Toroghi 2021.

Study characteristics
Methods	Trial design: open‐label, randomised clinical trial Type of publication: journal publication Setting: inpatient Recruitment dates: 26 October 2020 to 25 January 2021 Country: Iran Language: English Number of centres: 1 Trial registration number: IRCT20100228003449N31 Date of trial registration: 8 October 2020
Participants	Age: mean 59 years (SD 14) in the low‐dose group, mean 59 years (SD 17) in the intermediate‐dose group and mean 56 years (SD 16) in the high‐dose group Gender: 28 (59.6%) male in the low‐dose group, 21 (52.5%) male in the intermediate‐dose group, and 31 (58.6%) male in the high‐dose group Proportion of confirmed infections: PCR positivity inclusion criterion Ethnicity: not reported Number of participants (recruited/allocated/evaluated): Recruited: 144 Allocated: 48 low‐dose group, 48 intermediate‐dose group, 48 high‐dose group Evaluated: 47 low‐dose group, 40 intermediate‐dose group, 46 high‐dose group Severity of condition according to study definition: moderate to severe; moderate COVID‐19 was considered when clinical signs of pneumonia (fever, cough, dyspnoea, and high respiratory rate) were positive along with SpO2 between 90% and 93% on room air. Severe COVID‐19 was described as clinical signs of pneumonia plus respiratory rate > 30 breaths/min or SpO2 < 90% on room air. Severity of condition according to WHO score: moderate to severe ≥ 5 Co‐morbidities: hypertension, diabetes mellitus, ischaemic heart disease, hypothyroidism, respiratory disorders, cerebrovascular accident, dyslipidaemia, neuropsychiatric disorders, rheumatoid arthritis, Parkinson's disease, depression, malignancy, renal disorders, liver disorders, heart failure Inclusion criteria Hospitalised adult patients With moderate to severe COVID‐19 Requiring supplemental oxygen Reverse transcriptase‐polymerase chain reaction (RT‐PCR) of nasopharyngeal samples and a lung computed tomography (CT) scan Positive RT‐PCR test or compatible lung involvement was considered for diagnosis of COVID‐19 Exclusion criteria Contraindication of corticosteroids (uncontrolled diabetes mellitus, active bacteria, fungal or parasite infections, hypersensitivity reactions, close angle glaucoma, uncontrolled neuropsychiatric disorders, unstable cardiovascular disorders including acute myocardial infarction, acute thrombosis, uncontrolled hypertension, viral hepatitis, history of corticosteroids induced myopathy) Pregnancy lactation History of recent corticosteroids Other immunosuppressant drugs use Previous treatments: aspirin, angiotensin receptor blockers, statin, beta blocker, metformin, azithromycin, levothyroxine, sofosbuvir‐ledipasvir, insulin, doxycycline, hydroxychloroquine, immunosuppressants, supplements, other antibiotics, angiotensinogen converting enzyme inhibitors
Interventions	3 groups comparing different doses of dexamethasone Treatment details of intervention group (e.g. dose, route of administration, number of doses) Type of corticosteroids: dexamethasone 8 mg twice a day for up to 10 days or until hospital discharge 8 mg ≥ 3 times a day for up to 10 days or until hospital discharge Route of administration: IV Treatment details of control group (e.g. dose, route of administration, number of doses): Type of corticosteroids: dexamethasone Dose: 8 mg once a day for up to 10 days or until hospital discharge Route of administration: IV Concomitant therapy (e.g. description of standard care): administration of antivirals, anticoagulants, antibiotics, analgesics, fluids, electrolytes, supplemental oxygen, vitamins, minerals, nutritional supports, and stress ulcer prophylaxis Duration of follow‐up: probably 60 days Treatment cross‐overs: no Compliance with assigned treatment: yes
Outcomes	Primary study outcome: time to a clinical response that was described as improvement of at least 2 scores in the 8‐category ordinal scale of the National Institute of Health (NIH): (1) discharge, with no limitations in usual activity, (2) discharge, with some limitations in usual activity, (3) hospital admission without the requirement of supplemental oxygen, (4) hospital admission, requiring oxygen by mask or nasal cannula, (5) hospital admission requiring non‐invasive ventilation or high‐flow oxygen, (6) intubation and mechanical ventilation, (7) mechanical ventilation and additional organ support like vasopressors, renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO), and (8) death. 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: not 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: time to 50% decrease in serum CRP level, time to respiratory rate ≤ 20 breaths per minute, time to peripheral oxygen saturation ≥ 93%, hospital readmission, need for ICU admission, duration of hospital and ICU stay, need for mechanical ventilation
Identification
Notes	Date of publication: 27 November 2021 Sponsor/funding: the authors did not receive any funds for this work

AE: adverse event; ARDS: acute respiratory distress syndrome; COPD: chronic obstructive pulmonary disease; CPK: creatine phosphokinase; CT: computed tomography; ECMO: extracorporeal membrane oxygenation; FiO2: fraction of inspired oxygen; GI: gastrointestinal; h: hours; ICU: intensive care unit; IMV: invasive mechanical ventilation; IQR: interquartile range: IV: intravenous; LDH: lactate dehydrogenase; LMIC: low‐ and middle‐income countries; NIV: non‐invasive ventilation; PaO2: partial pressure of oxygen; PEEP: positive end‐expiratory pressure; RCT: randomised controlled trial; RT‐PCR: reverse transcription polymerase chain reaction; SAE: serious adverse event; SaO2: arterial oxygen saturation; SpO2: blood oxygen saturation; SD: standard deviation; WHO: World Health Organization