Continued Access Protocol To Evaluate the Effectiveness of the Portable Organ Care System (OCS) Liver for Preserving and Assessing Donor Livers for Transplantation.
Phase: NA
Conditions: Liver Transplant
Sponsor: TransMedics

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Clinical Protocol and Investigational Plan 
 
Continued Access Protocol to Evaluate the Effectiveness of the Portable Organ Care System 
(OCS™) Liver for Preserving and Assessing Donor Livers for Transplantation  
(OCS Liver PROTECT CAP) 
 
 
Number OCS-LVR102019 
December 9, 2019 
 
 
Sponsor: 
TransMedics, Inc. 
200 Minuteman Road, Suite 302 
Andover, MA 01810 
Sponsor Primary Contact: 
 
 
 
 
Sponsor Secondary Contact:  
 
 
 
 
 
 
 
UUCONFIDENTIAL – PROPRIETARY INFORMATION 
 
Protocol Rev 
Issue Date 
1.0 
October 11, 2019  
2.0 
December 9, 2019 
 

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TABLE OF CONTENTS 
OCS LIVER PROTECT CAP SYNOPSIS ......................................................................................... 5 
1. 
INTRODUCTION AND BACKGROUND .............................................................................. 8 
1.1. Background ...................................................................................................................... 8 
1.2. Potential Clinical Solutions to Overcome Limitations in Donor Liver Utilization ............. 9 
1.3. Subject Enrollment and Health Insurance ...................................................................... 10 
2. 
SUMMARY OF PRIOR TESTING AND INVESTIGATIONS ................................................... 10 
2.1. OCS Liver System Nonclinical Testing ............................................................................. 10 
2.2. OCS Liver PROTECT Study ............................................................................................... 10 
3. 
DEVICE DESCRIPTION .................................................................................................... 11 
4. 
TRIAL OBJECTIVES ......................................................................................................... 12 
4.1. Type of Trial .................................................................................................................... 12 
4.2. Trial Size and Subject Follow-up ..................................................................................... 12 
5. 
TRIAL ENDPOINTS ......................................................................................................... 12 
5.1. Primary Effectiveness Endpoint ..................................................................................... 12 
5.2. Secondary Effectiveness and OCS Donor Liver Assessment Endpoints .......................... 13 
5.3. Other Endpoints ............................................................................................................. 13 
5.4. Safety Endpoint .............................................................................................................. 14 
6. 
TRIAL POPULATION ...................................................................................................... 14 
6.1. Donor Eligibility Criteria ................................................................................................. 14 
6.1.1. Donor Inclusion Criteria ..................................................................................... 14 
6.1.2. Donor Exclusion Criteria ..................................................................................... 14 
6.2. Recipient Eligibility Criteria ............................................................................................ 15 
6.2.1. Recipient Inclusion Criteria ................................................................................ 15 
6.2.2. Recipient Exclusion Criteria ................................................................................ 15 
7. 
PRE-OPERATIVE TRIAL PROCEDURES ............................................................................. 15 
7.1. Subject Identification ..................................................................................................... 15 
7.2. Recipient Day of Transplant Assessment ....................................................................... 15 
7.3. Donor Screening and Acceptance .................................................................................. 16 
7.4. Donor Liver Retrieval and OCS Preservation and Assessment ....................................... 17 
7.5. Donor Liver Acceptance for Transplantation following OCS Liver Preservation ............ 20 
8. 
TRANSPLANT, IMMEDIATE POST-OPERATIVE AND LONG TERM FOLLOW-UP ................ 20 
8.1. Transplant Details .......................................................................................................... 20 
8.2. Post-transplant Functional Assessments Day 0 – Day 30: .............................................. 21 
8.3. Long-term Follow-up: 6 and 12 & 24 Months ................................................................ 22 
8.3.1. 6 and 12-Month Follow-up ................................................................................. 22 
8.3.2. 24-Month Follow-up .......................................................................................... 22 
9. 
EVALUATION OF ADVERSE EVENTS ............................................................................... 23 

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9.1. Evaluation of Liver Graft-Related Adverse Events (LGRAEs) .......................................... 23 
9.2. Serious Adverse Events (SAEs) ....................................................................................... 23 
9.3. Anticipated and Unanticipated Adverse Events ............................................................. 23 
9.4. Unanticipated Adverse Device Effect (UADE) ................................................................ 24 
9.5. Recording and Reporting of Adverse Event ................................................................... 25 
9.6. Relationship of an Adverse Events (AEs) to OCS Liver System ....................................... 25 
9.7. Severity .......................................................................................................................... 25 
9.8. Pre-Existing Conditions .................................................................................................. 25 
10. 
STATISTICAL METHODS ................................................................................................. 26 
10.1. 
General .................................................................................................................... 26 
10.2. 
Analysis Populations ............................................................................................... 26 
10.2.1. Per Protocol Population ..................................................................................... 26 
10.2.2. Modified Intent-to-Treat Population ................................................................. 26 
10.2.3. Donor Liver Population ...................................................................................... 26 
10.3. 
Data Analysis ........................................................................................................... 26 
10.3.1. Subject Disposition ............................................................................................. 27 
10.3.2. Major Protocol Deviations ................................................................................. 27 
10.3.3. Demographics and Baseline Characteristics ....................................................... 27 
10.3.4. Primary Effectiveness Endpoint ......................................................................... 27 
10.3.5. Secondary Effectiveness and OCS Donor Liver Assessment Endpoints .............. 28 
10.4. 
Analysis of Safety .................................................................................................... 28 
10.5. 
Sample Size Determination ..................................................................................... 29 
10.6. 
Statistical Analysis Plan ........................................................................................... 29 
10.7. 
Stopping Rule .......................................................................................................... 29 
11. 
RISK ANALYSIS .............................................................................................................. 30 
11.1. 
Potential Risks ......................................................................................................... 30 
11.2. 
Manner in Which the Risks Will be Minimized ....................................................... 30 
11.2.1. Potential Benefits ............................................................................................... 31 
11.2.2. Risk: Benefit Ratio .............................................................................................. 31 
12. 
DEVICE/SITE MANAGEMENT ......................................................................................... 31 
12.1. 
Packaging and Labeling ........................................................................................... 31 
12.2. 
Storage .................................................................................................................... 32 
12.3. 
Accountability ......................................................................................................... 32 
12.4. 
Device Complaints and Malfunctions ..................................................................... 32 
13. 
REGULATORY / ETHICS .................................................................................................. 32 
13.1. 
Institutional Review Boards (IRB) ............................................................................ 32 
13.2. 
Informed Consent ................................................................................................... 32 
14. 
DATA COLLECTION/RECORDS/REPORTS ........................................................................ 33 
14.1. 
Investigator Records ............................................................................................... 33 
14.2. 
Investigator Reports ................................................................................................ 34 
14.3. 
Source Documents .................................................................................................. 34 

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14.4. 
Archiving of Records ............................................................................................... 34 
15. 
CLINICAL MONITORING ................................................................................................ 35 
15.1. 
Monitoring .............................................................................................................. 35 
15.2. 
Pre-Trial Monitoring Procedures ............................................................................. 35 
15.2.1. Selection of Monitors ......................................................................................... 35 
15.2.2. Study Initiation Visit (SIV) ................................................................................... 35 
15.3. 
Interim Monitoring Visits ........................................................................................ 36 
15.4. 
Frequency of Monitoring Visits ............................................................................... 36 
15.5. 
Close-out Visit ......................................................................................................... 36 
15.6. 
Additional Auditing ................................................................................................. 36 
15.7. 
Protocol Deviations ................................................................................................. 36 
15.8. 
Clinical Events Committee ...................................................................................... 37 
15.9. 
Data Safety Monitoring Board ................................................................................ 37 
15.10. 
Investigator Device Training .................................................................................... 37 
15.11. 
Confidentiality ......................................................................................................... 37 
15.12. 
Amendment Policy .................................................................................................. 37 
16. 
REFERENCES ................................................................................................................. 38 
APPENDIX 1. 
LIVER TISSUE BIOPSY, BILE DUCT SPECIMEN, & SCORING 
PROTOCOL ........................................................................................................... 39 
APPENDIX 2. 
SCHEDULE OF CLINICAL ASSESSMENTS ................................................. 41 
 
 

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OCS LIVER PROTECT CAP SYNOPSIS 
Protocol Title 
Continued Access Protocol (CAP) to Evaluate the Effectiveness of The Portable Organ Care System (OCS™) Liver 
for Preserving and Assessing Donor Livers for Transplantation (OCS Liver PROTECT CAP) 
Objectives 
To continue to evaluate the effectiveness of the OCS Liver System to preserve and assess donor livers having 
one or more of the following characteristics: 
• 
Donor age ≥ 40 years old; or 
• 
Expected cross clamp time ≥ 6 hours; or 
• 
Donor after circulatory death (DCD) with age ≤ 55 years old; or 
• 
Steatotic liver > 0% and ≤ 40% macrosteatosis at time of retrieval (on pre-retrieval histology). 
Trial Design 
Prospective, single arm, continued access protocol  
 Trial Size 
A maximum of 21 participating sites to enroll 184 transplanted liver recipients 
Screening and 
Treatment  
• 
Primary Liver transplant candidates will be screened for trial eligibility.   
• 
Donor livers will be screened for trial eligibility.  Eligible donor livers will be preserved using the OCS 
Liver System (OCS). 
Donor Liver 
Eligibility Criteria 
Inclusion 
Donor meets at least one of the following: 
• 
Donor age ≥ 40 years old; or 
• 
Expected total cross clamp time ≥ 6 hours; or 
• 
Donor after circulatory death (DCD) with age ≤ 55 years old; or 
• 
Steatotic liver > 0% and ≤ 40% macrosteatosis at time of retrieval (based on retrieval biopsy readout 
(only if the donor liver was clinically suspected to be fatty by the retrieval surgeon at time of liver 
retrieval). 
 
