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

Anabel Franco-Moreno, María Soledad Acedo-Gutiérrez, Nicolás Labrador-San Martín, Clara Hernández-Blanco, Celia Rodríguez-Olleros, Fátima Ibáñez-Estéllez, Ana Suárez-Simón, Mateo Balado-Rico, Ana Rocío Romero-Paternina, David Alonso-Menchén, Belén Escolano-Fernández, Esther Piniella-Ruiz, Ester Alonso-Monge, Helena Notario-Leo, Carlos Bibiano-Guillén, Gabriela Peña-Lillo, Armando Antiqueira-Pérez, Rodolfo Romero-Pareja, Noemí Cabello-Clotet, Vicente Estrada-Pérez, Jesús Troya-García, María de Carranza-López, Ismael Escobar-Rodríguez, Nacho Vallejo-Maroto, Juan Torres-Macho, Anabel Franco-Moreno, María Soledad Acedo-Gutiérrez, Nicolás Labrador-San Martín, Clara Hernández-Blanco, Celia Rodríguez-Olleros, Fátima Ibáñez-Estéllez, Ana Suárez-Simón, Mateo Balado-Rico, Ana Rocío Romero-Paternina, David Alonso-Menchén, Belén Escolano-Fernández, Esther Piniella-Ruiz, Ester Alonso-Monge, Helena Notario-Leo, Carlos Bibiano-Guillén, Gabriela Peña-Lillo, Armando Antiqueira-Pérez, Rodolfo Romero-Pareja, Noemí Cabello-Clotet, Vicente Estrada-Pérez, Jesús Troya-García, María de Carranza-López, Ismael Escobar-Rodríguez, Nacho Vallejo-Maroto, Juan Torres-Macho

Abstract

Background: Corticosteroids 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. 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/design: This 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 the development of ARDS. Risk for the development of 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 a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment.

Discussion: If our hypothesis is correct, the results of this study will provide additional insights into 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 registration: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Keywords: Adult respiratory distress syndrome; COVID-19 pneumonia; Corticosteroids; Dexamethasone; Inflammatory biological markers; Laboratory markers; Mortality; Randomized controlled trial.

Conflict of interest statement

This study is funded by the pharmaceutical laboratory Kern Pharma, S.L. Dexamethasone will be provided free of charge for this study by Kern Pharma, S.L. The funding body had no input into the study design or in the writing of the manuscript.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design diagram

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Source: PubMed

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