Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

University of Trieste173 enrolled

Overview

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).

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.

Study Type

OBSERVATIONAL

Interventions

MethylprednisoloneDRUG

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.

standard careOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. SARS-CoV-2 positive 2. Age \>17 years and \< 80 years 3. P/F \< 250 mmHg 4. Bilateral pneumonia (infiltrates/interstitial) 5. CRP \>10mg/dL (or \>100mg/L) 6. Alternatively to 4-5-6 criteria a diagnosis of ARDS according to the Berlin definition (Ranieri M, et al. JAMA 2012) Exclusion Criteria: * Heart failure as predominant cause of acute respiratory failure * Decompensated liver cirrhosis * Cancer * Organ transplantation * HIV+ * dialysis * long-term oxygen therapy, home mechanical ventilation * Idiopathic pulmonary fibrosis * Progressive neuromuscular disorders (e.g. Duchenne, Pompe, ALS) * Dementia or decompensated psychiatric diseases * immunosuppressive treatments * Chronic use of corticosteroids * Use of Tocilizumab * pregnancy

Outcomes

Primary Outcomes

Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28

We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.

Time frame: 28 days

In-hospital Death Within 28 Days

We reported below the number of participants who died within 28 days, during the hospital stay.

Time frame: 28 days

Admission to Intensive Care Unit (ICU)

We reported below the number of participants admitted to ICU within 28 days.

Time frame: 28 days

Endotracheal Intubation (Invasive Mechanical Ventilation)

We reported below the number of participants who needed endotracheal intubation during ICU admission

Time frame: 28 days

Secondary Outcomes

Change in C-reactive Protein (CRP)

Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.

Time frame: 7 days

Number of Days Free From Mechanical Ventilation

number of days free from mechanical ventilation (both invasive and non-invasive) by day 28

Time frame: 28 days

Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes