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Clinical Trial Results:
A RANDOMIZED, OPEN-LABEL, MULTICENTER, CONTROLLED STUDY TO ASSESS SAFETY AND EFFICACY OF ELAD IN SUBJECTS WITH ALCOHOL-INDUCED LIVER DECOMPENSATION (AILD)

Summary
EudraCT number	2012-005563-27
Trial protocol	GB DE ES
Global end of trial date	07 May 2015

Results information
Results version number	v1(current)
This version publication date	30 Sep 2016
First version publication date	30 Sep 2016
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

VTI-208

ISRCTN number

US NCT number

NCT01471028

WHO universal trial number (UTN)

Sponsor organisation name

Vital Therapies, Inc.

Sponsor organisation address

15010 Avenue of Science, Suite 200, San Diego, United States, 92128

Public contact

Duane Nash, President, Vital Therapies, Inc., 001 858-673-6840, dnash@vitaltherapies.com

Scientific contact

Robert Ashley, Chief Technical Officer, Vital Therapies, Inc., 001 858-673-6840, rashley@vitaltherapies.com

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

31 Jul 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

07 May 2015

Global end of trial reached?

Yes

Global end of trial date

07 May 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) up to at least Study Day 91, with follow-up Protocol VTI-208E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTI-208 study termination (after the last surviving enrolled subject completes Study Day 91). This will be assessed using a Kaplan-Meier survival analysis of the ITT population utilizing a log-rank test.

Protection of trial subjects

Continuous monitoring of the ELAD System by trained ELAD Specialists during ELAD treatment. Administration of diphenhydramine or equivalent immediately prior to initiation of ELAD treatment to prevent hypersensitivity reactions.

Background therapy

The majority of subjects with AILD present with clinical characteristics of alcoholic hepatitis (AH). The Standard of Care (background therapy) for the secondary medical problems associated with AH was derived from the practice guidelines issued by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of Liver (EASL). These guidelines were applied to both the ELAD-treated and Control subjects during this study.

Evidence for comparator

VTI-208 was a randomized, multicenter, open-label, concurrent control study of subjects with AILD. Subjects meeting the eligibility requirements of the study received either standard of care treatment for AILD (as defined in the protocol) plus treatment with the ELAD System (ELAD group) or standard of care treatment for AILD alone (Control group). Treatment options for patients with AILD are limited. The majority of subjects with AILD present with clinical characteristics of AH. Patients with severe AH (defined as a Maddrey Discriminant Function of ≥32) have a poor prognosis, with 90-day survival of around 50%. Regimens that have been used for the past 40 years, including corticosteroids, theophylline with corticosteroids, pentoxifylline, and infliximab, have had no significant effect on the long term survival of patients with AILD. Of particular importance are the results of the UK NIHR-supported STOPAH study, a study in alcoholic hepatitis reporting out in 2015. Results from this study, which randomized 1103 subjects in 40 clinical sites in the UK, showed that the administration of steroids and pentoxifylline had no effect on survival at 90 days either alone or in combination. While a sham control is a potential comparator, regulatory and ethical bodies have determined that the administration of a sham extracorporeal therapy without the possibility of benefit is unethical, and therefore could not be considered for study VTI-208. Consequently, the best available standard of care in accord with AASLD and EASL guidelines was recommended in the VTI-208 study protocol for all participants irrespective of treatment arm.

Actual start date of recruitment

20 Mar 2013

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety, Ethical reason, Regulatory reason, Scientific research

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

United States: 176

Country: Number of subjects enrolled

Australia: 15

Worldwide total number of subjects

203

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)

198

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants with clinical (protocol-guided) or biopsy-proven evidence of AILD who met study inclusion/exclusion criteria were eligible for participation in the study. Subjects were recruited from March 2013 through February 2015 in the United States, United Kingdom and Australia.

Screening details

A total of 372 participants were screened, out of which 169 were screen failures, and 203 were randomized, of which 95 received ELAD treatment. Of the 203 subjects randomized, 193 had AH; 10 had non-AH AILD. Participants who successfully completed the initial 91-day treatment period were entered into a 5-year extension phase (VTI-208E) of the stud

Period 1 title

VTI-208

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Investigative staff who carried out follow-up treatment visits were blinded to participant treatment assignment. Home visit staff who carried out weekly home visits for participants discharged from the hospital were also blinded to participant treatment assignment. Sponsor staff, with the exception of those involved in the monitoring of study safety, were blinded to treatment outcomes. The Data and Safety Monitoring Board was blinded to study outcomes.

Are arms mutually exclusive

Yes

ELAD Treatment

Arm description

Participants randomized to the ELAD group received ELAD treatment plus protocol-directed Standard of Care treatment for a period of up to 5 days followed by Standard of Care treatment through Study Day 91.

Arm type

Experimental

Investigational medicinal product name

ELAD

Investigational medicinal product code

ELAD System

Other name

VTL C3A cells

Pharmaceutical forms

Living tissue equivalent

Routes of administration

Haemodialysis

Dosage and administration details

Four cartridges, each containing approximately 110 grams of VTL C3A cells (approximately 440 grams total or approximately 20% to 30% of the native liver, a residual mass necessary for survival). ELAD treatment duration spans for up to 5 days. Continuous extracorporeal circulation by central venous catheter allowing plasma fraction interaction with VTL C3A cells incorporated in ELAD C3A cell cartridges.

Control

Arm description

Participants randomized to the Control group received protocol-directed Standard of Care treatment in accord with AASLD and EASL guidelines for up to 91 days.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 1	ELAD Treatment	Control
Started	96	107
Completed Study VTI-208	56	63
Completed	56	63
Not completed	40	44
Adverse event, serious fatal	39	41
Consent withdrawn by subject	-	2
Lost to follow-up	1	1

Period 2 title

VTI-208E

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

ELAD Treatment

Arm description

Participants randomized to the ELAD group and who received ELAD treatment plus protocol-directed Standard of Care treatment for a period of up to 5 days during study VTI-208 were followed up for up to 5 years.

Arm type

Experimental

Investigational medicinal product name

ELAD

Investigational medicinal product code

ELAD System

Other name

VTL C3A cells

Pharmaceutical forms

Living tissue equivalent

Routes of administration

Haemodialysis

Dosage and administration details

Control

Arm description

Participants randomized to the Control group and who received protocol-directed Standard of Care during the VTI-208 study in accord with AASLD and EASL guidelines were followed up for up to 5 years.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	ELAD Treatment	Control
Started	56	63
Data Lock, 31 July 2015	56	63
Completed	48	51
Not completed	8	12
Adverse event, serious fatal	7	10
Consent withdrawn by subject	1	-
Lost to follow-up	-	2

Baseline characteristics

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Reporting group title

ELAD Treatment

Reporting group description

Reporting group title

Control

Reporting group description

Participants randomized to the Control group received protocol-directed Standard of Care treatment in accord with AASLD and EASL guidelines for up to 91 days.

Reporting group values	ELAD Treatment	Control	Total
Number of subjects	96	107	203
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	94	104	198
From 65-84 years	2	3	5
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	46.5 ( 9.06 )	44.8 ( 10.66 )	-
Gender categorical
Units: Subjects
Female	41	42	83
Male	55	65	120
Race
Units: Subjects
White	84	91	175
Black or African American	7	9	16
Asian	2	2	4
Native Hawaiian or Other Pacific Islander	0	0	0
American Indian or Alaskan Native	0	1	1
Other	3	4	7
Baseline MELD
Baseline value of the Model for End Stage Liver Disease score.
Units: MELD score
arithmetic mean (standard deviation)	27.6 ( 3.94 )	27.1 ( 3.79 )	-

End points

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Reporting group title

ELAD Treatment

Reporting group description

Reporting group title

Control

Reporting group description

Participants randomized to the Control group received protocol-directed Standard of Care treatment in accord with AASLD and EASL guidelines for up to 91 days.

Reporting group title

ELAD Treatment

Reporting group description

Reporting group title

Control

Reporting group description

Participants randomized to the Control group and who received protocol-directed Standard of Care during the VTI-208 study in accord with AASLD and EASL guidelines were followed up for up to 5 years.

Primary: Overall Survival

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End point title

Overall Survival

End point description

The primary endpoint of the study was a comparison of overall survival between the ELAD-treated and Control groups defined by a Kaplan-Meier analysis of survival up to at least Study Day 91, with protocol VTI-208E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (31 July 2015).

End point type

Primary

End point timeframe

Up to at least Study Day 91, with protocol VTI-208E providing additional survival data up to 5 years from randomization.

End point values	ELAD Treatment	Control
Number of subjects analysed	96	107
Units: subjects
Alive	48	51
Dead	46	51
Withdrew Consent	1	2
Lost to Follow-Up	1	3

Attachments

Summary - K-M Analysis of Overall Survival-ITT Pop
Table - K-M Analysis of Overall Survival-ITT Pop

Kaplan-Meier Analysis of Overall Survival

Statistical analysis description

The primary endpoint was assessed using a Kaplan-Meier survival analysis of the Intent-to-treat (ITT) population utilizing a log-rank test.

Comparison groups

ELAD Treatment v Control

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.027

Confidence interval

level

95%

sides

2-sided

lower limit

0.689

upper limit

1.53

Secondary: Proportion of Survivors at Study Day 91

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End point title

Proportion of Survivors at Study Day 91

End point description

Proportion of survivors at Study Day 91.

End point type

Secondary

End point timeframe

Up to Study Day 91.

End point values	ELAD Treatment	Control
Number of subjects analysed	96	107
Units: subjects
Alive	57	66
Dead	39	41

Attachments

Proportion of Survivors at Study Day 91-ITT

Proportion of Survivors at Study Day 91

Statistical analysis description

Proportion of Survivors at Study Day 91

Comparison groups

ELAD Treatment v Control

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05

Method

Chi-squared

Confidence interval

Adverse events

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Timeframe for reporting adverse events

Randomization through Study Day 91.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

ELAD Treatment

Reporting group description

Participants received ELAD treatment plus protocol-guided standard of care for a period of up to 5 days followed by standard of care through Study Day 91.

Reporting group title

Control

Reporting group description

Subjects randomized to the Control group received protocol-guided standard of care in accord with AASLD and EASL guidelines for up to 91 days.

