Trial Outcomes & Findings for The EVARREST® Fibrin Sealant Patch Liver Study (NCT NCT01993888)

NCT ID: NCT01993888

Last Updated: 2016-07-11

Results Overview

Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

102 participants

Primary outcome timeframe

Intraoperative, 4 minutes following randomization

Results posted on

2016-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	EVARREST Fibrin Sealant Patch EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin). EVARREST™ Fibrin Sealant Patch	Standard of Care (SoC) SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL). Standard of Care (SoC)
Overall Study STARTED	50	52
Overall Study COMPLETED	48	49
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	EVARREST Fibrin Sealant Patch EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin). EVARREST™ Fibrin Sealant Patch	Standard of Care (SoC) SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL). Standard of Care (SoC)
Overall Study Death	1	1
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

The EVARREST® Fibrin Sealant Patch Liver Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EVARREST Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin). EVARREST™ Fibrin Sealant Patch	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL). Standard of Care (SoC)	Total n=102 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=93 Participants	28 Participants n=4 Participants	54 Participants n=27 Participants
Age, Categorical >=65 years	24 Participants n=93 Participants	24 Participants n=4 Participants	48 Participants n=27 Participants
Age, Continuous	64 years STANDARD_DEVIATION 14.5 • n=93 Participants	63 years STANDARD_DEVIATION 10.9 • n=4 Participants	63 years STANDARD_DEVIATION 12.7 • n=27 Participants
Sex: Female, Male Female	20 Participants n=93 Participants	20 Participants n=4 Participants	40 Participants n=27 Participants
Sex: Female, Male Male	30 Participants n=93 Participants	32 Participants n=4 Participants	62 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=93 Participants	48 Participants n=4 Participants	96 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants	6 Participants n=4 Participants	10 Participants n=27 Participants
Race (NIH/OMB) White	43 Participants n=93 Participants	44 Participants n=4 Participants	87 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Region of Enrollment New Zealand	6 participants n=93 Participants	7 participants n=4 Participants	13 participants n=27 Participants
Region of Enrollment United States	18 participants n=93 Participants	18 participants n=4 Participants	36 participants n=27 Participants
Region of Enrollment United Kingdom	15 participants n=93 Participants	15 participants n=4 Participants	30 participants n=27 Participants
Region of Enrollment Australia	11 participants n=93 Participants	12 participants n=4 Participants	23 participants n=27 Participants
BMI (kg/m2)	27.5 kg/m^2 n=93 Participants	26.8 kg/m^2 n=4 Participants	27.4 kg/m^2 n=27 Participants
BMI (Grouped) Underweight	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
BMI (Grouped) Normal	13 participants n=93 Participants	14 participants n=4 Participants	27 participants n=27 Participants
BMI (Grouped) Overweight	19 participants n=93 Participants	16 participants n=4 Participants	35 participants n=27 Participants
BMI (Grouped) Obese	14 participants n=93 Participants	18 participants n=4 Participants	32 participants n=27 Participants
BMI (Grouped) Morbidly Obese	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants

PRIMARY outcome

Timeframe: Intraoperative, 4 minutes following randomization

Population: The primary endpoint analysis was based on the Intent to Treat (ITT) analysis set.

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization	48 participants with hemostatic success	24 participants with hemostatic success

SECONDARY outcome

Timeframe: Intraoperative, 10 minutes following randomization

Population: The proportion of subjects achieving hemostatic success at 10 minutes following randomization was evaluated as a secondary endpoint using the logistic model with treatment and site/institution included in the model.

Proportion of subjects achieving hemostatic success at 10 minutes following randomization and no further bleeding requiring treatment prior to initiation of wound closure.

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization	49 participants with hemostatic success	42 participants with hemostatic success

SECONDARY outcome

Timeframe: Intraoperative, an average of 4.2 minutes following randomization

Population: Time to hemostasis (TTH), defined as the absolute time to achieve hemostasis at or after 4 minutes from randomization was evaluated as a secondary endpoint. In one subject in the SoC group, manual compression was not maintained until the 4-minute endpoint, but was released early and a suture was applied, at which point the subject was hemostatic.

The absolute time to achieve hemostasis at or after 4 minutes from randomization.

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=51 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Absolute Time to Hemostasis	4.0 minutes Interval 4.0 to 15.9	4.7 minutes Interval 1.7 to 33.0

SECONDARY outcome

Timeframe: Up to 60-days following surgery

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Incidence of Re-bleeding Events From the TBS During the Study Follow-up Continuous bleeding	1 participants	24 participants
Incidence of Re-bleeding Events From the TBS During the Study Follow-up Re-bleeding	0 participants	3 participants
Incidence of Re-bleeding Events From the TBS During the Study Follow-up Durability of hemostasis	1 participants	1 participants
Incidence of Re-bleeding Events From the TBS During the Study Follow-up Application error	0 participants	1 participants