Exclusion 
Donor livers will be excluded if they meet any of the following criteria: 
• 
Living donors 
• 
Liver intended for split transplants 
• 
Positive serology (HIV, Hepatitis B surface antigen & Hepatitis C) 
• 
Presence of moderate or severe traumatic liver injury, or anatomical liver abnormalities that would 
compromise ex-vivo perfusion of the donor liver (i.e., accessory blood vessels or other abnormal 
anatomy that require surgical repair) and livers with active bleeding (e.g., hematomas) 
• 
Donor livers with macrosteatosis of > 40% based on retrieval biopsy readout. 
Recipient 
Eligibility Criteria 
Inclusion 
Recipients are required to meet all the following criteria on the day of transplant: 
• 
Registered primary Liver transplant candidate, male or female 
• 
Age ≥ 18 years old 
• 
Signed: (1) written informed consent document and (2) authorization to use and disclose protected 
health information. 
 
Exclusion 
Recipients will be excluded if they meet any of the following criteria on the day of transplant: 
• 
Acute, fulminant liver failure 
• 
Prior solid organ or bone marrow transplant 
• 
Chronic use of hemodialysis or diagnosis of chronic renal failure, defined as chronic serum creatinine of 
> 3 mg/dl for > 2 weeks and/or requiring hemodialysis 
• 
Multi-organ transplant 
• 
Ventilator dependent 
• 
Dependent on > 1 IV inotrope to maintain hemodynamics. 
Primary 
Effectiveness 
Incidence of Early liver Allograft Dysfunction (EAD) or primary non-function, defined as presence of one or 
more of the following criteria: 

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Endpoint 
• 
AST level > 2000 IU/ml within the first 7 postoperative days; 
• 
Bilirubin ≥ 10 mg/dl on postoperative day 7;  
• 
INR ≥ 1.6 on postoperative day 7; or  
• 
Primary non-functioning graft within the first 7 days (defined as irreversible graft dysfunction requiring 
emergency liver re-transplantation or death, in the absence of immunologic or surgical causes). 
Secondary 
Effectiveness and 
OCS Donor Liver 
Assessment 
Endpoints 
• 
OCS donor liver assessment during perfusion, defined as, among donor livers preserved using OCS for 
the entire preservation period, the proportion of livers on which measurements of all of the following 
during perfusion will be available on OCS device before transplant 
o 
Lactate level (every two hours) 
o 
Average bile production rate (based on total bile production volume and duration of OCS 
perfusion)  
o 
Hepatic Artery Pressure (continuously) 
o 
Portal Vein Pressure (continuously) 
• 
Patient survival at Day 30 post-transplantation 
• 
Patient survival at initial hospital discharge post liver transplantation. 
Other Endpoints 
• 
Length of initial post-transplant ICU stay  
• 
Length of initial post-transplant hospital stay 
• 
Evidence of ischemic biliary complications diagnosed at 6 and at 12 months post-transplant 
• 
Extent of reperfusion syndrome as assessed based on the rate of decrease of lactate over the 
following timepoints: 
o 
During anhepatic phase immediately before reperfusion of the transplanted liver 
o 
30-40 minutes after hepatic artery and portal vein reperfusion of the transplanted liver 
o 
90-120 minutes after reperfusion of the transplanted liver  
• 
Pathology sample score for liver tissue samples taken at the following timepoints: 
o 
Donor liver pre-retrieval  
o 
Post-OCS preservation at the end of back preparation and immediately before the start of re-
implantation 
o 
Post reperfusion 90-120 after reperfusion of the transplanted liver (prior to abdominal closure). 
Safety Endpoints  
Safety will be analyzed principally by examination of the frequency of liver graft-related serious adverse events 
(LGRSAEs) up to the 30-day follow-up after transplantation.  This endpoint is defined as the average number of 
LGRSAEs through the 30 days post-liver transplantation per subject, consisting of the following serious adverse 
events (at most one per type per person): 
• 
Primary non-function (defined as irreversible graft dysfunction requiring emergency liver re-
transplantation or death with the first 10 days, in the absence of immunologic or surgical causes) 
• 
Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile duct leaks) 
• 
Vascular complications (liver graft-related coagulopathy, hepatic artery stenosis, hepatic artery 
thrombosis and portal vein thrombosis); 
• 
Liver allograft infections (liver abscess, cholangitis, etc.). 
Follow-up 
Patients will be followed for 24 months from the date of transplantation (some of which will be post-market).  
 
The following data will be collected at 6 and 12 months: 
• Patient and graft survival  
• Liver graft-related SAEs (6 months only) 
• Liver graft-related re-hospitalization after initial discharge, and, if yes, the primary reason/diagnosis for 
the hospitalization and the length of stay 
• Information will also be collected on any diagnosis of ischemic biliary complications and, if so, the 
method of diagnosis and treatment. 
 
The following data will be collected at 24 months: 
• Patient and graft survival. 
• Results of standard clinical practice or for cause liver biopsy will be collected (if applicable). 
Analysis 
Populations 
• 
The Per Protocol (PP) Population will consist of all subjects who are transplanted and have no major 
protocol violations and for whom the donor liver received the complete preservation procedure.  The 

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primary analysis of effectiveness and of secondary and other endpoints will be based on the PP 
Population. 
• 
The Modified Intent-to-Treat Population (mITT) will consist of all subjects who are transplanted.  The 
mITT analyses will be considered secondary analyses of effectiveness. 
• 
The Donor Liver Population will consist of all donor livers which have preservation initiated using the 
OCS Liver System.   
Effectiveness 
Analysis 
The primary endpoint will be analyzed using the Per Protocol and mITT Populations.  The Per Protocol analysis 
will be considered the primary analysis.  Multiple imputation methods will be used for data imputation for any 
patients with missing values for this endpoint.  
 
Each secondary effectiveness endpoint will be summarized using counts and percentages and an exact 95% 
confidence interval for the true percentage based on the binomial distribution.  The secondary effectiveness 
endpoints will be analyzed using the PP and the mITT Populations.  The Per Protocol analysis will be considered 
the primary analysis. 
Safety Analysis 
The safety endpoints will be summarized using descriptive statistics.   
 
For livers that are not transplanted, the reason(s) for non-transplantation (including device failure) will be 
summarized using counts and percentages.  The number and percentage of donor livers in the Donor Liver 
Population for which these was a device failure will also be presented.   
Sample Size  
184 subjects at up to 21 U.S. sites 
Trial Sponsor 
TransMedics, Inc. 
200 Minuteman Road, Suite 302 
Andover, MA, USA 01810 
 
 
 

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associated with cold storage preservation.  It also imposes significant time and 
geographical limitations on the liver retrieval process, adversely impacting the 
utilization of available donor livers.  In addition, this time-dependent ischemic injury 
has been directly correlated to post-transplant complications (Pan, et al., 2018). 
• It lacks any perfusion capabilities to maintain the liver in a near-physiologic (in- vivo-
like) environment after the donor liver is retrieved from the body of the donor 
(Vogel, et al., 2012).  This limitation results in significant underutilization of the 
donor livers with fatty cells (macrosteatotic livers) and DCD livers.  This further limits 
the use of these donor livers that otherwise are functioning normally in the body of 
the donor.  
• It lacks any ability to evaluate organ metabolic state and function after procurement 
and preservation to determine the suitability of the donor livers for transplantation 
(Vogel, et al., 2012).  This significantly limits the utilization of donor livers that are 
subjected to the negative, non-physiologic conditions of brain death in the donor 
and it severely limits the utilization of DCD livers. 
1.2. 
Potential Clinical Solutions to Overcome Limitations in Donor Liver 
Utilization 
Over the past 15+ years, there has been a global focus on ex-vivo organ perfusion in a near 
physiologic condition as a promising technique to overcome the current challenges in organ 
preservation and to potentially increase utilization of donor organs (liver, lung, heart, and 
kidney) that are currently not used due to shortcomings of cold storage (Olthoff, et al., 2010). 
Isolated liver perfusion has been extensively studied for over 30+ years using a variety of 
different perfusates and perfusion temperatures.  More recently, there has been an 
international focus in the liver transplant clinical and scientific community on normothermic 
liver perfusion using blood based perfusate to minimize the negative impacts of cold ischemic 
preservation on donor livers for transplantation.  In addition, by maintaining livers in an active 
metabolic and functioning state, donor livers from heart beating or DCD donors can be assessed 
ex-vivo for suitability for transplantation.  
The TransMedics’ OCS Liver System technology is a portable system for ex-vivo perfusion and 
assessment of the donor livers for transplantation.  The OCS Liver System maintains the donor 
liver in a metabolically active and functioning state (producing bile), by perfusing the liver with 
warm oxygenated and nutrient enriched blood-based perfusion solution.  The OCS Liver System 
is intended to significantly reduce ischemia and reperfusion injuries on the donor livers and 
enable metabolic and functional assessment of donor livers to assess their suitability for 
transplantation.  The OCS Liver System may enable the following clinical advantages: 
• Reduction of the ischemia and reperfusion injuries on the donor livers during 
preservation, thus, eliminating the significant logistical and geographical barriers to 
Liver transplantation that currently exist with cold storage preservation. 
• Optimization of donor liver ex-vivo environment by optimizing oxygen and substrate 
delivery, while also maintaining near normothermic condition to avoid the negative 
impact of cold temperature on fatty livers. 