Serious adverse events	ELAD Treatment	Control
Total subjects affected by serious adverse events
subjects affected / exposed	73 / 95 (76.84%)	75 / 108 (69.44%)
number of deaths (all causes)	38	42
number of deaths resulting from adverse events	2	0
Vascular disorders
Cerebellar haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	7 / 95 (7.37%)	6 / 108 (5.56%)
occurrences causally related to treatment / all	3 / 8	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 2
Haematochezia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Hypotension
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritoneal haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Portal vein thrombosis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Septic shock
subjects affected / exposed	2 / 95 (2.11%)	4 / 108 (3.70%)
occurrences causally related to treatment / all	1 / 2	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1
Shock
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Shock haemorrhagic
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngeal haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Alcohol withdrawal syndrome
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypothermia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	7 / 95 (7.37%)	10 / 108 (9.26%)
occurrences causally related to treatment / all	1 / 7	0 / 10
deaths causally related to treatment / all	1 / 5	0 / 9
Pyrexia
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Epistaxis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	5 / 95 (5.26%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 1
Psychiatric disorders
Agitation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Drug abuse
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Bacterial test positive
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiac tamponade
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic encephalopathy
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences causally related to treatment / all	0 / 11	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences causally related to treatment / all	0 / 8	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Disseminated intravascular coagulation
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 95 (1.05%)	4 / 108 (3.70%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal varices haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Hepatobiliary disorders
Ascites
subjects affected / exposed	6 / 95 (6.32%)	13 / 108 (12.04%)
occurrences causally related to treatment / all	0 / 6	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	13 / 95 (13.68%)	10 / 108 (9.26%)
occurrences causally related to treatment / all	0 / 14	0 / 10
deaths causally related to treatment / all	0 / 12	0 / 10
Hepatitis alcoholic
subjects affected / exposed	2 / 95 (2.11%)	4 / 108 (3.70%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 3
Hepatorenal syndrome
subjects affected / exposed	3 / 95 (3.16%)	9 / 108 (8.33%)
occurrences causally related to treatment / all	0 / 4	0 / 9
deaths causally related to treatment / all	0 / 2	0 / 5
Hyperammonaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Cellulitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Emphysematous cystitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	4 / 95 (4.21%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 3	0 / 1
Renal failure acute
subjects affected / exposed	6 / 95 (6.32%)	12 / 108 (11.11%)
occurrences causally related to treatment / all	1 / 6	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 1
Renal impairment
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular weakness
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Peritonitis bacterial
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridial infection
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fungaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mycobacterial infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 95 (2.11%)	6 / 108 (5.56%)
occurrences causally related to treatment / all	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	4 / 95 (4.21%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 1
Urinary tract infection
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fluid overload
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences causally related to treatment / all	1 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 1
Generalised oedema
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperthyroidism
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	ELAD Treatment	Control
Total subjects affected by non serious adverse events
subjects affected / exposed	95 / 95 (100.00%)	107 / 108 (99.07%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Colonic polyp
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Vascular disorders
Abdominal compartment syndrome
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Aneurysm
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Angiopathy
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Aortic aneurysm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Aortic arteriosclerosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Arteriosclerosis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Arteriospasm coronary
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cardiovascular deconditioning
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Contusion
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences all number	8	6
Coronary artery disease
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cyanosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Deep vein thrombosis
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	2	1
Dizziness postural
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Gastric haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Gastric varices
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Gastrointestinal haemorrhage
subjects affected / exposed	4 / 95 (4.21%)	4 / 108 (3.70%)
occurrences all number	4	4
Gingival bleeding
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Haematochezia
subjects affected / exposed	3 / 95 (3.16%)	4 / 108 (3.70%)
occurrences all number	3	4
Haematoma
subjects affected / exposed	6 / 95 (6.32%)	3 / 108 (2.78%)
occurrences all number	6	3
Haemodynamic instability
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Haemoptysis
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Haemorrhage
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	5	0
Haemorrhage intracranial
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Haemorrhage urinary tract
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Haemorrhoids
subjects affected / exposed	5 / 95 (5.26%)	8 / 108 (7.41%)
occurrences all number	5	8
Haemothorax
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypertension
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Hypotension
subjects affected / exposed	29 / 95 (30.53%)	18 / 108 (16.67%)
occurrences all number	37	20
Hypovolaemic shock
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Melaena
subjects affected / exposed	5 / 95 (5.26%)	3 / 108 (2.78%)
occurrences all number	6	4
Mucosal haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Orthostatic hypotension
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pallor
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Penile haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Peripheral artery aneurysm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Petechiae
subjects affected / exposed	4 / 95 (4.21%)	2 / 108 (1.85%)
occurrences all number	5	2
Pharyngeal haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Portal hypertensive gastropathy
subjects affected / exposed	3 / 95 (3.16%)	9 / 108 (8.33%)
occurrences all number	3	9
Portal vein thrombosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Presyncope
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Procedural haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pulmonary alveolar haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pulmonary congestion
subjects affected / exposed	5 / 95 (5.26%)	0 / 108 (0.00%)
occurrences all number	5	0
Pulmonary hypertension
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Purpura
subjects affected / exposed	0 / 95 (0.00%)	3 / 108 (2.78%)
occurrences all number	0	3
Retroperitoneal haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Scrotal haematoma
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Septic shock
subjects affected / exposed	5 / 95 (5.26%)	1 / 108 (0.93%)
occurrences all number	5	1
Shock
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Shock haemorrhagic
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Spider naevus
subjects affected / exposed	5 / 95 (5.26%)	5 / 108 (4.63%)
occurrences all number	5	5
Splenic infarction
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Splenic varices
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Splenic vein thrombosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	2
Syncope
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Systemic inflammatory response syndrome
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences all number	2	3
Telangiectasia
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Urogenital haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Vaginal haemorrhage
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Varices oesophageal
subjects affected / exposed	3 / 95 (3.16%)	6 / 108 (5.56%)
occurrences all number	3	6
Vascular anomaly
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Vasodilitation
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Surgical and medical procedures
Biliary drainage
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Bladder catheterisation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Central venous catheterisation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Extubation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Intravenous catheter management
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Removal of foreign body from external ear
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Suture insertion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Wound drainage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
General disorders and administration site conditions
Administration site pain
