Randomized Open Investigation Determining Steroid Dose (ROIDS-Dose)

Randomized Open Investigation Determining Steroid Dose (ROIDS-Dose)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Weight-based dexamethasone dose

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.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Mangala Narasimhan, DO, Northwell Health

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): January 25, 2022
• Study Completion (Actual): March 29, 2022

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; respiratory failure; dexamethasone; steroids; COVID pneumonia
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: 21-0171

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes