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Clinical Trial Results:
Sarilumab Treatment In cytoKinE storm caused by infection with COVID-19.

Summary
EudraCT number	2020-001255-40
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

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Trial information

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Sponsor protocol code

STRIKE-SARS-COV2

ISRCTN number

US NCT number

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

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

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

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?

Main objective of the trial

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

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 follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 65

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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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.

Screening details

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

Number of subjects started

Number of subjects completed

Reason: Number of subjects

Physician decision: 2

Reason: Number of subjects

Consent withdrawn by subject: 3

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Sarilumab

Arm description

Treatment of severe COVID-19 with sarilumab

Arm type

Experimental

Investigational medicinal product name

Sarilumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in pre-filled 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.

Number of subjects in period 1 ^[1]	Sarilumab
Started	60
Completed	56
Not completed	4
Consent withdrawn by subject	4

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

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Reporting group title

Overall trial (overall period)

Reporting group description

Reporting group values	Overall trial (overall period)	Total
Number of subjects	60	60
Age categorical
Units: Subjects
Adults (18-64 years)	38	38
From 65-84 years	21	21
85 years and over	1	1
Age continuous
Units: years
arithmetic mean (standard deviation)	59.5 ( 13.5 )	-
Gender categorical
Units: Subjects
Female	14	14
Male	46	46
Race
Units: Subjects
Caucasian	40	40
Latin	8	8
Hispanic	5	5
Others	4	4
Missing	3	3
Patients reporting each severity rating on a 7-point severity ordinal scale
7-point severity ordinal scale: 1. Death 2. Hospitalised, on invasive mechanical ventilation or ECMO 3. Hospitalised, on non-invasive ventilation or high flow oxygen devices 4. Hospitalised, requiring supplemental oxygen 5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalised, not requiring supplemental oxygen – no longer requires ongoing medical care 7. Not hospitalised
Units: Subjects
Severity 1	0	0
Severity 2	1	1
Severity 3	6	6
Severity 4	40	40
Severity 5	13	13
Severity 6	0	0
Severity 7	0	0
Smoking status
The 36.7% has never smoked, where the rest smoked a mean (SD) 9.5 (9.9) cigarette per day since a mean (SD) of 23.1 (15.0) years with a mean (SD) of pack-years 16.2 (13.8).
Units: Subjects
Current some day smoker	1	1
Former smoker	17	17
Smoker	2	2
Never smoker	22	22
Unknown if ever smoked	18	18
