Clinical Trial Results:
Sarilumab Treatment In cytoKinE storm caused by infection with COVID19.
Summary


EudraCT number 
202000125540 
Trial protocol 
ES 
Global end of trial date 
10 Nov 2020

Results information


Results version number 
v1(current) 
This version publication date 
11 Jan 2022

First version publication date 
11 Jan 2022

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
STRIKESARSCOV2


Additional study identifiers


ISRCTN number 
  
US NCT number 
  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Clínica Universidad de Navarra


Sponsor organisation address 
Avenida de Pío XII, 36, Pamplona, Spain, 31008


Public contact 
UCEC, Clínica Universidad de Navarra, 34 948255 4002723, ucicec@unav.es


Scientific contact 
UCEC, Clínica Universidad de Navarra, 34 948255 4002723, ucicec@unav.es


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
16 Jul 2021


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
10 Nov 2020


Global end of trial reached? 
Yes


Global end of trial date 
10 Nov 2020


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
Principal objective: evaluate the impact of sarilumab on the progression of COVID 19associated respiratory failure as measured by the change in a severity rating on a 7point severity index.
Secondary objective:
 Assess the impact of sarilumab on markers of systemic inflammation and the coagulation cascade in the context of COVID19.
 Assess the impact of sarilumab on mortality caused by COVID19.
 Assess the impact of sarilumab on oxygenation.
 Evaluate the safety of sarilumab in patients with severe pneumonia caused by COVID19.


Protection of trial subjects 
Given the limited clinical evidence regarding the intravenous administration of sarilumab, the first five patients in the trial received an initial dose of 200 mg of sarilumab at V1 (day 1) and an optional second dose of 200 mg of sarilumab at V2 (24 hours later). To decide whether to administer 400 mg of sarilumab at V1 and an optional second dose of 400 mg at V2 in subsequent patients, a safety evaluation by an internal review committee was performed to assess the safety profile through clinical and laboratory abnormalities. The dose could be reduced to 200 mg in V2 according to medical discretion and the patient's clinical condition.


Background therapy 
Participants received full supportive care during the study, as well as treatment with antibiotics and analgesics, as appropriate. The use of corticosteroids as rescue was allowed if it was considered that there was no response to the study treatment.  
Evidence for comparator 
  
Actual start date of recruitment 
28 Apr 2020


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Spain: 65


Worldwide total number of subjects 
65


EEA total number of subjects 
65


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
41


From 65 to 84 years 
23


85 years and over 
1



Recruitment


Recruitment details 
The inclusion of the first patient was on 28/04/2020 and the last patient was recruited on 19/10/2020. The participating sites were Clínica Universitaria de Navarra and Hospital Universitario Infanta Leonor.  
Preassignment


Screening details 
65 patients were enrolled in the study, but 5 of them were screening failures and did not receive the study treatment.  
Preassignment period milestones


Number of subjects started 
65  
Number of subjects completed 
60  
Preassignment subject noncompletion reasons


Reason: Number of subjects 
Physician decision: 2  
Reason: Number of subjects 
Consent withdrawn by subject: 3  
Period 1


Period 1 title 
Overall trial (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Not applicable


Blinding used 
Not blinded  
Arms


Arm title

Sarilumab  
Arm description 
Treatment of severe COVID19 with sarilumab  
Arm type 
Experimental  
Investigational medicinal product name 
Sarilumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Solution for infusion in prefilled syringe


Routes of administration 
Infusion


Dosage and administration details 
Each patient received two separate doses of sarilumab 24 hours apart. Each dose was administered through intravenous infusion for one hour and consisted of 200 mg of sarilumab diluted in 100 mL of a solution at 0.9% of NaCl.




Notes [1]  The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 65 patients were enrolled in the study, but 5 of them were screening failures and did not receive the study treatment. 


Baseline characteristics reporting groups


Reporting group title 
Overall trial (overall period)


Reporting group description 
  



End points reporting groups


Reporting group title 
Sarilumab


Reporting group description 
Treatment of severe COVID19 with sarilumab  
Subject analysis set title 
Day 1


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 1.


Subject analysis set title 
Day 2


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 2.


Subject analysis set title 
Day 3


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 3.


Subject analysis set title 
Day 4


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 4.


Subject analysis set title 
Day 7


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 5.


Subject analysis set title 
Day 28


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Population: the patients who attended visit 6.


