Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial
Authors: Villar Jesús , Añón José M. , Ferrando Carlos , Aguilar Gerardo , Muñoz Tomás , Ferreres José , Ambrós Alfonso , Aldecoa César , Suárez-Sipmann Fernando , Thorpe Kevin E. , Jüni Peter , Slutsky Arthur S. ,   the DEXA-COVID19 Network, Ferrando Carlos , Mellado-Artigas Ricard , Fernández Javier , Hernández María , Castellá Manuel , Castro Pedro , Badia Joan Ramón , Aguilar Gerardo , Carbonell José A. , Badenes Rafael , Tornero Carlos , Ferreres José , Blasco María L. , Carbonell Nieves , Serrano Ainhoa , Juan Mar , Gómez-Herreras José I. , López Mario Lorenzo , Ambrós Alfonso , Martín Carmen , del Campo Rafael , Puig-Bernabeu Jaume , Ferrer Carolina , de Andrés José , Muñoz Tomás , Serna-Grande Pablo , Tamayo Gonzalo , Martínez-Ruíz Alberto , Bilbao-Villasante Iñaki , Villar Jesús , Fernández Rosa L. , Calvo César Pérez , Vidal Ánxela , Añón José M. , Figueira Juan Carlos , Asensio María José , Maseda Emilio , Suárez-Sipmann Fernando , Ramasco Fernando , Varela-Durán Marina , Díaz-Parada Pilar , Trenado-Álvarez Josep , Fernández María M. , Aldecoa César , Rico-Feijoo Jesús , Fernández Lorena , Sánchez-Ballesteros Jesús , Blanco-Schweizer Pablo , Martínez Domingo , Soler Juan A. , Slutsky Arthur S. , Jüni Peter , Thorpe Kevin E. , Thomas Rekha , Wysocki Kosma , de Verno Pamela , Lakhanpal Gurpreet , Juando-Prats Clara 
Published: August 2020

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 PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 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.

Discussion
This study will assess the role of dexamethasone in patients with established moderate-to-severe ARDS caused by SARS-CoV-2.

Trial registration
ClinicalTrials.gov NCT04325061. Registered on 25 March 2020 as DEXA-COVID19.