Trial Outcomes & Findings for WP01 - Normothermic Liver Preservation (NCT NCT02775162)

Last Updated: 2022-07-29

Results Overview

EAD is a binary outcome defined by the presence of one of the following 3 outcomes: * Serum bilirubin ≥ 10 mg/dL at day 7 post-transplant * International normalized ratio (INR) ≥ 1.6 at day 7 post-transplant * Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) \> 2000 IU/L within the first 7 days post-transplant

Recruitment status

COMPLETED

Study phase

Target enrollment

267 participants

Primary outcome timeframe

7 Days

Results posted on

2022-07-29

Participant Flow

Participant milestones

Participant milestones
Measure	Normothermic Machine Perfusion (NMP) Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Overall Study STARTED	136	131
Overall Study COMPLETED	122	121
Overall Study NOT COMPLETED	14	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

WP01 - Normothermic Liver Preservation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normothermic Machine Perfusion (NMP) n=136 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=131 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)	Total n=267 Participants Total of all reporting groups
Age, Continuous	57.4 Years STANDARD_DEVIATION 10.5 • n=5 Participants	57.2 Years STANDARD_DEVIATION 10.6 • n=7 Participants	57.3 Years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	48 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants	83 Participants n=7 Participants	176 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants	118 Participants n=7 Participants	239 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	127 Participants n=5 Participants	119 Participants n=7 Participants	246 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	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	136 participants n=5 Participants	131 participants n=7 Participants	267 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 Days

Population: There was one subject excluded from the primary endpoint analysis as there was only an attempt to transplant a randomized liver. The subject was deemed unable to proceed with the liver transplant and was followed through 30-days post-transplant for adverse event collection only.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=136 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=130 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Percentage of Participants With Early Allograft Dysfunction (EAD)	20.6 percentage of participants Interval 14.5 to 28.5	23.7 percentage of participants Interval 17.1 to 31.9

SECONDARY outcome

Timeframe: 10 Days

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Primary Non-Function is defined in this study as irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=135 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=129 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Primary Non-Function	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=127 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Graft Survival	124 Participants	122 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=127 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Subject Survival	121 Participants	123 Participants

SECONDARY outcome

Timeframe: 1 Day

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Post-Reperfusion Syndrome is defined in this study as a decrease in mean arterial pressure (MAP) of more than 30% from the baseline value for more than one minute during the first five minutes after reperfusion.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=136 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=130 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Post-Reperfusion Syndrome	8 Participants	19 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Bilirubin	0.6 mg/dL Interval 0.4 to 0.8	0.5 mg/dL Interval 0.4 to 0.7

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=72 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=75 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)	38.5 IU/L Interval 21.5 to 78.0	34.0 IU/L Interval 20.0 to 72.0

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Alanine Aminotransferase (ALT)	23.0 IU/L Interval 16.0 to 39.0	21.0 IU/L Interval 16.0 to 32.0

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Aspartate Transaminase (AST)	24.0 IU/L Interval 18.0 to 30.0	20.0 IU/L Interval 16.0 to 26.0

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=125 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Alkaline Phosphatase (ALP)	94.0 IU/L Interval 72.0 to 137.0	92.0 IU/L Interval 68.0 to 115.0

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

The international normalized ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. It is calculated using the following formula: INR = (PT \[test\] / PT \[control\])\^ISI INR = international normalized ratio PT \[test\] = tested prothrombin time PT \[control\] = control prothrombin time ISI = international sensitivity index

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=106 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=98 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via International Normalized Ratio (INR)	1.0 No Units Interval 1.0 to 1.1	1.0 No Units Interval 1.0 to 1.1

SECONDARY outcome

Timeframe: Days 1-7

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=102 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=97 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Measure Biochemical Liver Function Via Lactate	1.4 mmol/L Interval 1.0 to 2.1	1.5 mmol/L Interval 1.0 to 1.9

SECONDARY outcome

Timeframe: 1 Day

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Overall Degree of Ischemia Reperfusion Injury (IRI) was categorized as: * None/Minimal: None or Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with rare hepatocellular necrosis * Mild: Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with ≥ 1 cluster of necrotic hepatocytes * Moderate/Severe: Clusters of hepatocellular necrosis in \> 50% of lobules or 60% of parenchyma or panlobular necrosis in \> 1 lobule

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=133 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=122 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Pre-Reperfusion · None/Minimal	123 Participants	117 Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Pre-Reperfusion · Mild	10 Participants	5 Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Pre-Reperfusion · Moderate/Severe	0 Participants	0 Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Post-Reperfusion · None/Minimal	100 Participants	93 Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Post-Reperfusion · Mild	29 Participants	24 Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies Post-Reperfusion · Moderate/Severe	4 Participants	5 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=127 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=126 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Participants With Biliary Investigations and Biliary Interventions Biliary Investigations	14 Participants	16 Participants
Number of Participants With Biliary Investigations and Biliary Interventions Biliary Interventions	12 Participants	11 Participants

SECONDARY outcome

Timeframe: 1 Day

Population: The analysis population for this outcome reflects all livers randomized in the study; therefore, the number analyzed is greater than the participants enrolled.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=192 Livers Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=191 Livers Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Livers Randomized But Not Transplanted	56 Livers	61 Livers

SECONDARY outcome

Timeframe: 10 Days

Population: The analysis population for this outcome reflects all livers retrieved in the study; therefore, the number analyzed is greater than the participants enrolled, but less than the total livers randomized. There was one subject where there was only an attempt to transplant a randomized liver as the subject was deemed unable to proceed with the liver transplant.