Subject analysis set title 
Day 1 (N = N Day 2)


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 2.


Subject analysis set title 
Day 1 (N = N Day 3)


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 3.


Subject analysis set title 
Day 1 (N = N day 4)


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 4.


Subject analysis set title 
Day 1 (N = N Day 7)


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 5.


Subject analysis set title 
Day 1 (N = N Day 28)


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 6.



End point title 
Change in a severity rating on a 7point ordinal scale: day 7  
End point description 
Change in a severity rating on a 7point ordinal scale:
1. Death
2. Hospitalised, on invasive mechanical ventilation or ECMO
3. Hospitalised, on noninvasive ventilation or high flow oxygen devices
4. Hospitalised, requiring supplemental oxygen
5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID19 related or otherwise)
6. Hospitalised, not requiring supplemental oxygen – no longer requires ongoing medical care
7. Not hospitalised


End point type 
Primary


End point timeframe 
Day 7




Statistical analysis title 
Patients who worsened  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 7, using McNemar test.


Comparison groups 
Day 1 v Day 7


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
1.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
5.3  
Statistical analysis title 
Patients who remained stable  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 7, using McNemar test.


Comparison groups 
Day 1 v Day 7


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
30.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
18.7  
upper limit 
43.1  
Statistical analysis title 
Patients who improved  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 7, using McNemar test.


Comparison groups 
Day 1 v Day 7


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
67.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
54.9  
upper limit 
79.7 


End point title 
Change in a severity rating on a 7point ordinal scale: day 28  
End point description 
Change in a severity rating on a 7point ordinal scale:
1. Death
2. Hospitalised, on invasive mechanical ventilation or ECMO
3. Hospitalised, on noninvasive ventilation or high flow oxygen devices
4. Hospitalised, requiring supplemental oxygen
5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID19 related or otherwise)
6. Hospitalised, not requiring supplemental oxygen – no longer requires ongoing medical care
7. Not hospitalised


End point type 
Primary


End point timeframe 
Day 28




Statistical analysis title 
Patients who worsened  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 28, using McNemar test.


Comparison groups 
Day 1 v Day 28


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
1.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
5.3  
Statistical analysis title 
Patients who remained stable  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 28, using McNemar test.


Comparison groups 
Day 1 v Day 28


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0  
Statistical analysis title 
Patients who improved  
Statistical analysis description 
It was performed an analysis of contingency tables to see the evolution in 7point ordinal severity score between day 1 and day 28, using McNemar test.


Comparison groups 
Day 1 v Day 28


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Method 

Parameter type 
Percentage  
Point estimate 
98.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
94.7  
upper limit 
100 


End point title 
Percentage of patients reporting each severity rating on a 7point severity ordinal scale  
End point description 
7point severity ordinal scale:
1. Death
2. Hospitalised, on invasive mechanical ventilation or ECMO
3. Hospitalised, on noninvasive ventilation or high flow oxygen devices
4. Hospitalised, requiring supplemental oxygen
5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID19 related or otherwise)
6. Hospitalised, not requiring supplemental oxygen – no longer requires ongoing medical care
7. Not hospitalised


End point type 
Secondary


End point timeframe 
Day 7




No statistical analyses for this end point 


End point title 
Duration of mechanical ventilation measured by days of ventilation since treatment  
End point description 
"Duration of mechanical ventilation" is defined as: time from intubation date to extubation date (days)


End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Number of ventilator free days in the first 28 days  
End point description 
"Number of ventilator free days" is defined as: difference between 28 days and the duration with mechanical ventilation


End point type 
Secondary


End point timeframe 
Baseline to day 28




No statistical analyses for this end point 


End point title 
Number of patients requiring mechanical ventilation  
End point description 
Patients with at least one oxygen requirement


End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Number of patients admitted to the ICU  
End point description 
Patients with at least one entry in the intensive care unit (ICU)


End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC – axilla; > 37.2ºC –oral; > 37.8 –rectal or tympanic)  
End point description 
The analysis is only performed for those patients whose first temperature measurement has been> 36.6ºC (method axilar)


End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Changes from baseline in hemoglobin levels if available on day 2, 3, 4, 7, and 28  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the haemoglobin between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[1]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [1]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the haemoglobin between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.046 ^{[2]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [2]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the haemoglobin between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.552 ^{[3]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [3]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the haemoglobin between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.275 ^{[4]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [4]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the haemoglobin between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.018 ^{[5]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [5]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in platelet cell count if available on day 2, 3, 4, 7, and 28  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the platelet count between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[6]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [6]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the platelet count between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[7]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [7]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the platelet count between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[8]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [8]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the platelet count between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[9]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [9]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the platelet count between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.851 ^{[10]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [10]  Since the pvalue is over 0.05, there is no significant difference. 


