Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial
Authors: Franco-Moreno Anabel , Acedo-Gutiérrez María Soledad , Martín Nicolás Labrador-San , Hernández-Blanco Clara , Rodríguez-Olleros Celia , Ibáñez-Estéllez Fátima , Suárez-Simón Ana , Balado-Rico Mateo , Romero-Paternina Ana Rocío , Alonso-Menchén David , Escolano-Fernández Belén , Piniella-Ruiz Esther , Monge Ester Alonso , Leo Helena Notario Leo Helena Notario , Bibiano-Guillén Carlos , Peña-Lillo Gabriela , Antiqueira-Pérez Armando , Romero-Pareja Rodolfo , Cabello-Clotet Noemí , Estrada-Pérez Vicente , Troya-García Jesús , De Carranza-López María , Escobar-Rodríguez Ismael , Vallejo-Maroto Nacho , Torres-Macho Juan 
Published: May 2022

Abstract
BackgroundCorticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. No benefit in patients not requiring respiratory support at randomization was observed. However, we believe that the use of corticosteroids in patients with COVID-19 pneumonia might not be subject to a decision based solely on oxygen needs. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS, and thereby reduce death.Methods/designThis is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission, but are at risk factors for development ARDS. Risk for development ARDS is defined as levels of lactate dehydrogenase >245 U/L, C-reactive protein >100 mg/L, and lymphocyte count of <0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive an intravenous dose of 6 mg once daily from day 1 to day 3, followed by an oral dose of 6 mg once daily from day 4 to day 7. The primary outcome is a composite of development of moderate ARDS and all-cause mortality during the 30-day period following enrollment.DiscussionIf our hypothesis is correct, the results of this study will provide additional insights about the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease.Trial registrationClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.