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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard dexamethasone dose | No Intervention | Dexamethasone 6 mg IV daily for 10 days | |
| Weight-based dexamethasone dose | Experimental | Dexamethasone 0.2 mg/kg/day IV (maximum 20 mg daily) for 10 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Weight-based dexamethasone dose | Drug | Weight-based dexamethasone dose in COVID-19 patients with hypoxic respiratory failure |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mangala Narasimhan, DO | Northwell Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwell Health | New Hyde Park | New York | 11042 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32678530 | Background | RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. | |
| 32876694 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Dexamethasone Dose | Dexamethasone 6 mg IV daily for 10 days |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard Dexamethasone Dose | Dexamethasone 6 mg IV daily for 10 days |
| BG001 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 28 days |
|
Adverse events were assessed up to 28 days. Mortality was assessed through 28 days for the primary outcome but final disposition was assessed at end of hospitalization (e.g. death or discharge).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Dexamethasone Dose | Dexamethasone 6 mg IV daily for 10 days | 17 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Clinically significant hyperglycemia | Endocrine disorders | Systematic Assessment | Development of clinically significant hyperglycemia, defined as requiring ICU admission for treatment of hyperglycemia or requirement of an insulin infusion |
Study was not blinded. Small sample size may have reduced the ability to detect statistically significant differences among some of the secondary outcomes. Selecting a maximum dose of 20 mg in the weight-based dexamethasone group may have affected the results. As the standard of care for the treatment of COVID-19 changed over time, those changes may have affected patient care in undetectable ways, affecting the results of the trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stella Hahn | Northwell Health | 516-465-5400 | sthahn@northwell.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 3, 2021 | Jun 2, 2023 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 4, 2021 | Mar 4, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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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)
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| 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 |
| Background |
| WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Juni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Moller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 10.1001/jama.2020.17023. |
| 32876695 | Background | Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, Avezum A, Lopes RD, Bueno FR, Silva MVAO, Baldassare FP, Costa ELV, Moura RAB, Honorato MO, Costa AN, Damiani LP, Lisboa T, Kawano-Dourado L, Zampieri FG, Olivato GB, Righy C, Amendola CP, Roepke RML, Freitas DHM, Forte DN, Freitas FGR, Fernandes CCF, Melro LMG, Junior GFS, Morais DC, Zung S, Machado FR, Azevedo LCP; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-1316. doi: 10.1001/jama.2020.17021. |
| 32043986 | Background | Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7. |
| 32943404 | Background | Edalatifard M, Akhtari M, Salehi M, Naderi Z, Jamshidi A, Mostafaei S, Najafizadeh SR, Farhadi E, Jalili N, Esfahani M, Rahimi B, Kazemzadeh H, Mahmoodi Aliabadi M, Ghazanfari T, Sattarian M, Ebrahimi Louyeh H, Raeeskarami SR, Jamalimoghadamsiahkali S, Khajavirad N, Mahmoudi M, Rostamian A. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020 Dec 24;56(6):2002808. doi: 10.1183/13993003.02808-2020. Print 2020 Dec. |
| 36475114 | Derived | Rabascall CX, Lou BX, Dhar S, Hasan Z, Fryman C, Izard S, Makaryus M, Acharya S, Mastroianni F, Kamper M, Duenas S, Gong J, Shah D, Khanijo S, Ying D, Habibullah J, Kim DH, Butzko R, Oks M, Birnbaum B, Moore J, Singh AK, Quintero L, Lau M, Honigman J, Hilewitz A, Shah K, Simonson J, Agrawal A, Frank M, Tsegaye A, Narasimhan M, Greenberg H, Hahn SS. Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial. Cureus. 2022 Nov 4;14(11):e31086. doi: 10.7759/cureus.31086. eCollection 2022 Nov. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Steroid initiation prior to the study | Count of Participants | Participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Dexamethasone dose | Mean | Standard Deviation | mg |
|
| Pre-enrollment nadir oxygen saturation | Mean | Standard Deviation | % of oxygen saturation |
|
| Oxygen required on enrollment | Count of Participants | Participants |
|
| Oxygen modality on enrollment | Count of Participants | Participants |
|
| Charlson comorbidity index | Scale used to predict 10-year survival in patients with multiple comorbidities. Ranges from a minimum of 0 points to a maximum of 37 points. The higher the score, the worse estimated 10-year survival. | Mean | Standard Deviation | units on a scale |
|
| 4C mortality score | Score used to predict in-hospital mortality in patients admitted with COVID-19. Ranges from a minimum of 0 points to a maximum of 21 points. 0-3 points: Low risk (1.2 - 1.7% in-hospital mortality) 4-8 points: Intermediate risk (9.1 - 9.9% in-hospital mortality) 9-14 points: High risk (31.4 - 31.9% in-hospital mortality) 15-21 points: Very high risk (61.5% - 66.2% in-hospital mortality) | Mean | Standard Deviation | units on a scale |
|
| Other treatments for COVID-19 | Count of Participants | Participants |
|
|
|
| Secondary | Number of Participants Admitted to the ICU | Number of participants that required admission to the ICU | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Days of Stay in the Intensive Care Unit | ICU length of stay | Among patients admitted to the ICU | Posted | Mean | Standard Deviation | days | 28 days |
|
|
|
| Secondary | Days of Hospitalization | Duration of hospitalization | Posted | Mean | Standard Deviation | days | 28 days |
|
|
|
| Secondary | Number of Participants That Required Higher Levels of Oxygen Supplementation | Venturi mask, Non-rebreather mask, High-flow nasal cannula, Non-invasive ventilation | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Number of Participants That Required Invasive Mechanical Ventilation | Escalation to invasive mechanical ventilation | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Duration of Invasive Mechanical Ventilation | Total days requiring invasive mechanical ventilation | Among patients requiring invasive mechanical ventilation | Posted | Mean | Standard Deviation | days | 28 days |
|
|
|
| Secondary | Number of Participants That Required ECMO | Refractory hypoxemia requiring ECMO | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Number of Participants That Required Tracheostomy | Need for tracheostomy | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Number of Participants That Developed Secondary Bacterial or Fungal Infections | Culture positive evidence of secondary bacterial or fungal infections | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Number of Participants That Developed Clinically Significant Hyperglycemia | Defined as need for insulin drip or ICU admission to control hyperglycemia | Posted | Count of Participants | Participants | 28 days |
|
|
|
| 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. | Among patients discharged alive | Posted | Count of Participants | Participants | Until hospital discharge |
|
|
|
| Secondary | Subjective Symptoms at 28 Days | Subjective symptoms questionnaire at 28 days | Among patients alive at 28 days with a completed response | Posted | Count of Participants | Participants | 28 days |
|
|
|
| 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 | Posted | Count of Participants | Participants | At hospital discharge |
|
|
|
| 72 |
| 0 |
| 72 |
| 24 |
| 72 |
| EG001 | 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 | 12 | 70 | 0 | 70 | 13 | 70 |
|
| Secondary bacterial or fungal infections | Infections and infestations | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| Other |
|
| Expired |
|