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

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

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.

Keywords: Acute respiratory distress syndrome; Acute respiratory failure; COVID-19; Coronavirus disease 19; Corticosteroids; Dexamethasone; Lung protective ventilation.

Conflict of interest statement

The authors declare that they have no competing interests in relation to this manuscript.

Figures

Fig. 1
Fig. 1
Study design diagram
Fig. 2
Fig. 2
Schedule of events. *Data will be collected if patients are still in the Intensive Care Unit. MV, mechanical ventilation; SOFA, Sequential Organ Failure Assessment score

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