Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Completed

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

Interventions: Other: standard care
Drug: Methylprednisolone

Registration Number: NCT04323592

Lead Sponsor: University of Trieste

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 173

Inclusion Criteria

SARS-CoV-2 positive
Age >17 years and < 80 years
P/F < 250 mmHg
Bilateral pneumonia (infiltrates/interstitial)
CRP >10mg/dL (or >100mg/L)
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

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-exposed to Methylprednisolone	standard care	Concurrent patients fulfilling the same inclusion and exclusion criteria, never treated with steroids.
Exposed to Methylprednisolone	standard care	Consecutive SARS-CoV-2 positive patients with severe acute respiratory syndrome treated with methylprednisolone (MP) at low prolonged dose, fulfilling inclusion and exclusion criteria.
Exposed to Methylprednisolone	Methylprednisolone	Consecutive SARS-CoV-2 positive patients with severe acute respiratory syndrome treated with methylprednisolone (MP) at low prolonged dose, fulfilling inclusion and exclusion criteria.

Primary Outcome Measures

Name	Time	Method
Admission to Intensive Care Unit (ICU)	28 days	We reported below the number of participants admitted to ICU within 28 days.
Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28	28 days	We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.
In-hospital Death Within 28 Days	28 days	We reported below the number of participants who died within 28 days, during the hospital stay.
Endotracheal Intubation (Invasive Mechanical Ventilation)	28 days	We reported below the number of participants who needed endotracheal intubation during ICU admission

Secondary Outcome Measures

Name	Time	Method
Number of Days Free From Mechanical Ventilation	28 days	number of days free from mechanical ventilation (both invasive and non-invasive) by day 28
Change in C-reactive Protein (CRP)	7 days	Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.