INFORAAA: Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA

• Sponsor: Faron Pharmaceuticals Ltd (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03119701
• Collaborator: (none)
• Enrollment: 40
• Locations: 9
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study to assess effectiveness and safety of a drug FP-1201-lyo (Recombinant Human Interferon Beta-1a) in the Prevention of Multi-Organ Failure on patients after Open Surgery for a Ruptured Abdominal Aortic Aneurysm

Condition or Disease	Intervention/Treatment	Phase
Preventive Medicine; Multi Organ Failure	Drug: Interferon Beta-1A; Drug: Placebo	Phase 2

Detailed Description

This trial is multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm. Investigational medicinal product will be administered as post-surgical preventive treatment either 10µg FP-1201-lyo or placebo. Treatment will be administered daily every 24 hrs for 6 days. The first dose will be given after successful surgery at the point when the patient arrives to the Intensive Care Unit (ICU).

Both treatment groups will receive standard supportive care.

Aim is randomise and initiate treatment of 152 patients. For the final analysis, a minimum of 129 evaluable patients will be required.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm.Multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomised, Parallel Group 2:1 Comparison of the Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) and Placebo in the Prevention of Multi-Organ Failure on Patients Surviving Open Surgery for a Ruptured Abdominal Aortic Aneurysm
• Actual Study Start Date: Feb 18, 2017
• Actual Primary Completion Date: Sep 23, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FP-1201-lyo 10 µg FP-12-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.	Drug: Interferon Beta-1A; Lyophilisate for solution for injection.; Other Names: FP-1201-lyo ATC code L03AB07
Placebo Comparator: FP-1201-lyo Placebo FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection	Drug: Placebo; Lyophilisate for solution for injection as placebo.; Other Names: Placebo for investigational drug

Outcome Measures

Primary Outcome Measures

1. The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality [Day 30]

   Number of fatalities

Secondary Outcome Measures

1. The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality [Day 90]

   Number of fatalities

2. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) [Day 30]

   Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.

3. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis [Day 30 and Day 90]

   Number of days receiving hemodialysis. There were only few reported values other than zero.

4. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score [Day 30]

   Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero. Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.

5. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) [Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay]

   Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.

6. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples [Day 30]

   IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.

7. The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). [Day 90]

   Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.

8. Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters [Day 0 to Day 30]

   Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.

9. Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days [Day 30 or Day 90]

   Economic measurement: Length of ICU stay, in terms of ICU free days at D30 Length of hospital stay, in terms of hospital free days at D90 Length of stay at another health care facility at D90 The number of days on hemodialysis at D30 and at D90 The number of organ failure free days at D30 The number of ventilation free days at D30

Other Outcome Measures

1. Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker [Day 0 up to Day 13]

   Concentration of Myxovirus Resistant Protein A (MxA)

2. Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples [Day 0 up to Day 13]

   CD73 (ecto-5'-nucleotidase enzyme) concentration

3. Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples [Day 0 up to Day 13]

   IL-6 concentration.

4. Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples [Day 0 up to Day 13]

   HGF concentration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria during screening and prior to the first dose of study medication being administered on D0 (criteria 1 or 2 and all 3, 4 and 5):

1. Patients (male or female) presenting with a ruptured abdominal aortic aneurysm (RAAA) diagnosed by ultrasound or CT-scan in the emergency room

• all forms of infrarenal RAAAs with or without coexisting iliac aneurysms are included or

1. Patients (male or female) presenting with symptoms of RAAA known to have an infrarenal AAA and proceeding straight to open repair without radiological assessment and confirmed rupture (=retroperitoneal haematoma) in operation

and

1. Aneurysma repair must be infra-renal, i.e. the proximal anastomosis must be below the renal arteries and the renal arteries have to stay intact. Temporary above the renal clamping can be used for a maximum of 30 minutes (total clamping time)

and

1. Patients providing informed consent

and

1. Age of 18 years or higher

Exclusion Criteria:

To be eligible for inclusion into this study, each patient must not meet any of the following exclusion criteria during screening or prior to the first dose of study medication being administered:

