Prospective Trial to Evaluate the Effectiveness of The Portable Organ Care System (OCS) Liver for Preserving, Optimizing and Assessing Currently Seldom Utilized DCD Donor Livers for Transplantation
Phase: NA
Conditions: Liver Transplant
Sponsor: TransMedics

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Clinical Protocol and Investigational Plan 
 
Prospective Trial to Evaluate the Effectiveness of The Portable Organ Care 
System (OCS™) Liver for Preserving, Optimizing and Assessing Currently Seldom 
Utilized DCD Donor Livers for Transplantation (OCS™ Liver DCD Trial) 
 
Number OCS-LVR-092019 
 
 November 26, 2019 
 
 
Sponsor: 
TransMedics, Inc. 
 
200 Minuteman Road, Suite 302 
 
Andover, MA 01810 
 
Sponsor Primary Contact: 
 
 
 
 
 
 
 
Sponsor Secondary Contact:  
 
 
 
 
 
 
 
 
CONFIDENTIAL – PROPRIETARY INFORMATION 
 
Protocol Rev 
Issue Date 
1.0 
November26 , 2019 
 
 
 
 

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TABLE OF CONTENTS 
OCS™ LIVER DCD TRIAL SYNOPSIS .......................................................................................... 5 
TransMedics, Inc. ..................................................................................................................... 7 
200 Minuteman Road, Suite 302 ............................................................................................. 7 
Andover, MA, USA 01810 ........................................................................................................ 7 
1. 
INTRODUCTION AND BACKGROUND ............................................................................. 8 
1.1. Current Status of DCD Liver Transplants in the U.S. ........................................................ 8 
2. 
REPORTS OF PRIOR INVESTIGATIONS ............................................................................ 9 
2.1. OCS Liver System Nonclinical Testing ............................................................................... 9 
2.2. OCS Liver PROTECT Trial (G140192) ............................................................................... 10 
3. 
DEVICE DESCRIPTION .................................................................................................. 10 
4. 
TRIAL OBJECTIVES ....................................................................................................... 11 
4.1. Type of the Trial .............................................................................................................. 11 
4.2. Trial Size and Subject Follow-up ..................................................................................... 11 
4.3. Trial Endpoints ................................................................................................................ 11 
4.3.1. Primary Effectiveness Endpoint.......................................................................... 11 
4.3.2. Secondary Effectiveness Endpoints .................................................................... 12 
4.3.3. Other Endpoints ................................................................................................. 12 
4.3.4. Safety Endpoint .................................................................................................. 12 
5. 
TRIAL POPULATION .................................................................................................... 12 
5.1. Donor Eligibility Criteria.................................................................................................. 13 
5.1.1. Donor Inclusion Criteria ...................................................................................... 13 
5.1.2. Donor Exclusion Criteria ..................................................................................... 13 
5.2. Recipient Eligibility Criteria ............................................................................................ 13 
5.2.1. Recipient Inclusion Criteria ................................................................................. 13 
5.2.2. Recipient Exclusion Criteria ................................................................................ 14 
5.3. Screening Procedures ..................................................................................................... 14 
5.3.1. Recipient – Screening and Enrollment ............................................................... 14 
5.3.2. Donor Liver – Initial Screening, Retrieval and OCS Preservation ....................... 14 
5.3.3. Donor Liver Assessment on OCS Liver System and Acceptance for 
Transplantation ......................................................................................... 14 
5.4. Enrolled DCD Donor Livers and Recipients ..................................................................... 15 
6. 
DATA COLLECTION AND FOLLOW-UP .......................................................................... 15 
7. 
EVALUATION OF ADVERSE EVENTS ............................................................................. 16 
7.1. Evaluation of Liver Graft-Related Serious Adverse Events ............................................. 16 
7.2. Serious Adverse Events (SAEs) ....................................................................................... 16 
7.3. Anticipated Adverse Events ............................................................................................ 17 
7.4. Unanticipated Adverse Device Effect (UADE) ................................................................ 18 
7.5. Recording and Reporting of Adverse Event ................................................................... 18 
7.5.1. Relationship of an LGRSAE or SAE to OCS Liver ................................................. 18 

