Trial Outcomes & Findings for A Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 With Terlipressin (NCT NCT01143246)

Last Updated: 2022-11-29

Results Overview

Confirmed HRS Reversal: The percentage of participants with two serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 48 hours apart, on treatment, and without intervening renal replacement therapy or liver transplant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

196 participants

Primary outcome timeframe

within 14 days

Results posted on

2022-11-29

Participant Flow

The study was conducted at 52 active sites in the United States and Canada.

Participant milestones

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 NOT COMPLETED	45	51
Overall Study STARTED	97	99
Overall Study Intent to Treat (ITT)	97	99
Overall Study Safety Population (Treated Participants)	93	95
Overall Study COMPLETED	52	48

Reasons for withdrawal

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 Adverse Event	24	28
Overall Study Participant Withdrew Informed Consent	2	2
Overall Study Lost to Follow-up	0	1
Overall Study Death	16	15
Overall Study Reason not Specified	3	5

Baseline Characteristics

A Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 With Terlipressin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Terlipressin n=97 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.	Placebo n=99 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=196 Participants Total of all reporting groups
Age, Continuous	55.8 years STANDARD_DEVIATION 8.38 • n=5 Participants	54.8 years STANDARD_DEVIATION 8.50 • n=7 Participants	55.3 years STANDARD_DEVIATION 8.43 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	32 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	67 Participants n=7 Participants	119 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=5 Participants	84 Participants n=7 Participants	170 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 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	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	85 Participants n=5 Participants	92 Participants n=7 Participants	177 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	92 participants n=5 Participants	95 participants n=7 Participants	187 participants n=5 Participants

PRIMARY outcome

Timeframe: within 14 days

Population: ITT population.

Outcome measures

Outcome measures
Measure	Terlipressin n=97 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=99 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 Confirmed Hepatorenal Syndrome (HRS) Reversal	19.6 percentage of participants	13.1 percentage of participants

SECONDARY outcome

Timeframe: within 14 days

Population: ITT population.

HRS reversal is defined as at least one SCr value of ≤ 1.5 mg/dL on treatment (up to 24 hours after the last dose of study medication).

Outcome measures

Outcome measures
Measure	Terlipressin n=97 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=99 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	23.7 percentage of participants	15.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 90 days

Population: ITT population.

Transplant-Free Survival up to 90 days, defined as the time (in days) that each participant survives without liver transplantation from the day of randomization.

Outcome measures

Outcome measures
Measure	Terlipressin n=97 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=99 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 Transplant-free Survival	30.9 percentage of participants	26.3 percentage of participants

SECONDARY outcome

Timeframe: Up to 90 days

Population: ITT population.

Overall Survival up to 90 days, defined as the time (in days) that each participant survives from the day of randomization.

Outcome measures

Outcome measures
Measure	Terlipressin n=97 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=99 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 Overall Survival	57.7 percentage of participants	54.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 30 days post treatment (within 44 days)

Population: Safety population.

Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments which qualified for the definition of serious adverse event are reported.

Outcome measures

Outcome measures
Measure	Terlipressin n=93 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=95 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 Serious Adverse Events	66.7 percentage of participants	62.1 percentage of participants

