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

NCT04636671 | Completed Phase 3 DMC

• 1 other identifier: MEDEAS1
• Study Type: interventional
• Target: 690
• Locations: 1 country
• Sites: 1

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).

Conditions

Covid19; Viral Pneumonia Human Coronavirus; Severe Acute Respiratory Syndrome

Keywords

Methylprednisolone; Dexamethasone; COVID-19; Pneumonia

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival proportion at 28 days in both arms

  28 days

Secondary Outcomes (6)

• Reduction in the need for mechanical ventilation

  28 days

• Length of hospitalization

  From date of randomization until the date of hospital discharge, assessed up to 60 days

• Need for tracheostomy

  Day 28

• Reduction in systemic inflammation markers

  Day 3, 7 and 14

• Amelioration of oxygenation

  Day 3, 7 and 14

Study Arms (2)

Methylprednisolone

EXPERIMENTAL

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: 1. 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; 2. 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)

Drug: Methylprednisolone

Dexamethasone

ACTIVE COMPARATOR

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.

Drug: Dexamethasone

Interventions

Methylprednisolone DRUG

Per-protocol methylprednisolone administration and tapering (see arm description)

Methylprednisolone

Dexamethasone DRUG

Per-protocol dexamethasone administration (see arm description)

Dexamethasone

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Trieste: lead
• Centro di Riferimento Oncologico - Aviano: collaborator
• National Institute for the Infectious Diseases (L. Spallanzani) - Rome: collaborator

Study Sites (1)

Marco Confalonieri

Trieste, TS, 34149, Italy

Location

Related Publications (9)

• 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

• 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.

  PMID: 33026460 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

• 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.

  PMID: 33150472 BACKGROUND

• 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.

  PMID: 33072814 BACKGROUND

• 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.

  PMID: 32539990 BACKGROUND

• 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.

  PMID: 32554564 BACKGROUND

• Reccardini N, Confalonieri M, Ruaro B, Confalonieri P, Da Re B, Rocca A, Salton F. Early C-reactive protein reduction predicts survival in COVID-19 severe pneumonia treated with glucocorticoids. BMC Pulm Med. 2025 Sep 30;25(1):436. doi: 10.1186/s12890-025-03874-9.

  PMID: 41029298 DERIVED

• Salton F, Confalonieri P, Centanni S, Mondoni M, Petrosillo N, Bonfanti P, Lapadula G, Lacedonia D, Voza A, Carpene N, Montico M, Reccardini N, Meduri GU, Ruaro B; MEDEAS Collaborative Group; Confalonieri M; MEDEAS Collaborative Group; Citton GM, Lapadula G, Bozzi C, Tavano S, Pozzan R, Andrisano AG, Jaber M, Mari M, Trotta L, Mondini L, Barbieri M, Ruggero L, Antonaglia C, Soave S, Torregiani C, Bogatec T, Baccelli A, Nalesso G, Re B, Pavesi S, Barbaro MPF, Giuliani A, Ravaglia C, Poletti V, Scala R, Guidelli L, Golfi N, Vianello A, Achille A, Lucernoni P, Gaccione AT, Romagnoli M, Fraccaro A, Malacchini N, Malerba M, Ragnoli B, Zamparelli AS, Bocchino M, Blasi F, Spotti M, Miele C, Piedepalumbo F, Barone I, Baglioni S, Dodaj M, Franco C, Andrani F, Mangia A, Mancini A, Carrozzi L, Rafanelli A, Casto E, Rogliani P, Ora J, Carpagnano GE, Di Lecce V, Tamburrini M, Papi A, Contoli M, Luzzati R, Zatta M, Di Bella S, Caraffa E, Francisci D, Tosti A, Pallotto C, De Rosa FG, Pecori A, Franceschini M, Carlin M, Orsini V, Spolti A, Inannace M, Santantonio T, Meli R, Sauro S, Fedeli C, Mangini E, Biolo G, Nunnari A, Pietrangelo A, Corradini E, Bocchi D, Boarini C, Zucchetto A, Lanini S. Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS). Eur Respir J. 2023 Apr 20;61(4):2201514. doi: 10.1183/13993003.01514-2022. Print 2023 Apr.

  PMID: 36356972 DERIVED

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome; Pneumonia

Interventions

Methylprednisolone; Dexamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Marco Confalonieri, MD

  University of Trieste

  PRINCIPAL INVESTIGATOR

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: Professor

Model Details: Open-label, randomized controlled trial

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 19, 2020
• Study Start: April 14, 2021
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: May 17, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 36 months following article publication

Locations

IT (1)