Dequin 2020.

Study characteristics
Methods	Trial design: multicentre, double‐blind, randomised trial Type of publication: journal publication Setting: inpatient Recruitment dates: 7 March to 1 June 2020 Country: France Language: English Number of centres: 9 Trial registration number: NCT02517489 Date first posted: 7 August 2015
Participants	Age: Median age 63.1 years (IQR 51.5 to 70.8) in the intervention group Median age 66.3 years (IQR 53.5 to 72.7) in the control group Gender: 54 male (71.1%) and 22 female (28.9%) in the intervention group 50 male (68.5%) and 23 female (31.5%) in the control group Proportion of PCR‐confirmed infections Positive: 94.7% intervention arm; 98.8% control arm Negative: not reported Unclear: not reported Ethnicity: not reported Number of participants (recruited/allocated/evaluated): Recruited: 40 Allocated: 76 intervention group and 73 control group Evaluated: 76 in intervention group and 73 in control group Severity of condition according to study definition Mechanical ventilation (included noninvasive ventilation): 81.6% in the intervention group 59% in the control group High‐flow oxygen therapy: 13.2% in the intervention group 12.3% in the control group Nonrebreathing mask with reservoir bag: 5.3%% in the intervention group 6.8% in the control group Severity of condition according to WHO score: moderate to severe ≥ 5 Co‐morbidities: diabetes, COPD/asthma, immunosuppression Inclusion criteria Admitted to 1 of the 9 participating French ICUs for acute respiratory failure At least 18 years of age Biologically confirmed (RT‐PCR) or suspected (suggestive chest CT scan result in the absence of any other cause of pneumonia) COVID‐19 1 of 4 severity criteria had to be present: Need for mechanical ventilation with a PEEP of ≥ 5 cm H2O A ratio of PaO2 to FIo2 < 300 on high‐flow oxygen therapy with an FIO2 value of at least 50% For participants receiving oxygen through a reservoir mask, a PaO2:FIO2 ratio < 300, estimated using prespecified charts, or Pulmonary Severity Index > 130 Exclusion criteria Unable to meet inclusion deadlines Included in another interventional trial Septic shock Long‐term corticosteroid therapy Did not meet severity criteria Transferred to another ICU Medical team declined enrolment Under judicial protection Do‐not‐intubate order Moribund Declined to participate Required hydrocortisone for other medical condition Miscellaneous Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): yes
Interventions	Treatment details of intervention group (e.g dose, route of administration, number of doses): Type of corticosteroid: hydrocortisone Dose: 200 mg/day until day 7, then 100 mg/day for 4 days and 50 mg/day for 3 days, for a total of 14 days Route of administration: IV Treatment details of control group (e.g. dose, route of administration, number of doses): placebo Concomitant therapy (e.g. description of standard care): not reported Duration of follow‐up: last follow‐up on 29 June 2020 Treatment cross‐overs: no Compliance with assigned treatment: yes
Outcomes	Primary study outcome: treatment failure on day 21 (death or persistent dependence of mechanical ventilation or high‐flow oxygen therapy) 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): not 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: reported Specific adverse events: hospital‐acquired infections: reported Fungal infections: not 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: endotracheal intubation (for patients noninvasively ventilated at inclusion), prone position, ECMO, inhaled nitric oxide
Identification
Notes	Date of publication: 6 October 2020 Sponsor/funding: University Hospital, Tours