Randomized Open Investigation Determining Steroid Dose

Study Overview
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Brief Summary
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Dexamethasone has been approved for the treatment of severe COVID-19, but higher doses of steroids may be more effective. The purpose of this research study is to compare the current standard dose of dexamethasone 6 mg to a higher, weight-based dosing (0.2 mg/kg with maximum dose of 20 mg) to determine if it would be more effective against COVID-19 pneumonia.

Detailed Description
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Treatment for COVID-19 patients with respiratory failure has been vexing, but the use of steroids has shown promise. In a recent randomized control trial, dexamethasone 6 mg once daily showed a modest decrease in mortality among hospitalized COVID-19 patients who require oxygen supplementation or invasive mechanical ventilation. Other trials have shown that the inflammatory response to COVID-19 can be further attenuated at higher dosages of dexamethasone. These higher dosages have not been well studied and have not been directly compared to the current standard dose of dexamethasone 6 mg daily. We propose that a higher dexamethasone dose, equivalent to methylprednisolone 1 mg/kg/day which is routinely used to treat other inflammatory conditions of the lungs, may be more effective than the current standard dose in reducing mortality in COVID-19 patients with respiratory failure.

Official Title
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Randomized Open Investigation Determining Steroid Dose (ROIDS-Dose)

Conditions
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Covid19

Intervention / Treatment
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* Drug: Weight-based dexamethasone dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults greater or equal than 18 years old COVID-19 infection confirmed by positive PCR test Hypoxemia defined by an oxygen saturation < 94% or the need for supplemental oxygen Exclusion Criteria: Corticosteroid use for > 48h within the past 15 days prior to enrollment Use of steroids with doses higher than the equivalent to dexamethasone 6 mg Use of immunosuppressive drugs Pregnant women Chronic oxygen use Known history of dexamethasone allergy DNR / DNI Patient or proxy cannot consent

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: Patients will be randomized in a parallel fashion into either the standard dexamethasone dose of 6 mg or weight-based dexamethasone of 0.2 mg/kg (maximum dose of 20 mg)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard dexamethasone dose<br>Dexamethasone 6 mg IV daily for 10 days | |
| Experimental: Weight-based dexamethasone dose<br>Dexamethasone 0.2 mg/kg/day IV (maximum 20 mg daily) for 10 days | Drug: Weight-based dexamethasone dose<br>* Weight-based dexamethasone dose in COVID-19 patients with hypoxic respiratory failure<br>* Other names: Higher dexamethasone dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Mortality at 28 Days | All cause mortality at 28 days. Comment: Primary outcome was all cause mortality at 28 days but the patients were followed until end of admission for the final disposition (death or discharge) which accounts for the differences in the primary outcome of mortality at 28 days and the total number of deaths at discharge | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Admitted to the ICU | Number of participants that required admission to the ICU | 28 days | 
| Days of Stay in the Intensive Care Unit | ICU length of stay | 28 days | 
| Days of Hospitalization | Duration of hospitalization | 28 days | 
| Number of Participants That Required Higher Levels of Oxygen Supplementation | Venturi mask, Non-rebreather mask, High-flow nasal cannula, Non-invasive ventilation | 28 days | 
| Number of Participants That Required Invasive Mechanical Ventilation | Escalation to invasive mechanical ventilation | 28 days | 
| Duration of Invasive Mechanical Ventilation | Total days requiring invasive mechanical ventilation | 28 days | 
| Number of Participants That Required ECMO | Refractory hypoxemia requiring ECMO | 28 days | 
| Number of Participants That Required Tracheostomy | Need for tracheostomy | 28 days | 
| Number of Participants That Developed Secondary Bacterial or Fungal Infections | Culture positive evidence of secondary bacterial or fungal infections | 28 days | 
| Number of Participants That Developed Clinically Significant Hyperglycemia | Defined as need for insulin drip or ICU admission to control hyperglycemia | 28 days | 
| Number of Participants That Required Oxygen Supplementation a Discharge From the Hospital | Need for oxygen supplementation at hospital discharge Comment: Corrected total number of discharged patients alive to 55 in the Standard Dexamethasone Dose Arm. | Until hospital discharge | 
| Subjective Symptoms at 28 Days | Subjective symptoms questionnaire at 28 days | 28 days | 
| Disposition Upon Discharge | Home, home with physical therapy, other (skilled nursing facility, long-term acute care facility, long-term care facility / nursing home, acute rehabilitation facility, hospice care), expired | At hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexamethasone, COVID-19, COVID pneumonia, respiratory failure, steroids