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• Ex-vivo assessment of donor liver metabolic and functional state utilizing standard 
clinical tests of liver enzymes, bile production and lactate metabolism, enabling the 
transplanting clinical team to judge the suitability of the donor liver for 
transplantation and minimizing the risk of transplanting questionable donor livers 
into recipients. 
In summary, there is a public health need for technologies, like the OCS Liver System, that can 
address the current shortcomings of the standard of care cold storage preservation for liver 
transplantation.  Addressing the shortcomings of cold storage will allow increased utilization of 
donor livers, including fatty livers and DCD livers, and will help to overcome current 
geographical and logistical challenges to utilization of the existing donor pool.  Enabling more 
liver transplants will help to address the disparity between the number of patients on the 
waiting list and the availability of donor livers. 
 
1.3. 
Subject Enrollment and Health Insurance 
Approximately 30-40% of liver transplant recipients have their care paid for by Medicare due to 
their age or disability status.  Therefore, it is expected that Medicare patients will consent to 
participate in this study.  Since Medicare patients in need of transplantation do not differ from 
transplant candidates receiving coverage from other payors, Medicare patients will be treated 
in the same manner as all other study Subjects and will realize the same potential benefits and 
risks experienced by all other Subjects in the study. 
2. 
SUMMARY OF PRIOR TESTING AND INVESTIGATIONS 
2.1. 
 OCS Liver System Nonclinical Testing  
The OCS Liver System is CE-marked and has undergone extensive preclinical testing to 
demonstrate its safety, effectiveness, and readiness for clinical use, before placement on the 
EU market.  The Liver Perfusion Set has also been evaluated and tested in accordance with ISO-
10993 “Biological Evaluation of Medical Devices.”  These test results demonstrated that the 
device and its materials are biocompatible and suitable for their intended use.  The Liver 
Perfusion Set will be provided sterile using validated methods, and is appropriately packaged to 
maintain sterility.  The system has also undergone extensive preclinical bench testing for: 
electrical safety, electromagnetic compatibility, and validation and verification testing 
(including validation of the device software).  All tests and results have demonstrated that the 
OCS Liver System meets its expected performance specifications and is safe and suitable for 
clinical use. 
Functional animal studies have demonstrated the safety, suitability, and performance of the 
OCS Liver System for preservation of donor livers. 
2.2. 
OCS Liver PROTECT Study 
The PROTECT Study is a prospective, pivotal, randomized study of the OCS Liver being 
conducted in the U.S.  The objective of the study is to evaluate the effectiveness of the OCS to 

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Note:  The Liver Console figure (left) shows the LvPM mounted onto the system.  The LvPs figure (middle) 
only shows the LvPM components of the LvPS. 
4. 
TRIAL OBJECTIVES 
To evaluate the effectiveness of the OCS Liver System to preserve and assess donor livers 
having one or more of the following characteristics: 
• Donor age ≥ 40 years old; or 
• Expected cross clamp time ≥ 6 hours; or 
• Donor after circulatory death (DCD) with age ≤ 55 years old; or 
• Steatotic liver > 0% and ≤ 40% macrosteatosis at time of retrieval (on pre-retrieval 
histology). 
4.1. 
Type of Trial 
A prospective, multi-center, single arm Continued Access Protocol. 
4.2. 
Trial Size and Subject Follow-up 
This trial will enroll up to 184 transplanted recipients at up to 21 sites in the U.S.  All subjects 
will be followed for 24 months from the date of transplantation (some of which will be post-
market).  The summary of the follow-up is in Appendix 2 of this document. 
5. 
TRIAL ENDPOINTS 
5.1. 
Primary Effectiveness Endpoint 
Incidence of Early Liver Allograft Dysfunction (EAD) or primary non-function, defined as 
presence of one or more of the following criteria: 
• AST level > 2000 IU/ml within the first 7 postoperative days; 
• Bilirubin ≥ 10 mg/dl on postoperative day 7;  
• INR ≥ 1.6 on postoperative day 7; or  

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• Primary non-functioning graft within the first 7 days (defined as irreversible graft 
dysfunction requiring emergency liver re-transplantation or death, in the absence of 
immunologic or surgical causes). 
5.2. 
Secondary Effectiveness and OCS Donor Liver Assessment Endpoints 
• OCS donor liver assessment during perfusion, defined as, among donor livers 
preserved using OCS for the entire preservation period, the proportion of livers on 
which measurements of all of the following during perfusion will be available on OCS 
device before transplant: 
-  Lactate level (every two hours) 
- Average bile production rate (based on total bile production volume and 
duration of OCS perfusion) 
- Hepatic artery pressure (continuously)  
- Portal vein pressure (continuously) 
• Patient survival at Day 30 post-transplantation 
• Patient survival at initial hospital discharge post liver transplantation. 
5.3. 
Other Endpoints 
• Length of initial post-transplant ICU stay  
• Length of initial post-transplant hospital stay 
• Evidence of ischemic biliary complications diagnosed at 6 and at 12 months post-
transplant 
• Extent of reperfusion syndrome as assessed based on the rate of decrease of lactate 
over the following timepoints: 
- During anhepatic phase immediately before reperfusion of the transplanted liver 
- 30-40 minutes after hepatic artery and portal vein reperfusion of the 
transplanted liver 
- 90-120 minutes after reperfusion of the transplanted liver  
• Pathology sample score for liver tissue samples taken at the following timepoints: 
- Donor liver pre-retrieval  
- Post-OCS preservation at the end of back preparation and immediately before 
the start of re-implantation  
- 90-120 minutes after reperfusion of the transplanted liver (prior to abdominal 
closure).  

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5.4. 
Safety Endpoint 
Safety will be analyzed principally by examination of the frequency of liver graft-related serious 
adverse events (LGRSAEs) up to the 30-day follow-up after transplantation.  This endpoint is 
defined as the average number of LGRSAEs through the 30 days post-liver transplantation per 
subject, consisting of the following serious adverse events (at most one per type per person): 
• Primary non-function (defined as irreversible graft dysfunction requiring emergency 
liver re-transplantation or death with the first 10 days, in the absence of 
immunologic or surgical causes) 
• Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile 
duct leaks) 
• Vascular complications (liver graft-related coagulopathy, hepatic artery stenosis, 
hepatic artery thrombosis and portal vein thrombosis) 
• Liver allograft infections (liver abscess, cholangitis, etc.). 
6. 
TRIAL POPULATION  
The trial will include 184 Liver transplant recipients at up to 21 sites in the U.S.  
6.1. 
Donor Eligibility Criteria 
6.1.1. 
Donor Inclusion Criteria 
Donor liver meets at least one of the following: 
• Donor age ≥ 40 years old; or 
• Expected total cross clamp time ≥ 6 hours; or 
• Donor after circulatory death (DCD) with age ≤ 55 years old; or 
• Steatotic liver > 0% and ≤ 40% macrosteatosis at time of retrieval (based on retrieval 
biopsy readout only if the donor liver was clinically suspected to be fatty by the 
retrieval surgeon at time of liver retrieval). 
6.1.2. 
Donor Exclusion Criteria 
Donor livers will be excluded if they meet any of the following criteria: 
• Living donors 
• Liver intended for split transplants 
• Positive serology (HIV, Hepatitis B surface antigen & Hepatitis C) 
• Presence of moderate or severe traumatic liver injury, or anatomical liver 
abnormalities that would compromise ex- vivo preservation of the donor liver (i.e., 
accessory blood vessels or other abnormal anatomy that require surgical repair) and 
livers with active bleeding (e.g., hematomas) 

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• Donor livers with macrosteatosis of > 40% based on retrieval biopsy readout. 
6.2. 
Recipient Eligibility Criteria 
6.2.1. 
Recipient Inclusion Criteria 
Recipients are required to meet all the following criteria on the day of transplant: 
• Registered primary liver transplant candidate, male or female 
• Age ≥ 18 years old 
• Signed: (1) written informed consent document and (2) authorization to use and 
disclose protected health information. 
6.2.2. 
Recipient Exclusion Criteria 
Recipients will be excluded if they meet any of the following criteria on the day of transplant: 
• Acute, fulminant liver failure 
• Prior solid organ or bone marrow transplant 
• Chronic use of hemodialysis or diagnosis of chronic renal failure, defined as chronic 
serum creatinine of > 3 mg/dl for > 2 weeks and/or requiring hemodialysis 
• Multi-organ transplant 
• Ventilator dependent 
• Dependent on > 1 IV inotropic support to maintain hemodynamics.  
7. 
PRE-OPERATIVE TRIAL PROCEDURES 
7.1. 
Subject Identification  
All patients on the liver transplant waiting list who are being treated by trial investigators will 
be identified.  Those patients who initially appear eligible for the trial will have the trial 
thoroughly explained to them, be invited to participate, and will be asked to sign an informed 
consent for participation in the trial prior to treatment.  When a matching donor liver becomes 
available, the inclusion and exclusion criteria will be re-verified.  When a final decision is made 
to transplant the liver, the recipient will be assigned a subject identification number.  
7.2. 
Recipient Day of Transplant Assessment 
The purpose is to conduct a final assessment of whether the potential consented recipient still 
meets the eligibility criteria.  The following information will be verified and recorded on the day 
of transplant:  
• Eligibility:  Investigator will review and confirm that the potential consented 
recipient continues to meet all inclusion criteria and no exclusion criteria. 
• Demographics/Characteristics:   