End point title 
Changes from baseline in DDimer leves if available on day 2, 3, 4, 7, and 28  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the Ddimer levels between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
114


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.469 ^{[11]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [11]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the Ddimer levels between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
106


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.896 ^{[12]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [12]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the Ddimer levels between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.975 ^{[13]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [13]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the Ddimer levels between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
94


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.097 ^{[14]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [14]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the Ddimer levels between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
104


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[15]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [15]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Number of deaths due to any cause  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Organ failure (DIC, cardiac, hepatic, renal, cardiovascular)  
End point description 
Brescia, SOFA / Sequential organ failure assessment (SOFA) score (In agreement with hospital protocol)


End point type 
Secondary


End point timeframe 
Up to day 28




No statistical analyses for this end point 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: CReactive Protein (CRP)  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the CRP between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
114


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[16]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [16]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the CRP between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
108


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[17]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [17]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the CRP between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[18]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [18]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the CRP between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
94


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[19]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [19]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the CRP between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[20]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [20]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: Lactate dehydrogenase (LDH)  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the LDH between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
108


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.072 ^{[21]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [21]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the LDH between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
102


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.065 ^{[22]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [22]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the LDH between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
90


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.087 ^{[23]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [23]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the LDH between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
90


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019 ^{[24]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [24]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the LDH between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
100


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[25]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [25]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: serum ferritin  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the ferritin between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
104


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[26]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [26]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the ferritin between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.454 ^{[27]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [27]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the ferritin between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.21 ^{[28]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [28]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the ferritin between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
84


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[29]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [29]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the ferritin between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
100


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[30]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [30]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: Troponin  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the troponin between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.273 ^{[31]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [31]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the troponin between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
26


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.144 ^{[32]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [32]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the troponin between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.046 ^{[33]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [33]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the troponin between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
24


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.655 ^{[34]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [34]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the troponin between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
26


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.999 ^{[35]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [35]  Since the pvalue is over 0.05, there is no significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: Blood Urea Nitrogen (BUN)  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the BUN between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
116


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.047 ^{[36]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [36]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the BUN between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
104


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[37]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [37]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the BUN between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
84


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[38]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [38]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the BUN between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
80


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019 ^{[39]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [39]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the BUN between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
108


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.515 ^{[40]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [40]  Since the pvalue is over 0.05, there is no significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: creatinine  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the cretinine between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
116


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.206 ^{[41]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [41]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the cretinine between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
104


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.276 ^{[42]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [42]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
90


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.287 ^{[43]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [43]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the cretinine between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
86


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.07 ^{[44]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [44]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the cretinine between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
106


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.192 ^{[45]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [45]  Since the pvalue is over 0.05, there is no significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: Aspartate Transaminase (AST)  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the AST between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 1 (N = N Day 2) v Day 2


Number of subjects included in analysis 
92


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.026 ^{[46]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [46]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the AST between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
68


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.347 ^{[47]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [47]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the AST between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
60


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.018 ^{[48]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [48]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the AST between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.83 ^{[49]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [49]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the AST between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
100


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[50]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [50]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: Alanine Transaminase (ALT)  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the ALT between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
94


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[51]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [51]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the ALT between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
70


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[52]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [52]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the ALT between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
62


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[53]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [53]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the ALT between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
66


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[54]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [54]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the ALT between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
102


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.135 ^{[55]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [55]  Since the pvalue is over 0.05, there is no significant difference. 


