Covid19
Conditions
Keywords
dexamethasone, COVID-19, COVID pneumonia, respiratory failure, steroids
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.
Interventions
DRUGWeight-based dexamethasone dose
Weight-based dexamethasone dose in COVID-19 patients with hypoxic respiratory failure
Sponsors
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Days of Stay in the Intensive Care Unit | 28 days | ICU length of stay |
| Days of Hospitalization | 28 days | Duration of hospitalization |
| 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 |
| 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 Admitted to the ICU | 28 days | Number of participants that required admission to the ICU |
| 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 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 |
| Number of Participants That Required Tracheostomy | 28 days | Need for tracheostomy |
Countries
United States
Participant flow
Recruitment details
Patients underwent screening and randomization between March 19, 2021 and December 28, 2021 at seven hospitals in Northwell Health in New York. Randomization was performed using a computer-generated allocation sequence via the Research Electronic Data Capture (REDCap) system. Eligible patients were randomized in a 1:1 ratio stratified by the trial site to either the standard dose group or the intervention group.
Participants by arm
| Arm | Count |
|---|---|
| Standard Dexamethasone Dose Dexamethasone 6 mg IV daily for 10 days | 72 |
| Weight-based Dexamethasone Dose Dexamethasone 0.2 mg/kg/day IV (maximum 20 mg daily) for 10 days
Weight-based dexamethasone dose: Weight-based dexamethasone dose in COVID-19 patients with hypoxic respiratory failure | 70 |
| Total | 142 |
Baseline characteristics
| Characteristic | Standard Dexamethasone Dose | Weight-based Dexamethasone Dose | Total |
|---|---|---|---|
| 4C mortality score | 8.67 units on a scale STANDARD_DEVIATION 3.69 | 7.86 units on a scale STANDARD_DEVIATION 3.52 | 8.27 units on a scale STANDARD_DEVIATION 3.62 |
| Age, Continuous | 57.22 years STANDARD_DEVIATION 15.18 | 55.46 years STANDARD_DEVIATION 15.11 | 56.35 years STANDARD_DEVIATION 15.12 |
| BMI | 31.72 kg/m^2 STANDARD_DEVIATION 8.99 | 33.57 kg/m^2 STANDARD_DEVIATION 9.84 | 32.62 kg/m^2 STANDARD_DEVIATION 9.43 |
| Charlson comorbidity index | 2.18 units on a scale STANDARD_DEVIATION 1.92 | 1.90 units on a scale STANDARD_DEVIATION 1.95 | 2.04 units on a scale STANDARD_DEVIATION 1.93 |
| Dexamethasone dose | 6 mg STANDARD_DEVIATION 0 | 17.49 mg STANDARD_DEVIATION 2.66 | 11.66 mg STANDARD_DEVIATION 6.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 14 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 55 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Other treatments for COVID-19 Any COVID-19 vaccination | 8 Participants | 9 Participants | 17 Participants |
| Other treatments for COVID-19 Monoclonal antibodies | 0 Participants | 2 Participants | 2 Participants |
| Other treatments for COVID-19 Remdesivir | 65 Participants | 65 Participants | 130 Participants |
| Other treatments for COVID-19 Tocilizumab | 18 Participants | 17 Participants | 35 Participants |
| Oxygen modality on enrollment High flow nasal cannula | 14 Participants | 11 Participants | 25 Participants |
| Oxygen modality on enrollment Mechanical ventilation | 4 Participants | 1 Participants | 5 Participants |
| Oxygen modality on enrollment Nasal cannula | 42 Participants | 49 Participants | 91 Participants |
| Oxygen modality on enrollment Non-invasive ventilation | 2 Participants | 3 Participants | 5 Participants |
| Oxygen modality on enrollment Non-rebreather mask | 9 Participants | 5 Participants | 14 Participants |
| Oxygen modality on enrollment Venturi mask | 1 Participants | 1 Participants | 2 Participants |
| Oxygen required on enrollment | 72 Participants | 70 Participants | 142 Participants |
| Pre-enrollment nadir oxygen saturation | 83.92 % of oxygen saturation STANDARD_DEVIATION 10.72 | 84.43 % of oxygen saturation STANDARD_DEVIATION 7.96 | 84.17 % of oxygen saturation STANDARD_DEVIATION 9.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 9 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 26 Participants | 51 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 25 Participants | 52 Participants |
| Sex: Female, Male Female | 23 Participants | 20 Participants | 43 Participants |
| Sex: Female, Male Male | 49 Participants | 50 Participants | 99 Participants |
| Steroid initiation prior to the study | 68 Participants | 66 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 72 | 12 / 70 |
| other Total, other adverse events | 24 / 72 | 13 / 70 |
| serious Total, serious adverse events | 0 / 72 | 0 / 70 |
Outcome results
Primary
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
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | All Cause Mortality at 28 Days | 15 Participants |
| Weight-based Dexamethasone Dose | All Cause Mortality at 28 Days | 12 Participants |
Secondary
Days of Hospitalization
Duration of hospitalization
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Dexamethasone Dose | Days of Hospitalization | 14.83 days | Standard Deviation 17 |