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- Date of birth or Age 
- Gender, body mass index 
- Race and Ethnicity  
- Blood type and RH factor 
- Recipient Model for End-stage Liver Disease (MELD) Score 
- Recipient ID 
• Baseline Liver Function Tests: 
-  Bilirubin levels 
- Aspartate aminotransferase (AST) 
- Alanine aminotransferase (ALT) 
- Gamma-glutamyl transpeptidase (GGT) 
- Alkaline phosphatase 
- International normalized ratio (INR) 
- Serum Lactate level 
• Recipient Risk Factors & Medical History:  
- Indication for transplantation: The primary etiology of Liver failure will be 
recorded 
- History of Hepatitis C 
- History of liver cancer 
- History of diabetes. 
7.3. 
Donor Screening and Acceptance 
The investigator or a member of her/his transplant team will evaluate the donor and the quality 
and suitability of the liver for transplantation and for enrollment in the trial.  The following 
evaluations will be conducted and recorded: 
• Organ Donor Identification Number (i.e., UNOS Donor ID) 
• Demographics:  Age, Date of birth (if available), gender, race, and ethnicity 
• Donor Characteristics:  Blood type & RH factor, body mass index 
• Donor’s Cause of Death:  
- Cause of death and date and time of pronouncement of brain death 
- If the donor is a DCD donor, total time in minutes from discontinuation of 
support to cardiac stand still  
• Medical History:  

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- Add 50 ml of sterile water for injection using aseptic technique 
- Mix well to ensure all salt is dissolved. 
At the time of use the OCS operator will spike the stopper of the vial using a sterile 
OCS infusion line and connect to the OCS infusion delivery system.  
• The OCS Liver Preservation Parameters:  Donor livers will be perfused on the OCS 
Liver System with OCS parameters maintained within the following ranges 
- Hepatic Artery Pressure (mean HAP): 75-100 mmHg 
- Hepatic Artery Flow (HAF): 300-700 ml/min 
- Portal Vein Pressure (mean PVP): 4-8 mmHg 
- Portal Vein Flow (PVF): 700-1700 ml/min 
- Perfusate Temperature (Temp): 34°C 
- Oxygen gas flow 400-700 ml/min  
- Circulating arterial Lactate (Lact) trend: trending down over time. 
 
• Lactate and Liver Enzyme Levels During OCS Liver Perfusion Sampling Scheme:  The 
organ retrieval team will collect samples from the arterial port of the OCS perfusion 
circuit to measure lactate level using a standard blood analyzer according to the 
following protocol: 
- OCS Baseline arterial sample within the first 10-30 min of liver instrumentation. 
§ Lactate 
§ Liver enzymes: AST, ALT, GGT, total bilirubin, and ALP. 
- Lactate samples will continue to be collected from the device at approximately 
hourly intervals until lactate level is trending down, at this time, lactate samples 
should be done every 2 hours or after any active HAF or HAP adjustments. 
- OCS Final arterial sample before cooling liver on OCS 
§ Lactate 
§ Liver enzymes: AST, ALT, GGT, total bilirubin, and ALP. 
• Final Liver Cooling and Flush Arrest on OCS: all donor livers on OCS will be cooled 
and flushed on the OCS using cold PlasmaLyte® solution supplemented with sodium 
bicarbonate (NHCO3) 10 mml/L, Epoprostenol Sodium 2 mics/L, and 
Methylprednisolone ~160 mg/L flush below, according to the following protocol: 
- Hepatic Artery: 1 liter flush at ~50-70 mmHg pressure bag 
- Portal Vein: 2 liters gravity drain. 
• Liver Biopsy (see 13TAppendix 113T): a needle biopsy will be collected from donor livers 
preserved on OCS on the back table, post-preservation, immediately before re-
implantation.  

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• OCS Preservation Information: the following information will be collected 
- Device Information (serial number, etc.) 
- Device Malfunction(s) 
- OCS system data collected by the device during the preservation run and 
uploaded into the EDC database.  
• Donor Retrieval Details:  The following information will be collected at time of Liver 
retrieval 
- Date and time of cross clamp of donor aorta. 
• OCS Details (Liver Instrumentation details): 
-  Total cold ischemia time between initial donor cross clamp and start of OCS 
Liver perfusion. 
• OCS Parameters and Enabled Measurements: The following OCS Liver perfusion 
parameters and Liver metabolic conditions will be recorded: 
- HAP 
- HAF 
- PVP 
- PVF 
- Total Bile volume 
- OCS Liver arterial lactate level. 
7.5. 
Donor Liver Acceptance for Transplantation following OCS Liver 
Preservation 
All donor livers that are preserved on the OCS Liver System are expected to be transplanted 
into a matching consented recipient.  Any decision to turn down livers after they have been 
retrieved and preserved on OCS Liver System should be done with notification to the Site PI and 
the donor liver examined by the transplant center’s qualified liver transplant pathologist and/or 
tissue slides/samples to be sent to core lab for the study for further examination.  All reasons 
for turning down a donor liver after it has been preserved on the OCS Liver System will be 
collected in the eCRFs. 
8. 
TRANSPLANT, IMMEDIATE POST-OPERATIVE AND LONG TERM 
FOLLOW-UP 
8.1. 
Transplant Details  
The following information concerning the transplant procedure will be collected:  
• The organ recipient unique post-transplant patient identifier 

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• Total cross clamp duration in minutes (from donor cross-clamp application to 
removal of cross-clamp in the recipient) 
• Total cold ischemia time will be collected (OCS = cold ischemic time pre and post 
OCS Liver perfusion) 
• Any surgical complications encountered during surgery 
• Use of circulatory bypass will be recorded 
• Type of liver anastomosis 
- Bicaval anastomosis; or 
- Piggyback anastomosis 
• The total amount of any blood product and clotting factors transfusion will be 
collected (pRBCs, Fresh Frozen Plasma (FFP), platelets, etc.) 
• Any inotropic support needed to maintain hemodynamics will be collected 
• A liver tissue biopsy will be collected from the right lobe of the transplanted liver 
immediately before abdominal closure in the recipient.  The biopsy will be collected 
according to Liver Biopsy protocol in Appendix 1. 
 
8.2. 
Post-transplant Functional Assessments Day 0 – Day 30: 
• Early Liver Allograft Dysfunction (EAD) Surveillance in the first 7 days: 
- AST level > 2000 IU/ml within the first 7 postoperative days; 
- Bilirubin ≥ 10 mg/dl on postoperative day 7;  
- INR ≥ 1.6 on postoperative day 7; or  
- Primary non-functioning graft within 7days. 
• Inotropic Support to Maintain Hemodynamics at T0, T24 and T48 and T72 hours 
after ICU admission (if applicable) will be collected 
• Initial use of Mechanical Respiratory Support:  Duration of initial post-transplant 
invasive ventilator support will be recorded from the time of initial admission to ICU 
post-Liver transplant until extubation. 
• Initial Post-Transplant ICU Stay:  Intensive care unit (ICU) admission time, and date 
and time when clinical order for ICU discharge is written. 
• Renal Replacement Therapy:  Need for dialysis treatments in the first 10 days post 
liver transplantation for patients that did not have renal replacement prior to 
transplantation 
• Immunosuppression Medications:  The type of immunosuppression medication and 
dose will be recorded at day 7 and at time of discharge from the hospital.  
Immunosuppression induction will be recorded if applicable. 

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• Patient and Graft Survival at Day 30 and At Initial Hospital Discharge:  Patient and 
graft survival will be assessed on day 30 post-transplant and at initial hospital 
discharge post-liver transplantation. 
• Liver graft-related Serious Adverse Events:  All liver graft-related serious adverse 
events will be followed and documented until the investigator designates the event 
to be either resolved or its effect on the patient’s condition stabilized.  
• Medications:  Medications used to treat all serious liver graft-related adverse event 
(SAE)-related will be recorded in the trial electronic database until the SAE is 
resolved. 
These follow-ups will be attempted within ± 3 days of the designated periods except for the 
Early Liver Allograft Dysfunction (EAD) Surveillance, in the first 7 days which must be collected 
at the designated times.  The evaluations may be conducted over several days. 
8.3. 
Long-term Follow-up: 6 and 12 & 24 Months 
Follow-up data collection will be conducted at approximately 6, 12, and at 24 months post-
transplant.  
8.3.1. 
6 and 12-Month Follow-up  
 At approximately 6- and 12-months post-transplant, the patient will be evaluated at an office 
visit if this is the institution’s standard of care, and, if not, by phone contact by the site.  The 
patient’s medical record may be reviewed to confirm patient’s answers.  This follow-up will 
collect information on: 
• Patient and graft survival 
• Liver graft-related SAEs (6 months only) 
• Liver graft-related re-hospitalization after initial discharge, and, if yes, the primary 
reason/diagnosis for the hospitalization and the length of stay 
• Information will also be collected on any diagnosis of ischemic biliary complications 
and, if so, the method of diagnosis and treatment. 
The 6 and 12-month follow-up will be collected within ± 1 month of the designated period and 
will be recorded on the 6- and 12-month follow-up electronic form. 
8.3.2. 
24-Month Follow-up  
At approximately 24 months post-transplant (± 1 month), the patient will be evaluated at an 
office visit if this is the institution’s standard of care, and, if not, by phone contact by the site.  
The patient’s medical record may be reviewed to confirm patient’s answers.  This follow-up will 
collect information on: 
• Patient and graft survival 
• Results of standard clinical practice or for cause liver biopsy will be collected (if 
applicable). 

