Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19
MD Bruno M Tomazini, MD, MSc Israel S Maia, MD Alexandre B Cavalcanti, PhD Otavio Berwanger, PhD Regis G Rosa, PhD Viviane C Veiga, PhD Alvaro Avezum, MD, PhD Renato D Lopes, MD, PhD Flavia R Bueno, Maria Vitoria A O Silva, Franca P Baldassare, MD, PhD Eduardo L V Costa, MD Ricardo A B Moura, MD Michele O Honorato, MD Andre N Costa, PhD Lucas P Damiani, MSc Thiago Lisboa, PhD Letícia Kawano-Dourado, PhD Fernando G Zampieri, PhD Guilherme B Olivato, MD Cassia Righy, MD, PhD Cristina P Amendola, MD Roberta M L Roepke, MD Daniela H M Freitas, MD Daniel N Forte, Flávio G R Freitas, Caio C F Fernandes, MD; Gedealvares Livia M G Melro, Gedealvares F S Junior, Douglas Costa Morais, MD Stevin Zung, PhD Flávia R Machado, PhD Luciano C P Azevedo
JAMA, doi:10.1001/jama.2020.17021
Brazil III Investigators IMPORTANCE Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. OBJECTIVE To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. INTERVENTIONS Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148).
MAIN OUTCOMES AND MEASURES The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. RESULTS A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation)..
Author Contributions: Drs Tomazini and Azevedo had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Damiani conducted and is responsible for the data analysis.
Concept and design:
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