Parallel-group, randomised, controlled, non-inferiority trial of high-flow nasal cannula versus non-invasive ventilation for emergency patients with acute cardiogenic pulmonary oedema: study protocol

INTRODUCTION: High-flow nasal cannula (HFNC) is an innovative oxygen-delivering technique, which has been shown to effectively decrease the intubation risk in patients with hypoxaemic respiratory failure of various aetiologies compared with conventional oxygen therapy. Also, it has proved to be non-inferior to non-invasive positive pressure ventilation (NIPPV) in patients with hypoxaemic respiratory failure primarily due to pneumonia. Evidence on its benefits compared with NIPPV, which is the standard of care for patients with acute cardiogenic pulmonary oedema (ACPE) with hypoxaemic respiratory distress, is limited. Therefore, we planned this study to investigate the effects of HFNC compared with NIPPV for emergency patients with ACPE. METHODS AND ANALYSIS: In this single-centred, non-blinded, parallel-group, randomised, controlled, non-inferiority trial, we will randomly allocate 240 patients visiting the emergency department with ACPE in a 1:1 ratio to receive either HFNC or NIPPV for at least 4 hours using computer-generated mixed-block randomisation concealed by sealed opaque envelopes. The primary outcome is the intubation rate in 72 hours after randomisation. The main secondary outcomes are intolerance rate, mortality rate and treatment failure rate (a composite of intolerance, intubation and mortality). The outcome assessors and data analysts will be blinded to the intervention. These categorical outcomes will be analysed by calculating the risk ratio. Interim analyses evaluating the primary outcome will be performed after half of the expected sample size are recruited. ETHICS AND DISSEMINATION: This study protocol has been approved by the Siriraj Institutional Review Board (study ID: Si 271/2021). It has been granted the Siriraj Research and Development Fund. All participants or their authorised third parties will provide written informed consent prior to trial inclusion. The study results will be published in a peer-reviewed international journal and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: TCTR20210413001.