November 29, 2025
Background: The impact of noninvasive ventilation (NIV) managed outside the intensive care unit in patients with early acute respiratory failure remains unclear. This study aimed to determine whether the early addition of NIV prevents progression to severe acute respiratory failure.
Methods: This multinational, randomized, open-label controlled trial enrolled adults with mild acute respiratory failure (arterial oxygen partial pressure/fraction of inspired oxygen [PaO₂/FiO₂] ratio ≤200) across 11 hospitals in Italy, Greece, and Kazakhstan. Participants were randomized to receive either early NIV or usual care. Patients in the early NIV group received 2-hour cycles of NIV every 8 hours for up to 12 days. The primary outcome was progression to severe acute respiratory failure during hospitalization, defined by severe hypoxemia, severe respiratory distress, or hypercapnic acidaemia.
Results: Between May 6, 2012, and July 18, 2023, 524 patients (44.8% female; median age 73 years [interquartile range, 63-83 years]) were randomized, with one patient withdrawing consent. Progression to severe acute respiratory failure occurred in 49 of 265 patients (18.5%) in the early NIV group compared with 73 of 258 patients (28.3%) receiving usual care (relative risk, 0.65; 95% confidence interval, 0.48-0.90; p = 0.0080). Median hospital stay was 10 days (IQR, 6-16) in the early NIV group and 9 days (IQR, 5-16) in the usual care group (p = 0.30). Respiratory complications, 28-day mortality, and adverse events did not differ significantly between the two groups.
Conclusions: In patients with mild acute respiratory failure treated in non-intensive care wards, early noninvasive ventilation reduced progression to severe acute respiratory failure.
Clinical Trial Registration: NCT01572337.
Keywords: Continuous positive airway pressure; intensive care unit; intubation; noninvasive ventilation; respiratory insufficiency.
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