Acute Respiratory Distress Syndrome, Coronavirus Infection, Pneumonia, Viral
Conditions
Keywords
SARS-CoV2 virus, 2019-nCOV, Dexamethasone, ARDS, Corticosteroids, Respiratory failure
Brief summary
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
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.
Interventions
DRUGDexamethasone
Dexamethasone administration for 10 consecutive days after randomization.
Sponsors
Ache Laboratorios Farmaceuticos S.A.
Hospital Israelita Albert Einstein
Hospital do Coracao
Brazilian Research In Intensive Care Network
Hospital Sirio-Libanes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
1. 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). 2. Standard treatment (according to the treatment protocol for 2019-nCoV infection).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free days | 28 days after randomization | Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Brazil
Outcome results
None listed