Randomized Open Investigation Determining Steroid Dose

Phase 3

Completed

Conditions: Covid19

Interventions: Drug: Weight-based dexamethasone dose

Registration Number: NCT04834375

Lead Sponsor: Northwell Health

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 142

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Weight-based dexamethasone dose	Weight-based dexamethasone dose	Dexamethasone 0.2 mg/kg/day IV (maximum 20 mg daily) for 10 days

Primary Outcome Measures

Name	Time	Method
All Cause Mortality at 28 Days	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

Secondary Outcome Measures

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