Medical history: hypertension
Units: Subjects
No	39	39
Yes	21	21
Medical history: Diabetes mellitus
Units: Subjects
No	50	50
Yes	10	10
Medical history: cardiac disease
Units: Subjects
No	59	59
Yes	1	1
Medical history: Chronic Obstructive Pulmonary Disease
Units: Subjects
No	56	56
Yes	4	4
Medical history: cancer
Units: Subjects
No	57	57
Yes	3	3
COVID-19 history: fever
Units: Subjects
No	8	8
Yes	52	52
COVID-19 history: cough
Units: Subjects
No	15	15
Yes	45	45
COVID-19 history: dysgeusia
Units: Subjects
No	53	53
Yes	7	7
COVID-19 history: anosmia
Units: Subjects
No	51	51
Yes	9	9
COVID-19 history: odynophagia
Units: Subjects
No	58	58
Yes	2	2
COVID-19 history: nausea
Units: Subjects
No	56	56
Yes	4	4
COVID-19 history: diarrhea
Units: Subjects
No	53	53
Yes	7	7
COVID-19 history: myalgia
Units: Subjects
No	42	42
Yes	18	18
COVID-19 history: asthenia
Units: Subjects
No	37	37
Yes	23	23
COVID-19 history: other related symptoms
Units: Subjects
No	19	19
Yes	41	41
PCR SARS CoV 2
Units: Subjects
Positive	60	60
Negative	0	0
Chest radiography done
Units: Subjects
No	17	17
Yes	43	43
Chest radiography done: COVID-19 pneumonia
Units: Subjects
No	1	1
Yes	42	42
Missing	17	17
CT Scan done
Units: Subjects
No	27	27
Yes	33	33
CT Scan done: COVID-19 pneumonia
Units: Subjects
No	1	1
Yes	32	32
Missing	27	27
CT scan score for pulmonary involvement: rigth upper lobe
Units: Subjects
1-5% involvement	4	4
6-25% involvement	14	14
26-50% involvement	7	7
51-75% involvement	5	5
Missing	30	30
CT scan score for pulmonary involvement: middle lobe
Units: Subjects
1-5% involvement	10	10
6-25% involvement	8	8
26-50% involvement	7	7
51-75% involvement	3	3
Missing	32	32
CT scan score for pulmonary involvement: right lower lobe
Units: Subjects
1-5% involvement	4	4
6-25% involvement	9	9
26-50% involvement	8	8
51-75% involvement	4	4
100% involvement	6	6
Missing	29	29
CT scan score for pulmonary involvement: left upper lobe
Units: Subjects
1-5% involvement	7	7
6-25% involvement	9	9
26-50% involvement	6	6
51-75% involvement	7	7
100% involvement	1	1
Missing	30	30
CT scan score for pulmonary involvement: left lower lobe
Units: Subjects
1-5% involvement	4	4
6-25% involvement	11	11
26-50% involvement	4	4
51-75% involvement	5	5
100% involvement	5	5
Missing	31	31
Weight
Units: kilogram(s)
arithmetic mean (standard deviation)	83.9 ( 14.7 )	-
Height
Units: centimetres
arithmetic mean (standard deviation)	169.8 ( 9.5 )	-
Oxygen parameters: SaO2 (from pulsioximeter)
Units: Percentage %
arithmetic mean (standard deviation)	94.1 ( 1.9 )	-
Oxygen parameters: pH
Units: --
arithmetic mean (standard deviation)	7.4 ( 0.1 )	-
Oxygen parameters: PaO2
Units: mmHg
arithmetic mean (standard deviation)	71.4 ( 34.4 )	-
Oxygen parameters: PaCO2
Units: mmHg
arithmetic mean (standard deviation)	37.2 ( 7.4 )	-
Oxygen parameters: SaO2 (from arterial blood gases)
Units: Percentage %
arithmetic mean (standard deviation)	88.6 ( 15.1 )	-
Oxygen parameters: lactic acid (from arterial blood gases)
Units: mmol/L
arithmetic mean (standard deviation)	1.5 ( 0.6 )	-
Oxygen parameters: PaO2/FiO2 Index
Units: --
arithmetic mean (standard deviation)	257.5 ( 151.1 )	-
Oxygen parameters: SaO2/FiO2 Index
Units: --
arithmetic mean (standard deviation)	152.7 ( 49.8 )	-