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7.6. Pre-Existing Conditions ................................................................................................... 18 
8. 
STATISTICAL METHODS ............................................................................................... 19 
8.1. General ........................................................................................................................... 19 
8.2. Analysis Populations ....................................................................................................... 19 
8.2.1. Per Protocol Population ..................................................................................... 19 
8.2.2. Modified Intent-to-Treat Population ................................................................. 19 
8.2.3. Donor Liver Population ....................................................................................... 19 
8.3. Data Analysis .................................................................................................................. 19 
8.3.1. Subject Disposition ............................................................................................. 19 
8.3.2. Major Protocol Deviations .................................................................................. 19 
8.3.3. Demographics and Baseline Characteristics....................................................... 20 
8.3.4. Effectiveness Analysis ......................................................................................... 20 
8.4. Safety Analysis ................................................................................................................ 21 
8.5. Treatment of Missing Data ............................................................................................. 21 
8.6. Sample Size Determination ............................................................................................ 21 
8.7. Stopping Rule .................................................................................................................. 22 
9. 
RISK ANALYSIS ............................................................................................................ 22 
9.1. Potential Risks ................................................................................................................ 22 
9.2. Manner in Which the Risks Will be Minimized .............................................................. 23 
9.2.1. Potential Benefits ............................................................................................... 24 
9.2.2. Risk: Benefit Ratio ............................................................................................... 24 
10. 
DEVICE/SITE MANAGEMENT ....................................................................................... 24 
10.1. 
Packaging and Labeling ........................................................................................... 24 
10.2. 
Storage .................................................................................................................... 24 
10.3. 
Accountability .......................................................................................................... 25 
10.4. 
Device Complaints and Malfunctions...................................................................... 25 
11. 
REGULATORY / ETHICS ................................................................................................ 25 
11.1. 
Institutional Review Boards (IRB) ............................................................................ 25 
11.2. 
Informed Consent .................................................................................................... 25 
12. 
DATA COLLECTION/RECORDS/REPORTS ...................................................................... 26 
12.1. 
Investigator Records ................................................................................................ 26 
12.2. 
Investigator Reports ................................................................................................ 26 
12.3. 
Source Documents .................................................................................................. 27 
12.4. 
Archiving of Records ................................................................................................ 27 
13. 
CLINICAL MONITORING .............................................................................................. 27 
13.1. 
Monitoring ............................................................................................................... 27 
13.2. 
Pre-Trial Monitoring Procedures ............................................................................. 28 
13.2.1. Selection of Monitors ......................................................................................... 28 
13.2.2. Study Initiation Visit (SIV) ................................................................................... 28 
13.3. 
Interim Monitoring Visits ........................................................................................ 28 
13.4. 
Frequency of Monitoring Visits ............................................................................... 29 

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13.5. 
Close-out Visit.......................................................................................................... 29 
13.6. 
Additional Auditing .................................................................................................. 29 
13.7. 
Protocol Deviations ................................................................................................. 29 
13.8. 
Clinical Events Committee ....................................................................................... 30 
13.9. 
Data Safety Monitoring Board ................................................................................ 30 
13.10. 
Investigator Device Training .................................................................................... 30 
13.11. 
Confidentiality ......................................................................................................... 30 
13.12. 
Amendment Policy .................................................................................................. 30 
14. 
REFERENCES ............................................................................................................... 30 
APPENDIX 1. 
SCHEDULE OF CLINICAL ASSESSMENTS ............................................... 32 
 
 

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OCS™ LIVER DCD TRIAL SYNOPSIS 
Protocol Title 
Prospective Trial to Evaluate the Effectiveness of The Portable Organ Care System (OCS™) Liver 
for Preserving, Optimizing and Assessing Currently Seldom Utilized DCD Donor Livers for 
Transplantation (OCS™ Liver DCD Trial) 
Objectives 
To evaluate the safety and effectiveness of the OCS™ Liver to preserve, optimize the condition 
and assess livers from DCD donors that currently are seldom used for liver transplants due to 
limitations of cold static storage with extended warm ischemic time and older donors.  
Trial Design 
Prospective, pivotal, single-arm  
 Trial Size 
A maximum of 25 participating sites to enroll 130 transplanted liver recipients from DCD donors 
Donor Liver Eligibility 
Criteria 
Inclusion 
• 
Maastricht Category III DCD donor, defined as expected death after the withdrawal of 
life-supportive therapy (WLST);  
 
AND 
 
• 
Donor age 18-55 years and warm ischemic time (WIT) > 30 and ≤ 120 minutes, with WIT 
defined as time from withdrawal of life support to donor liver flush in the donor.  
 
