Severe Acute Respiratory Syndrome (SARS) PneumoniaMP-C19NCT04323592
Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome
An observational study of Severe Acute Respiratory Syndrome (SARS) Pneumonia and Coronavirus Infections, run by University of Trieste at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Severe Acute Respiratory Syndrome (SARS) Pneumonia, Coronavirus Infections, ARDS, Human
- What is being tested?
- Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 173 participants
- Where
- 1 siteItaly
- Study dates
- 23 Mar 2020to 10 May 2020
- How long will I take part?
- 4 Weeks
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients admitted to Respiratory High dependency units for severe acute respiratory syndrome associated to COVID-19
Who may be able to join
- 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)
Who cannot join
- Heart failure as predominant cause of acute respiratory failure
- Decompensated liver cirrhosis
- Cancer
- Organ transplantation
- HIV+
- dialysis
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome
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).
Read the detailed description
Comparison of two groups of patients SARS-CoV-2 positive with severe acute respiratory syndrome:
- Exposed to low prolonged doses of Methylprednisolone
- Not exposed to corticosteroids (standard of care alone)
The two group will be weighted by means of a propensity score according to:
- Sex
- Age
- C-reactive protein (CRP) at baseline
- Sequential Organ Failure Assessment (SOFA) score at baseline
- 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.
- 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.
- Unexposed patients will be selected from concurrent consecutive COVID-19 patients with the same inclusion and exclusion criteria and blinded to outcome data.
- Being tested
- Methylprednisolone, standard care
- Keywords
- SARS-CoV-2,, SARS, ARDS, Methylprednisolone
- Medical subject headings
- Severe Acute Respiratory Syndrome, Pneumonia, Coronavirus Infections, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
standard careOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Methylprednisolone; Other: standard care | |
| Non-exposed to Methylprednisolone | Concurrent patients fulfilling the same inclusion and exclusion criteria, never treated with steroids. Receives: Other: standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
In-hospital Death Within 28 Days
We reported below the number of participants who died within 28 days, during the hospital stay.
Measured: 28 days
Admission to Intensive Care Unit (ICU)
We reported below the number of participants admitted to ICU within 28 days.
Measured: 28 days
Endotracheal Intubation (Invasive Mechanical Ventilation)
We reported below the number of participants who needed endotracheal intubation during ICU admission
Measured: 28 days
Secondary outcomes (2)
Change in C-reactive Protein (CRP)
Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.
Measured: 7 days
Number of Days Free From Mechanical Ventilation
number of days free from mechanical ventilation (both invasive and non-invasive) by day 28
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2020
- Study start23 Mar 2020
- Primary completion10 May 2020
- Study completion10 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Severe Acute Respiratory Syndrome (SARS) PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 173 participants (actual)
- Target duration
- 4 Weeks
Sponsor and investigators
- Lead sponsor
- University of Trieste
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, marco confalonieri, University of Trieste
- Investigators
- Marco Confalonieri, MD, Principal investigator, University of Trieste
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04323592
- Sponsor's protocol ID
- MP-19 023_2020
- Acronym
- MP-C19
- Status last verified
- Jun 2020
- First submitted
- 19 Mar 2020
- Last updated
- 24 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymised data will be available only to data manager who can visualise clinical chart anytime when is needed
Publications
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.
PubMed 32218915Salton 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.
PubMed 33072814
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome
- ClinicalTrials.gov ID
- NCT04323592
- Acronym / sponsor ID
- MP-C19 / MP-19 023_2020
- Keywords
- SARS-CoV-2,, SARS, ARDS, Methylprednisolone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- University of TriesteUniversity, hospital or other
- Study start
- 23 Mar 2020 (actual)
- Primary completion
- 10 May 2020 (actual)
- Study completion
- 10 May 2020 (actual)
- First posted
- 26 Mar 2020 (actual)
- Results
- Posted 4 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Exposed to low prolonged doses of Methylprednisolone
- Not exposed to corticosteroids (standard of care alone)
The two group will be weighted by means of a propensity score according to:
- Sex
- Age
- C-reactive protein (CRP) at baseline
- Sequential Organ Failure Assessment (SOFA) score at baseline
- 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.
- 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.
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 4 Weeks
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed to Methylprednisolone | – | Drug: Methylprednisolone, Other: standard careConsecutive SARS-CoV-2 positive patients with severe acute respiratory syndrome treated with methylprednisolone (MP) at low prolonged dose, fulfilling inclusion and exclusion criteria. |
| Non-exposed to Methylprednisolone | – | Other: standard careConcurrent patients fulfilling the same inclusion and exclusion criteria, never treated with steroids. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients admitted to Respiratory High dependency units for severe acute respiratory syndrome associated to COVID-19
Key inclusion criteria (6 listed)
- SARS-CoV-2 positive
- Age >17 years and < 80 years
- P/F < 250 mmHg
- Bilateral pneumonia (infiltrates/interstitial)
- CRP >10mg/dL (or >100mg/L)
Key exclusion criteria (14 listed)
- Heart failure as predominant cause of acute respiratory failure
- Decompensated liver cirrhosis
- Cancer
- Organ transplantation
- HIV+
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneUsual 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. | Drug | Exposed to Methylprednisolone |
| standard careusual 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 | Other | Exposed to Methylprednisolone, Non-exposed to Methylprednisolone |
Primary outcome
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.
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.
Admission to Intensive Care Unit (ICU)
Time frame: 28 days
We reported below the number of participants admitted to ICU within 28 days.
Endotracheal Intubation (Invasive Mechanical Ventilation)
Time frame: 28 days
We reported below the number of participants who needed endotracheal intubation during ICU admission
2 secondary outcomes
Change in C-reactive Protein (CRP)
Time frame: 7 days
Number of Days Free From Mechanical Ventilation
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32218915Nicastri 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.
- Derived from this study: PubMed 33072814Salton 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.
- Individual participant dataSharing planned: No. Anonymised data will be available only to data manager who can visualise clinical chart anytime when is needed
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Confalonieri, MD principal investigator
University of Trieste
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Acute Respiratory Syndrome (SARS) Pneumonia and Coronavirus Infections, run by University of Trieste at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28 (time frame: 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04323592, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2020.