Covid19, Severe Acute Respiratory Syndrome, Viral Pneumonia Human Coronavirus
Conditions
Keywords
Methylprednisolone, Dexamethasone, COVID-19, Pneumonia
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).
Interventions
DRUGMethylprednisolone
Per-protocol methylprednisolone administration and tapering (see arm description)
DRUGDexamethasone
Per-protocol dexamethasone administration (see arm description)
Sponsors
Centro di Riferimento Oncologico - Aviano
National Institute for the Infectious Diseases (L. Spallanzani) - Rome
University of Trieste
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 28 days | Survival proportion at 28 days in both arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospitalization | 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 |
| Need for tracheostomy | Day 28 | Proportion of patients requiring tracheostomy in both arms |
| Reduction in the need for mechanical ventilation | 28 days | Number of days free from mechanical ventilation (either noninvasive or invasive) by study day 28 in both arms |
| Amelioration of oxygenation | Day 3, 7 and 14 | PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms |
| Disease progression | Day 3, 7 and 14 | WHO clinical progression scale at study day 3, 7 and 14 in both arms |
| Reduction in systemic inflammation markers | Day 3, 7 and 14 | C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms |
Countries
Italy
Outcome results
None listed