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

Abstract

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. 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 arterial oxygen tension to inspiratory oxygen fraction ratio (P_aO2/F_IO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and P_aO2/F_IO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge.

Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a P_aO2/F_IO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (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 prone positioning 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 prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

FIGURE 1

CONSORT diagram showing subject disposition in the trial.

FIGURE 2

Clinical status distribution over time, grouped by randomisation arm. At each time point, the left column represents the control arm and the right column represents the awake prone positioning (intervention) arm. CPAP: continuous positive airway pressure; HFNC: high-flow nasal cannula.

FIGURE 3

Risk of clinical progression and probability of oxygen weaning by randomisation arm. a) Intention-to-treat analysis for risk of clinical progression, defined as death, mechanical ventilation, need for high-flow nasal cannula (HFNC) or noninvasive ventilation with continuous positive airway pressure (CPAP). b) Intention-to-treat analysis for probability of oxygen discontinuation by randomisation arm. c) As-treated analysis for risk of clinical progression, defined as death, mechanical ventilation, need for HFNC or noninvasive ventilation with CPAP. d) As-treated analysis for probability of oxygen discontinuation by randomisation arm. The continuous line represents the control group, the dashed line represents the prone positioning group.

FIGURE 4

Arterial oxygen tension to inspiratory oxygen fraction ratio (P_aO2/F_IO2) over time by randomisation arm. Horizontal lines represent medians, boxes represent interquartile ranges, whiskers represent minimum and maximum values (excluding outliers), the markers represent means and outliers.