Trial Outcomes & Findings for Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome (NCT NCT04323592)
NCT ID: NCT04323592
Last Updated: 2020-06-24
Results Overview
We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.
Recruitment status
COMPLETED
Target enrollment
173 participants
Primary outcome timeframe
28 days
Results posted on
2020-06-24
Participant Flow
Participant milestones
| Measure |
Exposed to Methylprednisolone
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
|
Non-exposed to Methylprednisolone
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 Study
STARTED
|
83
|
90
|
|
Overall Study
COMPLETED
|
83
|
90
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
n=173 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=83 Participants
|
0 Participants
n=90 Participants
|
0 Participants
n=173 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=83 Participants
|
34 Participants
n=90 Participants
|
69 Participants
n=173 Participants
|
|
Age, Categorical
>=65 years
|
48 Participants
n=83 Participants
|
56 Participants
n=90 Participants
|
104 Participants
n=173 Participants
|
|
Age, Continuous
|
64.39 years
STANDARD_DEVIATION 10.73 • n=83 Participants
|
67.08 years
STANDARD_DEVIATION 8.24 • n=90 Participants
|
65.79 years
STANDARD_DEVIATION 9.58 • n=173 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=83 Participants
|
24 Participants
n=90 Participants
|
53 Participants
n=173 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=83 Participants
|
66 Participants
n=90 Participants
|
120 Participants
n=173 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Italy
|
83 Participants
n=83 Participants
|
90 Participants
n=90 Participants
|
173 Participants
n=173 Participants
|
|
C-reactive Protein
|
136.92 mg/L
STANDARD_DEVIATION 72.57 • n=83 Participants
|
148.64 mg/L
STANDARD_DEVIATION 75.59 • n=90 Participants
|
143.01 mg/L
STANDARD_DEVIATION 74.17 • n=173 Participants
|
|
PaO2/FiO2
|
152.02 ratio
STANDARD_DEVIATION 49.84 • n=83 Participants
|
151.01 ratio
STANDARD_DEVIATION 60.26 • n=90 Participants
|
151.50 ratio
STANDARD_DEVIATION 55.35 • n=173 Participants
|
|
Sequential Organ Failure Assessment (SOFA) Score
|
3 score
n=83 Participants
|
3 score
n=90 Participants
|
3 score
n=173 Participants
|
|
Lactates
|
1.76 mmol/L
STANDARD_DEVIATION 1.97 • n=83 Participants
|
1.34 mmol/L
STANDARD_DEVIATION 0.51 • n=90 Participants
|
1.52 mmol/L
STANDARD_DEVIATION 1.32 • n=173 Participants
|
|
Lymphocytes
|
622.28 cells/uL
STANDARD_DEVIATION 650.62 • n=83 Participants
|
954.5 cells/uL
STANDARD_DEVIATION 914.7 • n=90 Participants
|
938.94 cells/uL
STANDARD_DEVIATION 797.81 • n=173 Participants
|
|
D-dimer
|
780 ug/L Fibrinogen Equivalent Units (FEU)
n=83 Participants
|
890 ug/L Fibrinogen Equivalent Units (FEU)
n=90 Participants
|
813 ug/L Fibrinogen Equivalent Units (FEU)
n=173 Participants
|
|
lactate dehydrogenase (LDH)
|
380 U/L
STANDARD_DEVIATION 132.93 • n=83 Participants
|
413.06 U/L
STANDARD_DEVIATION 143.83 • n=90 Participants
|
396.41 U/L
STANDARD_DEVIATION 138.96 • n=173 Participants
|
|
Respiratory rate
|
23.74 Breaths per minute
STANDARD_DEVIATION 5.95 • n=83 Participants
|
25.27 Breaths per minute
STANDARD_DEVIATION 6.76 • n=90 Participants
|
24.55 Breaths per minute
STANDARD_DEVIATION 6.41 • n=173 Participants
|
PRIMARY outcome
Timeframe: 28 daysWe reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28
|
19 Participants
|
40 Participants
|
PRIMARY outcome
Timeframe: 28 daysWe reported below the number of participants who died within 28 days, during the hospital stay.
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
In-hospital Death Within 28 Days
|
6 Participants
|
21 Participants
|
PRIMARY outcome
Timeframe: 28 daysWe reported below the number of participants admitted to ICU within 28 days.
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
Admission to Intensive Care Unit (ICU)
|
15 Participants
|
27 Participants
|
PRIMARY outcome
Timeframe: 28 daysWe reported below the number of participants who needed endotracheal intubation during ICU admission
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
Endotracheal Intubation (Invasive Mechanical Ventilation)
|
15 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: 7 daysChange in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
Change in C-reactive Protein (CRP)
|
-82.08 mg/L
Standard Deviation 28.24
|
-34.34 mg/L
Standard Deviation 66.64
|
SECONDARY outcome
Timeframe: 28 daysnumber of days free from mechanical ventilation (both invasive and non-invasive) by day 28
Outcome measures
| Measure |
Exposed to Methylprednisolone
n=83 Participants
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
|
Non-exposed to Methylprednisolone
n=90 Participants
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
|
|---|---|---|
|
Number of Days Free From Mechanical Ventilation
|
19.11 days
Standard Deviation 8.73
|
14.34 days
Standard Deviation 11.65
|
Adverse Events
Exposed to Methylprednisolone
Serious events: 6 serious events
Other events: 23 other events
Deaths: 9 deaths
Non-exposed to Methylprednisolone
Serious events: 9 serious events
Other events: 21 other events
Deaths: 24 deaths
Serious adverse events
| Measure |
Exposed to Methylprednisolone
n=83 participants at risk
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
|
Non-exposed to Methylprednisolone
n=90 participants at risk
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
|
|---|---|---|
|
General disorders
Shock
|
0.00%
0/83 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Renal and urinary disorders
Acute renal failure
|
2.4%
2/83 • Number of events 2 • 28 days
|
4.4%
4/90 • Number of events 4 • 28 days
|
|
Vascular disorders
Disseminated intravascular coagulation
|
2.4%
2/83 • Number of events 2 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Cardiac disorders
Acute myocardial infarction
|
1.2%
1/83 • Number of events 1 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Nervous system disorders
Stroke
|
0.00%
0/83 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Vascular disorders
Pulmonary embolism
|
1.2%
1/83 • Number of events 1 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
Other adverse events
| Measure |
Exposed to Methylprednisolone
n=83 participants at risk
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
|
Non-exposed to Methylprednisolone
n=90 participants at risk
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
|
|---|---|---|
|
General disorders
Bacterial superinfection
|
1.2%
1/83 • Number of events 1 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Psychiatric disorders
Agitation
|
10.8%
9/83 • Number of events 9 • 28 days
|
2.2%
2/90 • Number of events 2 • 28 days
|
|
Endocrine disorders
Hyperglycemia
|
9.6%
8/83 • Number of events 8 • 28 days
|
0.00%
0/90 • 28 days
|
|
General disorders
Hypokalemia
|
7.2%
6/83 • Number of events 6 • 28 days
|
14.4%
13/90 • Number of events 13 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.2%
1/83 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Hepatobiliary disorders
Transaminase elevation
|
2.4%
2/83 • Number of events 2 • 28 days
|
2.2%
2/90 • Number of events 2 • 28 days
|
|
Cardiac disorders
QT elongation
|
8.4%
7/83 • Number of events 7 • 28 days
|
2.2%
2/90 • Number of events 2 • 28 days
|
|
Gastrointestinal disorders
Diarrhea
|
1.2%
1/83 • Number of events 1 • 28 days
|
6.7%
6/90 • Number of events 6 • 28 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place