Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

NCT04323592 | Completed Results DMC FDA Drug

• 1 other identifier: MP-19 023_2020
• Study Type: observational
• Target: 173
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

SARS-CoV-2,; SARS; ARDS; Methylprednisolone

Outcome Measures

Primary Outcomes (4)

• 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.

  28 days

• In-hospital Death Within 28 Days

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

  28 days

• Admission to Intensive Care Unit (ICU)

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

  28 days

• Endotracheal Intubation (Invasive Mechanical Ventilation)

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

  28 days

Secondary Outcomes (2)

• Change in C-reactive Protein (CRP)

  7 days

• Number of Days Free From Mechanical Ventilation

  28 days

Study Arms (2)

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; Other: standard care

Non-exposed to Methylprednisolone

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

Other: standard care

Interventions

Methylprednisolone DRUG

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.

Exposed to Methylprednisolone

standard care OTHER

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

Exposed to Methylprednisolone; Non-exposed to Methylprednisolone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients admitted to Respiratory High dependency units for severe acute respiratory syndrome associated to COVID-19

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Trieste: lead

Study Sites (1)

Marco Confalonieri

Trieste, TS, 34149, Italy

Location

Related Publications (2)

• Nicastri E, Petrosillo N, Ascoli Bartoli T, Lepore L, Mondi A, Palmieri F, D'Offizi G, Marchioni L, Murachelli S, Ippolito G, Antinori A. National Institute for the Infectious Diseases "L. Spallanzani", IRCCS. Recommendations for COVID-19 clinical management. Infect Dis Rep. 2020 Mar 16;12(1):8543. doi: 10.4081/idr.2020.8543. eCollection 2020 Feb 25.

  PMID: 32218915 BACKGROUND

• Salton F, Confalonieri P, Meduri GU, Santus P, Harari S, Scala R, Lanini S, Vertui V, Oggionni T, Caminati A, Patruno V, Tamburrini M, Scartabellati A, Parati M, Villani M, Radovanovic D, Tomassetti S, Ravaglia C, Poletti V, Vianello A, Gaccione AT, Guidelli L, Raccanelli R, Lucernoni P, Lacedonia D, Foschino Barbaro MP, Centanni S, Mondoni M, Davi M, Fantin A, Cao X, Torelli L, Zucchetto A, Montico M, Casarin A, Romagnoli M, Gasparini S, Bonifazi M, D'Agaro P, Marcello A, Licastro D, Ruaro B, Volpe MC, Umberger R, Confalonieri M. Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia. Open Forum Infect Dis. 2020 Sep 12;7(10):ofaa421. doi: 10.1093/ofid/ofaa421. eCollection 2020 Oct.

  PMID: 33072814 DERIVED

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

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; Pneumonia; Coronavirus Infections; Respiratory Distress Syndrome

Interventions

Methylprednisolone; Standard of Care

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Prof. Marco Confalonieri
• Organization: University of Trieste

mconfalonieri@units.it

+393356895168

Study Officials

• Marco Confalonieri, MD

  University of Trieste

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 4 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pulmonology and Critical care Dept.

Study Record Dates

• First Submitted: March 19, 2020
• First Posted: March 26, 2020
• Study Start: March 23, 2020
• Primary Completion: May 10, 2020
• Study Completion: May 10, 2020
• Last Updated: June 24, 2020
• Results First Posted: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)