Trial Outcomes & Findings for Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1 (NCT NCT02770716)

NCT ID: NCT02770716

Last Updated: 2022-11-29

Results Overview

Defined as the percentage of participants with 2 consecutive SCr values ≤ 1.5 mg/dL at least 2 hours apart, while on treatment by Day 14 or discharge (on treatment defined as up to 24 hours after the final dose of study drug), per protocol.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 300 participants
• Primary outcome timeframe: within 15 Days
• Results posted on: 2022-11-29

Participant Flow

The study was conducted at 60 active sites in the United States and Canada

Participant milestones

Measure	Terlipressin Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Overall Study STARTED	199	101
Overall Study Intent to Treat (ITT)	199	101
Overall Study Safety Analysis Set (SAS)	200	99
Overall Study Systemic Inflammatory Response Syndrome (SIRS) Subgroup	84	48
Overall Study COMPLETED	87	52
Overall Study NOT COMPLETED	112	49

Reasons for withdrawal

Measure	Terlipressin Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Overall Study Death	101	45
Overall Study Withdrawal by Subject	4	2
Overall Study Lost to Follow-up	1	0
Overall Study Various reasons	6	2

Baseline Characteristics

Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1

Baseline characteristics by cohort

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Total n=300 Participants Total of all reporting groups
Age, Continuous	54.0 years STANDARD_DEVIATION 11.34 • n=5 Participants	53.6 years STANDARD_DEVIATION 11.83 • n=7 Participants	53.8 years STANDARD_DEVIATION 11.49 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	42 Participants n=7 Participants	121 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	59 Participants n=7 Participants	179 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	13 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	165 Participants n=5 Participants	88 Participants n=7 Participants	253 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) White	177 Participants n=5 Participants	94 Participants n=7 Participants	271 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Canada	21 participants n=5 Participants	12 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment United States	178 participants n=5 Participants	89 participants n=7 Participants	267 participants n=5 Participants

PRIMARY outcome

Timeframe: within 15 Days

Population: ITT

Defined as the percentage of participants with 2 consecutive SCr values ≤ 1.5 mg/dL at least 2 hours apart, while on treatment by Day 14 or discharge (on treatment defined as up to 24 hours after the final dose of study drug), per protocol.

Outcome measures

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage of Participants With Verified HRS Reversal	29.1 percentage of participants	15.8 percentage of participants

PRIMARY outcome

Timeframe: within 25 days

Population: ITT

Defined as the percentage of participants with verified HRS reversal who lived at least 10 days without RRT, and were otherwise viable (per protocol) for inclusion in the primary endpoint analysis

Outcome measures

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis	91.3 percentage of participants	94.4 percentage of participants

SECONDARY outcome

Timeframe: within 14 days

Population: ITT

Defined as the percentage of participants with a SCr value no more than 1.5 mg/dL by Day 14 or discharge, and were viable (per protocol) for inclusion in the secondary endpoint analysis

Outcome measures

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage of Participants With HRS Reversal	36.2 percentage of participants	16.8 percentage of participants

SECONDARY outcome

Timeframe: Day 30

Population: ITT

Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30

Outcome measures

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage of Participants With Durable HRS Reversal	31.7 percentage of participants	15.8 percentage of participants

SECONDARY outcome

Timeframe: within 14 days

Population: ITT participants in the SIRS subgroup

Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge

Outcome measures

Measure	Terlipressin n=84 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=48 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage pf Participants in the SIRS Subgroup With HRS Reversal	33.3 percentage of participants	6.3 percentage of participants

SECONDARY outcome

Timeframe: Day 30

Population: ITT

Defined as the percentage of participants who had achieved verified HRS reversal by Day 15 or discharge and did not revert to baseline measures by day 30

Outcome measures

Measure	Terlipressin n=199 Participants Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=101 Participants Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30	24.1 percentage of participants	15.8 percentage of participants

