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

Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Sponsors

Lead sponsor: University of Trieste

Source 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.

Overall Status Completed
Start Date March 23, 2020
Completion Date May 10, 2020
Primary Completion Date May 10, 2020
Study Type Observational [Patient Registry]
Primary Outcome
Measure Time Frame
Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28 28 days
In-hospital Death Within 28 Days 28 days
Admission to Intensive Care Unit (ICU) 28 days
Endotracheal Intubation (Invasive Mechanical Ventilation) 28 days
Secondary Outcome
Measure Time Frame
Change in C-reactive Protein (CRP) 7 days
Number of Days Free From Mechanical Ventilation 28 days
Enrollment 173
Condition
Intervention

Intervention type: Drug

Intervention name: Methylprednisolone

Description: 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.

Arm group label: Exposed to Methylprednisolone

Intervention type: Other

Intervention name: standard care

Description: 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

Sampling method: Non-Probability Sample

Criteria:

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

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Marco Confalonieri, MD Principal Investigator University of Trieste
Location
facility Marco Confalonieri
Location Countries

Italy

Verification Date

June 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: University of Trieste

Investigator full name: marco confalonieri

Investigator title: Head of Pulmonology and Critical care Dept.

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Arm group label: Exposed to Methylprednisolone

Description: Consecutive SARS-CoV-2 positive patients with severe acute respiratory syndrome treated with methylprednisolone (MP) at low prolonged dose, fulfilling inclusion and exclusion criteria.

Arm group label: Non-exposed to Methylprednisolone

Description: Concurrent patients fulfilling the same inclusion and exclusion criteria, never treated with steroids.

Acronym MP-C19
Patient Data No
Study Design Info

Observational model: Cohort

Time perspective: Prospective

Source: ClinicalTrials.gov