End points

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Reporting group title

Sarilumab

Reporting group description

Treatment of severe COVID-19 with sarilumab

Subject analysis set title

Day 1

Subject analysis set type

Intention-to-treat

Subject analysis set description

Population: the patients who attended visit 1.

Subject analysis set title

Day 2

Subject analysis set type

Intention-to-treat

Subject analysis set description

Population: the patients who attended visit 2.

Subject analysis set title

Day 3

Subject analysis set type

Intention-to-treat

Subject analysis set description

Population: the patients who attended visit 3.

Subject analysis set title

Day 4

Subject analysis set type

Intention-to-treat

Subject analysis set description

Population: the patients who attended visit 4.

Subject analysis set title

Day 7

Subject analysis set type

Intention-to-treat

Subject analysis set description

Population: the patients who attended visit 5.

Subject analysis set title

Day 28

Subject analysis set type

Intention-to-treat

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

Intention-to-treat

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

Intention-to-treat

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

Intention-to-treat

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

Intention-to-treat

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

Intention-to-treat

Subject analysis set description

Patients who attended visit 1 and whose data were compared with the data of patients who attended visit 6.

Primary: Change in a severity rating on a 7-point ordinal scale: day 7

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End point title

Change in a severity rating on a 7-point ordinal scale: day 7

End point description

Change in a severity rating on a 7-point ordinal scale: 1. Death 2. Hospitalised, on invasive mechanical ventilation or ECMO 3. Hospitalised, on non-invasive ventilation or high flow oxygen devices 4. Hospitalised, requiring supplemental oxygen 5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 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

End point values	Day 1	Day 7
Number of subjects analysed	55	55
Units: Subjects
Severity 1	0	0
Severity 2	1	1
Severity 3	6	2
Severity 4	37	13
Severity 5	11	17
Severity 6	0	20
Severity 7	0	2

Patients who worsened

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

5.3

Patients who remained stable

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

30.9

Confidence interval

level

95%

sides

2-sided

lower limit

18.7

upper limit

43.1

Patients who improved

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

67.3

Confidence interval

level

95%

sides

2-sided

lower limit

54.9

upper limit

79.7

Primary: Change in a severity rating on a 7-point ordinal scale: day 28

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End point title

Change in a severity rating on a 7-point ordinal scale: day 28

End point description

End point type

Primary

End point timeframe

Day 28

End point values	Day 1	Day 28
Number of subjects analysed	56	56
Units: Subjects
Severity 1	0	0
Severity 2	1	1
Severity 3	6	1
Severity 4	37	1
Severity 5	11	0
Severity 6	0	0
Severity 7	0	53

Patients who worsened

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

5.3

Patients who remained stable

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Patients who improved

Statistical analysis description

It was performed an analysis of contingency tables to see the evolution in 7-point 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

Pre-specified

Analysis type

superiority

Method

Parameter type

Percentage

Point estimate

98.2

Confidence interval

level

95%

sides

2-sided

lower limit

94.7

upper limit

100

Secondary: Percentage of patients reporting each severity rating on a 7-point severity ordinal scale

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End point title

Percentage of patients reporting each severity rating on a 7-point severity ordinal scale

End point description

7-point severity ordinal scale: 1. Death 2. Hospitalised, on invasive mechanical ventilation or ECMO 3. Hospitalised, on non-invasive ventilation or high flow oxygen devices 4. Hospitalised, requiring supplemental oxygen 5. Hospitalised, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 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

End point values	Sarilumab
Number of subjects analysed	55
Units: Subjects
Severity 1	0
Severity 2	1
Severity 3	2
Severity 4	13
Severity 5	17
Severity 6	20
Severity 7	2

No statistical analyses for this end point

Secondary: Duration of mechanical ventilation measured by days of ventilation since treatment

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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

End point values	Sarilumab
Number of subjects analysed	51
Units: Days
arithmetic mean (standard deviation)	8.7 ( 7.7 )

No statistical analyses for this end point

Secondary: Number of ventilator free days in the first 28 days

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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

End point values	Sarilumab
Number of subjects analysed	49
Units: Days
arithmetic mean (standard deviation)	20.4 ( 5.5 )

No statistical analyses for this end point

Secondary: Number of patients requiring mechanical ventilation

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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

End point values	Day 1	Day 2	Day 3	Day 4	Day 7	Day 28
Number of subjects analysed	60	60	59	56	55	56
Units: Subjects
No	12	21	19	17	37	52
Yes	48	39	40	39	18	4

No statistical analyses for this end point

Secondary: Number of patients admitted to the ICU

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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

End point values	Sarilumab
Number of subjects analysed	60
Units: Subjects
No	53
Yes	7

No statistical analyses for this end point

Secondary: Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC – axilla; > 37.2ºC –oral; > 37.8 –rectal or tympanic)

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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

End point values	Sarilumab
Number of subjects analysed	30
Units: Days
arithmetic mean (standard deviation)	1.5 ( 0.7 )

No statistical analyses for this end point

Secondary: Changes from baseline in hemoglobin levels if available on day 2, 3, 4, 7, and 28