1. Moribund patient not eligible for treatment in ICU or expected to survive surgery

2. Markedly short life expectancy, e.g. advanced malignant disease

3. Current participation in another experimental treatment protocol

4. Significant congestive heart failure, defined as New York Heart Association (NYHA) class IV

5. Current treatment with Interferon (IFN) alpha or IFN beta

6. Dialysis therapy for chronic renal failure

7. Irreversible shock from haemorrhage

8. Unconsciousness or inability to give consent

9. Ruptured Endovascular Aortic Repair (rEVAR) first (prior attempt for endovascular aortic repair for the current rupture)

10. Diagnosed cirrhosis

11. Pregnancy and women with child bearing potential without negative pregnancy test

12. Rupture not confirmed by CT or intra-operatively (impending ruptures are excluded)

13. RAAA requiring repair of the renal arteries or the proximal aorta

• thoracoabdominal aneurysms requiring immediate repair

• damaged renal arteries during emergency clamping requiring repair

Note:

• temporary clamping above the renal arteries (max 30 min total clamping time above the renal arteries) does not lead to exclusion

• ligation of the left renal vein does not lead to exclusion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tartu University Hospital	Tartu		Estonia	51014
2	Helsinki University Hospital	Helsinki		Finland	FI-00290
3	Central Finland Central Hospital	Jyväskylä		Finland	FI-40620
4	South Karelia Central Hospital	Lappeenranta		Finland	FI-53130
5	Oulu University Hospital	Oulu		Finland	FI-90220
6	Tampere University Hospital	Tampere		Finland	FI-33520
7	Turku University Hospital	Turku		Finland	FFI-20520
8	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas		Lithuania	LT-50161
9	Vilnius University Hospital Santaros klinikos	Vilnius		Lithuania	LT-08661

Sponsors and Collaborators

• Faron Pharmaceuticals Ltd

Investigators

• Principal Investigator: Harri Hakovirta, MD, Turku University Hospital
• Principal Investigator: Maarit Venermo, MD, Helsinki University Central Hospital

Study Documents (Full-Text)

• Study Protocol - Apr 16, 2019
• Statistical Analysis Plan - Dec 19, 2019

More Information

Publications

None provided.

• Responsible Party: Faron Pharmaceuticals Ltd
• ClinicalTrials.gov Identifier: NCT03119701
• Other Study ID Numbers: FP1CLI006; 2014-000899-25
• First Posted: Apr 19, 2017
• Last Update Posted: Jan 14, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Faron Pharmaceuticals Ltd: Patients Surviving Open Surgery; Ruptured Abdominal Aortic Aneurysm
• Additional relevant MeSH terms: Multiple Organ Failure; Interferons; Interferon-beta; Interferon beta-1a

Study Results

Participant Flow

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Period Title: 6-day Dosing
STARTED	29	11
COMPLETED	22	8
NOT COMPLETED	7	3
Period Title: 6-day Dosing
STARTED	25	10
COMPLETED	22	9
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo	Total
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for Investigational drug.	Total of all reporting groups
Overall Participants	27	11	38
Age, Customized (Count of Participants)
< 70 years	7 25.9%	3 27.3%	10 26.3%
70-80 years	14 51.9%	6 54.5%	20 52.6%
> 80 years	6 22.2%	2 18.2%	8 21.1%
Sex: Female, Male (Count of Participants)
Female	4 14.8%	0 0%	4 10.5%
Male	23 85.2%	11 100%	34 89.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	27 100%	11 100%	38 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Finland	23 85.2%	8 72.7%	31 81.6%
Lithuania	3 11.1%	1 9.1%	4 10.5%
Estonia	1 3.7%	2 18.2%	3 7.9%
Baseline Height (centimetres) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimetres]	172.3 (6.34)	177.5 (7.59)	173.8 (7.05)
Baseline Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	82.0 (16.14)	95.9 (21.21)	86.0 (18.58)

