Bruno M.\u00a0Tomazini,\u00a0Israel S.\u00a0Maia,\u00a0Alexandre B.\u00a0Cavalcanti, et al<\/h3>\n\n\n\nJAMA.\u00a0<\/em>Published online September 2, 2020. doi:10.1001\/jama.2020.17021<\/h3>\n\n\n\nAbstract<\/h2>\n\n\n\nImportance<\/strong><\/h3>\n\n\n\nAcute 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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19\u2013associated ARDS.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nMulticenter, 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nTwenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n\u2009=151) or standard care alone (n\u2009=\u2009148).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe 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.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nA 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;\u00a0P<\/em>\u2009=\u2009.04). 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, \u22121.16; 95% CI, \u22121.94 to \u22120.38;\u00a0P<\/em>\u00a0= .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.<\/p>\n\n\n\n![\"\"\/](\"https:\/\/cdn.jamanetwork.com\/ama\/content_public\/journal\/jama\/0\/joi200102va_1599056045.95862.png?Expires=2147483647&Signature=G2E4P0cZ5Bfcz7PuJmrf4zascPn9AEjMjGu-f6rvvzJl3x7DaJ5rC91-t9PVYKfZFW~F4XP3PZzahZPH48HFkJCzH24H2kK55af-t9uqYfa6~ogZnfT6VJPqS99bkfI0XTsD9d0rYx19-Hc2y9u-dOBxEac2BD2R4A~eUjSvDts8plCPDKDR5jZQCTCxge6TawF3lCZgGtWn5NsdtDbpjMoSm1keMqnpS-cHUcyvsf-vlN4qkLjJv3wgUWkyHk0-oHLCyASKdLtncvc9KYtV~mlItlhnQjPjoVu~Lh6FccobOH2SY8GtKlmFMMnLwfjkV8oW5yn2nPDWmXQPkUZGAg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA\")
<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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) over 28 days.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
Abstract<\/h2>\n\n\n\nImportance<\/strong><\/h3>\n\n\n\nAcute 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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19\u2013associated ARDS.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nMulticenter, 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nTwenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n\u2009=151) or standard care alone (n\u2009=\u2009148).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe 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.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nA 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;\u00a0P<\/em>\u2009=\u2009.04). 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, \u22121.16; 95% CI, \u22121.94 to \u22120.38;\u00a0P<\/em>\u00a0= .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.<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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) over 28 days.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19\u2013associated ARDS.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nMulticenter, 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nTwenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n\u2009=151) or standard care alone (n\u2009=\u2009148).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe 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.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nA 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;\u00a0P<\/em>\u2009=\u2009.04). 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, \u22121.16; 95% CI, \u22121.94 to \u22120.38;\u00a0P<\/em>\u00a0= .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.<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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) over 28 days.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nTwenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n\u2009=151) or standard care alone (n\u2009=\u2009148).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe 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.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nA 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;\u00a0P<\/em>\u2009=\u2009.04). 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, \u22121.16; 95% CI, \u22121.94 to \u22120.38;\u00a0P<\/em>\u00a0= .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.<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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) over 28 days.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
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.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nA 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;\u00a0P<\/em>\u2009=\u2009.04). 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, \u22121.16; 95% CI, \u22121.94 to \u22120.38;\u00a0P<\/em>\u00a0= .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.<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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) over 28 days.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
<\/figure>\n\n\n\n