[Source: JAMA, full page: (LINK). Abstract, edited.]
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, MD1,2; Israel S. Maia, MD, MSc3,4; Alexandre B. Cavalcanti, MD, PhD3,4; Otavio Berwanger, MD, PhD5; Regis G. Rosa, MD, PhD4,6; Viviane C. Veiga, MD, PhD4,7; Alvaro Avezum, MD, PhD8; Renato D. Lopes, MD, PhD9,10; Flavia R. Bueno, MSc1; Maria Vitoria A. O. Silva1; Franca P. Baldassare1; Eduardo L. V. Costa, MD, PhD1,11; Ricardo A. B. Moura, MD1; Michele O. Honorato, MD1; Andre N. Costa, MD, PhD1,12; Lucas P. Damiani, MSc3; Thiago Lisboa, MD, PhD3,4,13; Letícia Kawano-Dourado, MD, PhD3; Fernando G. Zampieri, MD, PhD3,4; Guilherme B. Olivato, MD5,14; Cassia Righy, MD, PhD15,16; Cristina P. Amendola, MD17; Roberta M. L. Roepke, MD2,18; Daniela H. M. Freitas, MD11; Daniel N. Forte, MD, PhD1,19; Flávio G. R. Freitas, MD, PhD4,20; Caio C. F. Fernandes, MD21; Livia M. G. Melro, MD22; Gedealvares F. S. Junior, MD23; Douglas Costa Morais24; Stevin Zung, MD, PhD24; Flávia R. Machado, MD, PhD4,20; Luciano C. P. Azevedo, MD, PhD1,4,25; for the COALITION COVID-19 Brazil III Investigators
Author Affiliations: 1 Hospital Sírio-Libanês, São Paulo, Brazil; 2 Departamento de Cirurgia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 3 HCor Research Institute, São Paulo, Brazil; 4 Brazilian Research in Intensive Care Network (BRICNet), São Paulo, Brazil; 5 Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil; 6 Hospital Moinhos de Vento, Porto Alegre, Brazil; 7 BP–A Beneficência Portuguesa de São Paulo, São Paulo, Brazil; 8 International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil; 9 Brazilian Clinical Research Institute, São Paulo, Brazil; 10 Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina; 11 UTI Respiratória, Instituto do Coração (Incor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 12 Departamento de Cardiopneumologia, Instituto do Coração (Incor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 13 Hospital de Clinicas de Porto Alegre, Rio Grande do Sul, Brazil; 14 Hospital Vila Santa Catarina, São Paulo, Brazil; 15 Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil; 16 Laboratorio de Medicina Intensiva, Instituto Nacional de Infectologia, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 17 Barretos Cancer Hospital, Barretos, Brazil; 18 Intensive Care Unit, AC Camargo Cancer Center, São Paulo, Brazil; 19 UTI 09DN, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 20 Anesthesiology, Pain, and Intensive Care Department, Federal University of São Paulo, São Paulo, Brazil; 21 Hospital Mario Covas, FMABC, Santo Andre, Brazil; 22 Hospital Samaritano Paulista, São Paulo, Brazil; 23 Hospital Evangélico de Vila Velha, Vila Velha, Brazil; 24 Aché Laboratórios Farmacêuticos, São Paulo, Brazil; 25 Disciplina de Emergências Clínicas, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17021
Key Points
- Question – In patients with coronavirus disease 2019 (COVID-19) and moderate or severe acute respiratory distress syndrome (ARDS), does intravenous dexamethasone plus standard care compared with standard care alone increase the number of days alive and free from mechanical ventilation?
- Findings – In this randomized clinical trial that included 299 patients, the number of days alive and free from mechanical ventilation during the first 28 days was significantly higher among patients treated with dexamethasone plus standard care when compared with standard care alone (6.6 days vs 4.0 days).
- Meaning – Intravenous dexamethasone plus standard care, compared with standard of care alone, resulted in a statistically significant increase in the number of days alive and free of mechanical ventilation over 28 days.
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
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Keywords: SARS-CoV-2; COVID-19; Intensive Care; ARDS; Corticosteroids.
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