Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial

Abstract

Background: There are no specific generally accepted therapies for the coronavirus disease 2019 (COVID-19). The full spectrum of COVID-19 ranges from asymptomatic disease to mild respiratory tract illness to severe pneumonia, acute respiratory distress syndrome (ARDS), multisystem organ failure, and death. The efficacy of corticosteroids in viral ARDS remains unknown. We postulated that adjunctive treatment of established ARDS caused by COVID-19 with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and in mortality. Methods/design: This is a multicenter, randomized, controlled, parallel, open-label, superiority trial testing dexamethasone in 200 mechanically ventilated adult patients with established moderate-to-severe ARDS caused by confirmed SARS-CoV-2 infection. Established ARDS is defined as maintaining a PaO 2 /FiO 2 ≤ 200 mmHg on PEEP ≥ 10 cmH 2 O and FiO 2 ≥ 0.5 after 12 ± 3 h of routine intensive care. Eligible patients will be randomly assigned to receive either dexamethasone plus standard intensive care or standard intensive care alone. Patients in the dexamethasone group will receive an intravenous dose of 20 mg once daily from day 1 to day 5, followed by 10 mg once daily from day 6 to day 10. The primary outcome is 60-day mortality. The secondary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after randomization. All analyses will be done according to the intention-to-treat principle.

Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic

“…The major pharmaceuticals being evaluated include the antiviral agent remdesivir, interferon B-1a, monoclonal antibodies against interleukin 6 (IL-6) and IL-4, and dexamethasone. Dexamethasone ( Villar et al, 2020 ) and remdesivir ( Beigel et al., 2020 ) have shown efficacy in randomized controlled trials. Interestingly, administration of prednisolone, a glucocorticoid-like dexamethasone, showed a time-of-day-dependent effect in alleviating rheumatoid arthritis symptoms ( Buttgereit et al, 2008 ).…”

Severe coronavirus disease pneumonia in a pregnant woman at 25 weeks' gestation: A case report

“…It is used to treat COVID‐19, but is teratogenic and must not be administered during the early phase of pregnancy 12 . When dexamethasone is administered concomitantly with standard therapy for COVID‐19 patients with moderate‐to‐severe acute respiratory distress syndrome, the number of days of artificial ventilation, up to day 28 of treatment (i.e., days in which the patient is alive and mechanical ventilation is not used), increases in comparison with standard therapy alone 13 . Corticosteroids have anti‐inflammatory effects and may prevent or suppress harmful inflammatory reactions that may lead to lung damage and/or multiple organ failure 14 .…”

Why Haven’t We Found an Effective Treatment for COVID-19?

“…( 1 , 13 ). Indeed, the RECOVERY trial showed that patients suffering from the most severe COVID-19 symptoms and were on respiratory support had the best responses to glucocorticoid treatment ( 1 , 13 , 14 ). However, as pointed out by RECOVERY, the same treatment is not beneficial, and possibly even harmful, during the early stages of the disease when a natural antiviral response is required.…”