| Weight-based Dexamethasone Dose | Days of Hospitalization | 11.56 days | Standard Deviation 8.88 |
Secondary
Days of Stay in the Intensive Care Unit
ICU length of stay
Time frame: 28 days
Population: Among patients admitted to the ICU
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Dexamethasone Dose | Days of Stay in the Intensive Care Unit | 15.33 days | Standard Deviation 11.28 |
| Weight-based Dexamethasone Dose | Days of Stay in the Intensive Care Unit | 11.33 days | Standard Deviation 8.85 |
Secondary
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
Time frame: At hospital discharge
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Dexamethasone Dose | Disposition Upon Discharge | Home | 40 Participants |
| Standard Dexamethasone Dose | Disposition Upon Discharge | Home with physical therapy | 10 Participants |
| Standard Dexamethasone Dose | Disposition Upon Discharge | Other | 5 Participants |
| Standard Dexamethasone Dose | Disposition Upon Discharge | Expired | 17 Participants |
| Weight-based Dexamethasone Dose | Disposition Upon Discharge | Expired | 12 Participants |
| Weight-based Dexamethasone Dose | Disposition Upon Discharge | Home | 42 Participants |
| Weight-based Dexamethasone Dose | Disposition Upon Discharge | Other | 5 Participants |
| Weight-based Dexamethasone Dose | Disposition Upon Discharge | Home with physical therapy | 11 Participants |
Secondary
Duration of Invasive Mechanical Ventilation
Total days requiring invasive mechanical ventilation
Time frame: 28 days
Population: Among patients requiring invasive mechanical ventilation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Dexamethasone Dose | Duration of Invasive Mechanical Ventilation | 19.95 days | Standard Deviation 16.14 |
| Weight-based Dexamethasone Dose | Duration of Invasive Mechanical Ventilation | 10.90 days | Standard Deviation 8.88 |
Secondary
Number of Participants Admitted to the ICU
Number of participants that required admission to the ICU
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants Admitted to the ICU | 27 Participants |
| Weight-based Dexamethasone Dose | Number of Participants Admitted to the ICU | 12 Participants |
Secondary
Number of Participants That Developed Clinically Significant Hyperglycemia
Defined as need for insulin drip or ICU admission to control hyperglycemia
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Developed Clinically Significant Hyperglycemia | 5 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Developed Clinically Significant Hyperglycemia | 4 Participants |
Secondary
Number of Participants That Developed Secondary Bacterial or Fungal Infections
Culture positive evidence of secondary bacterial or fungal infections
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Developed Secondary Bacterial or Fungal Infections | 19 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Developed Secondary Bacterial or Fungal Infections | 9 Participants |
Secondary
Number of Participants That Required ECMO
Refractory hypoxemia requiring ECMO
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Required ECMO | 3 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Required ECMO | 2 Participants |
Secondary
Number of Participants That Required Higher Levels of Oxygen Supplementation
Venturi mask, Non-rebreather mask, High-flow nasal cannula, Non-invasive ventilation
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Required Higher Levels of Oxygen Supplementation | 32 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Required Higher Levels of Oxygen Supplementation | 31 Participants |
Secondary
Number of Participants That Required Invasive Mechanical Ventilation
Escalation to invasive mechanical ventilation
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Required Invasive Mechanical Ventilation | 19 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Required Invasive Mechanical Ventilation | 10 Participants |
Secondary
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.
Time frame: Until hospital discharge
Population: Among patients discharged alive
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Required Oxygen Supplementation a Discharge From the Hospital | 25 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Required Oxygen Supplementation a Discharge From the Hospital | 27 Participants |
Secondary
Number of Participants That Required Tracheostomy
Need for tracheostomy
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dexamethasone Dose | Number of Participants That Required Tracheostomy | 5 Participants |
| Weight-based Dexamethasone Dose | Number of Participants That Required Tracheostomy | 1 Participants |
Secondary
Subjective Symptoms at 28 Days
Subjective symptoms questionnaire at 28 days
Time frame: 28 days
Population: Among patients alive at 28 days with a completed response
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Dexamethasone Dose | Subjective Symptoms at 28 Days | Same/worse | 3 Participants |
| Standard Dexamethasone Dose | Subjective Symptoms at 28 Days | Better | 33 Participants |
| Weight-based Dexamethasone Dose | Subjective Symptoms at 28 Days | Better | 44 Participants |
| Weight-based Dexamethasone Dose | Subjective Symptoms at 28 Days | Same/worse | 2 Participants |