SECONDARY outcome

Timeframe: Up to 60-days following surgery

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Incidence of Adverse Events (AEs) Participants experienced at least one AE	45 participants	50 participants
Incidence of Adverse Events (AEs) Participants experienced at least one SAE	12 participants	16 participants
Incidence of Adverse Events (AEs) Participants experienced at least one Severe AE	8 participants	6 participants

SECONDARY outcome

Timeframe: Up to 60-days following surgery

Number of participants with adverse events that were potentially related to thrombic events

Outcome measures

Outcome measures
Measure	EVARREST™ Fibrin Sealant Patch n=50 Participants EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 Participants SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Incidence of Adverse Events That Were Potentially Related to Thrombotic Events	2 participants	0 participants

Adverse Events

EVARREST Fibrin Sealant Patch

Serious events: 12 serious events

Other events: 45 other events

Deaths: 0 deaths

Standard of Care (SoC)

Serious events: 16 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director of Ethicon Clinical R&D

Ethicon, Inc.

Phone: 908-218-2492

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	EVARREST Fibrin Sealant Patch n=50 participants at risk EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 participants at risk SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Blood and lymphatic system disorders Anaemia	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Cardiac disorders Atrial Fibrillation	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Cardiac disorders Bradycardia	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Ascites	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Constipation	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Diarrhoea	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Ileus	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Intestinal Perforation	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Localized Intraabdominal Fluid Collection	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Small Intestinal Obstruction	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Stomatitis	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Hepatobiliary disorders Hepatic Failure	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Abdominal Abscess	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Clostridium Difficile Colitis	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Gastroenteritis	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Haematoma Infection	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Liver Abscess	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Pneumonia	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Sepsis	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	3.8% 2/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Subdiaphragmatic Abscess	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Urinary Tract Infection	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Urosepsis	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Chemical Peritonitis	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Incisional Hernia	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Post-procedural Bile Leak	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Postoperative Ileus	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Wound Decomposition	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hypomagnesaemia	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Psychiatric disorders Delirium	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Renal and urinary disorders Renal Failure	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Renal and urinary disorders Renal Failure Acute	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	3.8% 2/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Renal and urinary disorders Renal Failure Chronic	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Vascular disorders Orthostatic Hypotension	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.

Measure	EVARREST Fibrin Sealant Patch n=50 participants at risk EVARREST™ Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Standard of Care (SoC) n=52 participants at risk SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).
Blood and lymphatic system disorders Anaemia	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	9.6% 5/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Blood and lymphatic system disorders Leukocytosis	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	3.8% 2/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Cardiac disorders Atrial Fibrillation	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Cardiac disorders Bradycardia	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Cardiac disorders Tachycardia	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	21.2% 11/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Abdominal Distension	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Abdominal Pain	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	13.5% 7/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Abdominal Pain Upper	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Acites	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Constipation	28.0% 14/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	42.3% 22/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Diarrhoea	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	13.5% 7/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Nausea	50.0% 25/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	44.2% 23/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Small Intestinal Obstruction	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Gastrointestinal disorders Vomiting	26.0% 13/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	26.9% 14/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
General disorders Oedema	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
General disorders Odema Peripheral	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
General disorders Pain	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
General disorders Pyrexia	26.0% 13/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	21.2% 11/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Pneumonia	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Urinary Tract Infection	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	9.6% 5/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Infections and infestations Wound Infection	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Post-procedural Bile Leak	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Postoperative Ileus	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Procedural Pain	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	19.2% 10/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Injury, poisoning and procedural complications Wound Secretion	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Investigations Blood Lactic Acid Increased	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	11.5% 6/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Investigations International Normalized Ratio Increased	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	3.8% 2/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Investigations Urine Output Decreased	8.0% 4/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Decreased Appetite	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hyperkalaemia	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hypokalaemia	24.0% 12/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	21.2% 11/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hypomagnesaemia	24.0% 12/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	23.1% 12/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Hypophosphataemia	22.0% 11/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	21.2% 11/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Malnutrition	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	0.00% 0/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Metabolism and nutrition disorders Vitamin D Deficiency	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Musculoskeletal and connective tissue disorders Back Pain	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	16.0% 8/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	9.6% 5/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Nervous system disorders Dizziness	12.0% 6/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	11.5% 6/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Nervous system disorders Lethargy	2.0% 1/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Psychiatric disorders Confusional State	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	11.5% 6/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Psychiatric disorders Hallucination	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Psychiatric disorders Insomnia	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Renal and urinary disorders Urinary Retention	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Atelectasis	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	17.3% 9/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	3.8% 2/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Hiccups	6.0% 3/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	1.9% 1/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 2/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	7.7% 4/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	10.0% 5/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	5.8% 3/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Skin and subcutaneous tissue disorders Pruritus	12.0% 6/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	13.5% 7/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Vascular disorders Hypertension	12.0% 6/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	9.6% 5/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.
Vascular disorders Hypotension	28.0% 14/50 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.	34.6% 18/52 • Adverse events were recorded from the time of randomization until 60 days following the study procedure.