Adverse Events

Terlipressin

Serious events: 142 serious events

Other events: 157 other events

Deaths: 101 deaths

Placebo

Serious events: 62 serious events

Other events: 82 other events

Deaths: 45 deaths

Serious adverse events

Measure	Terlipressin n=200 participants at risk Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=99 participants at risk Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Blood and lymphatic system disorders Anaemia	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Blood and lymphatic system disorders Leukocytosis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Acute left ventricular failure	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Atrial fibrillation	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Cardiac arrest	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Cardiac failure	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Cardiac tamponade	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Cardio-respiratory arrest	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Nodal arrhythmia	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Pericardial effusion	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Pericarditis	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Pulseless electrical activity	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Abdominal discomfort	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Abdominal distension	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Abdominal pain	5.0% 10/200 • Number of events 12 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Abdominal pain upper	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Ascites	1.5% 3/200 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Gastrointestinal haemorrhage	4.0% 8/200 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Haematemesis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Incarcerated umbilical hernia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Intestinal ischaemia	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Large intestine perforation	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Nausea	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Oesophageal varices haemorrhage	1.5% 3/200 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Rectal haemorrhage	0.50% 1/200 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.5% 3/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Vomiting	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Death	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Multiple organ dysfunction syndrome	5.5% 11/200 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	5.1% 5/99 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Oedema peripheral	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Peripheral swelling	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Alcoholic liver disease	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Chronic hepatic failure	7.0% 14/200 • Number of events 14 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	8.1% 8/99 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Cirrhosis alcoholic	2.5% 5/200 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hepatic cirrhosis	4.0% 8/200 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hepatic failure	5.5% 11/200 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	10.1% 10/99 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hepatic function abnormal	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hepatitis alcoholic	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hepatorenal syndrome	1.5% 3/200 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Jaundice	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Liver disorder	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Hepatobiliary disorders Non-alcoholic steatohepatitis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Immune system disorders Liver transplant rejection	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Bacteraemia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Bronchopulmonary aspergillosis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Cystitis	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Pneumonia	2.0% 4/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Pneumonia bacterial	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Respiratory tract infection	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Sepsis	5.0% 10/200 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Septic shock	3.5% 7/200 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Urosepsis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Injury, poisoning and procedural complications Laceration	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Investigations Blood creatinine abnormal	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Investigations Blood creatinine increased	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Investigations Body temperature fluctuation	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Investigations Transaminases increased	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Acidosis	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Dehydration	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Electrolyte imbalance	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Failure to thrive	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Fluid overload	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Hyperglycaemia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Hyperkalaemia	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Hypokalaemia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Metabolic acidosis	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Musculoskeletal and connective tissue disorders Arthralgia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Aphasia	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Coma hepatic	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Encephalopathy	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Haemorrhage intracranial	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Hepatic encephalopathy	4.5% 9/200 • Number of events 9 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Metabolic encephalopathy	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Psychiatric disorders Mental status changes	2.0% 4/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Renal and urinary disorders Acute kidney injury	3.0% 6/200 • Number of events 6 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Renal and urinary disorders Dysuria	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Renal and urinary disorders Renal failure	2.0% 4/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	4.0% 8/200 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	2.0% 2/99 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Aspiration	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.0% 4/200 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.0% 2/200 • Number of events 2 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Respiratory failure	10.5% 21/200 • Number of events 22 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Skin and subcutaneous tissue disorders Rash pruritic	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Arterial haemorrhage	0.00% 0/200 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Circulatory collapse	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Haematoma	0.50% 1/200 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Hypotension	2.0% 4/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Shock	2.5% 5/200 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.

Other adverse events

Measure	Terlipressin n=200 participants at risk Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.	Placebo n=99 participants at risk Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.
Blood and lymphatic system disorders Anaemia	6.5% 13/200 • Number of events 14 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	6.1% 6/99 • Number of events 6 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Bradycardia	5.0% 10/200 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Cardiac disorders Tachycardia	5.0% 10/200 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	8.1% 8/99 • Number of events 9 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Abdominal pain	19.0% 38/200 • Number of events 46 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	5.1% 5/99 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Ascites	5.0% 10/200 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Diarrhoea	13.0% 26/200 • Number of events 30 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	7.1% 7/99 • Number of events 7 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Nausea	16.0% 32/200 • Number of events 32 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	10.1% 10/99 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Gastrointestinal disorders Vomiting	8.5% 17/200 • Number of events 17 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	9.1% 9/99 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Chest pain	5.5% 11/200 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
General disorders Pyrexia	2.0% 4/200 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	7.1% 7/99 • Number of events 8 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Infections and infestations Urinary tract infection	3.0% 6/200 • Number of events 6 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	6.1% 6/99 • Number of events 6 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Fluid overload	7.5% 15/200 • Number of events 15 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	3.0% 3/99 • Number of events 3 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Metabolism and nutrition disorders Hypokalaemia	7.5% 15/200 • Number of events 17 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	7.1% 7/99 • Number of events 7 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 10/200 • Number of events 10 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	1.0% 1/99 • Number of events 1 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Nervous system disorders Hepatic encephalopathy	8.5% 17/200 • Number of events 19 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	11.1% 11/99 • Number of events 11 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.0% 24/200 • Number of events 25 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	5.1% 5/99 • Number of events 5 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.5% 11/200 • Number of events 13 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	0.00% 0/99 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	6.5% 13/200 • Number of events 13 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	4.0% 4/99 • Number of events 4 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.
Vascular disorders Hypotension	8.0% 16/200 • Number of events 16 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.	6.1% 6/99 • Number of events 6 • SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class.

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