Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Conditions Severe Acute Respiratory Syndrome (SARS) Pneumonia
Coronavirus Infections
ARDS, Human
Interventions Drug: Methylprednisolone
Other: standard care
Enrollment 173
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Period Title: Overall Study
Started 83 90
Completed 83 90
Not Completed 0 0
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone Total
Hide Arm/Group Description

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at low prolonged dose.

At admission, inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering until normal CRP values (+20%) are reached.

Methylprednisolone: Methylprednisolone given at low prolonged dose infusion after initial 80mg iv bolus at admission followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

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
  • pronati

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

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
Total of all reporting groups
Overall Number of Baseline Participants 83 90 173
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 90 participants 173 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  42.2%
34
  37.8%
69
  39.9%
>=65 years
48
  57.8%
56
  62.2%
104
  60.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 83 participants 90 participants 173 participants
64.39  (10.73) 67.08  (8.24) 65.79  (9.58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 90 participants 173 participants
Female
29
  34.9%
24
  26.7%
53
  30.6%
Male
54
  65.1%
66
  73.3%
120
  69.4%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Italy Number Analyzed 83 participants 90 participants 173 participants
83
 100.0%
90
 100.0%
173
 100.0%
C-reactive Protein  
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 83 participants 90 participants 173 participants
136.92  (72.57) 148.64  (75.59) 143.01  (74.17)
PaO2/FiO2  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 83 participants 90 participants 173 participants
152.02  (49.84) 151.01  (60.26) 151.50  (55.35)
Sequential Organ Failure Assessment (SOFA) Score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Score
Number Analyzed 83 participants 90 participants 173 participants
3
(2 to 4)
3
(2 to 4)
3
(2 to 4)
[1]
Measure Description:

Sum of subscales scoring the function of: nervous system, kidneys, coagulation, respiratory system, cardiovascular system, liver.

Values ranging 0-24; higher values represent worse outcome.

Lactates  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 83 participants 90 participants 173 participants
1.76  (1.97) 1.34  (0.51) 1.52  (1.32)
Lymphocytes  
Mean (Standard Deviation)
Unit of measure:  cells/uL
Number Analyzed 83 participants 90 participants 173 participants
622.28  (650.62) 954.5  (914.7) 938.94  (797.81)
D-dimer  
Median (Inter-Quartile Range)
Unit of measure:  ug/L Fibrinogen Equivalent Units (FEU)
Number Analyzed 83 participants 90 participants 173 participants
780
(530 to 1207)
890
(506.75 to 1757)
813
(518 to 1560.5)
lactate dehydrogenase (LDH)  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 83 participants 90 participants 173 participants
380  (132.93) 413.06  (143.83) 396.41  (138.96)
Respiratory rate  
Mean (Standard Deviation)
Unit of measure:  Breaths per minute
Number Analyzed 83 participants 90 participants 173 participants
23.74  (5.95) 25.27  (6.76) 24.55  (6.41)
1.Primary Outcome
Title Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28
Hide Description We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Measure Type: Count of Participants
Unit of Measure: Participants
19
  22.9%
40
  44.4%
2.Primary Outcome
Title In-hospital Death Within 28 Days
Hide Description We reported below the number of participants who died within 28 days, during the hospital stay.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Measure Type: Count of Participants
Unit of Measure: Participants
6
   7.2%
21
  23.3%
3.Primary Outcome
Title Admission to Intensive Care Unit (ICU)
Hide Description We reported below the number of participants admitted to ICU within 28 days.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Measure Type: Count of Participants
Unit of Measure: Participants
15
  18.1%
27
  30.0%
4.Primary Outcome
Title Endotracheal Intubation (Invasive Mechanical Ventilation)
Hide Description We reported below the number of participants who needed endotracheal intubation during ICU admission
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Measure Type: Count of Participants
Unit of Measure: Participants
15
  18.1%
26
  28.9%
5.Secondary Outcome
Title Change in C-reactive Protein (CRP)
Hide Description Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Mean (Standard Deviation)
Unit of Measure: mg/L
-82.08  (28.24) -34.34  (66.64)
6.Secondary Outcome
Title Number of Days Free From Mechanical Ventilation
Hide Description number of days free from mechanical ventilation (both invasive and non-invasive) by day 28
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description:

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
Overall Number of Participants Analyzed 83 90
Mean (Standard Deviation)
Unit of Measure: days
19.11  (8.73) 14.34  (11.65)
Time Frame 28 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Hide Arm/Group Description

SARS-CoV-2 positive patients with severe acute respiratory syndrome consecutively treated with methylprednisolone (MP) at prolonged dose.

