COVID-19-associated ARDS Treated With Dexamethasone: Alliance Covid-19 Brasil III

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract, and its outbreak deemed a pandemic in early March 2020. Estimates show around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which due to its severity, consumes most Intensive Care Units (ICU) resources and is the leading mortality cause in this population. Given its burden, therapies that reduce the duration of mechanical ventilation or decrease the morbimortality are needed. Studies indicate that inflammation and cytokine storm might be involved in the pathophysiological pathway to ARDS in these patients. Corticosteroids have been tested in deferent scenarios of ARDS, including viral pneumonia, and the early use of dexamethasone is safe and appears to reduce the duration of mechanical ventilation in ARDS patients. A recent small retrospective study evaluating the role of corticosteroids found no association between corticosteroids and hospital length of stay, virus clearance, and symptoms' duration. However, the retrospective nature of data, small sample size (31 patients), and no protocol for corticosteroids administration undermine its results. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in ventilator-free days at 28 days in patients with moderate and severe ARDS due to SARS-CoV2 virus in Brazil.

• Dexamethasone (Drug), also known as Decadron, Dexasone, Diodex, Hexadrol, Maxidex: Dexamethasone administration for 10 consecutive days after randomization.

Primary outcomes

• Ventilator-free days [28 days after randomization]: Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.

Secondary outcomes

• Evaluation of the clinical status [15 days after randomization]: Evaluation of the clinical status of patients on the 15th day after randomization defined by the 6-point Ordinal Scale, this scale ranges from 1 (Not hospitalized) to 6 (Death) with higher scores meaning worse outcomes.
• All-cause mortality [28 days after randomization]: All-cause mortality rates at 28 days after randomization.
• Mechanical ventilation duration [28 days after randomization]: Number of days of mechanical ventilation from randomization to day 28.
• Sequential Organ Failure Assessment (SOFA) Score [Score at 48 hours, 72 hours and 7 days after randomization]: Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization

Other outcomes

• Intensive Care Unit free days [28 days after randomization]: Intensive Care Unit free days, defined as alive and discharged from the intensive care unit, at 28 days after randomization.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Probable or confirmed infection by SARS-CoV2
* Intubated and mechanically ventilated
* Moderate/severe ARDS defined by the Berlin criteria (PaO2/FiO2 ≤200mmHg with PEEP ≥5cmH20)
* Onset of moderate/severe ARDS in less than 48 hours before randomization

Exclusion Criteria:

* Pregnancy or active lactation
* Known history of dexamethasone allergy
* Daily use of corticosteroids in the past 15 days
* Clinical indication for corticosteroids use for other diseases (i.e refractory septic shock)
* Patients who did use corticosteroids during hospital stay for periods equal or greater than two days
* Use of immunosuppressive drugs
* Cytotoxic chemotherapy in the past 21 days
* Neutropenia due to hematological or solid malignancies with bone marrow invasion
* Patient expected to die in the next 24 hours

• Results publication: Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, Avezum A, Lopes RD, Bueno FR, Silva MVAO, Baldassare FP, Costa ELV, Moura RAB, Honorato MO, Costa AN, Damiani LP, Lisboa T, Kawano-Dourado L, Zampieri FG, Olivato GB, Righy C, Amendola CP, Roepke RML, Freitas DHM, Forte DN, Freitas FGR, Fernandes CCF, Melro LMG, Junior GFS, Morais DC, Zung S, Machado FR, Azevedo LCP; COALITION COVID-19 Brazil III Investigators. 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 Oct 6;324(13):1307-1316. doi: 10.1001/jama.2020.17021. PMID 32876695

• Study Protocol and Statistical Analysis Plan (PDF, 2020-06-10)

• Luciano Cesar Pontes Azevedo, Ph.D, Principal investigator, Teaching Director of Teaching & Research Institute Sírio-Libanês Hospital