Munch 2021b.

Study characteristics
Methods	Trial design: multicentre, triple‐blind, randomised controlled trial Type of publication: journal publication Setting: inpatient (ICU) Recruitment dates: August 2020 and May 2021 Country: Denmark, India, Sweden, Switzerland Language: English Number of centres: 31 Trial registration number: NCT04509973, CTRI/2020/10/028731 Date of trial registration: 11 August 2020
Participants	Age: Median age (IQR): 65 years (56 to 74) in the high‐dose group Median age (IQR): 64 years (54 to 72) in the low‐dose group Gender: 346 male (70%) in the high‐dose group, 331 male (68%) in the low‐dose group 151 female (30%) in the high‐dose group, 154 female (32%) in the low‐dose group Ethnicity: not stated, but 369 participants were recruited in India, an LMIC Number of participants (recruited/allocated/evaluated): 1000/503 in the high‐dose group and 497 in the low‐dose group/491 in the high‐dose group and 480 in the low‐dose group Severity of condition according to study definition: required supplementary oxygen at a flow rate of at least 10 L/min, noninvasive ventilation or continuous positive airway pressure for hypoxaemia, or invasive mechanical ventilation Severity of condition according to WHO score: moderate to severe ≥ 5 Co‐morbidities: diabetes, ischaemic heart disease or heart failure, chronic obstructive pulmonary disease Inclusion criteria: 18 years or older, hospitalised with confirmed SARS‐CoV‐2 infection, and required (1) supplementary oxygen at a flow rate of at least 10 L/min (independent of delivery system), (2) noninvasive ventilation or continuous positive airway pressure for hypoxaemia, or (3) invasive mechanical ventilation Exclusion criteria: (1) were treated with systemic glucocorticoids in doses higher than 6 mg of dexamethasone equivalents for indications other than COVID‐19 or had been treated with systemic glucocorticoids for COVID‐19 for 5 days or longer, (2) had invasive fungal infection or active tuberculosis, (3) had known hypersensitivity to dexamethasone, and (4) were pregnant Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): dexamethasone, remdesivir, convalescent plasma, systemic antibacterial agents, vasopressors or inotropes, IL‐6 receptor antagonists, janus kinase inhibitors
Interventions	Details of intervention: dexamethasone Dose: 12 mg/day for up to 10 days Route of administration: intravenous Treatment details of control group (e.g. dose, route of administration): 6 mg/day intravenous dexamethasone for up to 10 days Concomitant therapy: no
Outcomes	Primary study outcome: the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days after randomisation Review outcomes: inpatient setting Mortality: all‐cause mortality at day 14 or any longer observation period, in‐hospital all‐cause mortality: reported Improvement of clinical status during the longest observation period available: Ventilator‐free days (defined as days alive and free from mechanical ventilation): reported Participants discharged alive. Participants should be discharged without clinical deterioration or death: not reported Deterioration of clinical status during the longest observation period available: New need for invasive mechanical ventilation or death; that is, transition to WHO 7 to 9 if 6 or lower at baseline (see Figure 1): not reported Serious adverse events, defined as the number of participants with any event: reported Adverse events (any grade), defined as the number of participants with any event: not reported Specific adverse events: hospital‐acquired infections: reported Fungal infections: reported Quality of life, including fatigue and neurological status, assessed with standardised scales (e.g. WHOQOL‐100) during the longest period available: not reported New need for dialysis during the longest period available: not reported Viral clearance, assessed with reverse transcription polymerase chain reaction (RT‐PCR) test for SARS‐CoV‐2 at baseline, up to 3, 7, and 15 days: not reported Additional study outcomes: the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, health‐related quality of life measured using the 5‐dimension, 5‐level European Quality of Life questionnaire and the European Quality of Life visual analogue scale, will be assessed at 180 days after randomisation
Identification
Notes	Date of publication: 21 October 2021 Sponsor/funding: Novo Nordisk Foundation