Outcome Measures

1. Primary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Description	Number of fatalities
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Count of Participants [Participants]	6 22.2%	2 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.21 to 8.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Description	Number of fatalities
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Count of Participants [Participants]	7 25.9%	2 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 0.28 to 10.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
Description	Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Median (Full Range) [days]	25.0	29.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Description	Number of days receiving hemodialysis. There were only few reported values other than zero.
Time Frame	Day 30 and Day 90

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that had sufficient data to allow for calculation of the outcome measure.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	21	9
Day 30	0.9 (4.15)	0.0 (0.00)
Day 90	0.6 (2.68)	0.0 (0.00)

5. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score
Description	Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero. Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Mean (Standard Deviation) [days]	0.0 (0.00)	0.0 (0.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Description	Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.
Time Frame	Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The number of participants analyzed reflects the number of patients that were alive and had sufficient data to allow for calculation of the outcome measure.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	19	9
Day 1	15.4 (12.37)	10.3 (4.80)
Day 2	12.2 (3.58)	12.1 (6.01)
Day 3	13.1 (4.62)	10.3 (5.35)
Day 4	11.4 (6.60)	8.6 (5.32)
Day 5	10.5 (3.14)	12.5 (5.45)
Day 6	11.4 (5.29)	15.0 (0)
Day 9	11.0 (5.48)
Day 13	10.8 (4.49)

7. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
Description	IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

At the Baseline Visit, 2 patients in the FP-1201-lyo treatment group and 1 patient in the placebo treatment group were not tested for anti-drug antibodies.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	25	10
Baseline	0 0%	0 0%
Day 30	0 0%	0 0%

8. Secondary Outcome

Title	The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
Description	Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
No symptoms - 0	5 18.5%	2 18.2%
No significant disability - 1	5 18.5%	5 45.5%
Slight disability - 2	3 11.1%	1 9.1%
Moderate disability - 3	2 7.4%	0 0%
Moderately severe disability - 4	3 11.1%	0 0%
Severe disability - 5	2 7.4%	1 9.1%
Death - 6	7 25.9%	2 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3620
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Mantel Haenszel
	Comments	Exact Mantel-Haenszel Chi-Square Test

9. Secondary Outcome

Title	Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Description	Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
Time Frame	Day 0 to Day 30

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Safety (FAS-S) consisted of all randomised patients receiving study treatment and comprised the analysis set on which the evaluation of safety is based.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	29	11
Product-related TEAEs	17	1
Severe TEAEs	28	2
Serious TEAEs	26	5
TEAEs Leading to Study Product Discontinuation	7	1
TEAEs Leading to Death	7	1

10. Secondary Outcome

Title	Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days
Description	Economic measurement: Length of ICU stay, in terms of ICU free days at D30 Length of hospital stay, in terms of hospital free days at D90 Length of stay at another health care facility at D90 The number of days on hemodialysis at D30 and at D90 The number of organ failure free days at D30 The number of ventilation free days at D30
Time Frame	Day 30 or Day 90

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E). As the study was discontinued, analyses were performed on the available data gathered thus far.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
ICU free days at Day 30	16.8 (12.39)	21.9 (11.06)
Days in hospital at Day 90	18.1 (9.84)	13.8 (9.97)
Days in another facility at Day 90	11.8 (23.79)	7.0 (19.80)
Days on hemodialysis at Day 30	0.9 (4.15)	0.0 (0.00)
Days on hemodialysis at Day 90	0.6 (2.68)	0.0 (0.00)
Organ failure free days at Day 30	0.0 (0.00)	0.0 (0.00)
Ventilation free days at Day 30	20.6 (10.62)	25.1 (8.85)

11. Other Pre-specified Outcome

Title	Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
Description	Concentration of Myxovirus Resistant Protein A (MxA)
Time Frame	Day 0 up to Day 13

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Baseline	3.5	6.0
Day 1	15.0	5.1
Day 2	19.8	3.8
Day 3	21.2	3.3
Day 4	36.4	4.1
Day 5	48.3	3.1
Day 6	50.4	3.6
Day 9	14.3	4.8
Day 13	3.9	8.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	Day 2, Day 3, Day 4, Day 5, and Day 6.
	Method	ANOVA
	Comments	Repeated measures ANOVA