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The 24-month follow-up will be collected within ± 1 month of the designated period and will be 
recorded on the 24-month follow-up electronic form. 
9. 
EVALUATION OF ADVERSE EVENTS 
9.1. 
Evaluation of Liver Graft-Related Adverse Events (LGRAEs) 
Liver Graft-Related Adverse Events (LGRAEs) are those which have any untoward effect on the 
health or safety of the patient and that are related to the transplanted liver function (except for 
acute rejection).  LGRAEs will be collected from the time a subject is transplanted with a liver 
preserved on OCS until the completion of the 30-day follow-up evaluation.  A LGRAE will be 
followed until resolution or stabilization of the event. 
9.2. 
Serious Adverse Events (SAEs) 
An adverse event will be classified as serious if it meets any of the following criteria: 
• Results in, leads to, or contributes to, a death 
• Is life-threatening 
• Results in permanent disability or incapacity (i.e., permanent impairment of a body 
function or permanent damage to a body structure) 
• Requires in-patient hospitalization or prolongs hospitalization 
• Necessitates medical or surgical intervention to preclude a permanent disability or 
incapacity 
• Results in fetal distress, fetal death or a congenital anomaly/birth defect. 
Only liver graft-related SAEs will be followed until their resolution. 
9.3. 
Anticipated and Unanticipated Adverse Events 
The investigator will assess each adverse event for whether it is anticipated or unanticipated.  
An unanticipated adverse event is defined as any adverse effect on health or safety, or any life-
threatening problem or death caused by, or associated with, a device if that effect, problem or 
death was not previously identified in nature, severity or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the safety, or welfare of 
subjects. 
Adverse events are associated with liver transplant procedures and have been documented 
within the first 30 days after liver transplant, and are therefore anticipated.  The list of events 
includes, but is not limited to: 
• Acute rejection 
• Atrial and ventricular arrhythmias 
• Bleeding 
• Hemodynamic instability 
• Death 
• Fever 
• Early liver allograft dysfunction (EAD) 
• Respiratory failure 

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• Liver primary non-function 
• Bile leaks 
• Hepatic artery thrombosis 
• Portal vein thrombosis 
• Cholangitis 
• Liver abscess 
• Diaphragmatic injury 
• Phrenic nerve injury 
• Sepsis 
• Renal dysfunction and/or failure 
• Hyperammonaemia 
• Malignancy (post-transplant 
lymphoproliferative disorder (PTLD) 
• Multiple organ failure 
• Myocardial infarction 
• Neurological dysfunction 
• Hepatic dysfunction 
• Diabetes due to steroid and anti-
rejection medications 
• Pancreatitis 
• Peptic ulceration 
• Gastritis 
• Gastro esophageal reflux disease 
(GERD) 
• Aspiration  
• Cardiac tamponade 
• Pneumo-mediastinum 
• Pneumothorax 
• Hemothorax 
• Ascites 
• Pleural effusion 
• Venous thromboembolism (deep 
venous thrombosis [DVT]) 
• Pulmonary embolism (PE) 
• Abdominal wound dehiscence 
• Organ deemed not transplantable after 
retrieval 
• Stroke 
• Psychosis 
• Ileus  
• Bowel obstruction 
• GI Bleeding (upper or lower) 
• Cerebrovascular accident 
• Peripheral vascular clotting or 
occlusion due insertion of mechanical 
support or equivalent 
• Delirium, confusion and neurological 
complications 
• Hepatic coma 
• Retransplantation 
• Limb gangrene due to vascular 
occlusion due insertion of mechanical 
support 
• Use of mechanical circulatory support 
• Coagulopathy 
• Blood product transfusion 
• Transfusion reaction 
• Hyperacute rejection 
• Anastomotic site complications; 
narrowing, bleeding or occlusion 
• Bowel thromboembolic complications 
and gangrene 
• Protamine and other anti-heparin 
medication reaction 
• Heparin induced thrombocytopenia
 
9.4. 
Unanticipated Adverse Device Effect (UADE)   
An UADE means any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified or encountered before at least once in standard clinical practice, in nature, 
severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated with 
a device that relates to the rights, safety, or welfare of subjects. 

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9.5. 
Recording and Reporting of Adverse Event 
All liver graft-related adverse events and serious adverse events are to be captured until post-
transplant day 30 or until initial hospital discharge, whichever comes first.  The description of 
the adverse event will include: the date of onset, duration, severity, seriousness, the 
relationship of the event to the trial treatment, anticipated or not, and any treatment required.  
All liver graft-related serious adverse events occurring during the course of the first 30 days 
post-transplant will be reported to TransMedics, Inc., as well as documented on the 
appropriate electronic case report form(s).  For all liver graft-related SAEs, the investigator is 
required to supply any additional data that may be deemed necessary by the Sponsor.  
Additionally, any serious adverse events (SAE) and unanticipated adverse device effects (UADE) 
should be reported to TransMedics, Inc., as soon as possible after the investigator learns of the 
event.  LGRAEs will be recorded up to the 30-day follow-up or through hospital discharge only if 
longer than 30 days.  For any particular patient, the CEC, if required to protect patient safety, 
may specify a different follow-up period.  The Sponsor is responsible for the classification and 
reporting of liver graft-related adverse events to the appropriate regulatory authorities, and for 
the on-going safety evaluation of the trial in accordance with ISO 14155 and governing 
regulatory requirements. 
9.6. 
Relationship of an Adverse Events (AEs) to OCS Liver System  
The investigator will assess the relationship of the Adverse Event (AE) to the OCS Liver System.  
The relationship will be assessed using the following categories:  
• Definitely Related:  There is a reasonable causal and temporal relationship between 
preservation with the OCS Liver System and the adverse event. 
• Probably Related:  It is more likely than not that there is a reasonable causal 
relationship between preservation with the OCS Liver System and the adverse event. 
• Unlikely Related:  There is a temporal relationship with preservation with the OCS 
Liver System and the adverse event, but there is not a reasonable causal relationship 
between the trial device and the event. 
• Unrelated:  There is no relationship between preservation with the OCS Liver System 
and the adverse event. 
9.7. 
Severity 
The investigator will rate the severity of the adverse event using the following categories: 
• Mild:  The adverse event is transient and/or easily tolerated by the subject. 
• Moderate:  The adverse event causes the subject discomfort and interrupts the 
subject's usual activities. 
• Severe:  The adverse event causes considerable interference with the subject's usual 
activities. 
9.8. 
Pre-Existing Conditions 
Pre-existing diseases or conditions will not be reported as adverse events. 

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10. 
STATISTICAL METHODS 
10.1. 
General 
Continuous variables will be summarized using descriptive statistics, specifically the mean, 
median, standard deviation, minimum, and maximum.  Categorical variables will be 
summarized using frequencies and percentages.  
All statistical procedures will be performed using SAS Version 9.3 or higher. 
10.2. 
Analysis Populations 
10.2.1. 
Per Protocol Population 
The Per Protocol (PP) Population will consist of all subjects who are transplanted and have no 
major protocol violations and for whom the donor liver received the complete preservation 
procedure.  The major protocol violations that will exclude a subject from this population are 
the following:  
• Ineligible for the study according to the recipient inclusion and exclusion criteria 
• Ineligible for the study according to the donor organ inclusion and exclusion criteria 
• Failure to complete adequate post-transplant assessments to support the primary, 
secondary or safety endpoints 
• Other major protocol violations. 
The primary analysis of effectiveness and of secondary and other endpoints will be based on 
the PP Population. 
10.2.2. 
Modified Intent-to-Treat Population 
The Modified Intent-to-Treat Population (mITT) will consist of all subjects who are transplanted.  
The mITT analyses will be considered secondary analyses of effectiveness.  The safety analysis 
will also be based on the mITT population. 
10.2.3. 
Donor Liver Population 
The Donor Liver Population will consist of all donor livers which have preservation initiated 
using the OCS Liver System.   
10.3. 
Data Analysis 
The statistical analysis plan (SAP) will provide details on the statistical methods planned for this 
study and will be finalized prior to the database lock.  Statistical summaries described in the 
sections below will primarily be provided for all subjects (i.e., overall summary) in the analysis 
populations of interest unless otherwise stated. 

