BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.

Bloomsbury Institute of Intensive Care Medicine Division of Medicine University College London Gower Street London WC1E 6BT UK

Department of Anaesthesia and Intensive Care 1st Faculty of Medicine General University Hospital Prague and Charles University U Nemocnice 499 2 128 08 Prague Czech Republic

Department of Anaesthesia and Intensive Care 3rd Faculty of Medicine University Hospital Královské Vinohrady and Charles University Šrobárova 1150 100 34 Prague Czech Republic

Department of Anaesthesiology and Intensive Care 1st Faculty of Medicine Military University Hospital Praha and Charles University U Vojenské nemocnice 1200 169 02 Prague Czech Republic

Department of Anaesthesiology and Intensive Care Medicine 2nd Faculty of Medicine University Hospital Motol and Charles University 5 Úvalu 84 1 150 06 Prague Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Faculty of Medicine in Pilsen University Hospital Plzeň and Charles University alej Svobody 80 304 60 Plzeň Lochotín Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Faculty of Medicine St Anne's University Hospital and Masaryk University Pekařská 664 53 656 91 Brno Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Faculty of Medicine University Hospital Brno and Masaryk University Jihlavská 20 625 00 Brno Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Faculty of Medicine University Hospital Olomouc and Palacky University 1 P Pavlova 185 6 779 00 Olomouc Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Faculty of Medicine University Hospital Ostrava and University Ostrava 17 listopadu 1790 708 52 Ostrava Poruba Czech Republic

Department of Anaesthesiology and Intensive Care Medicine Tomáš Baťa Regional Hospital Havlíčkovo nábřeží 600 762 75 Zlín Czech Republic

Department of Paediatric Anaesthesiology and Intensive Care Medicine Faculty of Medicine University Hospital Brno and Masaryk University Jihlavská 20 625 00 Brno Czech Republic

Department of Pharmacology CZECRIN Faculty of Medicine Masaryk University Kamenice 5 62500 Brno Czech Republic

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Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial

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NCT04663555