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Baseline visit
	Method	ANOVA
	Comments	Repeated measures ANOVA

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments	Day 1
	Method	ANOVA
	Comments	Repeated measures ANOVA

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	Day 9
	Method	ANOVA
	Comments	Repeated measures ANOVA

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments	Day 13
	Method	ANOVA
	Comments	Repeated measures ANOVA

12. Other Pre-specified Outcome

Title	Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
Description	CD73 (ecto-5'-nucleotidase enzyme) concentration
Time Frame	Day 0 up to Day 13

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Baseline	2.1	2.2
Day 1	2.0	2.2
Day 2	2.2	2.2
Day 3	2.0	2.3
Day 4	2.3	2.6
Day 5	3.0	3.5
Day 6	3.8	3.8
Day 9	3.9	3.8
Day 13	2.9	2.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	Patients with an observation below the lower limit of quantification (LLOQ) value at baseline for CD73 were set to have the LLOQ value (LLOQ = 4 ng/ml) at baseline for subgroup determination purposes (2-fold increase in CD73 from baseline). Values below the LLOQ were set to LLOQ/2 = 2 ng/mL.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	The threshold for statistical significance was p = 0.05.
	Method	ANOVA
	Comments	Repeated measures ANOVA

13. Other Pre-specified Outcome

Title	Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
Description	IL-6 concentration.
Time Frame	Day 0 up to Day 13

Outcome Measure Data

Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	27	11
Baseline	328.9	378.9
Day 1	493.1	460.2
Day 3	181.4	130.7
Day 6	164.1	79.1
Day 9	107.9	74.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FP-1201-lyo 10 µg, FP-1201-lyo Placebo
	Comments	Observations of zero were imputed as 1 pg/ml before logarithmic transformation.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments	The threshold for statistical significance was p = 0.05.
	Method	ANOVA
	Comments	Repeated measures ANOVA

14. Other Pre-specified Outcome

Title	Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples
Description	HGF concentration.
Time Frame	Day 0 up to Day 13

Outcome Measure Data

Analysis Population Description

Data were not collected or analyzed due to the small groups and interference of corticosteroids it was not meaningful to perform the analyzes.

Arm/Group Title	FP-1201-lyo 10 µg	FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Measure Participants	0	0