The final clinical decision whether to accept or reject a donor liver prior to initiation of 
the OCS Liver perfusion, will be according to an individual transplant center’s internal 
clinical cut-off for the upper limit for warm ischemic time (but not to exceed 120 
minutes);  
 
OR 
 
• 
Donor age > 55 years and with WIT ≤ 120 minutes, with WIT defined as time from 
withdrawal of life support to donor liver flush in the donor.  
 
The final clinical decision whether to accept or reject a donor liver prior to initiation of 
the OCS Liver perfusion, will be according to an individual transplant center’s internal 
clinical cut-off for the upper limit for warm ischemic time (but not to exceed 120 
minutes). 
 
Exclusion 
• 
Presence of moderate or severe traumatic liver injury and livers with active bleeding 
(e.g., hematomas, laceration) 
• 
HIV and/or Hepatitis B surface antigen positive serology 
• 
Liver intended for split transplants. 
Recipient 
Eligibility Criteria 
Inclusion 
• 
Registered primary liver transplant candidate  
• 
Age ≥ 18 years old 
• 
Obtained informed consent. 
 
Exclusion 
• 
Acute, fulminant liver failure 
• 
Prior solid organ or bone marrow transplant 

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• 
Ventilator dependent on day of transplant/donor organ offer. 
Primary Effectiveness 
Endpoint 
Liver Graft Survival through 6 months post-transplant, as defined per UNOS data collection 
criteria for Graft Status after liver transplantation*. 
 
* If patient dies and the death was a result of some other factor unrelated to graft failure, the 
graft will be considered functioning not failed (https://unos.org/wp-
content/uploads/unos/Adult_TRF_Liver.pdf) 
Secondary 
Effectiveness and OCS 
Donor Liver 
Assessment Endpoints 
• 
Rate of donor liver utilization after OCS Liver perfusion, defined as the number of eligible 
donor livers that were instrumented and perfused on OCS Liver and successfully 
transplanted, divided by the number of eligible donor livers that were instrumented and 
perfused on OCS. 
• 
Incidence of ischemic biliary cholangiopathy at 6 months post-transplant; 
• 
Incidence of Early liver Allograft Dysfunction (EAD) or primary non-function, defined as 
presence of one or more of the following criteria: 
o AST level >2000 IU/l within the first 7 postoperative days (for hospitalized 
patients only) 
o Bilirubin≥10 mg/dl on postoperative day 7, ± 1 day (for hospitalized patients 
only) 
o INR ≥ 1.6 on postoperative day 7, ± 1 day (for hospitalized patients only). 
Other Endpoints 
The proportion of patient and graft survival at day 30 days, 6 months, 12 months, 24 months, 
36 months, 48 months, and 60 months. 
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 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, in the absence of immunologic or surgical causes) 
• 
Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile 
duct leaks) 
• 
Vascular complications (non-surgical hepatic artery stenosis, hepatic artery thrombosis 
and portal vein thrombosis) 
• 
Liver graft-related coagulopathy 
• 
Liver allograft infections (liver abscess, cholangitis). 
Follow-up 
Patient and graft survival will be collected for up to 5 years post-transplant; including post-
market follow-up.  
Analysis Populations 
• 
The Per Protocol (PP) Population will consist of all subjects who are transplanted in the 
study with a liver preserved on OCS and have no major protocol violations.  The primary 
analysis of effectiveness will be based on the PP Population. 
• 
The Modified Intent-to-Treat Population (mITT) will consist of all subjects who are 
transplanted in the study with a liver preserved on OCS.  The mITT population will be 
considered a sensitivity analyses of effectiveness.  The safety analysis will also be based on 
the mITT population.  
• 
The Donor Liver (DL) Population will consist of all donor livers eligible for the study that 
were instrumented on the OCS. 
Effectiveness Analysis 
The primary effectiveness endpoint will show that the 6-month graft survival rate meets an 
objective performance goal (OPG) defined as 0.765 (76.5%).  This OPG was determined based 
on the 2019 SRTR/OPTN annual data report showing that 6-month graft survival for the 

