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
Open accessAbstract
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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Randomized trials showed dexamethasone lowered 28-day death rates, especially in severe cases.
“Indeed, dexamethasone was shown to be beneficial, particularly in patients with severe disease courses where it reduced 28-day mortality in randomized clinical trials (RECOVERY Collaborative Group et al., 2021; Tomazini et al., 2020; WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al., 2020).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Tomazini et al., 2020
Examining interim outcome data can bias trial results and interpretation and introduce analytical and ethical challenges when interim analyses are not prespecified or lead to early study termination.
“Examining interim outcome data can bias trial results and interpretation and introduce analytical and ethical challenges when interim analyses are not prespecified or lead to early study termination.”
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- Authors
- Tomazini, B. M., Maia, I. S., Cavalcanti, A. B., Berwanger, O., Rosa, R. G., Veiga, V. C., Avezum, A., Lopes, R. D., Bueno, F. R., Silva, M. V. A. O., Baldassare, F. P., Costa, E. L. V., Moura, R. A. B., Honorato, M. O., Costa, A. N., Damiani, L. P., Lisboa, T., Kawano-Dourado, L., Zampieri, F. G., Olivato, G. B., Righy, C., Amendola, C. P., Roepke, R. M. L., Freitas, D. H. M., Forte, D. N., Freitas, F. G. R., Fernandes, C. C. F., Melro, L. M. G., Junior, G. F. S., Morais, D. C., Zung, S., Machado, F. R., Azevedo, L. C. P., & COALITION COVID-19 Brazil III Investigators
- Affiliations
- Universidade de São Paulo (BR)
- Brazilian Research in Intensive Care Network (BR)
- Hospital Israelita Albert Einstein (BR)
- Brazilian Research in Intensive Care Network (BRICNet), São Paulo, Brazil
- International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
- Brazilian Clinical Research Institute, São Paulo, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
- Hospital Sírio-Libanês (BR)
- HCor Research Institute, São Paulo, Brazil
- Hospital de Clínicas de Porto Alegre (BR)
- Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
- Barretos Cancer Hospital, Barretos, Brazil
- Hospital Estadual Mário Covas (BR)
- Hospital Samaritano Paulista, São Paulo, Brazil
- Hospital Evangélico de Vila Velha, Vila Velha, Brazil
- Aché (Brazil) (BR)
- Corresponding author
- Azevedo, Luciano C. P.
- ORCID
- Tomazini, Bruno M.
- Maia, Israel S.
- Cavalcanti, Alexandre B.
- Berwanger, Otavio
- Veiga, Viviane C.
- Costa, Eduardo L. V.
- Honorato, Michele O.
- Damiani, Lucas P.
- Lisboa, Thiago
- Zampieri, Fernando G.
- Olivato, Guilherme B.
- Roepke, Roberta M. L.
- Freitas, Daniela H. M.
- Forte, Daniel N.
- Freitas, Flávio G. R.
- Fernandes, Caio C. F.
- Morais, Douglas Costa
- Zung, Stevin
- Azevedo, Luciano C. P.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-10-06
- Volume
- 324
- Issue
- 13
- Pages
- 1307
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7489411
- OpenAlex
- W3082108964
- Cited by
- 1,241
- References
- 34
- Citations by year
- 2026: 25 · 2025: 64 · 2024: 121 · 2023: 171 · 2022: 289 · 2021: 476 · 2020: 94
- FWCI
- 145.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Faculdade de Medicina do ABC
- Faculdade de Medicina da Universidade de São Paulo
- Sociedade Beneficente Israelita Brasileira Albert Einstein
- Universidade Estadual Paulista
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Keywords
- dexamethasone, acute respiratory distress syndrome, COVID-19 pandemic, ventilator-free days, mechanical ventilation, corticosteroid therapy, 28-day mortality, SOFA score, organ dysfunction, intensive care unit, early trial termination, lung injury, COVID-19 pneumonia, corticosteroid dose comparison, ICU-free days, mechanical ventilation duration
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Aged, Anti-Inflammatory Agents, Brazil, Dexamethasone, Female, Humans, Male, Middle Aged, Pneumonia, Viral, Respiration, Artificial, Respiratory Distress Syndrome, Coronavirus Infections, Catheter-Related Infections, Early Termination of Clinical Trials, Pandemics, Administration, Intravenous
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