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: g/dL
arithmetic mean (standard deviation)	13.4 ( 1.2 )	13.4 ( 1.2 )	13.5 ( 1.1 )	13.8 ( 1.5 )	13.9 ( 1.3 )	13.6 ( 1.3 )	13.6 ( 1.2 )	13.6 ( 1.2 )	13.6 ( 1.2 )	13.6 ( 1.3 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[1]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[1] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.046 ^[2]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[2] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.552 ^[3]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[3] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.275 ^[4]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[4] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[5]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[5] - Since the p-value is under 0.05, there is a significant difference.

Secondary: Changes from baseline in platelet cell count if available on day 2, 3, 4, 7, and 28

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: 10^9/L
arithmetic mean (standard deviation)	257.0 ( 100.3 )	282.2 ( 113.0 )	322.2 ( 124.1 )	360.1 ( 142.2 )	219.5 ( 86.0 )	221.8 ( 79.4 )	220.2 ( 78.6 )	230.8 ( 80.7 )	222.8 ( 81.5 )	224.5 ( 80.1 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[6] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[7]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[7] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[8] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[9] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.851 ^[10]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[10] - Since the p-value is over 0.05, there is no significant difference.

Secondary: Changes from baseline in D-Dimer leves if available on day 2, 3, 4, 7, and 28

Top of page

End point title

Changes from baseline in D-Dimer 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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	57	53	48	47	52	57	53	48	47	52
Units: ng/mL
arithmetic mean (standard deviation)	981.8 ( 821.9 )	957.7 ( 1117.9 )	1065.2 ( 1883.5 )	933.8 ( 1180.6 )	609.6 ( 1190.2 )	936.3 ( 875.3 )	917.9 ( 894.6 )	858.5 ( 757.3 )	965.7 ( 940.4 )	919.6 ( 900.7 )

Day 1 vs day 2

Statistical analysis description

In order to observe the evolution of the D-dimer levels between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.469 ^[11]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[11] - Since the p-value is over 0.05, there is no significant difference.

Day 1 vs day 3

Statistical analysis description

In order to observe the evolution of the D-dimer levels between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.896 ^[12]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[12] - Since the p-value is over 0.05, there is no significant difference.

Day 1 vs day 4

Statistical analysis description

In order to observe the evolution of the D-dimer levels between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.975 ^[13]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[13] - Since the p-value is over 0.05, there is no significant difference.

Day 1 vs day 7

Statistical analysis description

In order to observe the evolution of the D-dimer levels between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.097 ^[14]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[14] - Since the p-value is over 0.05, there is no significant difference.

Day 1 vs day 28

Statistical analysis description

In order to observe the evolution of the D-dimer levels between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[15] - Since the p-value is under 0.05, there is a significant difference.

Secondary: Number of deaths due to any cause

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End point title

Number of deaths due to any cause

End point description

End point type

Secondary

End point timeframe

Up to day 28

End point values	Sarilumab
Number of subjects analysed	60
Units: Subjects
Dead	1
Not dead	59

No statistical analyses for this end point

Secondary: Organ failure (DIC, cardiac, hepatic, renal, cardiovascular)

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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

End point values	Day 1	Day 2	Day 3	Day 4	Day 7	Day 28
Number of subjects analysed	31	26	25	25	21	17
Units: Subjects
0.	12	17	14	16	14	16
1.	15	6	3	1	4	0
2.	3	3	4	4	2	0
3.	0	0	3	3	1	0
4.	0	0	1	0	0	1
5.	1	0	0	1	0	0

No statistical analyses for this end point

Secondary: Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: C-Reactive Protein (CRP)

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End point title

Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: C-Reactive Protein (CRP)

End point description

End point type

Secondary

End point timeframe

Up to day 28

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	57	54	49	47	55	57	54	49	47	55
Units: mg/dL
arithmetic mean (standard deviation)	12.2 ( 21.1 )	4.3 ( 4.6 )	2.4 ( 2.6 )	1.7 ( 7.5 )	1.2 ( 3.2 )	19.1 ( 40.3 )	19.4 ( 41.4 )	20.0 ( 43.2 )	21.5 ( 44.0 )	18.7 ( 40.3 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[16] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[17] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[18] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[19]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[19] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[20] - Since the p-value is under 0.05, there is a significant difference.