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10.3.1. 
 Subject Disposition 
Subject disposition will be summarized and presented for the number and percentage of 
subjects who were enrolled, screen failures, completed the study, and discontinued early 
(including reasons for discontinuations). 
10.3.2. 
Major Protocol Deviations 
Major protocol deviations will be identified and documented based on a review of potential 
deviations.  The potential major protocol deviations will be identified before database lock, 
either through programmatic checks of study data (e.g., inclusion/exclusion criteria violations), 
as well as through review of selected data listings (e.g., site-entered comments).  The potential 
major protocol deviations to be reviewed include, but are not limited to, subjects who did not 
meet inclusion/exclusion criteria or eligibility was not adequately verified. 
Individual major protocol deviations will be presented in a data listing.  The number and 
percentage of subjects with major protocol deviations will be summarized by the type of 
deviations. 
10.3.3. 
Demographics and Baseline Characteristics 
Demographics, including (age, gender, race, and ethnicity where applicable), and other baseline 
characteristics collected at screening, such as height, weight, body mass index will be 
summarized using descriptive statistics.  These data will be presented as a listing.  
10.3.4. 
Primary Effectiveness Endpoint  
The primary effectiveness endpoint for this study is the incidence of Early Liver Allograft 
Dysfunction (EAD) or primary non-function, defined as presentation of one or more of the 
following criteria: 
• AST level > 2000 IU/ml within the first 7 postoperative days; 
• Bilirubin ≥ 10 mg/dl on postoperative day 7;  
• INR ≥ 1.6 on postoperative day 7; or  
• Primary non-functioning graft within the first 7 days. 
This endpoint will be analyzed using the Per Protocol and mITT Populations.  The Per Protocol 
analysis will be considered the primary analysis.   
Subgroup analyses of the primary effectiveness endpoint will be performed for the following 
subgroups of patients: 
• DCD (donation after circulatory death) patients 
• Fatty liver patients 
• Donor Age 
• Recipient with MELD > 30. 
No data imputation or statistical tests will be performed for these subgroup analyses. 

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10.3.5. 
Secondary Effectiveness and OCS Donor Liver Assessment Endpoints 
The secondary effectiveness endpoints for this trial are as follows: 
• OCS donor liver assessment during perfusion, defined as, among donor livers 
preserved using OCS for the entire preservation period, the proportion of livers on 
which measurements of all of the following during perfusion will be available on OCS 
device before transplant 
- Lactate level (every two hours) 
- Average bile production rate (based on total bile production volume and 
duration of OCS perfusion) 
- Hepatic artery pressure (continuously) 
- Portal vein pressure (continuously) 
• OCS Measurements during organ perfusion 
• Patient survival at Day-30 post-transplantation 
• Patient survival at time of initial hospital discharge post-transplantation. 
These endpoints will be analyzed using the Per Protocol and mITT Populations, with the Per 
Protocol analysis being considered the primary analysis.  Multiple imputation methods will be 
used for data imputation for patients with missing values for these endpoints. 
Subgroup analyses of the secondary endpoints will be performed for the same subgroups of 
patients as for the primary effectiveness endpoint.  No data imputation or statistical tests will 
be performed for these subgroup analyses. 
10.4. 
Analysis of Safety 
Safety will be analyzed principally by examination of the frequency of liver graft-related serious 
adverse events (SAEs) up to the 30-day follow-up after transplantation.  This endpoint is 
defined as the average number of liver graft-related serious adverse events through the 30 days 
post-liver transplantation per subject, consisting of the following serious adverse events (at 
most one per type per person): 
• Primary non-function (defined as irreversible graft dysfunction requiring emergency 
liver re-transplantation or death within the first 10 days, in the absence of 
immunologic or surgical causes) 
• Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile 
duct leaks) 
• Vascular complications (liver graft-related coagulopathy, hepatic artery stenosis, 
hepatic artery thrombosis and portal vein thrombosis) 
• Liver allograft infections (liver abscess, cholangitis, etc.). 
In addition, the numbers and percentages of subjects experiencing at least one liver graft-
related AE, at least one (definitely or probably-related) device-related AE, at least one 
unanticipated AE, and at least one serious AE, and the number and percentage of deaths will all 

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11. 
RISK ANALYSIS 
This clinical trial has been designed to ensure that the benefits and knowledge gained from the 
trial outweigh the potential risks to the subjects.  The subjects are adults undergoing primary 
liver transplants.  
11.1. 
Potential Risks 
The potential risks to subjects from participation in this clinical trial include the following:  
• Potential Risks Associated with Liver Transplant Procedures:   
Potential risks associated with any liver transplant procedure include post-operative 
complications, such as graft failure, primary graft dysfunction, rejection, infection and 
other organs/systems complications, graft vessel disease (an expression of chronic 
rejection), abnormal kidney function, diabetes, high level of cholesterol, high blood 
pressure, cancer and neurological complications. 
• Potential Risks Associated with the OCS Liver System:   
Subjects have the risk of not receiving organs preserved with the OCS Liver System 
under certain conditions including: (1) the OCS Liver System may not function properly, 
or there may not be personnel available trained in the use of the OCS Liver System or (2) 
the OCS Liver System may malfunction, or the medical staff may make an error which 
could lead to damage of the donor liver.  If this occurs, the subject will have to wait for a 
new donor liver to become available.  In no case does the recipient lose their place on 
the waiting list.  
As with any medical device, there is always a risk of extremely rare or previously 
unknown side effects developing from the treatment.  However, at this time, there are 
no known potential risks other than those associated with liver transplant procedures 
performed under the current standard of care. 
• Potential Risk of Using a Donor Liver that is Unsuitable for Transplantation: 
Regardless of the preservation system that is used, there is the risk that a patient can 
receive a liver that does not adequately function.  There is the possibility that the donor 
liver may not meet transplantability criteria after OCS preservation and would be turned 
down for transplant.  The anticipated frequency of this event is known.  There is a risk 
that the surgeon may transplant a liver that does not function or functions poorly after 
transplant.  This risk exists for any liver preservation technology. 
11.2. 
Manner in Which the Risks Will be Minimized 
The Sponsor has relied upon a number of different means, including the device design, risk 
analysis and management process, preclinical testing, prior clinical testing and the clinical 
protocol itself, to minimize the risks to subjects and to protect their safety and welfare.  
The OCS Liver System has undergone extensive preclinical and animal studies to demonstrate 
that the device performs as intended and all material are biocompatible.  Previous clinical 
studies, including the Liver PROTECT study, have demonstrated the safety of the device. 

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In addition, this clinical protocol incorporates several procedures to minimize the risks to 
subjects and to ensure the benefits of the clinical trial outweigh its potential risks. 
• The donor liver acceptance criteria after OCS Liver System perfusion and assessment are 
based on clinically relevant markers for perfusion of donor livers on OCS and clinical 
standards of accepting conventional donor livers for transplantation.  Thus, the donor 
liver will be fully assessed based on the current standards of evaluating donor livers 
before acceptance for transplantation.  
• As with any liver transplant procedure, subjects will be monitored before, during and 
after the operative procedure.  The investigators have extensive experience with liver 
transplants and will be trained (or have already been trained) on the use the OCS Liver 
System to further minimize risk. 
• The trial will be monitored to ensure the identification, documentation, and analysis of 
adverse events; and to ensure compliance with the protocol and procedures that are in 
place for conducting research to protect the safety and well-being of all subjects. 
Lastly, the OCS Liver PROTECT study has not raised any questions regarding safety of the device, 
and no safety issues or concerns have been raised by the study’s independent DSMB. 
 
11.2.1. 
Potential Benefits 
The low utilization of donor livers has contributed to the severe shortage of donor livers.  The 
OPTN/SRTR Annual Report indicates that, 12 months after listing, 18% of patients will die or 
become delisted (Kim, et al., 2019). 
The OCS Liver System’s preservation and assessment capabilities could potentially increase the 
rate of utilization of donor livers and reduce waiting list time and mortality.  In addition, the 
OCS Liver System’s ability to assess donor livers allows for the assessment of the function of the 
donor liver before it is transplanted. 
11.2.2. 
Risk: Benefit Ratio 
Based on the above, the benefits of using OCS Liver System technology to preserve and assess 
livers to ensure their suitability for liver transplantation outweigh the potential risks to trial 
subjects.  
12. 
DEVICE/SITE MANAGEMENT 
12.1. 
Packaging and Labeling 
The OCS Liver Perfusion Set and accessories will be supplied sterile and are intended and 
labeled for single use. 
The OCS and its components will be clearly labeled as an investigational device according to 21 
CFR 812.5.  The labeling provides instructions for use for the device.  A copy of the Instructions 
for Use (IFU) will be provided to each investigational site. 

