tetano
Editor, Senior Moderator
JAMA
. 2020 Sep 2.
doi: 10.1001/jama.2020.17021. Online ahead of print.
Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial
Bruno M Tomazini[SUP] 1 2 [/SUP], Israel S Maia[SUP] 3 4 [/SUP], Alexandre B Cavalcanti[SUP] 3 4 [/SUP], Otavio Berwanger[SUP] 5 [/SUP], Regis G Rosa[SUP] 4 6 [/SUP], Viviane C Veiga[SUP] 4 7 [/SUP], Alvaro Avezum[SUP] 8 [/SUP], Renato D Lopes[SUP] 9 10 [/SUP], Flavia R Bueno[SUP] 1 [/SUP], Maria Vitoria A O Silva[SUP] 1 [/SUP], Franca P Baldassare[SUP] 1 [/SUP], Eduardo L V Costa[SUP] 1 11 [/SUP], Ricardo A B Moura[SUP] 1 [/SUP], Michele O Honorato[SUP] 1 [/SUP], Andre N Costa[SUP] 1 12 [/SUP], Lucas P Damiani[SUP] 3 [/SUP], Thiago Lisboa[SUP] 3 4 13 [/SUP], Let?cia Kawano-Dourado[SUP] 3 [/SUP], Fernando G Zampieri[SUP] 3 4 [/SUP], Guilherme B Olivato[SUP] 5 14 [/SUP], Cassia Righy[SUP] 15 16 [/SUP], Cristina P Amendola[SUP] 17 [/SUP], Roberta M L Roepke[SUP] 2 18 [/SUP], Daniela H M Freitas[SUP] 11 [/SUP], Daniel N Forte[SUP] 1 19 [/SUP], Fl?vio G R Freitas[SUP] 4 20 [/SUP], Caio C F Fernandes[SUP] 21 [/SUP], Livia M G Melro[SUP] 22 [/SUP], Gedealvares F S Junior[SUP] 23 [/SUP], Douglas Costa Morais[SUP] 24 [/SUP], Stevin Zung[SUP] 24 [/SUP], Fl?via R Machado[SUP] 4 20 [/SUP], Luciano C P Azevedo[SUP] 1 4 25 [/SUP], COALITION COVID-19 Brazil III Investigators
Affiliations
Abstract
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) over 28 days.
Trial registration: ClinicalTrials.gov Identifier: NCT04327401.
. 2020 Sep 2.
doi: 10.1001/jama.2020.17021. Online ahead of print.
Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial
Bruno M Tomazini[SUP] 1 2 [/SUP], Israel S Maia[SUP] 3 4 [/SUP], Alexandre B Cavalcanti[SUP] 3 4 [/SUP], Otavio Berwanger[SUP] 5 [/SUP], Regis G Rosa[SUP] 4 6 [/SUP], Viviane C Veiga[SUP] 4 7 [/SUP], Alvaro Avezum[SUP] 8 [/SUP], Renato D Lopes[SUP] 9 10 [/SUP], Flavia R Bueno[SUP] 1 [/SUP], Maria Vitoria A O Silva[SUP] 1 [/SUP], Franca P Baldassare[SUP] 1 [/SUP], Eduardo L V Costa[SUP] 1 11 [/SUP], Ricardo A B Moura[SUP] 1 [/SUP], Michele O Honorato[SUP] 1 [/SUP], Andre N Costa[SUP] 1 12 [/SUP], Lucas P Damiani[SUP] 3 [/SUP], Thiago Lisboa[SUP] 3 4 13 [/SUP], Let?cia Kawano-Dourado[SUP] 3 [/SUP], Fernando G Zampieri[SUP] 3 4 [/SUP], Guilherme B Olivato[SUP] 5 14 [/SUP], Cassia Righy[SUP] 15 16 [/SUP], Cristina P Amendola[SUP] 17 [/SUP], Roberta M L Roepke[SUP] 2 18 [/SUP], Daniela H M Freitas[SUP] 11 [/SUP], Daniel N Forte[SUP] 1 19 [/SUP], Fl?vio G R Freitas[SUP] 4 20 [/SUP], Caio C F Fernandes[SUP] 21 [/SUP], Livia M G Melro[SUP] 22 [/SUP], Gedealvares F S Junior[SUP] 23 [/SUP], Douglas Costa Morais[SUP] 24 [/SUP], Stevin Zung[SUP] 24 [/SUP], Fl?via R Machado[SUP] 4 20 [/SUP], Luciano C P Azevedo[SUP] 1 4 25 [/SUP], COALITION COVID-19 Brazil III Investigators
Affiliations
- PMID: 32876695
- DOI: 10.1001/jama.2020.17021
Abstract
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) over 28 days.
Trial registration: ClinicalTrials.gov Identifier: NCT04327401.