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Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome (MP-C19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04323592
Recruitment Status : Completed
First Posted : March 26, 2020
Results First Posted : June 4, 2020
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
marco confalonieri, University of Trieste

Study Description
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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).


Condition or disease Intervention/treatment
Severe Acute Respiratory Syndrome (SARS) Pneumonia Coronavirus Infections ARDS, Human Drug: Methylprednisolone Other: standard care

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.
Study Design
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Study Type : Observational [Patient Registry]
Actual Enrollment : 173 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 4 Weeks
Official Title: Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome
Actual Study Start Date : March 23, 2020
Actual Primary Completion Date : May 10, 2020
Actual Study Completion Date : May 10, 2020

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Exposed to 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.
 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
Non-exposed to Methylprednisolone
Concurrent patients fulfilling the same inclusion and exclusion criteria, never treated with steroids.
 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


Outcome Measures
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Primary Outcome Measures :
  1. Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28 [ Time Frame: 28 days ]
    We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.

  2. In-hospital Death Within 28 Days [ Time Frame: 28 days ]
    We reported below the number of participants who died within 28 days, during the hospital stay.

  3. Admission to Intensive Care Unit (ICU) [ Time Frame: 28 days ]
    We reported below the number of participants admitted to ICU within 28 days.

  4. Endotracheal Intubation (Invasive Mechanical Ventilation) [ Time Frame: 28 days ]
    We reported below the number of participants who needed endotracheal intubation during ICU admission


Secondary Outcome Measures :
  1. Change in C-reactive Protein (CRP) [ Time Frame: 7 days ]
    Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.

  2. Number of Days Free From Mechanical Ventilation [ Time Frame: 28 days ]
    number of days free from mechanical ventilation (both invasive and non-invasive) by day 28


Biospecimen Retention:   None Retained
Previous specific informed consent, blood samples of some patients treated with methylprednisolone were collected, in order to have the possibility to do

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients admitted to Respiratory High dependency units for severe acute respiratory syndrome associated to COVID-19
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04323592


Locations
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Italy
Marco Confalonieri
Trieste, TS, Italy, 34149
Sponsors and Collaborators
University of Trieste
Investigators
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Principal Investigator: Marco Confalonieri, MD University of Trieste
  Study Documents (Full-Text)

Documents provided by marco confalonieri, University of Trieste:
Informed Consent Form  [PDF] March 23, 2020
Statistical Analysis Plan  [PDF] March 23, 2020
Study Protocol  [PDF] March 23, 2020

More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: marco confalonieri, Head of Pulmonology and Critical care Dept., University of Trieste
ClinicalTrials.gov Identifier: NCT04323592    
Other Study ID Numbers: MP-19 023_2020
First Posted: March 26, 2020    Key Record Dates
Results First Posted: June 4, 2020
Last Update Posted: June 24, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Anonymised data will be available only to data manager who can visualise clinical chart anytime when is needed

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by marco confalonieri, University of Trieste:
SARS-CoV-2,
SARS
ARDS
Methylprednisolone
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome
Syndrome
Disease
Pathologic Processes
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiration Disorders
 Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones