO2 ≥ 95%. HFNC only given if participants had a do‐not‐intubate order or for whom standard oxygen had failed. NIV only used as long as hypercapnia or pulmonary oedema were present.
Outcomes Mortality within 28 days; hospital and ICU mortality; number needing MV by day 28; respiratory rate (normal values, 12‐20), lowest PaO2/FiO2, patient comfort score (range 0 to 10 = severe discomfort to perfect comfort); dyspnoea score (range 0 to 10 = no dyspnoea to severe dyspnoea); ICU and hospital lengths of stay; incidence of ICU‐acquired infections
Notes Funding/declarations of interest: funded by the French Ministry of Health. Supplies for high‐flow oxygen from Fisher & Paykel Healthcare Ltd. Funders had no role in the design and conduct of the study, nor in preparation of the manuscript etc.
Some authors received fees from one or more of: Gilead; Astellas; Baxter; Alexion; Ablynx; Merk Sharp and Dohme, Fisher & Paykel Healthcare, Xenios; Boehringer Ingelheim; Pfizer; Astute; Bristol‐Myers Squibb; Jazz Pharma; Sanofi‐Aventis; Resmed; Philips; Hamilton; Medtronic; French Ministry of Health. One author serves on a data and safety monitoring board for the French Ministry of Health.
Study dates: 19 May 2016 to 31 December 2017
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Use of an electronic system
Allocation concealment (selection bias) Low risk Quote: "Randomization was achieved using an electronic system incorporated in the electronic case report from to ensure allocation concealment".
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.
Blinding of outcome assessors (objective outcomes) Low risk Quote: "No blinding of adjudication was performed for outcome assessments". The assessors were unblinded; we did not anticipate that this would influence the assessment of objective outcome measures.
Blinding of outcome assessors (subjective measures) Low risk Participants were the outcome assessors for comfort and dyspnoea on a standardized scale: we did not anticipate that this would influence the assessment of these outcome measures.
Incomplete outcome data (attrition bias)
All outcomes Low risk Loss of only two participants
Selective reporting (reporting bias) Low risk Study was prospectively registered with a clinical trials register (NCT02739451). Outcomes relevant to the review were reported as described in the clinical trials register.
Other bias Low risk We identified no other sources of bias.