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recipients of DCD livers is 88.5%, with an 12% margin to allow for the fact that extended warm 
ischemia times and other risk factors are allowed and expected in this study.  As noted above, 
the UNOS statistic upon which the OPG is based does not include deaths that are unrelated to 
graft failure, and the primary effectiveness endpoint will be defined similarly to the UNOS 
national statistics. 
The formal statistical hypothesis test is as follows: 
H0:  πOCS liver ≤ 0.765, and 
H1:  πOCS liver > 0.765 
where πOCS liver is the 6-month graft survival rate for organs preserved on the OCS Liver 
System. 
The primary 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 
lower bound of confidence interval should be greater than 0.765 to reject the null hypothesis 
H0.  
If any patient has missing 6-month graft survival in the end of study, the Kaplan-Meier 
estimates will be used to test null hypothesis.  Subject not having 6-month graft survival will be 
censored at the date of last contact during the study.  The lower limit of Kaplan-Meier 
estimates of 95% confidence interval at 6 months should be greater than 0.765 to reject the 
null hypothesis H0. 
Each secondary effectiveness endpoint, except the rate of donor liver utilization after OCS 
perfusion, 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 rate of 
donor liver utilization after OCS perfusion will be summarized using counts and percentages and 
an exact 95% confidence interval for the true percentage based on the binomial distribution.  
This endpoint will be analyzed using the donor liver population.  
Safety Analysis 
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 will be summarized using descriptive statistics.  A 95% confidence interval for the 
mean based on the t-distribution will be presented.   
Sample Size 
Determination 
Sample size calculations are based on the following specifications: 
1. Comparison to Objective Performance Goal (OPG) 
2. Endpoint is 6-month graft survival 
3. One-sided, exact binomial test  
4. Alpha = 0.025 
5. Power = 80%   
6. True proportion = 0.88 
7. Objective Performance Goal = 0.765. 
 
Based on the above specifications, a sample size of 101 subjects is required.  The sample size 
will be increased to 130 to allow for a sufficient number of subjects in the per protocol 
population. 
Trial Sponsor 
TransMedics, Inc. 
200 Minuteman Road, Suite 302 
Andover, MA, USA 01810 

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1. 
INTRODUCTION AND BACKGROUND 
Today, liver transplantation is universally accepted as the only treatment option for end-stage 
liver disease, acute fulminant hepatic failure, hepatocellular carcinoma, hilar 
cholangiocarcinoma and several metabolic disorders.  However, the availability of donor liver 
allografts has not kept pace with the demand.  For example, in the 2019 SRTR/OPTN Annual 
Report, there were 13,239 candidates on the liver transplant waiting list, with only 7,630 
transplants performed in that same year.  These realities have led to efforts to expand the 
existing deceased donor pool, including the use of donors after circulatory death (DCD).   
However, early experience with DCD livers was not favorable, as prolonged donor warm 
ischemia time (DWIT) and ischemia-reperfusion injury associated with cold storage likely played 
a large role in the high rate of primary non-function, hepatic artery thrombosis, ischemic 
cholangiopathy, and allograft failure (Jadlowiec and Taner, 2016).  There have been several 
large retrospective analyses which have identified DCD donor-related variables associated with 
recipient outcomes. 
Mateo, et al. (2006) performed an analysis of the UNOS database comparing recipients of DCD 
donors to DBD donors.  The DCD group was comprised of 367 liver grafts from DCD donors over 
the years 1996-2003, while the control group comprised 33,111 DBD donor livers during that 
same time period.  Overall graft survival from DCD donors were significantly inferior to those 
from DBD donors, with the one-year graft survival for DCD donors at 71% compared to 80% for 
DBD donors.  In this study, the authors considered DCD donor livers with DWIT ≤ 30 minutes to 
be “low risk” and those with DWIT > 30 minutes to be “high risk.”  
Mathur, et al. (2010) used data from the Scientific Registry of Transplant Recipients (SRTR) to 
investigate donor and recipient risk factors associated with inferior DCD outcomes.  A 
retrospective cohort of 1,567 recipients of DCD liver transplants was obtained.  Recipients were 
transplanted in the years 2001-2009.  Notably, the mean donor age in this study was 35.2 ± 
15.4 years, the mean cold ischemia time was 7.5 hours and the mean donor warm ischemia 
time (DWIT) was 16 minutes.  Significant increases in graft failure were noted with: DWIT ≥ 35 
minutes (HR 1.84, p=0.002), donor age 50-60 years (HR= 1.39, p=0.0047) and donor age ≥ 60 
(HR 1.88, p=0.0011).  This study illustrates the donor WIT distribution among the 1,567 
recipients.  Only 3.8% of the DCD liver transplant recipients had grafts transplanted with donor 
warm ischemia times greater than 35 minutes. 
Eren, et al. (2016) published a review of studies to date on DCD liver transplants, including a 
summary table of published single center studies on outcomes of recipients of DCD livers 
compared to DBD livers.  The majority of studies, published from 2003-2005 had mean donor 
age less than 40 years and donor WIT less than 25 minutes.  The majority of studies showed 
that donor age > 50 years and DWIT > 30 minutes are risk factors for graft failure associated 
with DCD liver transplants. 
1.1. 
Current Status of DCD Liver Transplants in the U.S. 
The 2019 OPTN/SRTR Annual report demonstrates that DCD liver transplants are rarely 
performed in the U.S. (Kim, et al., 2019).  Of the 7483 liver transplants in 2017, only 514 (6.9%) 
were from DCD donors.  Furthermore, there is a large pool of unutilized DCD donors.  In 2017, 
the percentage of livers not transplanted out of all DCD donors was 30%, compared to 9% for 

