Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

Prolonged Low Doses of 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 2020-03-23
Completion Date 2020-05-10
Primary Completion Date 2020-05-10
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

2020-06-01

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

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.

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

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