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12.2. 
Storage 
The investigational devices will be stored in a secure place.  Access should be strictly limited to 
the investigators and their designees.  Neither the investigators nor any designees may provide 
the investigational device to any subject not participating in this trial.  Special storage 
instructions for the components are described in detail in the IFU.   
12.3. 
Accountability 
The investigator or designee will maintain an inventory record of investigational devices 
received, used for treatment, otherwise discarded, and returned to the Sponsor to ensure that 
the investigational device will not be dispensed to any person who is not a subject under the 
terms and conditions set forth in this protocol. 
12.4. 
Device Complaints and Malfunctions 
The investigator will inform the Sponsor of any complaints or malfunctions during the course of 
the trial.  The Sponsor will investigate all device complaints and malfunctions. 
13. 
REGULATORY / ETHICS 
This clinical trial will be conducted in accordance with the requirements of the FDA 
Investigational Device Exemptions regulation (21 CFR Parts 50, 56, 812, and 45 CFR part 46), 
and in accordance with good clinical practices. 
13.1. 
Institutional Review Boards (IRB)  
In accordance with the conditions imposed by the reviewing Institutional Review Board (IRB) to 
applicable regulations from Federal agency (i.e. U.S. Food and Drug Administration (FDA), with 
local regulations, prior to initiation of any trial procedures, the protocol, informed consent 
template and device labeling (if requested) will be submitted to each site’s IRB for review and 
approval.  In addition, any amendments to the protocol or informed consent form will be 
reviewed and approved (if necessary) by the IRB.  The Sponsor must receive a letter 
documenting the IRB’s approval at the clinical site prior to the initiation of the trial at that 
particular site.  
13.2. 
Informed Consent 
Informed consent will be obtained and documented prior to initiation of any procedures that 
are performed solely for the purpose of the research trial. 
Investigators have both an ethical and legal responsibility to ensure that each patient being 
considered for inclusion in this trial is given a full explanation of the protocol.  This will be 
documented via a written informed consent form approved as part of the full trial approval 
granted by the Institutional Review Board (IRB) for the site.  The investigator agrees to also 
obtain approval from the Sponsor and IRB for any written informed consent form used in the 
trial.   

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The approved written informed consent form will be signed and dated by the subject and the 
individual obtaining the consent.  The subject will be given a copy of the signed informed 
consent form.  The original will be kept in the patient’s file by the investigator. 
14. 
DATA COLLECTION/RECORDS/REPORTS 
14.1. 
Investigator Records 
Prior to participation in the investigation, the investigator will provide the following 
documentation to the Sponsor: 
• Investigator Agreement, signed by the investigator and disclosure of any financial 
interest 
• A copy of the primary investigator’s curriculum vitae (CV), as well as copies of CVs for 
any co-investigators 
• Written approval of the trial from the IRB 
• A copy of the approved informed consent document. 
During the trial, investigators will be responsible for complete and accurate entry of data into 
the trial’s database, and will be required to maintain on file the following accurate, complete 
and current records relating to this trial: 
• All relevant correspondences and required reports that pertain to the trial 
• Records of receipt, use or disposition of the investigational device, including the type 
and quantity of the device; the dates of receipt; the lot number; the names of all 
persons who received, used or disposed of each device; and why and how any units of 
the device have been returned to the Sponsor, repaired, or otherwise disposed 
• Records of each subject’s case history and exposure to the device 
• Signed and dated consent forms 
• Relevant observations, including records concerning adverse events, condition of each 
subject upon entering and results of diagnostic tests 
• Protocol, and any amendments 
• Subject recruiting materials 
• Investigator curricula vitae. 
The investigator will not dispose of any records relevant to this trial without (1) written 
permission from the Sponsor, and (2) providing an opportunity for the Sponsor to collect such 
records.  The investigator will take responsibility for maintaining adequate and accurate 
electronic or hard copy source documents of all observations and data generated during this 
trial.  Such documentation is subject to inspection by the Sponsor and regulatory authorities. 

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14.2. 
Investigator Reports 
In accordance with the FDA reporting requirements, the investigators will be required to 
prepare and submit to the Sponsor the following complete, accurate, and timely reports on this 
investigation when necessary: 
• The investigator will notify the Sponsor of a subject death occurring during the 
investigation as soon as possible after learning of the subject’s death.   
• The investigator shall submit to the Sponsor and to the reviewing IRB a report of any 
unanticipated adverse device effects (UADE) occurring during an investigation as 
soon as possible, but in no event later than 10 working days after the investigator 
first learns of the event.  
• The investigator will notify the Sponsor of the withdrawal of IRB approval as soon as 
possible, but no later than 5 working days after the investigator first learns of the 
withdrawal. 
• The investigator will provide current progress reports to the Sponsor and reviewing 
IRB at regular intervals but at least on an annual basis.  
• The investigator will notify the Sponsor and the IRB of any deviation from the 
investigational plan to protect the life and physical well-being of a subject in an 
emergency as soon as possible after the emergency occurred. 
• The investigator will notify the Sponsor and IRB that an informed consent was not 
obtained from a subject as soon as possible after such an occurrence. 
• The investigator will provide a final summary report within 3 months after 
termination or completion of the trial to the IRB.  The site trial completion report 
may serve as the trial completion for the Sponsor. 
• The investigator will provide any other information upon the request of the IRB, or 
the Sponsor. 
14.3. 
Source Documents 
Source documents are defined as the results of original observations and activities of a clinical 
investigation.  Examples of source documents include progress notes, electronic data, computer 
printouts, screening logs, and recorded data from automated instruments.  All data entered 
into the trial database must have a corresponding source document.  All source documents 
pertaining to this trial will be maintained by the investigators and made available for inspection 
by authorized persons.  The Sponsor may request copies of select redacted source documents.  
14.4. 
Archiving of Records 
Essential trial documents must be maintained by the Investigator for at least 2 years after the 
last marketing approval by a regulatory body, as determined by the Sponsor.  The documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements.  Records will be kept in a secure, dry location controlled by the institution. 

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15. 
CLINICAL MONITORING 
15.1. 
Monitoring 
The Sponsor has ethical, legal and scientific obligations to carefully follow this trial in a detailed 
and orderly manner in accordance with established research principles.  The Sponsor's monitors 
will visit the center during the trial in addition to maintaining frequent telephone and written 
communications.  The following guidelines are provided to describe the Sponsor’s procedures 
for monitoring the clinical trial.  If the investigator is not complying with the signed Investigator 
Agreement, the protocol, or any condition of the trial, (e.g., incomplete data forms) the 
Sponsor has the right to terminate the investigator’s participation in the trial.  The Sponsor is 
responsible for selecting trial monitors qualified by training and experience to conduct 
monitoring of the trial and for ensuring the quality of the trial monitoring visits by the monitor.  
The Sponsor’s general monitoring procedures for investigational studies are described below. 
15.2. 
Pre-Trial Monitoring Procedures 
15.2.1. 
Selection of Monitors  
All monitors will be qualified by education, training, and experience.  Importantly, all monitors 
will be trained on this protocol and critical data elements prior to conducting site monitoring 
visits. 
15.2.2. 
Study Initiation Visit (SIV) 
TransMedics will be responsible for documenting that each investigator clearly understands and 
accepts the responsibilities and obligations incurred in conducting a clinical trial.  The monitor 
will ensure, prior to trial initiation, that the investigator: 
• Understands the requirements of the trial 
• Understands the nature of the clinical protocol 
• Understands his/her reporting obligations 
• Understands the requirements for device accountability 
• Understands and accepts the obligations to obtain informed consent 
• Understands and accepts the obligation to obtain IRB review and approval of the clinical 
investigation before it is initiated and to ensure continuing review of the trial by the IRB, 
and to keep the Sponsor informed of all IRB actions concerning the trial 
• Has adequate facilities, support staff, and access to an adequate number of suitable 
subjects to conduct the investigation 
• Has the required documentation on file, including IRB approval and a signed investigator 
agreement 
• Will submit financial disclosure information.  

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15.3. 
Interim Monitoring Visits 
Interim monitoring visits will be conducted periodically by TransMedics after scheduling a 
mutually convenient date with the site.  The monitor will visit each site as needed to ensure the 
following: 
• Facilities continue to be adequate and acceptable. 
• Informed consent has been obtained. 
• The protocol is being properly followed and carried out by appropriate site trial staff. 
• The IRB has approved or been notified of any protocol changes. 
• Accurate, complete and current records are being maintained, and the information 
recorded and submitted to the Sponsor is representative of the subject’s record and 
other source documents. 
• Accurate, complete and timely adverse event reports are being submitted to the 
Sponsor. 
• The reason for a subject’s withdrawal from the trial has been documented. 
• Reports are being submitted to the IRB and Sponsor. 
15.4. 
Frequency of Monitoring Visits 
The frequency of monitoring visits will be determined on the basis of several factors, including 
the duration of the trial, number of subjects enrolled, number of investigators/sites, complexity 
of the trial, and number of outstanding issues from previous visits.   
15.5. 
Close-out Visit 
The close-out visit may be combined with a monitoring visit.  The following tasks will be 
completed at the close-out visit:  
• Ensure that all electronic forms have been completed. 
• Ensure that any database queries have been resolved. 
• Remind the investigator of the obligation to retain study records and any other post-
study obligations. 
15.6. 
Additional Auditing 
Regulatory authorities may also audit the investigator during or after the trial.  The investigator 
will contact the Sponsor immediately if this occurs, and will fully cooperate with the audits 
conducted at a reasonable time in a reasonable manner. 
15.7. 
Protocol Deviations 
This trial will be conducted as described in this protocol, except for an emergency situation in 
which the protection, safety, and well-being of a subject requires a protocol deviation, based on 
the judgment of the investigator (or a responsible, appropriately trained professional 
designated by the investigator).  If the deviation from the protocol is necessary to protect the 

