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

Study Overview
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Brief Summary
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The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Most cases are mild or asymptomatic. However, around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which is the leading mortality cause 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. Nevertheless, no large, randomized, controlled trial was performed evaluating the role of corticosteroids in patients with ARDS due SARS-CoV2 virus. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in patients with moderate and severe ARDS due to SARS-CoV2 virus.

Detailed Description
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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.

Official Title
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COVID-19-associated ARDS Treated With DEXamethasone: an Open-label, Randomized, Controlled Trial: CoDEX (Alliance Covid-19 Brasil III)

Conditions
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Coronavirus Infection, Pneumonia, Viral, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Dexamethasone. After randomization, dexamethasone 20mg IV 1x/day for 5 days, followed by 10mg IV 1xd for 5 days + standard treatment (according to the treatment protocol for 2019-nCoV infection). Standard treatment (according to the treatment protocol for 2019-nCoV infection).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Dexamethasone. After randomization, dexamethasone [20mg IV 1x/day for 5 days, followed by 10mg IV 1xd for 5 days] + standard treatment (according to the treatment protocol for 2019-nCoV infection). | Drug: Dexamethasone<br>* Dexamethasone administration for 10 consecutive days after randomization.<br>* Other names: Maxidex;|
| No Intervention: Control<br>Standard treatment (according to the treatment protocol for 2019-nCoV infection). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days | Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization. | 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the clinical status | 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. | 15 days after randomization | 
| All-cause mortality | All-cause mortality rates at 28 days after randomization. | 28 days after randomization | 
| Mechanical ventilation duration | Number of days of mechanical ventilation from randomization to day 28. | 28 days after randomization | 
| Sequential Organ Failure Assessment (SOFA) Score | Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization | Score at 48 hours, 72 hours and 7 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV2 virus, 2019-nCOV, Dexamethasone, ARDS, Corticosteroids, Respiratory failure