Adverse Events

Time Frame	The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90.
Adverse Event Reporting Description	The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Arm/Group Title	FP-1201-lyo 10 µg		FP-1201-lyo Placebo
Arm/Group Description	FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.		FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
All Cause Mortality
	FP-1201-lyo 10 µg		FP-1201-lyo Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/29 (24.1%)		2/11 (18.2%)
Serious Adverse Events
	FP-1201-lyo 10 µg		FP-1201-lyo Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/29 (44.8%)		3/11 (27.3%)
Cardiac disorders
Myocardial ischaemia	1/29 (3.4%)	1	0/11 (0%)	0
Gastrointestinal disorders
Gastric ulcer haemorrhage	1/29 (3.4%)	1	0/11 (0%)	0
Gastrointestinal necrosis	2/29 (6.9%)	2	0/11 (0%)	0
Intestinal ischaemia	3/29 (10.3%)	3	1/11 (9.1%)	1
Large intestine perforation	3/29 (10.3%)	3	0/11 (0%)	0
General disorders
Condition aggravated	1/29 (3.4%)	1	0/11 (0%)	0
Multiple organ dysfunction syndrome	4/29 (13.8%)	4	0/11 (0%)	0
Immune system disorders
Anaphylactic reaction	1/29 (3.4%)	1	0/11 (0%)	0
Infections and infestations
Pneumonia	0/29 (0%)	0	1/11 (9.1%)	1
Sepsis	1/29 (3.4%)	1	0/11 (0%)	0
Septic shock	1/29 (3.4%)	1	0/11 (0%)	0
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/29 (3.4%)	1	0/11 (0%)	0
Pulmonary contusion	0/29 (0%)	0	1/11 (9.1%)	1
Road traffic accident	0/29 (0%)	0	1/11 (9.1%)	1
Sternal fracture	0/29 (0%)	0	1/11 (9.1%)	1
Nervous system disorders
Ischaemic cerebral infarction	1/29 (3.4%)	1	0/11 (0%)	0
Paraplegia	1/29 (3.4%)	1	0/11 (0%)	0
Spinal epidural haematoma	1/29 (3.4%)	1	0/11 (0%)	0
Renal and urinary disorders
Renal failure	1/29 (3.4%)	1	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	1/29 (3.4%)	1	0/11 (0%)	0
Respiratory disorder	1/29 (3.4%)	1	0/11 (0%)	0
Respiratory failure	1/29 (3.4%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	FP-1201-lyo 10 µg		FP-1201-lyo Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/29 (93.1%)		9/11 (81.8%)
Blood and lymphatic system disorders
Anaemia	1/29 (3.4%)	1	0/11 (0%)	0
Haemorrhagic anaemia	0/29 (0%)	0	1/11 (9.1%)	1
Leukocytosis	1/29 (3.4%)	1	0/11 (0%)	0
Thrombocytopenia	1/29 (3.4%)	1	0/11 (0%)	0
Cardiac disorders
Atrial fibrillation	5/29 (17.2%)	5	3/11 (27.3%)	4
Cardiac failure congestive	1/29 (3.4%)	1	0/11 (0%)	0
Tachycardia	1/29 (3.4%)	1	0/11 (0%)	0
Tachycardia paroxysmal	1/29 (3.4%)	1	0/11 (0%)	0
Eye disorders
Eye irritation	1/29 (3.4%)	1	0/11 (0%)	0
Gastrointestinal disorders
Constipation	3/29 (10.3%)	3	0/11 (0%)	0
Diarrhoea	2/29 (6.9%)	2	0/11 (0%)	0
Ileus	1/29 (3.4%)	1	0/11 (0%)	0
Nausea	2/29 (6.9%)	2	0/11 (0%)	0
General disorders
Chills	1/29 (3.4%)	1	0/11 (0%)	0
Pain	1/29 (3.4%)	1	0/11 (0%)	0
Pyrexia	6/29 (20.7%)	6	1/11 (9.1%)	1
Systemic inflammatory response syndrome	1/29 (3.4%)	1	0/11 (0%)	0
Hepatobiliary disorders
Hepatic failure	2/29 (6.9%)	2	0/11 (0%)	0
Infections and infestations
Candida infection	2/29 (6.9%)	2	0/11 (0%)	0
Catheter site infection	0/29 (0%)	0	1/11 (9.1%)	1
Clostridium difficile colitis	1/29 (3.4%)	1	0/11 (0%)	0
Device related infection	2/29 (6.9%)	2	0/11 (0%)	0
Fungal skin infection	1/29 (3.4%)	1	0/11 (0%)	0
Infection	1/29 (3.4%)	1	0/11 (0%)	0
Influenza	0/29 (0%)	0	1/11 (9.1%)	1
Lung infection	1/29 (3.4%)	1	0/11 (0%)	0