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DBD donors.  The most recent report provides the nationwide average graft survival for all 
recipients of DCD liver transplants.  As shown in Figure 1 below, at six months post-transplant, 
graft survival for DCD livers was 88.5%, compared to 91.5% for DBD recipients. 
Figure 1: 
Graft survival for DCD and DBD liver grafts through 5 years post-transplant 
from OPTN national data (Figure LI 66 from Kim, et al., 2019) 
 
 
However, it must be emphasized that the national averages reflect standard of care DCD liver 
transplants in which WIT < 30 minutes and donor age and other risk factors are very carefully 
managed.  There is an unmet need for new technologies that can expand the donor pool and 
allow improved utilization of DCD livers with acceptable clinical outcomes to balance the 
growing demand for liver transplantation and lack of viable therapies for these patients with 
end-stage liver disease.  The purpose of this study is to explore the use of the OCS Liver System 
to preserve, optimize the condition and assess DCD livers that are currently not utilized for liver 
transplantation in the U.S. today.  If successful, this study will demonstrate that the OCS Liver 
System can be used to expand the donor pool and allow more life-saving liver transplants to be 
available for patients on the waiting list. 
2. 
REPORTS OF PRIOR 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 

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(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 were also provided in the OCS Liver PROTECT Trial G140192 that 
demonstrated the safety, suitability, and performance of the OCS Liver System for preservation 
of donor livers. 
The design of the OCS Liver System for the subject IDE is identical to that being studied under 
G140192.  The change in indication does not impact the applicability of the nonclinical 
information previously submitted to G140192.  Accordingly, new nonclinical information is not 
warranted to support initiation of the subject IDE.   
2.2. 
OCS Liver PROTECT Trial (G140192) 
The PROTECT Study is a prospective, pivotal, randomized study of the OCS Liver being 
conducted in the United States.  The objective of the study is to evaluate the effectiveness of 
the OCS to preserve and assess donor livers intended for transplantation meeting current 
standard donor liver transplant acceptance criteria and one or more of the following 
characteristics: 
• Donor age ≥ 40 years old;  
• Expected total cross clamp/cold ischemic time ≥ 6 hours; or 
• Donor after Cardiac Death (DCD donor) 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)). 
The control group received donor livers meeting the same inclusion/exclusion criteria that were 
preserved using static cold storage. T he PROTECT study is on-going and data are still being 
collected and no statistical analyses have been performed.  The PROTECT study data has been 
periodically reviewed by an independent Data Safety Monitoring Board (DSMB) and no study 
concerns have been identified. 
3. 
DEVICE DESCRIPTION 
The OCS™ Liver System is an integrated portable platform designed to maintain donor livers in a 
near physiologic, normothermic perfused state.  The OCS™ Liver System consists of: 
• The Portable Console & Monitor:  This is a compact electromechanical device that 
contains an integrated pulsatile perfusion pump, batteries, blood warmer, pressure, 
flow and saturation meters.  In addition, it has an integrated wireless monitor that 
allows the clinical operator to control and display critical perfusion parameters of 
the preserved donor Livers. 
• Single Use Sterile Perfusion Set:  At the core of the OCS Liver System is a sterile, 
biocompatible perfusion module that maintains the organ’s physiologic environment 
and has embedded sensors to optimize and monitor the Liver perfusion parameters 

