Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19

Study Overview
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Brief Summary
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After RECOVERY trial publication, low dose (6 mg dexamethasone for 10 days) was recommended as the usual care treatment in hospitalized patients with respiratory failure by COVID-19 needing oxygen therapy. RECOVERY trial showed how the use of dexamethasone 6 mg / day for ten days compared to standard treatment without the use of corticosteroids in hospitalized patients reduced mortality at 28 days (22.9% with dexamethasone vs 25.7% without dexamethasone). In the dexamethasone group, the incidence of mortality was lower than standard treatment in patients with hypoxia and the need for mechanical ventilation (29.3% with dexamethasone vs 41.4% without dexamethasone), in patients admitted to the hospital ward with a need for oxygen therapy (23.3% with dexamethasone vs 26.2% without dexamethasone), but they did not find differences between those admitted patients who did not need oxygen therapy. There are two other studies (DEXA-COVID-19 and CoDEX) where they observed benefits of the use of dexamethasone 20 mg / day 5 days, and 10 mg / day 5 days (total 10 days) in patients admitted for respiratory distress syndrome (ARDS) and COVID-19. At present, it is unclear what dose of dexamethasone is most beneficial in patients with COVID-19 and respiratory failure.

Detailed Description
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Objective: The investigators aim to assess the efficacy of high dose of dexamethasone (20 mg / day 5 days, and 10 mg/day 5 days) versus low dose of dexamethasone (6 mg/day 10 days) in patients with respiratory failure by COVID-19.

Official Title
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Efficacy of Low or High Dose of Dexamethasone in Patients With Respiratory Failure by COVID-19

Conditions
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Covid19, Corticosteroids

Intervention / Treatment
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* Drug: Dexamethasone high dose
* Drug: Dexamethasone low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Hospitalized COVID-19 patients admitted to the Hospital. Patients requiring supplemental oxygen. Level 4 using the World Health Organization 7-point Ordinal Scale for clinical improvement Patients requiring corticosteroids (dexamethasone) according to Hospital protocol. Exclusion Criteria: Pregnancy or active lactation. Patient is expected to die in the next 48 hours. Known history of dexamethasone allergy or known contraindication to the use of corticosteroids. Daily use of corticosteroids in the past 15 days. Indication for corticosteroids use for other clinical conditions (e.g. refractory septic shock). Consent refusal for participating in the trial. Different level of 4 in Level 4 using the World Health Organization 7-point Ordinal Scale for clinical improvement.

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: Randomized, controlled, open-label trial involving hospitalized adult patients with respiratory failure needing oxygen therapy, caused by COVID-19.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose group<br>Dexamethasone 6mg/day for 10 days | Drug: Dexamethasone low dose<br>* Low doses: dexamethasone 6 mg/day 10 days.<br>|
| Active Comparator: High dose group<br>Dexamethasone 20mg/day for 5 days + Dexamethasone 10mg/day for 5 days (Total 10 days) | Drug: Dexamethasone high dose<br>* High doses: dexamethasone 20 mg/day 5 days + 10 mg/day 5 days (total 10 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with treatment failure at day 11 | defined as death, need of ICU and extracorporeal membrane oxygenation, need of non-invasive ventilation or nasal high-flow oxygen therapy, or worsening of the condition clinic of the patient during treatment (two of these: need to increase Fraction of inspired oxygen inspired>20%, need for fraction inspired oxygenation>50%, increase in respiratory rate>25, increase in inflammatory markers). | Day 11 after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients without the need for oxygen support at day 11. |  | Day 11 after randomization | 
| 28-days mortality |  | 28 days after randomization | 
| 90-days mortality |  | 90 days after randomization | 
| Clinical status of patients using the World Health Organization 7-point Ordinal Scale for clinical improvement during 10 days of treatment | 1:Not hospitalized, 2:Hospitalized and not treatment, 3: Hospitalized with treatment, not requiring supplemental oxygen, 4:Hospitalized requiring supplemental oxygen, 5:Hospitalized, requiring non-invasive ventilation or nasal high-flow oxygen therapy, 6: Hospitalized requiring invasive ventilation or Extracorporeal (ECMO) | 10 days after randomization | 
| Percentage of patients needing Intensive Care Unit admission |  | 28 days after randomization | 
| Percentage of patients needing invasive mechanical ventilation or extracorporeal membrane oxygenation |  | 28 days after randomization | 
| Percentage of patients needing non-invasive ventilation or nasal high-flow oxygen therapy |  | 28 days after randomization | 
| Length of stay in the hospital |  | 90 days after randomization | 
| Infectious complications during hospital admission |  | 90 days after randomization | 
| Adverse drug reactions |  | 11 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, respiratory failure, corticosteroids