Early noninvasive ventilation in general wards for acute respiratory failure: an international, multicentre, open-label, randomised trial

Background: The impact of noninvasive ventilation (NIV) managed outside the intensive care unit in patients with early acute respiratory failure remains unclear. We aimed to determine whether adding early NIV prevents the progression to severe respiratory failure. Methods: In this multinational, randomised, open-label controlled trial, adults with mild acute respiratory failure (arterial oxygen partial pressure/fraction of inspiratory oxygen [PaO₂/FiO₂] ratio ≥200) were enrolled across 11 hospitals in Italy, Greece, and Kazakhstan. Patients were randomised to receive early NIV or usual care. Patients in the early NIV group received 2-h cycles of NIV applied every 8 h for up to 12 days. The primary outcome was the progression to severe acute respiratory failure, defined by severe hypoxaemia, severe respiratory distress, or hypercapnic acidaemia during hospitalisation. Results: Between May 6, 2012, and July 18, 2023, we randomised 524 patients (44.8% female; median age 73 yr, interquartile range [IQR] 63–83 yr). One patient withdrew consent. Progression to severe acute respiratory failure occurred in 49/265 (18.5%) patients randomised to early NIV, compared with 73/258 (28.3%) patients receiving usual care (relative risk 0.65, 95% confidence interval 0.48–0.90, P=0.0080). Median length of hospital stay was 10 (IQR 6–16) days in the early NIV group and 9 (IQR 5–16) days in the usual care group (P=0.30). Respiratory complications, 28-day mortality, and adverse events were not different between early NIV and usual care. Conclusions: In patients with mild acute respiratory failure treated in nonintensive care wards, early NIV reduced the progression to severe acute respiratory failure. Clinical trial registration: NCT01572337.