COVID-19-associated ARDS treated with DEXamethasone (CoDEX): study design and rationale for a randomized trial

Abstract

Objective The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. Methods This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.

Effects of corticosteroids on Covid-19 patients: A systematic review and meta-analysis on clinical outcomes

“…In contrast, five studies demonstrated that the use of corticosteroids was associated with an increased risk of death in hospital settings [ [19] , [20] , [21] , [22] , [23] ]. While, in remaining studies the results on mortality benefits were equivocal for the use of corticosteroids [ [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] ]. In all remaining studies, there was no significant difference in mortality between the corticosteroid group and controls.…”

Quality of life and long-term outcomes after hospitalization for COVID-19: Protocol for a prospective cohort study (Coalition VII)

“…Patients aged 18 years or older, requiring hospitalization due to proven or suspected SARS-CoV-2 infection and meeting eligibility criteria for Coalition I (NCT04322123), ( 14 ) Coalition II (NCT04321278), ( 15 ) Coalition III (Codex; NCT04327401), ( 16 , 17 ) Coalition IV (Action; NCT04394377) and Coalition VI (Tocibras; NCT04403685) ( 18 ) randomized clinical trials ( Table 1 ) will be enrolled. Patients with a positive polymerase chain reaction result for SARS-CoV-2 will be considered as proven cases.…”

A Journey From SARS-CoV-2 to COVID-19 and Beyond: A Comprehensive Insight of Epidemiology, Diagnosis, Pathogenesis, and Overview of the Progress into Its Therapeutic Management

“…FDA has also included it in the list of drugs for temporary compounding by outsourcing facilities and pharmacy compounders ( FDA, 2020a ). Some clinical trials are also being conducted to evaluate its effectiveness against COVID-19 ( Maskin et al, 2020 ; Tomazini et al, 2020 ).…”