Randomized Open Investigation Determining Steroid Dose

NCT04834375 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 21-0171
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Keywords

dexamethasone; COVID-19; COVID pneumonia; respiratory failure; steroids

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Number of Participants Admitted to the ICU

  28 days

• Days of Stay in the Intensive Care Unit

  28 days

• Days of Hospitalization

  28 days

• Number of Participants That Required Higher Levels of Oxygen Supplementation

  28 days

• Number of Participants That Required Invasive Mechanical Ventilation

  28 days

Study Arms (2)

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

Drug: Weight-based dexamethasone dose

Interventions

Weight-based dexamethasone dose DRUG

Weight-based dexamethasone dose in COVID-19 patients with hypoxic respiratory failure

Also known as: Higher dexamethasone dose

Weight-based dexamethasone dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell Health

New Hyde Park, New York, 11042, United States

Location

Related Publications (6)

• 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.

  PMID: 32678530 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.

  PMID: 32876694 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.

  PMID: 32876695 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.

  PMID: 32043986 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.

  PMID: 32943404 BACKGROUND

• 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.

  PMID: 36475114 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Stella Hahn
• Organization: Northwell Health

sthahn@northwell.edu

516-465-5400

Study Officials

• Mangala Narasimhan, DO

  Northwell Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Medical Director, Northwell Sleep Disorders Center

Model Details: 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)

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 8, 2021
• Study Start: March 19, 2021
• Primary Completion: January 25, 2022
• Study Completion: March 29, 2022
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)