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

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	54	51	45	45	50	54	51	45	45	50
Units: UI/L
arithmetic mean (standard deviation)	387.5 ( 128.9 )	397.0 ( 144.6 )	375.9 ( 135.8 )	346.8 ( 132.9 )	271.0 ( 75.4 )	373.8 ( 119.1 )	370.1 ( 121.6 )	360.7 ( 119.0 )	382.1 ( 127.1 )	365.9 ( 97.0 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.072 ^[21]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[21] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.065 ^[22]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[22] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.087 ^[23]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[23] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[24]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[24] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[25]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[25] - Since the p-value is under 0.05, there is a significant difference.

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

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	52	48	44	42	50	52	48	44	42	50
Units: ng/mL
arithmetic mean (standard deviation)	1489.2 ( 873.9 )	1332.1 ( 791.8 )	1205.5 ( 729.5 )	1065.6 ( 879.8 )	457.1 ( 269.2 )	1328.9 ( 773.5 )	1256.9 ( 753.3 )	1332.9 ( 773.4 )	1355.4 ( 836.6 )	1289.9 ( 815.5 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[26]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[26] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.454 ^[27]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[27] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21 ^[28]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[28] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[29]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[29] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[30]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[30] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	14	13	15	12	13	14	13	15	12	13
Units: ng/L
arithmetic mean (standard deviation)	8.9 ( 14.8 )	6.8 ( 9.5 )	9.7 ( 12.2 )	4.9 ( 9.4 )	6.2 ( 10.3 )	9.4 ( 15.8 )	7.4 ( 10.0 )	11.7 ( 15.5 )	4.9 ( 9.1 )	6.2 ( 10.1 )

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.273 ^[31]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[31] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.144 ^[32]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[32] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.046 ^[33]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[33] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.655 ^[34]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[34] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999 ^[35]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[35] - Since the p-value is over 0.05, there is no significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	58	52	42	40	54	58	52	42	40	54
Units: mg/dL
arithmetic mean (standard deviation)	36.5 ( 21.5 )	37.2 ( 21.6 )	37.5 ( 24.3 )	38.7 ( 26.0 )	32.2 ( 19.7 )	33.9 ( 20.0 )	33.2 ( 20.7 )	33.0 ( 22.3 )	34.2 ( 23.2 )	33.7 ( 20.7 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.047 ^[36]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[36] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[37]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[37] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[38]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[38] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[39]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[39] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.515 ^[40]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[40] - Since the p-value is over 0.05, there is no significant difference.

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

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	58	52	45	43	53	58	52	45	43	53
Units: mg/dL
arithmetic mean (standard deviation)	0.88 ( 0.27 )	0.84 ( 0.23 )	0.86 ( 0.24 )	0.87 ( 0.26 )	0.88 ( 0.29 )	0.89 ( 0.26 )	0.87 ( 0.23 )	0.88 ( 0.24 )	0.90 ( 0.27 )	0.91 ( 0.26 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.206 ^[41]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[41] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.276 ^[42]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[42] - Since the p-value is over 0.05, there is no significant difference.

Day 1 vs day 4

Comparison groups

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

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.287 ^[43]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[43] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07 ^[44]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[44] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.192 ^[45]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[45] - Since the p-value is over 0.05, there is no significant difference.

