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Methylprednisolone vs. Dexamethasone in COVID-19 Pneumonia (MEDEAS RCT) (MEDEAS)

Primary Purpose

Covid19, Viral Pneumonia Human Coronavirus, Severe Acute Respiratory Syndrome

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Methylprednisolone
Dexamethasone
Sponsored by
University of Trieste
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring Methylprednisolone, Dexamethasone, COVID-19, Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Able to understand and sign the informed consent
  2. SARS-CoV-2 positive on at least one upper respiratory swab or bronchoalveolar lavage
  3. PaO2 <= 60 mmHg or SpO2 <= 90% or on oxygen therapy (any), CPAP or NPPV at randomization
  4. Age >= 18 years old at randomization

Exclusion Criteria:

  1. On invasive mechanical ventilation (either intubated or tracheostomized)
  2. Heart failure as the main cause of acute respiratory failure
  3. On long-term oxygen or home mechanical ventilation
  4. Decompensated liver cirrhosis
  5. Immunosuppression (i.e., cancer on treatment, post-organ transplantation, HIV-positive, on immunosuppressant therapy)
  6. On chronic steroid therapy or other immunomodulant therapy (e.g., azathioprine, methotrexate, mycophenolate, convalescent/hyperimmune plasma)
  7. Chronic renal failure with dialysis dependence
  8. Progressive neuro-muscular disorders
  9. Cognitively impaired, dementia or decompensated psychiatric disorder
  10. Quadriplegia/Hemiplegia or quadriparesis/hemiparesis
  11. Do-not-resuscitate order
  12. Participating in other clinical trial including experimental compound with proved or expected activity against SARS-CoV-2 infection
  13. Any other condition that in the opinion of the investigator may significantly impact with patient's capability to comply with protocol intervention
  14. Refuse to participate in the study or absence of signed informed consent form.

Sites / Locations

  • Marco Confalonieri

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Methylprednisolone

Dexamethasone

Arm Description

A. On day 1, loading dose of methylprednisolone (MP) 80 mg IV in 30 minutes, promptly followed by continuous infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h. B. From day 2 to day 8: infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h. C. From day 9 and beyond: If not intubated patient and PaO2/FiO2 > 200, taper to MP 20 mg IV in 30 minutes three times a day for 3 days, then MP 20 mg IV twice daily for 3 days, then MP 20 mg IV once daily for 2 days, then switch to MP 16 mg/day PO for 2 days, then MP 8mg/day PO for 2 days, then MP 4mg/day PO for 2 days; If intubated patient or PaO2/FiO2 <= 200 with at least 5 cmH2O CPAP, continue infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h until PaO2/FiO2 > 200 then taper as in a)

A. Dexamethasone (DM) 6 mg IV in 30 minutes or PO from day 1 to day 10 or until hospital discharge (if sooner). B. After day 10 study treatment is interrupted.

Outcomes

Primary Outcome Measures

Survival
Survival proportion at 28 days in both arms

Secondary Outcome Measures

Reduction in the need for mechanical ventilation
Number of days free from mechanical ventilation (either noninvasive or invasive) by study day 28 in both arms
Length of hospitalization
Number of days of hospitalization for patients discharged alive in both arms
Need for tracheostomy
Proportion of patients requiring tracheostomy in both arms
Reduction in systemic inflammation markers
C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms
Amelioration of oxygenation
PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms
Disease progression
WHO clinical progression scale at study day 3, 7 and 14 in both arms

Full Information

First Posted
November 18, 2020
Last Updated
May 16, 2022
Sponsor
University of Trieste
Collaborators
Centro di Riferimento Oncologico - Aviano, National Institute for the Infectious Diseases (L. Spallanzani) - Rome
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1. Study Identification

Unique Protocol Identification Number
NCT04636671
Brief Title
Methylprednisolone vs. Dexamethasone in COVID-19 Pneumonia (MEDEAS RCT)
Acronym
MEDEAS
Official Title
Randomized Controlled Trial of Methylprednisolone Versus Dexamethasone in COVID-19 Pneumonia (MEDEAS Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 14, 2021 (Actual)
Primary Completion Date
May 4, 2022 (Actual)
Study Completion Date
May 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Trieste
Collaborators
Centro di Riferimento Oncologico - Aviano, National Institute for the Infectious Diseases (L. Spallanzani) - Rome