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Asthenia
subjects affected / exposed	6 / 95 (6.32%)	12 / 108 (11.11%)
occurrences all number	7	14
Catheter site haemorrhage
subjects affected / exposed	9 / 95 (9.47%)	4 / 108 (3.70%)
occurrences all number	10	4
Chest pain
subjects affected / exposed	8 / 95 (8.42%)	5 / 108 (4.63%)
occurrences all number	9	5
Cyst
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Device component issue
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Device damage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Device occlusion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Effusion
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	2
Fatigue
subjects affected / exposed	7 / 95 (7.37%)	6 / 108 (5.56%)
occurrences all number	7	7
Feeling abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Gait disturbance
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Hyperthermia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypothermia
subjects affected / exposed	4 / 95 (4.21%)	1 / 108 (0.93%)
occurrences all number	4	1
Inflammation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Infusion site haemorrhage
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Local swelling
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Malaise
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Medical device complication
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	3	1
Mucosal dryness
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Multi-organ failure
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Pain
subjects affected / exposed	7 / 95 (7.37%)	9 / 108 (8.33%)
occurrences all number	8	10
Puncture site haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Puncture site pain
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pyrexia
subjects affected / exposed	25 / 95 (26.32%)	10 / 108 (9.26%)
occurrences all number	28	10
Secretion discharge
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Temperature intolerance
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Ulcer
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Oedema peripheral
subjects affected / exposed	32 / 95 (33.68%)	33 / 108 (30.56%)
occurrences all number	38	41
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Reproductive system and breast disorders
Breast mass
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Cervical dysplasia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Genital swelling
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Gynaecomastia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Menorrhagia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Prostatic calcification
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Scrotal irritation
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Scrotal oedema
subjects affected / exposed	1 / 95 (1.05%)	4 / 108 (3.70%)
occurrences all number	2	4
Scrotal pain
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Vaginal infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Vaginal lesion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Acquired diaphragmatic eventration
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Acute respiratory distress syndrome
subjects affected / exposed	4 / 95 (4.21%)	2 / 108 (1.85%)
occurrences all number	5	2
Acute respiratory failure
subjects affected / exposed	6 / 95 (6.32%)	2 / 108 (1.85%)
occurrences all number	6	2
Asthma
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Atelectasis
subjects affected / exposed	14 / 95 (14.74%)	6 / 108 (5.56%)
occurrences all number	15	6
Bronchial disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Bronchospasm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Cough
subjects affected / exposed	6 / 95 (6.32%)	8 / 108 (7.41%)
occurrences all number	6	8
Dry throat
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Dyspnoea
subjects affected / exposed	21 / 95 (22.11%)	21 / 108 (19.44%)
occurrences all number	25	26
Epistaxis
subjects affected / exposed	10 / 95 (10.53%)	6 / 108 (5.56%)
occurrences all number	11	6
Hepatic hydrothorax
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hiccups
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Hyperventilation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypopnoea
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Hypoventilation
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Hypoxia
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Increased bronchial secretion
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Influenza
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Laryngitis bacterial
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Lower respiratory tract infection
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Lung consolidation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Lung disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Lung infiltration
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Lung neoplasm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Nasal congestion
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Nasal dryness
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Non-cardiac chest pain
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Obstructive airways disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oropharyngeal pain
subjects affected / exposed	5 / 95 (5.26%)	4 / 108 (3.70%)
occurrences all number	5	4
Pharyngeal erythema
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Pleural effusion
subjects affected / exposed	12 / 95 (12.63%)	14 / 108 (12.96%)
occurrences all number	12	14
Pleuritic pain
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pneumonia aspiration
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Pneumothorax
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	4	1
Productive cough
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Pulmonary mass
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pulmonary oedema
subjects affected / exposed	7 / 95 (7.37%)	5 / 108 (4.63%)
occurrences all number	8	5
Rales
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences all number	8	6
Respiration abnormal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Respiratory acidosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Respiratory alkalosis
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Respiratory distress
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
respiratory failure
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Respiratory tract congestion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Rhinitis allergic
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Rhonchi
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Sleep apnoea syndrome
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Tachypnoea
subjects affected / exposed	7 / 95 (7.37%)	6 / 108 (5.56%)
occurrences all number	7	7
Vocal cord disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	3 / 95 (3.16%)	4 / 108 (3.70%)
occurrences all number	3	4
Psychiatric disorders
Adjustment disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Aggression
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Agitation
subjects affected / exposed	16 / 95 (16.84%)	8 / 108 (7.41%)
occurrences all number	17	8
Alcohol abuse
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Amnesia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	2	0
Anxiety
subjects affected / exposed	21 / 95 (22.11%)	9 / 108 (8.33%)
occurrences all number	22	10
Apraxia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Catatonia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Circadian rhythm sleep disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Confusional state
subjects affected / exposed	14 / 95 (14.74%)	3 / 108 (2.78%)
occurrences all number	14	3
Delirium
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Delirium tremens
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Delusion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Depression
subjects affected / exposed	7 / 95 (7.37%)	7 / 108 (6.48%)
occurrences all number	7	7
Emotional distress
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Failure to thrive
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Hallucination
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Hallucination, auditory
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Hallucination, visual
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypophagia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Irritability
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Irritable bowel syndrome
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Korsakoff's syndrome
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Memory impairment
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Mental status changes
subjects affected / exposed	4 / 95 (4.21%)	2 / 108 (1.85%)
occurrences all number	4	2
Panic attack
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Poor quality sleep
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Restlessness
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Selective mutism
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Speech disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Stupor
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Suicidal ideation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Drug abuse
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	2
Investigations
Acinetobacter test positive
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Alanine aminotransferase increased
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Alpha 1 foetoprotein increased
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	3
Ammonia abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Ammonia increased
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Antibiotic resistant staphylococcus test positive
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Aspartate aminotransferase increased
subjects affected / exposed	7 / 95 (7.37%)	0 / 108 (0.00%)
occurrences all number	7	0
Aspiration bronchial
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Bacterial test positive
subjects affected / exposed	5 / 95 (5.26%)	1 / 108 (0.93%)
occurrences all number	5	1
Blood aldosterone decreased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood amylase increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood bilirubin increased