Pneumonia	2/29 (6.9%)	2	0/11 (0%)	0
Postoperative wound infection	1/29 (3.4%)	1	0/11 (0%)	0
Pyelonephritis	1/29 (3.4%)	1	0/11 (0%)	0
Urinary tract infection	1/29 (3.4%)	1	0/11 (0%)	0
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/29 (3.4%)	1	0/11 (0%)	0
Anaemia postoperative	1/29 (3.4%)	1	0/11 (0%)	0
Periprocedural myocardial infarction	0/29 (0%)	0	1/11 (9.1%)	1
Post procedural constipation	1/29 (3.4%)	1	0/11 (0%)	0
Post procedural haemorrhage	1/29 (3.4%)	1	0/11 (0%)	0
Post procedural oedema	1/29 (3.4%)	1	0/11 (0%)	0
Postoperative delirium	1/29 (3.4%)	1	1/11 (9.1%)	1
Procedural pain	0/29 (0%)	0	1/11 (9.1%)	1
Wound dehiscence	0/29 (0%)	0	1/11 (9.1%)	1
Wound secretion	0/29 (0%)	0	1/11 (9.1%)	1
Investigations
Alanine aminotransferase increased	1/29 (3.4%)	1	0/11 (0%)	0
Aspartate aminotransferase increased	2/29 (6.9%)	2	0/11 (0%)	0
Blood alkaline phosphatase increased	2/29 (6.9%)	2	0/11 (0%)	0
Blood bilirubin increased	1/29 (3.4%)	1	0/11 (0%)	0
Blood calcium decreased	1/29 (3.4%)	1	0/11 (0%)	0
Blood creatine increased	1/29 (3.4%)	1	0/11 (0%)	0
Blood potassium decreased	2/29 (6.9%)	2	0/11 (0%)	0
Blood pressure increased	1/29 (3.4%)	1	0/11 (0%)	0
Blood sodium increased	1/29 (3.4%)	1	0/11 (0%)	0
C-reactive protein increased	3/29 (10.3%)	3	1/11 (9.1%)	1
Haemoglobin decreased	4/29 (13.8%)	4	1/11 (9.1%)	1
Hepatic enzyme increased	3/29 (10.3%)	3	0/11 (0%)	0
Inflammatory marker increased	1/29 (3.4%)	1	0/11 (0%)	0
Intra-abdominal pressure increased	1/29 (3.4%)	1	0/11 (0%)	0
Liver function test abnormal	2/29 (6.9%)	2	1/11 (9.1%)	1
Neutrophil count increased	1/29 (3.4%)	1	0/11 (0%)	0
Urine output decreased	2/29 (6.9%)	2	0/11 (0%)	0
White blood cell count increased	2/29 (6.9%)	2	0/11 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/29 (3.4%)	1	0/11 (0%)	0
Hypokalaemia	3/29 (10.3%)	3	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/29 (0%)	0	1/11 (9.1%)	1
Soft tissue necrosis	1/29 (3.4%)	1	0/11 (0%)	0
Nervous system disorders
Akathisia	1/29 (3.4%)	1	0/11 (0%)	0
Psychiatric disorders
Agitation	1/29 (3.4%)	1	1/11 (9.1%)	1
Anxiety	2/29 (6.9%)	2	0/11 (0%)	0
Confusional state	4/29 (13.8%)	4	2/11 (18.2%)	2
Delirium	2/29 (6.9%)	2	1/11 (9.1%)	1
Disorientation	0/29 (0%)	0	1/11 (9.1%)	1
Restlessness	1/29 (3.4%)	1	0/11 (0%)	0
Sleep disorder	1/29 (3.4%)	1	0/11 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/29 (6.9%)	2	0/11 (0%)	0
Oliguria	1/29 (3.4%)	1	0/11 (0%)	0
Renal failure	1/29 (3.4%)	1	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	2/29 (6.9%)	2	0/11 (0%)	0
Atelectasis	0/29 (0%)	0	1/11 (9.1%)	1
Bronchospasm	1/29 (3.4%)	1	0/11 (0%)	0
Emphysema	1/29 (3.4%)	1	0/11 (0%)	0
Lung infiltration	1/29 (3.4%)	1	0/11 (0%)	0
Obstructive airways disorder	0/29 (0%)	0	1/11 (9.1%)	1
Pleural effusion	2/29 (6.9%)	2	1/11 (9.1%)	1
Pulmonary embolism	1/29 (3.4%)	1	0/11 (0%)	0
Respiratory failure	1/29 (3.4%)	1	0/11 (0%)	0
Vascular disorders
Embolism arterial	0/29 (0%)	0	1/11 (9.1%)	2
Hypertension	4/29 (13.8%)	4	2/11 (18.2%)	2
Hypotension	1/29 (3.4%)	1	0/11 (0%)	0
Hypovolaemic shock	1/29 (3.4%)	1	0/11 (0%)	0
Peripheral ischaemia	0/29 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

The study was prematurely stopped and due to this the planned statistical power for the primary comparisons was not reached.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.