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life and physical well-being of a subject in an emergency, such protocol deviations will be 
reported to the Sponsor and the IRB as soon as possible, but no later than 5 working days after 
the emergency occurred.   
In the event of a deviations from the protocol due to an accident or mistake (e.g., protocol-
mandated assessment not performed or done out of window), the site will document the 
deviation on the Protocol Deviation eCRF.  All efforts should be made to keep protocol 
deviations to a minimum.  
15.8. 
Clinical Events Committee 
The Sponsor will utilize an independent Clinical Events Committee (CEC).  Responsibilities of the 
CEC and frequency/scheduling of CEC meetings will be performed as outlined in the CEC 
charter. 
15.9. 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will be established by the Sponsor to 
periodically assess the progress of the trial, the safety data and the primary effectiveness and 
safety endpoints.  The DSMB will make recommendations to the Sponsor regarding 
continuation, modification or termination of the clinical trial.  Further details on member 
responsibilities and frequency/scheduling of DSMB meetings are contained in the DSMB 
charter.  
15.10. 
Investigator Device Training 
Device training will be provided to all new team members at an investigational site who have 
no experience with the OCS Liver System operation, prior to patient enrollment in the trial.  
Device training, when necessary, will be conducted at the TransMedics clinical training facility 
or equivalent training facility.  
15.11. 
Confidentiality 
All information generated in this trial will be considered highly confidential and must not be 
disclosed to any persons not directly concerned with the trial without written prior permission 
from the Sponsor.  Authorized regulatory officials and Sponsor personnel (or their 
representatives) will be allowed full access to inspect and copy the records.  All investigational 
devices and/or other materials collected shall be used solely in accordance with this protocol, 
unless otherwise agreed to in writing by the Sponsor.  Subjects will be identified only by unique 
subject numbers on the case report forms.   
15.12. 
Amendment Policy 
The investigator will not make any changes to this protocol without prior written consent from 
the Sponsor and subsequent approval by the IRB, except if the deviation from the protocol is 
necessary to protect the life and physical well-being of a subject in an emergency 

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16. 
REFERENCES 
1. Kim, et al., OPTN/SRTR 2017 Annual Data Report: Liver. Scientific Registry of Transplant 
Recipients; 2019. 
2. Olthoff, et al. Validation of a Current Definition of Early Allograft Dysfunction in Liver 
Transplant Recipients and Analysis of Risk factors. Liver Transplantation 16(8):943-949, 
2010. 
3. Pan, et al. Cold Ischemia Time Is an Important Risk Factor for Post-Liver Transplant 
Prolonged Length of Stay. Liver Transplantation, Vol. 24, No. 6, 2018. 
4. Vogel, et al. The Role of Normothermic Extracorporeal Perfusion in Minimizing Ischemia 
Reperfusion Injury. Transplantation Reviews 26 (2012) 156-162. 
5. Wertheim, et al. major Challenges Limiting Liver Transplantation in the United States. 
Am J Transplant. 2011 September; 11 (9): 1773-1784. 
6. Zhai, et al. Ischemia-Reperfusion Injury in Liver Transplantation-From Bench to Bedside. 
Nat Rev Gastroenterol Hepatol. 2013 February; 10 (2): 79-89. 

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APPENDIX 1. 
LIVER TISSUE BIOPSY, BILE DUCT SPECIMEN, & SCORING 
PROTOCOL 
Liver Parenchyma Tissue Sample:   
• Each tissue specimen is a 2.0 cm long 16-gauge needle biopsy taken perpendicular to 
the liver capsule from the right lobe.  It should be stressed that the needle NOT be 
inserted parallel to the capsule. 
• The tissue sample can then be placed in 10% neutral-buffered formalin, which is 
standard at most institutions.   
• The specimen container must be CLEARLY LABELED with an anonymous code and 
specimen information.  Bar coding is preferable.   
• The label should also contain the timing of the biopsy:  a) donor pre-retrieval; b) post-
preservation (before implant); and c) post-reperfusion. 
Timing of Liver Biopsy Samples: 
• Liver tissue samples taken at the following timepoints: 
- Donor liver pre-retrieval.  Only donor livers that are clinically suspected to be 
fatty by retrieval team visualization, will require a pre-retrieval biopsy readout to 
estimate the degree of macrosteatosis and confirm eligibility (≤40% 
macrosteatosis) 
- Post-OCS preservation at the end of back preparation and immediately before 
the start of re-implantation  
- 90-120 minutes after reperfusion of the transplanted liver (prior to abdominal 
closure). 
Bile Duct Specimens (if applicable):   
• Any tissue trimmed from the bile duct or cystic duct should be placed into 10% neutral 
buffered formalin, as above, and CLEARLY LABELED, as to the center and participant and 
location of the sample.  For example, 001-001 "distal common bile duct trimming."   
Timing of Bile Duct Specimen: 
• Pathology sample of common bile duct taken post-preservation: 
- Post preservation at the end of back preparation and immediately before the 
start of re-implantation OR 
- Post reperfusion-Prior to biliary anastomosis. 
 
Refer to core lab collection manual in the PROTECT Study Manual  

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Score 
PARENCHYMAL CHANGES: 
Total biopsy length:_________ mm 
Total number of portal tracts: __________  
Biopsy Adequate:  Yes   
No 
Overall architectural integrity:   
normal/intact 
mild  
moderate 
severe distortion 
1.  Lobular necrosis: 
      
1.1  Overall severity: 
   
( ) NONE  
( ) MILD  ( ) MOD  ( ) SEV   
( ) N/A 
      
1.2  Primary location: 
 
( ) Periportal  
( ) Midzonal   
( ) Perivenular  (  ) Panlobular 
(  ) NA 
      
1.3  Secondary location  
( ) Periportal  
( ) Midzonal   
( ) Perivenular  (  ) Panlobular 
(  ) NA 
      
1.4  Tertiary location: 
 
( ) Periportal  
( ) Midzonal   
( ) Perivenular  (  ) Panlobular 
(  ) NA 
2.  Lobular inflammation: 
 
2.1  Overall severity: 
 
( ) NONE  
( ) MILD  ( ) MOD  ( ) SEV   
( ) N/A 
 
2.2   Primary location: 
 
( ) Periportal  
( ) Midzonal   
( ) Perivenular  (  ) Panlobular 
(  ) NA 
 
2.3  Secondary location: 
( ) Periportal  
( ) Midzonal   
( ) Perivenular  (  ) Panlobular 
(  ) NA 
3.  Lobular inflammation type: 
 
3.1  Primary type: 
(  ) Neutrophils   (  ) Eosinophils 
(  ) Macrophage/monocyte 
(  ) Lymphocytes (  ) Plasma cells 
 
3.2  Secondary type: 
 
(  ) Neutrophils   (  ) Eosinophils   
(  ) Macrophage/monocyte  
(  ) Lymphocytes    
(  ) Plasma cells 
 
3.3  Tertiary type: 
 
(  ) Neutrophils   (  ) Eosinophils   
(  ) Macrophages/monocytes 
(  ) Lymphocytes  (  ) Plasma cells 
4.  Lobular Steatosis: 
 
4.1  Overall severity: 
 
( ) NONE  
( ) MILD  ( ) MOD  ( ) SEV  ( ) N/A 
 
4.2 Predominant distribution:  ( ) Periportal  (  )Midzonal  (  ) Perivenular  (  ) Panlobular (  ) NA 
5.  Liver Sinusoidal Endothelial Cell (LSEC) integrity/coverage (based on CD31 staining) 
 
5.1  Overall percentage of sinusoids covered ______ (nearest 10%) 
 
5.2  Primary LSEC loss:   
( ) Periportal   
( )Midzonal   
( ) Perivenular  
(  ) Panlobular 
 
(  ) NA 
 
5.3  Secondary LSEC loss:   ( ) Periportal   
( )Midzonal   
( ) Perivenular   
(  ) Panlobular  
 
(  ) NA 
 
EXTRA-HEPATIC BILE DUCT CHANGES:  
(adapted from Hansen et al. Virchows Arch 2012;461:41-48; and op den Dries 37T43TJ Hepatol37T43T. 2014 Jun;60(6):1172-9): 
1.  Surface epithelial loss:   (  ) 0: no loss 
 
(  ) 1:  ≤ 50% 
 
(  ) > 50% 
2.  Bleeding: 
 
 
(  ) 0: no bleeding   
(  ) 1:  ≤ 50% 
 
(  ) > 50% 
3.  Thrombi: 
 
 
(  ) 0: no thrombi    
(  ) 1:  thrombi present 
4.  Vascular lesions: 
 
(  ) 0: no lesions     
(  ) 1:  ≤ 50% vessels 
(  ) > 50% vessels  
5.  Arteriolonecrosis: 
 
(  ) 0: no lesions    (  ) 1:  ≤ 50% vessels  
(  ) > 50% vessels 
6.  Duct necrosis:  
(  ) 0: no lesions (  ) 1:  <25%   
 
(  ) 2: 25-50%    (  ) 3: 50-75%  
(  ) > 75% necrosis 
7.  Inflammation:   
 
(  ) 0: none;   (  ) 1:  at least > 10 leukocytes/HPF;    (  ) 2: >50/HPF 
8.  Subluminal gland injury:   
(  ) 0: no injury 
(  ) 1:  ≤ 50% 
(  ) > 50% 
9.  Deep gland injury: 
 
(  ) 0: no loss 
 
(  ) 1:  ≤ 50% 
(  ) > 50%