Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome
Condition: Severe Acute Respiratory Syndrome (SARS) Pneumonia; Coronavirus Infections; ARDS, Human
MeSH terms: Coronavirus Infections; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Syndrome
Study type: Observational [Patient Registry]

Summary: 
      COVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution
      to the lack of ICU beds and increasing deaths day after day.

      A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed
      impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically
      ill patients. Moreover, the Italian Infectious Disease leading institution guidelines for
      COVID-19 clinical management included as an option for patients with "incipient worsening of
      respiratory functions" methylprednisolone treatment at an approximate dose of 80mg.

      The main objective of this multi-centre observational trial is to analyse the association of
      low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute
      respiratory syndrome with composite primary end-point (ICU referral, need for intubation,
      in-hospital death at day 28).
    

Detailed description: 
      Comparison of two groups of patients SARS-CoV-2 positive with severe acute respiratory
      syndrome:

        1. Exposed to low prolonged doses of Methylprednisolone

        2. Not exposed to corticosteroids (standard of care alone)

      The two group will be weighted by means of a propensity score according to:

        1. Sex

        2. Age

        3. C-reactive protein (CRP) at baseline

        4. Sequential Organ Failure Assessment (SOFA) score at baseline

        5. PaO2/FiO2 ratio at baseline (ratio of arterial oxygen partial pressure to fractional
           inspired oxygen)

      Anti-viral agents, chloroquine, respiratory support (any), and antibiotics (any) are allowed
      in each study group. Corticosteroids use, other than per-protocol Methylprednisolone in the
      exposed group is a reason for dropout.

        1. The exposed group is treated with Methylprednisolone at study entry (baseline) according
           to a protocol based on the Italian national recommendations for COVID-19 management: a
           loading dose of 80 mg IV, followed by an infusion of 80 mg/day in 240 mL normal saline
           at 10 mL/h. The infusion is continued for at least eight days and until achieving either
           a PaO2:FiO2 > 350 mmHg or a CRP < 20 mg/L. Treatment is then switched to oral
           administration of Methylprednisolone 16 mg or 20 mg IV twice daily until CRP returns to
           < 20% of normal range and/or PaO2:FiO2 > 400 or SatHbO2 ≥ 95%. The decision to apply the
           protocol to Covid-19 is left to the discretion of the treating team for each individual
           patient.

        2. Unexposed patients will be selected from concurrent consecutive COVID-19 patients with
           the same inclusion and exclusion criteria and blinded to outcome data.
    

Intervention name(s): Methylprednisolone; standard care
Intervention type(s): Drug; Other
Intervention description(s): Usual standard of care plus Methylprednisolone (MP) 80 mg/kg IV bolus, followed by MP infusion of 80 mg/day in 240 mL normal saline at 10 mL/h. The infusion is continued for at least eight days and until achieving either a PaO2:FiO2 > 350 mmHg or a CRP < 20 mg/L. Treatment is then switched to oral administration of Methylprednisolone 16 mg or 20 mg IV twice daily until CRP returns to < 20% of normal range and/or PaO2:FiO2 > 400 or SatHbO2 ≥ 95%. The decision to apply the protocol to Covid-19 is left to the discretion of the treating team for each individual patient.; usual standard of care:
oxygen therapy (regular or high-flow) and monitoring
empiric antibiotic therapy
mechanical ventilation (invasive or noninvasive)
ECMO when needed and available
pronation when possible
other treatment which can be used are: antivirals, chloroquine, vitamins
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Consecutive patients admitted to Respiratory High dependency units for severe acute
        respiratory syndrome associated to COVID-19
      
Biospecimen description: 
      Previous specific informed consent, blood samples of some patients treated with
      methylprednisolone were collected, in order to have the possibility to do
    
Keywords: SARS-CoV-2,; SARS; ARDS; Methylprednisolone