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

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	46	34	30	32	50	46	34	30	32	50
Units: UI/L
arithmetic mean (standard deviation)	55.2 ( 34.6 )	69.5 ( 67.9 )	71.0 ( 51.2 )	56.0 ( 51.3 )	32.4 ( 20.0 )	49.2 ( 28.1 )	53.2 ( 27.8 )	46.6 ( 18.3 )	57.0 ( 31.0 )	50.3 ( 28.9 )

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026 ^[46]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[46] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.347 ^[47]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[47] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[48]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[48] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.83 ^[49]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[49] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[50]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[50] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	47	35	31	33	51	47	35	31	33	51
Units: UI/L
arithmetic mean (standard deviation)	69.9 ( 61.3 )	94.5 ( 88.9 )	116.9 ( 111.3 )	164.5 ( 178.1 )	68.2 ( 51.9 )	56.0 ( 44.2 )	60.5 ( 45.1 )	53.0 ( 33.7 )	70.0 ( 46.6 )	56.4 ( 44.9 )

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[51]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[51] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[52] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[53] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[54]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[54] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.135 ^[55]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[55] - Since the p-value is over 0.05, there is no significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	43	37	36	38	47	43	37	36	38	47
Units: mg/dL
arithmetic mean (standard deviation)	0.32 ( 0.1 )	0.33 ( 0.13 )	0.33 ( 0.13 )	0.40 ( 0.13 )	0.54 ( 0.19 )	0.41 ( 0.2 )	0.46 ( 0.23 )	0.43 ( 0.23 )	0.45 ( 0.23 )	0.42 ( 0.22 )

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[56]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[56] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[57] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[58]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[58] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.238 ^[59]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[59] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[60]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[60] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: 10^9/L
arithmetic mean (standard deviation)	6.2 ( 4.0 )	6.6 ( 3.6 )	6.8 ( 2.8 )	8.8 ( 4.5 )	6.5 ( 2.4 )	7.5 ( 3.1 )	7.7 ( 3.2 )	7.7 ( 3.1 )	8.0 ( 3.2 )	7.8 ( 3.1 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[61]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[61] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.021 ^[62]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[62] - Since the p-value is under 0.05, there is a significant difference.

Day 1 vs day 4

Comparison groups

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

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.096 ^[63]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[63] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.298 ^[64]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[64] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[65]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[65] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: 10^9/L
arithmetic mean (standard deviation)	4.7 ( 4.0 )	4.9 ( 3.5 )	4.9 ( 2.6 )	6.2 ( 4.1 )	3.9 ( 2.3 )	6.0 ( 3.2 )	6.1 ( 3.3 )	6.2 ( 3.2 )	6.5 ( 3.3 )	6.2 ( 3.2 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[66] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[67]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[67] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[68]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[68] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.462 ^[69]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[69] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[70]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[70] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: 10^9/L
arithmetic mean (standard deviation)	1.1 ( 0.4 )	1.2 ( 0.5 )	1.3 ( 0.6 )	1.8 ( 0.8 )	1.8 ( 0.6 )	1.1 ( 0.4 )	1.0 ( 0.4 )	1.0 ( 0.4 )	1.0 ( 0.4 )	1.0 ( 0.5 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.956 ^[71]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[71] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[72]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[72] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[73]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[73] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[74]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[74] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[75]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[75] - Since the p-value is under 0.05, there is a significant difference.

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

Top of page

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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	60	55	49	48	56	60	55	49	48	56
Units: 10^9/L
arithmetic mean (standard deviation)	0.38 ( 0.21 )	0.42 ( 0.22 )	0.46 ( 0.25 )	0.61 ( 0.26 )	0.60 ( 0.23 )	0.43 ( 0.21 )	0.42 ( 0.21 )	0.43 ( 0.22 )	0.42 ( 0.21 )	0.42 ( 0.21 )

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.03 ^[76]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[76] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

= 0.556 ^[77]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[77] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.511 ^[78]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[78] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[79]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[79] - Since the p-value is under 0.05, there is a significant difference.

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 p-value 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

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[80] - Since the p-value is under 0.05, there is a significant difference.

