Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial

Study Overview
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Brief Summary
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There is compelling data indicating that there is an excessive inflammatory response in some patients with COVID-19 leading them to develop ARDS that can be severe with a very poor prognosis. Many of these patients require very long mechanical ventilation times to survive, which have led to the collapse of the health system in some regions of the world. The current evidence for the treatment of these severe forms is inconsistent and most scientific societies and governmental or international organizations recommend evaluating treatments with randomized clinical trials. Corticosteroids, being non-specific anti-inflammatory drugs, could shorten the duration of respiratory failure and improve the prognosis. Due to the lack of solid data available regarding this serious disease, our objective is to randomly evaluate the efficacy and safety of the use of dexamethasone, a parenteral corticosteroid approved in Argentina, in patients with ARDS with confirmed respiratory infection due to SARS-CoV-2 (COVID-19). After RECOVERY trial prepublication, low dose (6 mg QD for 10 days) dexamethasone was recommended as the usual care treatment for severe COVID-19. At this time only 3 patients had been included in the trial. Thus, we updated our recommendations for centers and decided to compare two different doses of this glucocorticoid for the treatment of ADRS due to COVID-19.

Official Title
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High Versus Low Dose Dexamethasone for the Treatment of COVID-19 Related ARDS: a Multicenter and Randomized Open-label Clinical Trial

Conditions
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Respiratory Distress Syndrome, Adult, Covid-19

Intervention / Treatment
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* Drug: High-Dose Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARDS according to Berlin's definition PCR confirmed COVID-19 Length of mechanical ventilation less or equal to 72 hours Exclusion Criteria: Pregnancy or breast-feeding women Terminal illness with very poor prognosis according to the investigator judgement Therapeutic limitation Known immunocompromised condition Chronic use of systemic corticosteroids Participation in another randomized crinical trial More than 5 days of treatment of low dose dexamethasone for COVID-19 Abscence of informed consent Active participation in other randomized clinical trial

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose Dexamethasone<br>Intravenous Dexamethasone 16 mg qd from day 1 to 5 followed by 8 mg qd from day 6 to 10 | Drug: High-Dose Dexamethasone<br>* IV Dexamethasone administered once daily: 16 mg from day 1 to 5 and 8 mg from day 6 to 10<br>* Other names: Corticosteroid;|
| No Intervention: Usual care - low dose Dexamethasone<br>Intravenous Dexamethasone 6 mg qd for 10 days based on RECOVERY trial | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days at 28 days | Days without ventilator support in the first 28 days following randomization | 28 days after randomization | 
| Time to successful discontinuation from mechanical ventilation | Time to event (successful discontinuation from mechanical ventilation) | 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-days mortality | Dead rate within 28 days of randomization | 28 days after randomization | 
| Rate of nosocomial infections | Rate of ventilator associated pneumonia, blood stream infection, urinary tract infection or candidemia in the first 28 days following randomization | 28 days after randomization | 
| SOFA variation | Variation in SOFA over the first 10 days after randomization | 10 days after randomization | 
| Use of prone position | Cumulative hours spent on prone position | 10 days after randomization | 
| Delirium | Frequency of delirium at ICU discharge | 28 days after randomization | 
| Muscle weakness | mMRC score at ICU discharge | 28 days after randomization | 
| 90-day mortality | Death rate within 90 days of randomization | 90 days after randomization | 
| Peak daily blood glucose | Interaction between treatment and daily change in glucose | 10 days after randomization |