COVID-19 Dexamethasone - CoDEX

Sep 08, 2020
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Coalition COVID-19 Brazil
Date Published:
09/02/2020
Date Updated:
09/08/2020
Original Posted Date:
09/08/2020
References

Contribution To Literature:

The CoDEX trial showed that dexamethasone on top of standard care is superior to standard care alone among patients with moderate to severe ARDS secondary to COVID-19.

Description:

The goal of the trial was to assess the safety and efficacy of dexamethasone on top of standard care for patients with moderate to severe acute respiratory distress syndrome (ARDS) on mechanical ventilation secondary to coronavirus disease 2019 (COVID-19).

Study Design

Patients were randomized in a 1:1 fashion to either dexamethasone + standard care (n = 151) or standard care alone (n = 148). Dexamethasone was given as 20 mg intravenously once daily for 5 days, followed by 10 mg intravenously once daily for an additional 5 days or until intensive care unit (ICU) discharge, whichever occurred first. This was an open-label trial.

  • Total number of enrollees: 299
  • Duration of follow-up: 28 days
  • Mean patient age: 61 years
  • Percentage female: 38%

Inclusion criteria:

  • Age ≥18 years
  • Confirmed or suspected COVID-19 infection
  • Receiving mechanical ventilation within 48 hours of meeting criteria for moderate to severe ARDS with partial pressure of arterial blood oxygen to fraction of inspired oxygen (Pao<sub>2</sub>:FIo<sub>2</sub>) ratio of 200 or less

Exclusion criteria:

  • Pregnancy or active lactation
  • Known history of dexamethasone allergy
  • Corticosteroid use in the past 15 days for nonhospitalized patient
  • Use of corticosteroids during the present hospital stay for >1 day
  • Indication for corticosteroid use for other clinical conditions (e.g., refractory septic shock)
  • Use of immunosuppressive drugs
  • Cytotoxic chemotherapy in the past 21 days
  • Neutropenia due to hematological or solid malignancies with bone marrow invasion
  • Consent refusal
  • Expected death in the next 24 hours

Other salient features/characteristics:

  • Time since symptom onset: 9.5 days; time on mechanical ventilation: 1 day

Principal Findings:

The primary outcome, days alive and ventilator free at 28 days, for dexamethasone + standard care vs. standard care, was 6.6 vs. 4.0 days (p = 0.02).

Secondary outcomes for dexamethasone + standard care vs. standard care:

  • All-cause mortality: 56.3% vs. 61.5% (p = 0.31)
  • Duration of mechanical ventilation: 12.5 vs. 13.9 days (p = 0.18)
  • Ventilator-associated pneumonia: 12.6% vs. 19.6% (p > 0.05)
  • Insulin use for hyperglycemia: 31.1% vs. 28.4% (p > 0.05)

Interpretation:

The results of this trial indicate that dexamethasone on top of standard care is superior to standard care alone among patients with moderate to severe ARDS secondary to COVID-19. The primary outcome of days alive and ventilator free at 28 days was reduced, although overall mortality was similar between the two arms. RECOVERY was a much larger trial that showed a mortality benefit with dexamethasone. Both trials suggest a salutary effect of dexamethasone on mechanically ventilated patients with COVID-19.

References:

Tomazini BM, Maia IS, Cavalcanti AB, et al. 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. JAMA 2020;Sep 2:[Epub ahead of print].

Editorial: Prescott HC, Rice TW. Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic. JAMA 2020;Sep 2:[Epub ahead of print].

Clinical Topics: COVID-19 Hub, Prevention

Keywords: Coronavirus, Coronavirus Infections, COVID-19, Dexamethasone, Hyperglycemia, Pneumonia, Ventilator-Associated, Primary Prevention, Respiration, Artificial, Respiratory Distress Syndrome, severe acute respiratory syndrome coronavirus 2, Ventilators, Mechanical


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