A Phase 3 interventional study of Methylprednisolone and Dexamethasone in Covid19, Viral Pneumonia Human Coronavirus and Severe Acute Respiratory Syndrome, sponsored by University of Trieste. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-05-17.
Sponsored by University of Trieste · Phase 3, Interventional, and Treatment
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).
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 690 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →University of Trieste is the lead sponsor of 39 studies on the registry; 8 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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 methylprednisolone administration and tapering (see arm description)
Per-protocol dexamethasone administration (see arm description)
Survival
Survival proportion at 28 days in both arms
Time frame: 28 days
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
Time frame: 28 days
Length of hospitalization
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
Need for tracheostomy
Proportion of patients requiring tracheostomy in both arms
Time frame: Day 28
Reduction in systemic inflammation markers
C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms
Time frame: Day 3, 7 and 14
Amelioration of oxygenation
PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms
Time frame: Day 3, 7 and 14
Disease progression
WHO clinical progression scale at study day 3, 7 and 14 in both arms
Time frame: Day 3, 7 and 14
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
This study is completed, as verified in May 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Trieste