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Blood cortisol decreased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood creatinine increased
subjects affected / exposed	5 / 95 (5.26%)	4 / 108 (3.70%)
occurrences all number	5	4
Blood fibrinogen decreased
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Blood glucose fluctuation
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood lactate dehydrogenase increased
subjects affected / exposed	6 / 95 (6.32%)	1 / 108 (0.93%)
occurrences all number	6	1
Blood lactic acid abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood lactic acid increased
subjects affected / exposed	4 / 95 (4.21%)	1 / 108 (0.93%)
occurrences all number	4	1
Blood magnesium decreased
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Blood phosphorus abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood phosphorus decreased
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Blood potassium abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood pressure decreased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood pressure systolic decreased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blood urea increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Body surface area increased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Body temperature decreased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Body temperature increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Breath sounds abnormal
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Cardiac murmur
subjects affected / exposed	10 / 95 (10.53%)	8 / 108 (7.41%)
occurrences all number	10	10
Clostridium test positive
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Computerised tomogram head
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Culture urine positive
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Drug screen positive
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Electrocardiogram QRS complex abnormal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Enterococcus test positive
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Full blood count abnormal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Fungal test positive
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Haematocrit decreased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Haemoglobin decreased
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	5	2
Intraocular pressure increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Laboratory test abnormal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Liver function test abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Low density lipoprotein increased
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Oxygen saturation decreased
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Procalcitonin increased
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Pulmonary function test decreased
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	2	2
Respiratory rate increased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Serum ferritin increased
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Sputum culture positive
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Total lung capacity decreased
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Urine colour abnormal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Urine output decreased
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Volume blood decreased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Weight decreased
subjects affected / exposed	5 / 95 (5.26%)	1 / 108 (0.93%)
occurrences all number	5	1
Injury, poisoning and procedural complications
Catheter site discharge
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Catheter site haematoma
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Catheter site related reaction
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Colon injury
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Excoriation
subjects affected / exposed	10 / 95 (10.53%)	5 / 108 (4.63%)
occurrences all number	10	6
Fall
subjects affected / exposed	8 / 95 (8.42%)	5 / 108 (4.63%)
occurrences all number	8	7
Febrile nonhaemolytic transfusion reaction
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Feeding tube complication
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Incision site complication
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Incision site pain
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Injection site haematoma
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Injection site haemorrhage
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Rib fracture
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Spinal column injury
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Transfusion reaction
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Vessel puncture site haematoma
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Wound
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Wound complication
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Wound secretion
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Alcohol poisoning
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Procedural pain
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Congenital, familial and genetic disorders
Arteriovenous malformation
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Cardiac disorders
Arrhythmia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Atrial fibrillation
subjects affected / exposed	5 / 95 (5.26%)	2 / 108 (1.85%)
occurrences all number	6	2
Atrial flutter
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Bradycardia
subjects affected / exposed	4 / 95 (4.21%)	4 / 108 (3.70%)
occurrences all number	4	7
Cardiac arrest
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	2	0
Cardiac failure
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Cardiac failure congestive
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Cardiomegaly
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Chest discomfort
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hyperdynamic left ventricle
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Left ventricular dysfunction
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Left ventricular hypertrophy
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Mitral valve incompetence
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Palpitations
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pulmonary valve incompetence
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Right atrial dilatation
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Sinus tachycardia
subjects affected / exposed	7 / 95 (7.37%)	1 / 108 (0.93%)
occurrences all number	7	1
Supraventricular tachycardia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tachycardia
subjects affected / exposed	17 / 95 (17.89%)	10 / 108 (9.26%)
occurrences all number	19	10
Tricuspid valve incompetence
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Ventricular tachycardia
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Nervous system disorders
Asterixis
subjects affected / exposed	9 / 95 (9.47%)	16 / 108 (14.81%)
occurrences all number	9	16
Ataxia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Balance disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cerebral atrophy
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Coma
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	2	1
Coma hepatic
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	5	1
Complex regional pain syndrome
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Convulsion
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	3
Coordination abnormal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Depressed level of consciousness
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Facial spasm
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Headache
subjects affected / exposed	11 / 95 (11.58%)	7 / 108 (6.48%)
occurrences all number	14	7
Hepatic encephalopathy
subjects affected / exposed	36 / 95 (37.89%)	29 / 108 (26.85%)
occurrences all number	45	30
Hereditary cerebral degeneration
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Hyperreflexia
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Hypoaesthesia
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	4	1
Hyporeflexia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hyporesponsive to stimuli
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Insomnia
subjects affected / exposed	14 / 95 (14.74%)	15 / 108 (13.89%)
occurrences all number	14	15
Lethargy
subjects affected / exposed	4 / 95 (4.21%)	5 / 108 (4.63%)
occurrences all number	4	5
Metabolic encephalopathy
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Mobility decreased
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Myoclonic epilepsy
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Myoclonus
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Neuralgia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Neuropathy peripheral
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	2
Nystagmus
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Paraesthesia
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences all number	2	3
Pupils unequal
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Restless legs syndrome
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Somnolence
subjects affected / exposed	4 / 95 (4.21%)	5 / 108 (4.63%)
occurrences all number	4	5
Tension headache
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tremor
subjects affected / exposed	14 / 95 (14.74%)	10 / 108 (9.26%)
occurrences all number	14	11
Dizziness
subjects affected / exposed	2 / 95 (2.11%)	12 / 108 (11.11%)
occurrences all number	3	15
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	42 / 95 (44.21%)	17 / 108 (15.74%)
occurrences all number	47	19
Anaemia macrocytic
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Anisocytosis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Coagulopathy
subjects affected / exposed	29 / 95 (30.53%)	13 / 108 (12.04%)
occurrences all number	34	15
Disseminated intravascular coagulation
subjects affected / exposed	7 / 95 (7.37%)	0 / 108 (0.00%)
