COVID-19-associated ARDS treated with DEXamethasone (CoDEX): Study design and rationale for a randomized trial

  1. Bruno M. Tomazini
  2. Israel S. Maia
  3. Flavia R. Bueno
  4. Maria Vitoria A.O. Silva
  5. Franca Pellison Baldassare
  6. Eduardo Leite V. Costa
  7. Ricardo A.B. Moura
  8. Michele Honorato
  9. André N. Costa
  10. Alexandre B. Cavalcanti
  11. Regis Rosa
  12. Álvaro Avezum
  13. Viviane C. Veiga
  14. Renato D. Lopes
  15. Lucas P. Damiani
  16. Flávia R. Machado
  17. Otavio Berwanger
  18. Luciano C.P. Azevedo
  19. for the COALITION COVID-19 Brazil III Investigators

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

OBJECTIVES

The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV2 infection (Coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop Acute Respiratory Distress Syndrome (ARDS). Several clinical trials evaluated the role of corticosteroids in non-COVID-19 ARDS with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe ARDS due to confirmed or probable COVID-19.

METHODS

This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48h before randomization) moderate or severe ARDS, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (intervention group) or standard treatment without dexamethasone (control group). Patients in the intervention group will receive dexamethasone 20mg IV once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until Intensive Care Unit (ICU) discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment (SOFA) Score evaluation at 48h, 72h and 7 days and ICU-free days within 28.

ETHICS AND DISSEMINATION

This trial was approved by the Brazilian National Committee of Ethics in Research (Comissão Nacional de Ética em Pesquisa - CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete.

ClinicalTrials.gov identifier

NCT04327401

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.24.20139303: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical considerations and dissemination: The trial was designed according to the guidelines for good clinical practice and followed the principles of the Declaration of Helsinki and was approved by the Brazilian National Committee of Ethics in Research (Comissão Nacional de Ética em Pesquisa - CONEP).
    Consent: Also, we expect that virtually none of the patients will be able to give consent due to their clinical condition.
    RandomizationStudy design: The COVID-19-associated ARDS treated with DEXamethasone: CoDEX is a pragmatic, prospective, randomized, stratified, multicenter, open-label, superiority, controlled trial including 350 patients with moderate or severe ARDS due to confirmed or probable COVID-19 in 51 Intensive Care Units in Brazil.
    BlindingEach patient must fulfil all the following inclusion criteria to be eligible for enrolment: Exclusion criteria are: Study Protocol: Blinding: This is an open-label trial where the investigators, caregivers and patients are not blinded regarding the intervention.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We acknowledge our trial has some limitations. It is an open-label trial, which can interfere in the use of other immunomodulatory therapies such as the use of convalescent plasma, tocilizumab or hydroxychloroquine, especially in the control group. However, we choose an objective primary outcome with clear definitions, which reduces the influence of the open label nature in the outcome assessment. If we confirm our hypothesis of benefit of using dexamethasone in ARDS due to SARS-CoV2 infection, the consequences for public health will be enormous, especially considering the COVID-19 pandemic. Given the unprecedented impact in global health and the lack of ICU beds in most countries during the pandemic, an increase in days alive and free of mechanical ventilation should help unburden the health care systems worldwide and will represent a noteworthy improvement in ARDS treatment.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04327401TerminatedCOVID-19-associated ARDS Treated With Dexamethasone: Allianc…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.06.24.20139303v1 on medRxiv
  3. Version published to 10.5935/0103-507x.20200063