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

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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

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	17	15	13	12	20	17	15	13	12	20
Units: 10^9/L
arithmetic mean (standard deviation)	0.05 ( 0.05 )	0.04 ( 0.05 )	0.09 ( 0.07 )	0.06 ( 0.05 )	0.15 ( 0.10 )	0.07 ( 0.09 )	0.07 ( 0.09 )	0.08 ( 0.10 )	0.08 ( 0.10 )	0.06 ( 0.08 )

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.859 ^[81]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[81] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.789 ^[82]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[82] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.386 ^[83]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[83] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.965 ^[84]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[84] - Since the p-value is over 0.05, there is no significant difference.

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 p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[85]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[85] - Since the p-value is under 0.05, there is a significant difference.

Other pre-specified: Change from baseline of cytokine levels associated with the cytokine storm, including, among others, IL-6 on day 1 vs any other determination done up to day 28

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End point title

Change from baseline of cytokine levels associated with the cytokine storm, including, among others, IL-6 on day 1 vs any other determination done up to day 28

End point description

End point type

Other pre-specified

End point timeframe

Up to day 28

End point values	Day 2	Day 3	Day 4	Day 7	Day 28	Day 1 (N = N Day 2)	Day 1 (N = N Day 3)	Day 1 (N = N day 4)	Day 1 (N = N Day 7)	Day 1 (N = N Day 28)
Number of subjects analysed	32	30	29	29	24	32	30	29	29	24
Units: g/mL
arithmetic mean (standard deviation)	399.4 ( 572.2 )	352.3 ( 503.3 )	382.2 ( 612.3 )	165.7 ( 299.7 )	21.5 ( 35.7 )	33.2 ( 23.4 )	36.9 ( 27.6 )	37.4 ( 28.7 )	35.5 ( 26.7 )	29.4 ( 21.1 )

Day 1 vs day 2

Statistical analysis description

In order to observe the evolution of the IL-6 levels between day 1 and day 2, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[86]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[86] - Since the p-value is under 0.05, there is a significant difference.

Day 1 vs day 3

Statistical analysis description

In order to observe the evolution of the IL-6 levels between day 1 and day 3, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[87]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[87] - Since the p-value is under 0.05, there is a significant difference.

Day 1 vs day 4

Statistical analysis description

In order to observe the evolution of the IL-6 levels between day 1 and day 4, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[88]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[88] - Since the p-value is under 0.05, there is a significant difference.

Day 1 vs day 7

Statistical analysis description

In order to observe the evolution of the IL-6 levels between day 1 and day 7, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[89]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[89] - Since the p-value is under 0.05, there is a significant difference.

Day 1 vs day 28

Statistical analysis description

In order to observe the evolution of the IL-6 levels between day 1 and day 28, the Wilcoxon test was used with a significance level of 0.05. In cases where a p-value 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

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[90]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[90] - Since the p-value is under 0.05, there is a significant difference.

Adverse events

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Timeframe for reporting adverse events