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Low-dose glucocorticoid treatment is the only intervention shown to significantly reduce mortality in cases of COVID-19 pneumonia requiring oxygen supplementation or ventilatory support. In particular, a large UK randomized controlled trial (RECOVERY trial) demonstrated the efficacy of dexamethasone at a dosage of 6mg/day for 10 days in reducing mortality compared to usual therapy, with a greater impact on patients requiring mechanical ventilation (36% reduction) or oxygen therapy (18% reduction) than on those who did not need respiratory support (doi: 10.1056/NEJMoa2021436). However, there is still paucity of information guiding glucocorticoid administration in severe pneumonia/ARDS and no evidence of the superiority of a steroid drug -nor of a therapeutic scheme- compared to the others, which led to a great heterogeneity of treatment protocols and misinterpretation of available findings. In a recent longitudinal observational study conducted in Italian respiratory high-dependency units, a protocol with prolonged low-dose methylprednisolone demonstrated a 71% reduction in mortality and the achievement of other secondary endpoints such as an increase in ventilation-free days by study day 28 in a subgroup of patients with severe pneumonia and high levels of systemic inflammation (doi: 10.1093/ofid/ofaa421). The treatment was well tolerated and did not affect viral shedding from the airways. In light of these data, the present study aims to compare the efficacy of a methylprednisolone protocol and that of a dexamethasone protocol based on previous evidence in increasing survival by day 28, as well as in reducing the need and duration for mechanical ventilation, among hospitalized patients requiring noninvasive respiratory support (oxygen supplementation and/or noninvasive ventilation).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Viral Pneumonia Human Coronavirus, Severe Acute Respiratory Syndrome
Keywords
Methylprednisolone, Dexamethasone, COVID-19, Pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Open-label, randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
690 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methylprednisolone
Arm Type
Experimental
Arm Description
A. On day 1, loading dose of methylprednisolone (MP) 80 mg IV in 30 minutes, promptly followed by continuous infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h. B. From day 2 to day 8: infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h. C. From day 9 and beyond: If not intubated patient and PaO2/FiO2 > 200, taper to MP 20 mg IV in 30 minutes three times a day for 3 days, then MP 20 mg IV twice daily for 3 days, then MP 20 mg IV once daily for 2 days, then switch to MP 16 mg/day PO for 2 days, then MP 8mg/day PO for 2 days, then MP 4mg/day PO for 2 days; If intubated patient or PaO2/FiO2 <= 200 with at least 5 cmH2O CPAP, continue infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h until PaO2/FiO2 > 200 then taper as in a)
Arm Title
Dexamethasone
Arm Type
Active Comparator
Arm Description
A. Dexamethasone (DM) 6 mg IV in 30 minutes or PO from day 1 to day 10 or until hospital discharge (if sooner). B. After day 10 study treatment is interrupted.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
Per-protocol methylprednisolone administration and tapering (see arm description)
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Per-protocol dexamethasone administration (see arm description)
Primary Outcome Measure Information:
Title
Survival
Description
Survival proportion at 28 days in both arms
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Reduction in the need for mechanical ventilation
Description
Number of days free from mechanical ventilation (either noninvasive or invasive) by study day 28 in both arms
Time Frame
28 days
Title
Length of hospitalization
Description
Number of days of hospitalization for patients discharged alive in both arms
Time Frame
From date of randomization until the date of hospital discharge, assessed up to 60 days
Title
Need for tracheostomy
Description
Proportion of patients requiring tracheostomy in both arms
Time Frame
Day 28
Title
Reduction in systemic inflammation markers
Description
C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms
Time Frame
Day 3, 7 and 14
Title
Amelioration of oxygenation
Description
PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms
Time Frame
Day 3, 7 and 14
Title
Disease progression
Description
WHO clinical progression scale at study day 3, 7 and 14 in both arms
Time Frame
Day 3, 7 and 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to understand and sign the informed consent SARS-CoV-2 positive on at least one upper respiratory swab or bronchoalveolar lavage PaO2 <= 60 mmHg or SpO2 <= 90% or on oxygen therapy (any), CPAP or NPPV at randomization Age >= 18 years old at randomization Exclusion Criteria: On invasive mechanical ventilation (either intubated or tracheostomized) Heart failure as the main cause of acute respiratory failure On long-term oxygen or home mechanical ventilation Decompensated liver cirrhosis Immunosuppression (i.e., cancer on treatment, post-organ transplantation, HIV-positive, on immunosuppressant therapy) On chronic steroid therapy or other immunomodulant therapy (e.g., azathioprine, methotrexate, mycophenolate, convalescent/hyperimmune plasma) Chronic renal failure with dialysis dependence Progressive neuro-muscular disorders Cognitively impaired, dementia or decompensated psychiatric disorder Quadriplegia/Hemiplegia or quadriparesis/hemiparesis Do-not-resuscitate order Participating in other clinical trial including experimental compound with proved or expected activity against SARS-CoV-2 infection Any other condition that in the opinion of the investigator may significantly impact with patient's capability to comply with protocol intervention Refuse to participate in the study or absence of signed informed consent form.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco Confalonieri, MD
Organizational Affiliation
University of Trieste
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marco Confalonieri
City
Trieste
State/Province
TS
ZIP/Postal Code
34149
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results of this study after deidentification, as well as study protocol, statistical analysis plan, informed consent form, clinical study report and analytic code will be made available to Researchers who provide a written proposal for their purposes. Proposals must be submitted to the study PI or co-PI up to 36 months following article publication. Requestors must sign a data access agreement.
IPD Sharing Time Frame
36 months following article publication
Citations:
PubMed Identifier
32678530
Citation
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.
Results Reference
background
PubMed Identifier
33026460
Citation
Arabi YM, Chrousos GP, Meduri GU. The ten reasons why corticosteroid therapy reduces mortality in severe COVID-19. Intensive Care Med. 2020 Nov;46(11):2067-2070. doi: 10.1007/s00134-020-06223-y. Epub 2020 Oct 7. No abstract available.
Results Reference
background
PubMed Identifier
32876694
Citation
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.
Results Reference
background
PubMed Identifier
33150472
Citation
Meduri GU, Annane D, Confalonieri M, Chrousos GP, Rochwerg B, Busby A, Ruaro B, Meibohm B. Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med. 2020 Dec;46(12):2284-2296. doi: 10.1007/s00134-020-06289-8. Epub 2020 Nov 4.
Results Reference
background
PubMed Identifier
33072814
Citation
Salton F, Confalonieri P, Meduri GU, Santus P, Harari S, Scala R, Lanini S, Vertui V, Oggionni T, Caminati A, Patruno V, Tamburrini M, Scartabellati A, Parati M, Villani M, Radovanovic D, Tomassetti S, Ravaglia C, Poletti V, Vianello A, Gaccione AT, Guidelli L, Raccanelli R, Lucernoni P, Lacedonia D, Foschino Barbaro MP, Centanni S, Mondoni M, Davi M, Fantin A, Cao X, Torelli L, Zucchetto A, Montico M, Casarin A, Romagnoli M, Gasparini S, Bonifazi M, D'Agaro P, Marcello A, Licastro D, Ruaro B, Volpe MC, Umberger R, Confalonieri M. Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia. Open Forum Infect Dis. 2020 Sep 12;7(10):ofaa421. doi: 10.1093/ofid/ofaa421. eCollection 2020 Oct.
Results Reference
background
PubMed Identifier
32539990
Citation
WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Epub 2020 Jun 12. Erratum In: Lancet Infect Dis. 2020 Oct;20(10):e250.
Results Reference
background
PubMed Identifier
32554564
Citation
Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020 Jun 17;369:m115. doi: 10.1136/bmj.m115.
Results Reference
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Methylprednisolone vs. Dexamethasone in COVID-19 Pneumonia (MEDEAS RCT)

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