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

May 16, 2022 updated by: Confalonieri Marco, MD, University of Trieste

Randomized Controlled Trial of Methylprednisolone Versus Dexamethasone in COVID-19 Pneumonia (MEDEAS Trial)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

690

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • TS
      • Trieste, TS, Italy, 34149
        • Marco Confalonieri

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methylprednisolone

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
Per-protocol methylprednisolone administration and tapering (see arm description)
Active Comparator: Dexamethasone

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
Per-protocol dexamethasone administration (see arm description)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: 28 days
Survival proportion at 28 days in both arms
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in the need for mechanical ventilation
Time Frame: 28 days
Number of days free from mechanical ventilation (either noninvasive or invasive) by study day 28 in both arms
28 days
Length of hospitalization
Time Frame: From date of randomization until the date of hospital discharge, assessed up to 60 days
Number of days of hospitalization for patients discharged alive in both arms
From date of randomization until the date of hospital discharge, assessed up to 60 days
Need for tracheostomy
Time Frame: Day 28
Proportion of patients requiring tracheostomy in both arms
Day 28
Reduction in systemic inflammation markers
Time Frame: Day 3, 7 and 14
C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms
Day 3, 7 and 14
Amelioration of oxygenation
Time Frame: Day 3, 7 and 14
PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms
Day 3, 7 and 14
Disease progression
Time Frame: Day 3, 7 and 14
WHO clinical progression scale at study day 3, 7 and 14 in both arms
Day 3, 7 and 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Trieste

Collaborators

Centro di Riferimento Oncologico - Aviano
National Institute for the Infectious Diseases (L. Spallanzani) - Rome

Investigators

  • Principal Investigator: Marco Confalonieri, MD, University of Trieste

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 14, 2021

Primary Completion (Actual)

May 4, 2022

Study Completion (Actual)

May 4, 2022

Study Registration Dates

First Submitted

November 18, 2020

First Submitted That Met QC Criteria

November 18, 2020

First Posted (Actual)

November 19, 2020

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEDEAS1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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