Inclusion criteria checked, the patient undergo 80mg iv bolus of MP followed by infusion (10cc/h) of MP in 240cc 0.9% saline every day until PaO2/FiO2 increase over 350 and/or CRP decrease below 20mg/L, then MP is administered PO tapering slowly until normal CRP values (+20%) are reached.

Methylprednisolone: after initial 80mg iv bolus followed by 80mg in 240cc 0.9% saline administered iv at 10cc/h speed for at least 7 day or more. Duration of Methylprednisolone treatment depends from CRP and P/F values already described in arm/group description

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)
  • pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins

Concurrent patients with the same inclusion/section exclusion criteria never treated with steroids, strictly matched according to gender and age (+/-10 years) and other three parameters:

CRP, SOFA score, PaO2:FiO2 -> each parameter must be <20% difference between case and control.

standard care: usual standard of care:

  • respiratory support
  • empiric antibiotic therapy
  • mechanical ventilation (invasive or noninvasive)pronation when possible
  • other treatment which can be used are: antivirals, chloroquine, vitamins
All-Cause Mortality
Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Affected / at Risk (%) Affected / at Risk (%)
Total   9/83 (10.84%)      24/90 (26.67%)    
Hide Serious Adverse Events
Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/83 (7.23%)      9/90 (10.00%)    
Cardiac disorders     
Acute myocardial infarction *  1/83 (1.20%)  1 1/90 (1.11%)  1
General disorders     
Shock *  0/83 (0.00%)  0 1/90 (1.11%)  1
Nervous system disorders     
Stroke *  0/83 (0.00%)  0 1/90 (1.11%)  1
Renal and urinary disorders     
Acute renal failure *  2/83 (2.41%)  2 4/90 (4.44%)  4
Vascular disorders     
Disseminated intravascular coagulation *  2/83 (2.41%)  2 1/90 (1.11%)  1
Pulmonary embolism *  1/83 (1.20%)  1 1/90 (1.11%)  1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Exposed to Methylprednisolone Non-exposed to Methylprednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/83 (27.71%)      21/90 (23.33%)    
Cardiac disorders     
QT elongation *  7/83 (8.43%)  7 2/90 (2.22%)  2
Endocrine disorders     
Hyperglycemia *  8/83 (9.64%)  8 0/90 (0.00%)  0
Gastrointestinal disorders     
Diarrhea *  1/83 (1.20%)  1 6/90 (6.67%)  6
General disorders     
Bacterial superinfection *  1/83 (1.20%)  1 1/90 (1.11%)  1
Hypokalemia *  6/83 (7.23%)  6 13/90 (14.44%)  13
Hepatobiliary disorders     
Transaminase elevation *  2/83 (2.41%)  2 2/90 (2.22%)  2
Psychiatric disorders     
Agitation *  9/83 (10.84%)  9 2/90 (2.22%)  2
Respiratory, thoracic and mediastinal disorders     
Pneumothorax *  1/83 (1.20%)  1 0/90 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Marco Confalonieri
Organization: University of Trieste
Phone: +393356895168 ext 4667
EMail: mconfalonieri@units.it
Layout table for additonal information
Responsible Party: marco confalonieri, University of Trieste
ClinicalTrials.gov Identifier: NCT04323592    
Other Study ID Numbers: MP-19 023_2020
First Submitted: March 19, 2020
First Posted: March 26, 2020
Results First Submitted: May 21, 2020
Results First Posted: June 4, 2020
Last Update Posted: June 24, 2020