occurrences all number	7	0
Haemolysis
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Haemolytic anaemia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Heparin-induced thrombocytopenia
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Hypochromasia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypofibrinogenaemia
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Hypoprothrombinaemia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Leukaemoid reaction
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Leukocytosis
subjects affected / exposed	13 / 95 (13.68%)	13 / 108 (12.04%)
occurrences all number	16	13
Lymphadenopathy
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Pancytopenia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Splenomegaly
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Thrombocytopenia
subjects affected / exposed	33 / 95 (34.74%)	12 / 108 (11.11%)
occurrences all number	36	12
White blood cell disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Eye disorders
Dry eye
subjects affected / exposed	4 / 95 (4.21%)	1 / 108 (0.93%)
occurrences all number	4	1
Eye discharge
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Eye swelling
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Keratitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Keratopathy
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Limbal swelling
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Scleral discolouration
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Scleral disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Scleral oedema
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	3	0
Ulcerative keratitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Vision blurred
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Abdominal distension
subjects affected / exposed	16 / 95 (16.84%)	8 / 108 (7.41%)
occurrences all number	17	10
Abdominal pain
subjects affected / exposed	27 / 95 (28.42%)	22 / 108 (20.37%)
occurrences all number	37	29
Abdominal tenderness
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences all number	3	3
Anastomotic ulcer
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Anorectal discomfort
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Bacterascites
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Breath odour
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Colitis
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Constipation
subjects affected / exposed	19 / 95 (20.00%)	10 / 108 (9.26%)
occurrences all number	20	10
Diarrhoea
subjects affected / exposed	19 / 95 (20.00%)	17 / 108 (15.74%)
occurrences all number	20	19
Diverticulum gastric
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Diverticulum intestinal
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Dry mouth
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Duodenal ulcer
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Duodenogastric reflux
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Dyspepsia
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Dysphagia
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Faecal incontinence
subjects affected / exposed	3 / 95 (3.16%)	3 / 108 (2.78%)
occurrences all number	3	3
Faeces discoloured
subjects affected / exposed	4 / 95 (4.21%)	4 / 108 (3.70%)
occurrences all number	4	4
Faeces pale
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Flatulence
subjects affected / exposed	5 / 95 (5.26%)	2 / 108 (1.85%)
occurrences all number	5	2
Frequent bowel movements
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Functional gastrointestinal disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Gastric mucosal lesion
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Gastritis
subjects affected / exposed	0 / 95 (0.00%)	3 / 108 (2.78%)
occurrences all number	0	3
Gastritis erosive
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Gastrointestinal oedema
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Gastrointestinal sounds abnormal
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Glossitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Haematemesis
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	5
Hiatus hernia
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Ileus
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Impaired gastric emptying
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Inguinal hernia
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Mouth haemorrhage
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Mouth ulceration
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Nausea
subjects affected / exposed	15 / 95 (15.79%)	23 / 108 (21.30%)
occurrences all number	18	27
Odynophagia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oesophageal ulcer
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Oesophagitis
subjects affected / exposed	0 / 95 (0.00%)	3 / 108 (2.78%)
occurrences all number	0	3
Oral discharge
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Oral disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oral pain
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pancreatitis
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Peptic ulcer
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Peritoneal disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pneumatosis intestinalis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pneumoperitoneum
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Proctalgia
subjects affected / exposed	0 / 95 (0.00%)	4 / 108 (3.70%)
occurrences all number	0	4
Rectal haemorrhage
subjects affected / exposed	8 / 95 (8.42%)	4 / 108 (3.70%)
occurrences all number	9	4
Rectal ulcer
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Retroperitoneal haematoma
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Small intestinal obstruction
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tongue coated
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tongue disorder
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Tooth disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Toothache
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Umbilical hernia
subjects affected / exposed	3 / 95 (3.16%)	3 / 108 (2.78%)
occurrences all number	3	3
Vomiting
subjects affected / exposed	14 / 95 (14.74%)	17 / 108 (15.74%)
occurrences all number	17	21
Oesophageal varices haemorrhage
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hepatobiliary disorders
Ascites
subjects affected / exposed	34 / 95 (35.79%)	30 / 108 (27.78%)
occurrences all number	37	40
Bile duct obstruction
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Biliary colic
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Caput medusae
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences all number	2	3
Cholecystitis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Cholelithiasis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cholestasis
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Cirrhosis alcoholic
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Foetor hepaticus
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Gallbladder disorder
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Hepatic cirrhosis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hepatic failure
subjects affected / exposed	2 / 95 (2.11%)	3 / 108 (2.78%)
occurrences all number	3	3
Hepatic fibrosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hepatitis alcoholic
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hepatomegaly
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Hepatorenal syndrome
subjects affected / exposed	11 / 95 (11.58%)	11 / 108 (10.19%)
occurrences all number	12	13
Hyperammonaemia
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Jaundice
subjects affected / exposed	2 / 95 (2.11%)	4 / 108 (3.70%)
occurrences all number	2	4
Ocular icterus
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Portal hypertension
subjects affected / exposed	2 / 95 (2.11%)	4 / 108 (3.70%)
occurrences all number	2	4
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Anogenital warts
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Blister
subjects affected / exposed	0 / 95 (0.00%)	3 / 108 (2.78%)
occurrences all number	0	3
Cellulitis
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Decubitus ulcer
subjects affected / exposed	5 / 95 (5.26%)	0 / 108 (0.00%)
occurrences all number	5	0
Dermatitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	2	0
Dry skin
subjects affected / exposed	0 / 95 (0.00%)	5 / 108 (4.63%)
occurrences all number	0	5
Ecchymosis
subjects affected / exposed	9 / 95 (9.47%)	6 / 108 (5.56%)
occurrences all number	9	9
Erythema
subjects affected / exposed	3 / 95 (3.16%)	3 / 108 (2.78%)
occurrences all number	3	4
Eschar
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Face oedema
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Facial wasting
subjects affected / exposed	1 / 95 (1.05%)	4 / 108 (3.70%)
occurrences all number	1	4
Folliculitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Herpes simplex
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hyperhidrosis
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Hyperkeratosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Laceration
subjects affected / exposed	4 / 95 (4.21%)	1 / 108 (0.93%)
occurrences all number	4	1
Nail discolouration
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Night sweats
subjects affected / exposed	1 / 95 (1.05%)	2 / 108 (1.85%)
occurrences all number	1	2
Onychomycosis
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Palmar erythema
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Perianal erythema
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Pruritus
subjects affected / exposed	19 / 95 (20.00%)	19 / 108 (17.59%)
occurrences all number	20	20
Psoriasis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Rash
subjects affected / exposed	7 / 95 (7.37%)	11 / 108 (10.19%)
occurrences all number	7	12
Rash pustular
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Scab
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Scratch
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	3	1
Skin disorder
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Skin erosion
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Skin exfoliation
