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

Miriam Fezzi; Laura Antolini; Alessandro Soria; Luca Bisi; Francesca Iannuzzi; Francesca Sabbatini; Marianna Rossi; Silvia Limonta; Alban Rugova; Paola Columpsi; Nicola Squillace; Sergio Foresti; Ester Pollastri; Maria Grazia Valsecchi; Guglielmo Marco Migliorino; Paolo Bonfanti; Giuseppe Lapadula

doi:10.1183/23120541.00181-2023

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

ERJ Open Res. 2023 Aug 14;9(4):00181-2023. doi: 10.1183/23120541.00181-2023. eCollection 2023 Jul.

Authors

Miriam Fezzi¹, Laura Antolini², Alessandro Soria³, Luca Bisi³, Francesca Iannuzzi³, Francesca Sabbatini³, Marianna Rossi³, Silvia Limonta³, Alban Rugova³, Paola Columpsi³, Nicola Squillace³, Sergio Foresti³, Ester Pollastri³, Maria Grazia Valsecchi², Guglielmo Marco Migliorino^{1

3}, Paolo Bonfanti^{1

3}, Giuseppe Lapadula^{1

3}

Affiliations

¹ School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
² Bicocca Bioinformatics Biostatistics and Bioimaging Center - B4, University of Milano-Bicocca, Milan, Italy.
³ Infectious Diseases Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.

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.