Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label, randomised controlled trial (the EPCoT Study)

Background: Prone positioning (PP) is routinely used among patients with COVID-19 requiring mechanical ventilation (MV). However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose PaO2/FiO2 ratio (P/F) was >200 mmHg and who did not require MV or Continuous Positive Airway Pressure (CPAP) at hospital admission. Patients were randomised 1:1 to PP on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, MV, CPAP and P/F <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: Sixty-one subjects were enrolled, 29 adjudicated to PP and 32 to the control group. By day 28, 24/61 (39.3%) patients met the primary outcome: 16 because of P/F ratio <200 mmHg, 5 CPAP and 3 MV. Three patients died. Using an intention-to-treat approach, 15/29 patients in PP group versus 9/32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to PP (HR 2.38 [95%CI 1.04-5.43]; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained PP for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77; [95%CI 0.79-3.94]; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms, in any of the analyses conducted. Conclusions: We observed no clinical benefit from PP among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.