NCT04323592

Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 173 (actual)
• Sponsor: University of Trieste · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Severe Acute Respiratory Syndrome (SARS) Pneumonia
• Coronavirus Infections
• ARDS, Human

Interventions

Type	Name	Description
DRUG	Methylprednisolone	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.
OTHER	standard care	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

Timeline

• Start date: 2020-03-23
• Primary completion: 2020-05-10
• Completion: 2020-05-10
• First posted: 2020-03-26
• Last updated: 2020-06-24
• Results posted: 2020-06-04

Locations

1 site across 1 country: Italy

Regulatory

• FDA-regulated drug study