Effect of dexamethasone in patients with ARDS and COVID-19 (REMED)
Patients Population :
Dexamethasone 20 mg daily versus dexamethasone 6 mg daily
Primary endpoint: Number of ventilator-free days at 28 days after randomization
Systemic corticosteroids have the potential to limit hyperinflammatory response by modulating the immune system. This effect is mediated mainly by binding to the glucocorticoid receptor (GR) α. Their effectiveness was proved in heterogeneous ARDS patients recently.
In patients with COVID-19 pneumonia in need for oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. This therapy is mandated by the results of RECOVERY trial. After this trial was published, three randomized trials comparing hydrocortisone or dexamethasone against placebo were stopped prematurely. All these studies were included in the subsequent individual patients' data (IPD) meta-analysis. However, the dose of 6 mg of dexamethasone is currently being reappraised.
The aforementioned study in non-COVID-19 ARDS patients used 20 mg of dexamethasone per day, which is roughly equivalent to the methylprednisolone regimen (1 mg/kg/day) studied in early severe ARDS patients. Only these moderate doses (80–100 mg of methylprednisolone, equivalent to 15–19 mg of dexamethasone) have the full potential to modulate the immune response by saturating GRα receptors. Importantly, prematurely stopped CoDEX trial comparing dexamethasone against placebo in COVID-19 ARDS patients used an initial daily dose of 20 mg of dexamethasone versus placebo.
In the light of these facts, 6 mg of dexamethasone given to COVID-19 patients with different severity of illness (WHO classification group 5–10) may miss important therapeutic potential or may prevent a potential deleterious effects of a full dose therapeutic corticosteroid. Authors hypothesize that the patients with moderate to severe ARDS undergoing mechanical ventilation may benefit from higher doses of dexamethasone.