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Skin irritation
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Skin lesion
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Skin ulcer
subjects affected / exposed	5 / 95 (5.26%)	3 / 108 (2.78%)
occurrences all number	5	3
Stasis dermatitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Swelling face
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Renal and urinary disorders
Acute prerenal failure
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Anuria
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Azotaemia
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Costovertebral angle tenderness
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cystitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Dysuria
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Haematuria
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Hydronephrosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Incontinence
subjects affected / exposed	4 / 95 (4.21%)	0 / 108 (0.00%)
occurrences all number	4	0
Micturition urgency
subjects affected / exposed	0 / 95 (0.00%)	2 / 108 (1.85%)
occurrences all number	0	2
Nephrolithiasis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Nocturia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oliguria
subjects affected / exposed	6 / 95 (6.32%)	0 / 108 (0.00%)
occurrences all number	6	0
Polyuria
subjects affected / exposed	4 / 95 (4.21%)	2 / 108 (1.85%)
occurrences all number	4	2
Pyelonephritis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Renal disorder
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Renal failure
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Renal failure acute
subjects affected / exposed	22 / 95 (23.16%)	21 / 108 (19.44%)
occurrences all number	23	25
Renal impairment
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Urethral pain
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Urinary incontinence
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Urinary retention
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Urinary tract pain
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Endocrine disorders
Diabetes mellitus
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	7 / 95 (7.37%)	3 / 108 (2.78%)
occurrences all number	7	3
Back pain
subjects affected / exposed	9 / 95 (9.47%)	13 / 108 (12.04%)
occurrences all number	12	16
Chills
subjects affected / exposed	4 / 95 (4.21%)	3 / 108 (2.78%)
occurrences all number	4	3
Groin pain
subjects affected / exposed	2 / 95 (2.11%)	0 / 108 (0.00%)
occurrences all number	2	0
Joint range of motion decreased
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Joint swelling
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Muscle atrophy
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences all number	8	6
Muscle spasms
subjects affected / exposed	5 / 95 (5.26%)	3 / 108 (2.78%)
occurrences all number	5	3
Musculoskeletal discomfort
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Musculoskeletal pain
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Myalgia
subjects affected / exposed	5 / 95 (5.26%)	0 / 108 (0.00%)
occurrences all number	5	0
Myopathy
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Neck pain
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Osteoarthritis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Osteopenia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pain in extremity
subjects affected / exposed	7 / 95 (7.37%)	4 / 108 (3.70%)
occurrences all number	7	5
Rotator cuff syndrome
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Sarcopenia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Spinal disorder
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Spinal osteoarthritis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Muscular weakness
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Flank pain
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Infections and infestations
Aspergillosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Bacteraemia
subjects affected / exposed	16 / 95 (16.84%)	7 / 108 (6.48%)
occurrences all number	18	8
Candidiasis
subjects affected / exposed	9 / 95 (9.47%)	3 / 108 (2.78%)
occurrences all number	10	3
Candiduria
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Clostridial infection
subjects affected / exposed	4 / 95 (4.21%)	6 / 108 (5.56%)
occurrences all number	4	6
Clostridium difficile colitis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Device related infection
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Diverticulitis
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Endocarditis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Enterococcal infection
subjects affected / exposed	2 / 95 (2.11%)	2 / 108 (1.85%)
occurrences all number	2	2
Escherichia infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Fungaemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Fungal infection
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	3	2
Fungal skin infection
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Gastroenteritis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Helicobacter infection
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Lyme disease
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oesophageal candidiasis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Oral candidiasis
subjects affected / exposed	8 / 95 (8.42%)	6 / 108 (5.56%)
occurrences all number	8	6
Oral herpes
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Paronychia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Peritonitis bacterial
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Pharyngitis streptococcal
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Pneumonia
subjects affected / exposed	13 / 95 (13.68%)	10 / 108 (9.26%)
occurrences all number	13	10
Propionibacterium infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Respiratory tract infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Sepsis
subjects affected / exposed	7 / 95 (7.37%)	7 / 108 (6.48%)
occurrences all number	7	8
Septic encephalopathy
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Staphylococcal infection
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tinea infection
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Tooth abscess
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Urinary tract infection
subjects affected / exposed	14 / 95 (14.74%)	16 / 108 (14.81%)
occurrences all number	19	19
Viral infection
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	3 / 95 (3.16%)	2 / 108 (1.85%)
occurrences all number	4	2
Adrenal insufficiency
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Cachexia
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	3
Decreased appetite
subjects affected / exposed	7 / 95 (7.37%)	7 / 108 (6.48%)
occurrences all number	7	7
Dehydration
subjects affected / exposed	6 / 95 (6.32%)	5 / 108 (4.63%)
occurrences all number	6	6
Electrolyte imbalance
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Fluid overload
subjects affected / exposed	8 / 95 (8.42%)	4 / 108 (3.70%)
occurrences all number	8	4
Fluid retention
subjects affected / exposed	1 / 95 (1.05%)	3 / 108 (2.78%)
occurrences all number	1	4
Generalised oedema
subjects affected / exposed	9 / 95 (9.47%)	4 / 108 (3.70%)
occurrences all number	9	4
Goitre
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hepatic steatosis
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Hyperbilirubinaemia
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Hypercalcaemia
subjects affected / exposed	2 / 95 (2.11%)	1 / 108 (0.93%)
occurrences all number	2	1
Hyperchloraemia
subjects affected / exposed	3 / 95 (3.16%)	0 / 108 (0.00%)
occurrences all number	3	0
Hyperglycaemia
subjects affected / exposed	19 / 95 (20.00%)	10 / 108 (9.26%)
occurrences all number	21	12
Hyperkalaemia
subjects affected / exposed	8 / 95 (8.42%)	4 / 108 (3.70%)
occurrences all number	8	6
Hypermagnesaemia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hypernatraemia
subjects affected / exposed	8 / 95 (8.42%)	5 / 108 (4.63%)
occurrences all number	8	5
Hyperphosphataemia
subjects affected / exposed	6 / 95 (6.32%)	3 / 108 (2.78%)
occurrences all number	7	3
Hypervolaemia
subjects affected / exposed	3 / 95 (3.16%)	1 / 108 (0.93%)
occurrences all number	3	1
Hypoalbuminaemia
subjects affected / exposed	4 / 95 (4.21%)	7 / 108 (6.48%)
occurrences all number	4	7
Hypocalcaemia
subjects affected / exposed	18 / 95 (18.95%)	3 / 108 (2.78%)
occurrences all number	24	5
Hypochloraemia
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Hypoglycaemia
subjects affected / exposed	6 / 95 (6.32%)	4 / 108 (3.70%)
occurrences all number	6	4
Hypokalaemia
subjects affected / exposed	21 / 95 (22.11%)	29 / 108 (26.85%)
occurrences all number	23	34
Hypomagnesaemia
subjects affected / exposed	21 / 95 (22.11%)	14 / 108 (12.96%)
occurrences all number	25	14
Hyponatraemia
subjects affected / exposed	8 / 95 (8.42%)	15 / 108 (13.89%)
occurrences all number	8	17
Hypophosphataemia
subjects affected / exposed	23 / 95 (24.21%)	14 / 108 (12.96%)
occurrences all number	23	14
Hypoproteinaemia
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hypothyroidism
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Hypovolaemia
subjects affected / exposed	5 / 95 (5.26%)	5 / 108 (4.63%)
occurrences all number	5	5
Lactic acidosis
subjects affected / exposed	5 / 95 (5.26%)	2 / 108 (1.85%)
occurrences all number	7	2
Lactose intolerance
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Localised oedema
subjects affected / exposed	1 / 95 (1.05%)	1 / 108 (0.93%)
occurrences all number	1	1
Malnutrition
subjects affected / exposed	5 / 95 (5.26%)	5 / 108 (4.63%)
occurrences all number	5	5
Metabolic acidosis
subjects affected / exposed	16 / 95 (16.84%)	13 / 108 (12.04%)
occurrences all number	16	14
Metabolic alkalosis
subjects affected / exposed	1 / 95 (1.05%)	0 / 108 (0.00%)
occurrences all number	1	0
Oedema
subjects affected / exposed	9 / 95 (9.47%)	12 / 108 (11.11%)
occurrences all number	9	15
Osteoporosis
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Vitamin D deficiency
subjects affected / exposed	0 / 95 (0.00%)	1 / 108 (0.93%)
occurrences all number	0	1
Zinc deficiency
subjects affected / exposed	0 / 95 (0.00%)	4 / 108 (3.70%)
occurrences all number	0	4