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and bile production.  In addition, the perfusion module enables perfusate sampling 
in order to monitor the liver’s metabolic condition. 
• OCS Liver Bile Salts: This is sodium taurocholic acid used for infusion to the 
circulating perfusate to replenish bile salt levels in the circulating perfusate  during 
ex-vivo perfusion on the OCS Liver System. 
A detailed description of the device can be found in the OCS Liver System Instructions for Use.  
Figure 2: 
OCS Liver System 
OCS Liver Console 
OCS Liver Perfusion Set 
OCS Liver Bile Salts 
 
 
 
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 safety and effectiveness of the OCS™ Liver to preserve, optimize the condition 
and assess livers from DCD donors that currently are seldom used for liver transplants due to 
limitations of cold static storage with extended warm ischemic time and older donors.  
4.1. 
Type of the Trial 
A prospective, multi-center, single-arm controlled pivotal trial.  
4.2. 
Trial Size and Subject Follow-up 
This trial will be conducted at up to 25 institutions in the United States and will include up to 
130 transplanted liver recipients from DCD donors.  All subjects will be followed for 5 years 
post-transplant.   
4.3. 
Trial Endpoints 
4.3.1. 
Primary Effectiveness Endpoint 
Liver graft survival through 6 months post-transplant, as defined per UNOS data collection 
criteria for graft status after liver transplantation*. 

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* If patient dies and the death was a result of some other factor unrelated to graft failure, the 
graft will be considered functioning not failed (see https://unos.org/wp-
content/uploads/unos/Adult_TRF_Liver.pdf). 
4.3.2. 
Secondary Effectiveness Endpoints 
• Rate of donor liver utilization after OCS Liver perfusion, defined as the number of 
eligible donor liver that were instrumented and perfused on OCS Liver and successfully 
transplanted, divided by the number of eligible donor livers that were instrumented and 
perfused on OCS.  
• Incidence of ischemic biliary cholangiopathy at 6 months post-transplant. 
• Incidence of Early liver Allograft Dysfunction (EAD) or primary non-function, defined as 
presence of one or more of the following criteria: 
o AST level >2000 IU/l within the first 7 postoperative days (Day 7 for hospitalized 
patients only) 
o Bilirubin≥10 mg/dl on postoperative day 7, ± 1 day (Day 7 for hospitalized 
patients only) 
o INR ≥ 1.6 on postoperative day 7, ± 1 day (Day 7 for hospitalized patients only). 
4.3.3. 
Other Endpoints 
• The proportion of patient and graft survival at Day 30, 6 months, 12 months, 24 months, 
36 months, 48 months, and 60 months. 
4.3.4. 
Safety Endpoint 
Safety will be analyzed 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 liver graft-related serious adverse events through the 30 days post-liver 
transplant (per subject, consisting of the following events; at most one per type per person): 
• Primary non-function (defined as irreversible graft dysfunction requiring emergency 
liver re-transplantation or death, in the absence of immunologic or surgical causes) 
• Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile duct 
leaks) 
• Vascular complications (non-surgical hepatic artery stenosis, hepatic artery thrombosis 
and portal vein thrombosis) 
• Liver graft-related coagulopathy 
• Liver allograft infections (liver abscess, cholangitis, etc.). 
5. 
TRIAL POPULATION  
Patients with end-stage liver disease requiring liver transplantation.  

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5.1. 
Donor Eligibility Criteria 
5.1.1. 
Donor Inclusion Criteria 
• Maastricht Category III DCD donor, defined as expected death after the withdrawal of 
life-supportive therapy (WLST);  
 
AND 
 
• Donor age 18-55 years and warm ischemic time (WIT) > 30 and ≤ 120 minutes, with WIT 
defined as time from withdrawal of life support to donor liver flush in the donor.  
 