Throughout the duration of the trial

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Sarilumab

Reporting group description

Treatment of severe COVID-19 with sarilumab

Serious adverse events	Sarilumab
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 60 (30.00%)
number of deaths (all causes)	1
number of deaths resulting from adverse events	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	3 / 60 (5.00%)
occurrences causally related to treatment / all	3 / 3
deaths causally related to treatment / all	0 / 0
Neutrophil count decreased
subjects affected / exposed	3 / 60 (5.00%)
occurrences causally related to treatment / all	2 / 3
deaths causally related to treatment / all	0 / 0
Transaminases increased
subjects affected / exposed	4 / 60 (6.67%)
occurrences causally related to treatment / all	4 / 4
deaths causally related to treatment / all	0 / 0
Nervous system disorders
Spinal cord compression
subjects affected / exposed	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	4 / 60 (6.67%)
occurrences causally related to treatment / all	4 / 4
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	1 / 60 (1.67%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Respiratory failure
subjects affected / exposed	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Sarilumab
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 60 (45.00%)
Vascular disorders
Cyanosis
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Condition aggravated
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
General physical health deterioration
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Pyrexia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 60 (5.00%)
occurrences all number	3
Dyspnoea
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Hypoxia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Rales
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Use of accessory respiratory muscles
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Delirium
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Depression
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Insomnia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Sleep disorder
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Aspartate aminotransferase increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Blood pressure decreased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
C-reactive protein increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Fibrin D dimer increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Hypophonesis
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Interleukin level increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Neutrophil count decreased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Oxygen saturation decreased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Serum ferritin decreased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Serum ferritin increased
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Transaminases increased
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Conduction disorder
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Nervous system disorders
Headache
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Somnolence
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Neutropenia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Thrombocytopenia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	3 / 60 (5.00%)
occurrences all number	3
Diarrhoea
subjects affected / exposed	2 / 60 (3.33%)
occurrences all number	2
Dyspepsia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Odynophagia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Rash
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Renal and urinary disorders
Renal impairment
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Infections and infestations
COVID-19
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Pneumonia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Hypernatraemia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Hypokalaemia
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1
Malnutrition
subjects affected / exposed	1 / 60 (1.67%)
occurrences all number	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 Aug 2020

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

Were there any global interruptions to the trial? No

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.

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

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Clinical trials

Clinical Trial Results: Sarilumab Treatment In cytoKinE storm caused by infection with COVID-19.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in a severity rating on a 7-point ordinal scale: day 7

Primary: Change in a severity rating on a 7-point ordinal scale: day 7

Primary: Change in a severity rating on a 7-point ordinal scale: day 28

Primary: Change in a severity rating on a 7-point ordinal scale: day 28

Secondary: Percentage of patients reporting each severity rating on a 7-point severity ordinal scale

Secondary: Percentage of patients reporting each severity rating on a 7-point severity ordinal scale

Secondary: Duration of mechanical ventilation measured by days of ventilation since treatment

Secondary: Duration of mechanical ventilation measured by days of ventilation since treatment

Secondary: Number of ventilator free days in the first 28 days

Secondary: Number of ventilator free days in the first 28 days

Secondary: Number of patients requiring mechanical ventilation

Secondary: Number of patients requiring mechanical ventilation

Secondary: Number of patients admitted to the ICU

Secondary: Number of patients admitted to the ICU

Secondary: Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC – axilla; > 37.2ºC –oral; > 37.8 –rectal or tympanic)

Secondary: Time to resolution of fever without antipyretics for at least 48 hours (Tº > 36.6ºC – axilla; > 37.2ºC –oral; > 37.8 –rectal or tympanic)

Secondary: Changes from baseline in hemoglobin levels if available on day 2, 3, 4, 7, and 28

Secondary: Changes from baseline in hemoglobin levels if available on day 2, 3, 4, 7, and 28

Secondary: Changes from baseline in platelet cell count if available on day 2, 3, 4, 7, and 28

Secondary: Changes from baseline in platelet cell count if available on day 2, 3, 4, 7, and 28

Secondary: Changes from baseline in D-Dimer leves if available on day 2, 3, 4, 7, and 28

Secondary: Changes from baseline in D-Dimer leves if available on day 2, 3, 4, 7, and 28

Secondary: Number of deaths due to any cause

Secondary: Number of deaths due to any cause

Secondary: Organ failure (DIC, cardiac, hepatic, renal, cardiovascular)

Secondary: Organ failure (DIC, cardiac, hepatic, renal, cardiovascular)

Secondary: Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: C-Reactive Protein (CRP)

Secondary: Changes from baseline in inflammatory parameters and other laboratory tests available on day 2, 3, 4, 7, and 28: C-Reactive Protein (CRP)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Other pre-specified: Change from baseline of cytokine levels associated with the cytokine storm, including, among others, IL-6 on day 1 vs any other determination done up to day 28

Other pre-specified: Change from baseline of cytokine levels associated with the cytokine storm, including, among others, IL-6 on day 1 vs any other determination done up to day 28

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Sarilumab Treatment In cytoKinE storm caused by infection with COVID-19.