Number of livers that did not experience at least one of the following safety events: * Early Allograft Dysfunction (EAD) * Discard of a Retrieved Liver * Primary Non-Function (PNF)

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=152 Livers Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=140 Livers Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Number of Livers That Did Not Experience a Safety Event	147 Livers	137 Livers

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=134 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=127 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Assessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay Length of ICU Stay	4.6 Days Standard Deviation 7.5	4.2 Days Standard Deviation 6.2
Assessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay Total Length of Hospital Stay	14.3 Days Standard Deviation 17.1	13.3 Days Standard Deviation 18.1

SECONDARY outcome

Timeframe: 6 Months

Population: The overall number of participants analyzed reflects participants in each arm who were eligible to be included in the analysis and had complete data.

The EQ-5D-5L Questionnaire is the standard layout for recording an adult person's current self-reported health state. It consists of a standard format for respondents to record their health state according to the EQ-5D-5L descriptive system and the EQ Visual Analog Scale (VAS). EQ-5D-5L index scores range from 0 to 1.0 on a scale where 0 = death and 1.0 = perfect health. EQ-5D-5L is the name of the instrument and is not an acronym.

Outcome measures

Outcome measures
Measure	Normothermic Machine Perfusion (NMP) n=121 Participants Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=116 Participants Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Compare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire	0.9 score on a scale Standard Deviation 0.1	0.8 score on a scale Standard Deviation 0.1

Adverse Events

Normothermic Machine Perfusion (NMP)

Serious events: 95 serious events

Other events: 125 other events

Deaths: 10 deaths

Standard of Care (Ice)

Serious events: 93 serious events

Other events: 123 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Robert Bovy, VP of Regulatory Affairs, North America

OrganOx Ltd

Phone: 608-556-4429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Normothermic Machine Perfusion (NMP) n=136 participants at risk Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use. Normothermic Machine Perfusion (NMP)	Standard of Care (Ice) n=131 participants at risk Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy. Standard of Care (Ice)
Endocrine disorders Hyperglycemia	47.1% 64/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	51.9% 68/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Blood and lymphatic system disorders Leukopenia	24.3% 33/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	21.4% 28/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Blood and lymphatic system disorders Anemia	19.1% 26/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	26.0% 34/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Blood and lymphatic system disorders Hematology Other	6.6% 9/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	9.2% 12/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Blood and lymphatic system disorders Thrombocytopenia	8.1% 11/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	6.9% 9/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Gastrointestinal disorders Diarrhea	17.6% 24/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	21.4% 28/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Gastrointestinal disorders Constipation	18.4% 25/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	19.8% 26/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Gastrointestinal disorders Nausea/Vomiting	13.2% 18/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	15.3% 20/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Gastrointestinal disorders Gastrointestinal Other	14.0% 19/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	13.7% 18/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Nervous system disorders Tremors	15.4% 21/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	14.5% 19/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Nervous system disorders Headache	12.5% 17/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	11.5% 15/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Psychiatric disorders Altered Mental Status	11.0% 15/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	6.9% 9/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Nervous system disorders Insomnia	6.6% 9/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	9.9% 13/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Renal and urinary disorders Renal Dysfunction/Acute Kidney Injury	27.2% 37/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	31.3% 41/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Renal and urinary disorders Genitourinary Other	3.7% 5/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	7.6% 10/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Renal and urinary disorders Urinary Retention	4.4% 6/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	6.9% 9/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Renal and urinary disorders UTI	5.1% 7/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	5.3% 7/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Cardiac disorders Hypertension	18.4% 25/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	19.1% 25/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Cardiac disorders Hypotension	8.8% 12/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	13.7% 18/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Cardiac disorders Tachycardia	7.4% 10/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	6.9% 9/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Cardiac disorders Hypovolemia	5.1% 7/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	5.3% 7/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Hypomagnesemia	17.6% 24/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	19.8% 26/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Hyperkalemia	13.2% 18/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	18.3% 24/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Hypokalemia	2.9% 4/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	9.2% 12/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Extremities Edema	21.3% 29/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	21.4% 28/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Pleural Effusion	8.1% 11/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	7.6% 10/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Hepatobiliary disorders Graft Dysfunction	11.0% 15/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	13.7% 18/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Hepatobiliary disorders Rejection	8.1% 11/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	5.3% 7/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Infections and infestations Blood Infection	11.8% 16/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	9.2% 12/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Infections and infestations Infection Other	7.4% 10/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	11.5% 15/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Other Systemic Disease/Event	13.2% 18/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	22.1% 29/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Pain	10.3% 14/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	11.5% 15/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Musculoskeletal and connective tissue disorders Musculoskeletal Other	23.5% 32/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	20.6% 27/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Respiratory, thoracic and mediastinal disorders Respiratory Other	7.4% 10/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	7.6% 10/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Respiratory, thoracic and mediastinal disorders Pneumonia	7.4% 10/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	3.8% 5/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Skin and subcutaneous tissue disorders Dermatologic Other	11.0% 15/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	13.0% 17/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
Hepatobiliary disorders EAD - ALT or AST	11.8% 16/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	13.0% 17/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).
General disorders Bleeding - Transfusion Required	2.2% 3/136 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).	8.4% 11/131 • Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).