JAMA · 2020
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.
СтатьяМногоцентровое исследованиеРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tomazini Bruno M, Maia Israel S, Cavalcanti Alexandre B, Berwanger Otavio, Rosa Regis G, Veiga Viviane C, Avezum Alvaro, Lopes Renato D, Bueno Flavia R, Silva Maria Vitoria A O, Baldassare Franca P, Costa Eduardo L V, Moura Ricardo A B, Honorato Michele O, Costa Andre N, Damiani Lucas P, Lisboa Thiago, Kawano-Dourado Letícia, Zampieri Fernando G, Olivato Guilherme B, Righy Cassia, Amendola Cristina P, Roepke Roberta M L, Freitas Daniela H M, Forte Daniel N, Freitas Flávio G R, Fernandes Caio C F, Melro Livia M G, Junior Gedealvares F S, Morais Douglas Costa, Zung Stevin, Machado Flávia R, Azevedo Luciano C P, COALITION COVID-19 Brazil III Investigators
Аннотация
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.
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.
Предметные рубрики MeSH
Administration, IntravenousAgedAnti-Inflammatory AgentsBetacoronavirusBrazilCOVID-19Catheter-Related InfectionsCoronavirus InfectionsDexamethasoneEarly Termination of Clinical TrialsFemaleHumansMaleMiddle AgedPandemicsPneumonia, ViralRespiration, ArtificialRespiratory Distress SyndromeSARS-CoV-2COVID-19 Drug Treatment