End point title 
Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: total bilirrubin  
End point description 

End point type 
Secondary


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the total bilirrubin between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 1 (N = N Day 2) v Day 2


Number of subjects included in analysis 
86


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[56]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [56]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the total bilirrubin between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
74


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[57]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [57]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the total bilirrubin between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
72


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[58]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [58]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the total bilirrubin between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
76


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.238 ^{[59]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [59]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the total bilirrubin between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
94


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[60]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [60]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in white blood cell count if available on day 2, 3, 4, 7, and 28: leucocytes  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the leucocytes between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[61]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [61]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the leucocytes between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.021 ^{[62]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [62]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.096 ^{[63]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [63]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the leucocytes between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.298 ^{[64]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [64]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the leucocytes between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.018 ^{[65]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [65]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in white blood cell count if available on day 2, 3, 4, 7, and 28: neutrophils  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the neutrophils between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[66]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [66]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the neutrophils between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006 ^{[67]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [67]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the neutrophils between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007 ^{[68]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [68]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the neutrophils between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.462 ^{[69]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [69]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the neutrophils between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[70]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [70]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in white blood cell count if available on day 2, 3, 4, 7, and 28: linfocytes  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the linfocytes between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.956 ^{[71]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [71]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the linfocytes between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[72]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [72]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the linfocytes between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[73]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [73]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the linfocytes between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[74]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [74]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the linfocytes between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[75]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [75]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in white blood cell count if available on day 2, 3, 4, 7, and 28: monocytes  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the monocytes between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
120


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.03 ^{[76]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [76]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the monocytes between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.556 ^{[77]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [77]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the monocytes between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
98


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.511 ^{[78]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [78]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the monocytes between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[79]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [79]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the monocytes between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[80]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [80]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Changes from baseline in white blood cell count if available on day 2, 3, 4, 7, and 28: eosinophils  
End point description 

End point type 
Secondary


End point timeframe 
Up to 28 days or discharge




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the eosinophils between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 1 (N = N Day 2) v Day 2


Number of subjects included in analysis 
34


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.859 ^{[81]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [81]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the eosinophils between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.789 ^{[82]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [82]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the eosinophils between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
26


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.386 ^{[83]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [83]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the eosinophils between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
24


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.965 ^{[84]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [84]  Since the pvalue is over 0.05, there is no significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the eosinophils between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012 ^{[85]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [85]  Since the pvalue is under 0.05, there is a significant difference. 


End point title 
Change from baseline of cytokine levels associated with the cytokine storm, including, among others, IL6 on day 1 vs any other determination done up to day 28  
End point description 

End point type 
Other prespecified


End point timeframe 
Up to day 28




Statistical analysis title 
Day 1 vs day 2  
Statistical analysis description 
In order to observe the evolution of the IL6 levels between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 2 v Day 1 (N = N Day 2)


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[86]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [86]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 3  
Statistical analysis description 
In order to observe the evolution of the IL6 levels between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 3 v Day 1 (N = N Day 3)


Number of subjects included in analysis 
60


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[87]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [87]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 4  
Statistical analysis description 
In order to observe the evolution of the IL6 levels between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 4 v Day 1 (N = N day 4)


Number of subjects included in analysis 
58


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[88]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [88]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 7  
Statistical analysis description 
In order to observe the evolution of the IL6 levels between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 7 v Day 1 (N = N Day 7)


Number of subjects included in analysis 
58


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005 ^{[89]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [89]  Since the pvalue is under 0.05, there is a significant difference. 

Statistical analysis title 
Day 1 vs day 28  
Statistical analysis description 
In order to observe the evolution of the IL6 levels between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05.
In cases where a pvalue less than 0.05 appear, it refers to the existence of statistical significance.


Comparison groups 
Day 28 v Day 1 (N = N Day 28)


Number of subjects included in analysis 
48


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.018 ^{[90]}  
Method 
Wilcoxon (MannWhitney)  
Confidence interval 

Notes [90]  Since the pvalue is under 0.05, there is a significant difference. 


Adverse events information


Timeframe for reporting adverse events 
Throughout the duration of the trial


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
23.0


Reporting groups


Reporting group title 
Sarilumab


Reporting group description 
Treatment of severe COVID19 with sarilumab  


Frequency threshold for reporting nonserious adverse events: 1%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

07 Aug 2020 
Deletion of Exclusion criterion 7 (use of corticosteroids) and exclusion criterion 18 (positive serology for HIV, Hepatitis B and C). 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
The study is limited by the absence of a control group, so data must be interpreted with caution. However, judging from contemporary registries, mortality in the study was below that expected for the patient population.  
Online references 

http://www.ncbi.nlm.nih.gov/pubmed/33662012 http://www.ncbi.nlm.nih.gov/pubmed/33676590 http://www.ncbi.nlm.nih.gov/pubmed/33831046 http://www.ncbi.nlm.nih.gov/pubmed/33063540 