Adverse Events

Terlipressin

Serious events: 62 serious events

Other events: 87 other events

Deaths: 41 deaths

Placebo

Serious events: 59 serious events

Other events: 82 other events

Deaths: 45 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Call Center

Mallinckrodt

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Disclosure of individual investigator/site results is restricted for 18 months after final evaluation of study results or after release of a cooperative publication including all study from all sites, whichever occurs first. The sponsor has 60 days to review and comment on the publication and can request removal of any confidential information prior to public disclosure or publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Terlipressin n=93 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=95 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 Leukocytosis	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Blood and lymphatic system disorders Pancytopenia	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Arrhythmia	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Atrial Fibrillation	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Cardiac Arrest	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Cardiac Failure Congestive	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Cardio-Respiratory Arrest	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Cardiogenic Shock	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Cyanosis	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Myocardial Ischaemia	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Stress Cardiomyopathy	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Tachyarrhythmia	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Abdominal Compartment Syndrome	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Abdominal Pain	5.4% 5/93 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Ascites	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	3.2% 3/95 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Colitis Ischaemic	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Gastrointestinal Haemorrhage	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Ileus Paralytic	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Intestinal Ischaemia	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Intra-abdominal Haemorrhage	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Nausea	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Oesophageal Perforation	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Oesophageal Varices Haemorrhage	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Pancreatitis Acute	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Vomiting	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Asthenia	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Cardiac Death	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Chest Pain	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Multiple Organ Dysfunction Syndrome	12.9% 12/93 • Number of events 12 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	6.3% 6/95 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Pyrexia	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Bile Duct Necrosis	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Chronic Hepatic Failure	9.7% 9/93 • Number of events 10 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	8.4% 8/95 • Number of events 8 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Cirrhosis Alcoholic	1.1% 1/93 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Hepatic Artery Thrombosis	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Hepatic Cirrhosis	0.00% 0/93 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Hepatic Failure	4.3% 4/93 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	6.3% 6/95 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.

Other adverse events
Measure	Terlipressin n=93 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=95 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	10.8% 10/93 • Number of events 10 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	9.5% 9/95 • Number of events 10 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Blood and lymphatic system disorders Coagulopathy	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Cardiac disorders Bradycardia	9.7% 9/93 • Number of events 10 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	2.1% 2/95 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Abdominal distension	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Abdominal pain	28.0% 26/93 • Number of events 27 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	22.1% 21/95 • Number of events 22 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Diarrhoea	23.7% 22/93 • Number of events 22 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Nausea	12.9% 12/93 • Number of events 12 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	12.6% 12/95 • Number of events 12 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Gastrointestinal disorders Vomiting	9.7% 9/93 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Oedema peripheral	6.5% 6/93 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	8.4% 8/95 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
General disorders Pyrexia	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Hepatobiliary disorders Hepatorenal syndrome	2.2% 2/93 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	9.5% 9/95 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Infections and infestations Urinary tract infection	4.3% 4/93 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	6.3% 6/95 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Fluid overload	9.7% 9/93 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Hyperglycaemia	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	2.1% 2/95 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Hyperphosphataemia	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Hypokalaemia	11.8% 11/93 • Number of events 11 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Hypophosphataemia	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	2.1% 2/95 • Number of events 2 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Metabolism and nutrition disorders Metabolic acidosis	10.8% 10/93 • Number of events 10 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	7.4% 7/95 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Musculoskeletal and connective tissue disorders Muscle spasms	6.5% 6/93 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Nervous system disorders Asterixis	8.6% 8/93 • Number of events 8 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 4 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Nervous system disorders Headache	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Nervous system disorders Hepatic encephalopathy	8.6% 8/93 • Number of events 8 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	11.6% 11/95 • Number of events 11 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Nervous system disorders Lethargy	9.7% 9/93 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	3.2% 3/95 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Psychiatric disorders Anxiety	6.5% 6/93 • Number of events 8 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	3.2% 3/95 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Psychiatric disorders Insomnia	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	3.2% 3/95 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Psychiatric disorders Mental status changes	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.9% 12/93 • Number of events 12 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	8.4% 8/95 • Number of events 9 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 2/93 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.4% 5/93 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	1.1% 1/95 • Number of events 1 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.5% 7/93 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	4.2% 4/95 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	8.6% 8/93 • Number of events 8 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	5.3% 5/95 • Number of events 5 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	0.00% 0/95 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Skin and subcutaneous tissue disorders Ecchymosis	6.5% 6/93 • Number of events 6 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	3.2% 3/95 • Number of events 3 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.
Vascular disorders Hypotension	18.3% 17/93 • Number of events 18 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.	7.4% 7/95 • Number of events 7 • All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment. Participants experiencing multiple episodes of a given adverse event are counted once within each preferred term and within each system organ class in the Safety population.