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Were there any global substantial amendments to the protocol? Yes

30 May 2012

Amendment 1, Version 14.0 - All sites - The number of planned subjects was increased to 200 in order to increase the power to achieve the planned significance level of 0.05 while maintaining the same assumptions for the treatment effect.

27 Nov 2012

Amendment 2, Version 15.0 - All sites - The inclusion/exclusion criteria were updated to provide clarity to the definition of the patient population. The protocol was updated to be in accord with ISO 14155, the EU Device Directives, and pertinent US device regulations.

14 Aug 2013

Amendment 4, Version 17.0 - UK only - Standard of Care treatment guidelines for viral hepatitis were added. A quality of life questionnaire (EQ-5D-5L) was added. Procedures related to subjects lost to follow-up were defined.

30 Sep 2013

Amendment 3, Version 16.0 - All sites - This amendment was never initiated and no patients were consented or randomized under this protocol version.

25 Oct 2013

Amendment 5, Version 18.0 - UK only - Added instruction for sites to notify VTL immediately if any ultrafiltrate culture results were positive, and provided clarification that collection of AEs/SAEs should begin at randomization; not the signing of consent. There was also incorporation of pertinent ISO 14155 wording regarding IRB/EC notification of protocol deviations and amendments.

12 Apr 2014

Amendment 6 - Global - Global harmonization of the protocol to better assist investigators and clinical sites in the conduct of the trial, specifically related to: screening and enrollment, lab and imaging data collection and allowable windows for collection, physical exam and encephalopathy assessment, and follow-up evaluations. Significant changes in this protocol amendment included the following: -The statistical sections were updated to reflect the Statistical Analysis Plan; -Specific instructions for reporting of ultrafiltrate culture results were added; -The adverse event reporting sections were revised, and a Clinical Trial Pharmacovigilance Investigator Guide was added; and -A validated Quality of Life Questionnaire (EQ-5D-5L) was added for VTI-208 and VTI-208E.

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.

None

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Clinical trials

Clinical Trial Results:
A RANDOMIZED, OPEN-LABEL, MULTICENTER, CONTROLLED STUDY TO ASSESS SAFETY AND EFFICACY OF ELAD IN SUBJECTS WITH ALCOHOL-INDUCED LIVER DECOMPENSATION (AILD)

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Subject disposition

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Baseline characteristics

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End points

Primary: Overall Survival

Primary: Overall Survival

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Secondary: Proportion of Survivors at Study Day 91

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Clinical trials

Clinical Trial Results: A RANDOMIZED, OPEN-LABEL, MULTICENTER, CONTROLLED STUDY TO ASSESS SAFETY AND EFFICACY OF ELAD IN SUBJECTS WITH ALCOHOL-INDUCED LIVER DECOMPENSATION (AILD)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Survival

Primary: Overall Survival

Secondary: Proportion of Survivors at Study Day 91

Secondary: Proportion of Survivors at Study Day 91

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A RANDOMIZED, OPEN-LABEL, MULTICENTER, CONTROLLED STUDY TO ASSESS SAFETY AND EFFICACY OF ELAD IN SUBJECTS WITH ALCOHOL-INDUCED LIVER DECOMPENSATION (AILD)