ISRCTN33037282.

Methods	Trial design: open‐label, RCT Sample size: 680 Setting: inpatient Language: English Number of centres: 3 Type of intervention (treatment/prevention): treatment
Participants	Inclusion criteria Able to understand and sign the informed consent SARS‐CoV‐2 positive on at least 1 upper respiratory swab or bronchoalveolar lavage PaO2 ≤ 60 mmHg or SpO2 ≤ 90% or on HFNC, CPAP or NPPV at randomisation Age ≥ 18 years old at randomisation Exclusion criteria On IMV (either intubated or tracheostomised) Heart failure as the main cause of acute respiratory failure On long‐term oxygen or home mechanical ventilation Decompensated liver cirrhosis Immunosuppression (i.e. cancer on treatment, post‐organ transplantation, HIV‐positive, on immunosuppressant therapy) Chronic renal failure with dialysis dependence Progressive neuromuscular disorders Cognitively impaired, dementia or decompensated psychiatric disorder Quadriplegia/hemiplegia or quadriparesis/hemiparesis Do‐not‐resuscitate order Previous or current use of remdesivir Participating in other clinical trial including experimental compound with proved or expected activity against SARS‐CoV‐2 infection Any other condition that in the opinion of the investigator may significantly impact with patient's capability to comply with protocol intervention
Interventions	Details of intervention: per‐protocol methylprednisolone administration and tapering A. On day 1, loading dose of methylprednisolone 80 mg IV in 30 min, promptly followed by continuous infusion of methylprednisolone 80 mg/d in 240 mL of normal saline at 10 mL/h B. From day 2 to day 8: infusion of methylprednisolone 80 mg/d in 240 mL of normal saline at 10 mL/h C. From day 9 and beyond: If not intubated patient and PaO2/FiO2 > 200, taper to methylprednisolone 20 mg IV in 30 min 3/d for 3 days, then methylprednisolone 20 mg IV twice daily for 3 days, then methylprednisolone 20 mg IV once daily for 2 days, then switch to methylprednisolone 16 mg/d orally for 2 days, then methylprednisolone 8 mg/d orally for 2 days, then MP 4 mg/d orally for 2 days If intubated patient or PaO2/FiO2 ≤ 200 with at least 5 cm H2O CPAP, continue infusion of methylprednisolone 80 mg/d in 240 mL of normal saline at 10 mL/h until PaO2/FiO2 > 200 then taper as in A Treatment details of control group: per‐protocol dexamethasone administration A. Dexamethasone 6 mg IV in 30 min or orally from day 1 to day 10 or until hospital discharge (if sooner) B. After day 10 study treatment is interrupted Concomitant therapy: no
Outcomes	Primary study outcome Recovery time measured in days using patient records Recovery time determined as the time until hospital discharge when each of the following criteria were met: Decrease in laboratory severity markers Improvement in symptoms Decrease in oxygen requirement until nasal cannula or supplementary oxygen removal and at least 2 doses of the respective treatment have been received
Notes	Recruitment status: completed Prospective completion date: 30 April 2021 Date last update was posted: 19 November 2020 Sponsor/funding: Clínica Medellín ‐ Grupo Quirónsalud