AbstractBackgroundHigh-flow nasal cannula oxygen therapy (HFNC) is recommended by some scholars as an optimized respiratory support method for blunt chest trauma (BCT) patients. The basis of this recommendation is limited, however, and the efficacy of HFNC or noninvasive ventilation (NIV) in BCT patients has not yet been rigorously explored. This study aims to determine if HFNC is non-inferior to NIV in reducing treatment failure in moderate to severe BCT patients with acute respiratory failure.MethodsThis will be a prospective, open-label, multicenter, non-inferiority, randomized controlled trial. Moderate to severe BCT patients with acute respiratory failure (100mmHg < PaO₂/FiO₂≦ 200mmHg) who do not need immediate intubation will be randomized to HFNC or NIV within 48 h after trauma. The primary outcome is treatment failure, defined as invasive ventilation or a switch in respiratory support modality (from HFNC to NIV or vice-versa). Secondary outcomes include arterial blood gas analysis and vital signs at 2 and 12 h after initiating HFNC or NIV treatment, as well as patients’ comfort scores, dyspnea scores, daily number of nursing airway care interventions, incidence of pneumonia or pneumothorax, facial skin breakdown, duration of NIV or HFNC, 28-day mortality, and total ICU and hospital lengths of stay. Based on anαerror of 5% and aβerror of 80%, with a non-inferiority limit of 9%, a sample size of 562 will be required to accomplish the trial goal, considering potential patient dropouts and nonparametric analysis.DiscussionWe hypothesize that HFNC will be non-inferior to NIV in reducing treatment failure in moderate to severe BCT with acute respiratory failure. The results should be useful for judging whether HFNC could be an effective alternative to NIV to treat moderate to severe BCT patients, especially for those who do not tolerate or have contraindications for NIV.Trial registrationChinese Clinical Trial RegistryChiCTR1800017313. Registered on July 24, 2018.