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).
Drug: Methylprednisolone
Per-protocol methylprednisolone administration and tapering (see arm description)
Drug: Dexamethasone
Per-protocol dexamethasone administration (see arm 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.
Marco Confalonieri
Trieste, TS, Italy
Marco Confalonieri, MD, Principal Investigator
University of Trieste