The final clinical decision whether to accept or reject a donor liver prior to initiation of 
the OCS Liver perfusion, will be according to an individual transplant center’s internal 
clinical cut-off for the upper limit for warm ischemic time (but not to exceed 120 
minutes);  
 
 
OR 
 
• Donor age > 55 years and with WIT ≤ 120 minutes, with WIT defined as time from 
withdrawal of life support to donor liver flush in the donor.  
 
The final clinical decision whether to accept or reject a donor liver prior to initiation of 
the OCS Liver perfusion, will be according to an individual transplant center’s internal 
clinical cut-off for the upper limit for warm ischemic time (but not to exceed 120 
minutes). 
 
5.1.2. 
Donor Exclusion Criteria 
Donor livers will be excluded if they meet any of the following criteria: 
• Presence of moderate or severe traumatic liver injury and livers with active bleeding 
(e.g., hematomas, laceration) 
• HIV and/or Hepatitis B surface antigen positive serology 
• Liver intended for split transplants. 
5.2. 
Recipient Eligibility Criteria 
5.2.1. 
Recipient Inclusion Criteria 
Recipients are required to meet all the following criteria on the day of transplant: 
• Registered primary liver transplant candidate  
• Age ≥ 18 years old 
• Obtained informed consent.  

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5.2.2. 
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 
• Ventilator dependent on day of transplant/donor organ offer. 
5.3. 
Screening Procedures 
5.3.1. 
Recipient – Screening and Enrollment  
Recipients will be screened for potential eligibility for the trial.  Those patients who initially 
appear eligible will have the trial thoroughly explained to them and will be asked for consent 
for participation.   
A recipient will be considered enrolled in the trial only when a matching DCD liver is identified, 
procured, preserved on OCS and transplanted into a consented eligible recipient.  Data will be 
collected according to the Schedule of Assessments found in Appendix 1. 
5.3.2. 
Donor Liver – Initial Screening, Retrieval and OCS Preservation 
The retrieval team will evaluate the donor and the quality and suitability of the liver for 
transplantation in general and for inclusion in the trial.  After final evaluation of the donor liver 
in the donor’s abdomen and upon acceptance into the trial, the investigators will retrieve and 
preserve the donor liver using the OCS Liver System according to the Instructions for Use.  
Data collected that relates to organ retrieval, OCS preservation and assessment will be 
collected according to the Schedule of Assessments in Appendix 1. 
5.3.3. 
 Donor Liver Assessment on OCS Liver System and Acceptance for Transplantation 
All donor livers that are preserved on OCS Liver System MUST meet all three conditions of the 
following clinical criteria to be eligible for transplantation into a recipient: 
• DCD Donor livers on OCS Liver System are deemed to be clinically acceptable for 
transplantation by the Site Principal Investigator based on their clinical judgment and 
interpretation of OCS Liver System’s hemodynamic and metabolic parameters; 
• OCS Liver System perfusate lactate levels that are trending down on OCS Liver System 
from initial sample to final sample taken during OCS Liver perfusion and below 10 
mmol/l at the end of OCS perfusion; 
• Able to achieve and maintain OCS Liver System perfusion parameters for the organ; 
mean Hepatic Artery Pressures (HAP), Hepatic Artery Flows (HAF) , mean Portal Vein 
Pressure (PVP) and Portal Vein Flow (PVF) as recommended in the IFU. 
Any decision to turn down livers after they have been retrieved, preserved and assessed on 
OCS™ Liver System should be made by the Site Principal Investigator (or should be made in 
consultation with the site Principal Investigator), and the clinical reason for turning down the 
donor liver for transplantation will be documented. 

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5.4. 
Enrolled DCD Donor Livers and Recipients  
• Recipient Enrollment: for the assessment of post-transplant outcomes, a consented 
potential recipient will be considered enrolled in the trial when they are transplanted 
with any DCD donor liver preserved and assessed on OCS Liver System. 
• DCD Donor Liver Enrollment: for the assessment of donor liver utilization rate, a DCD 
donor liver will be considered enrolled in the trial if it meets the eligibility criteria for 
donor liver inclusion and was instrumented on the OCS Liver System for ex-vivo 
perfusion and assessment.  
6. 
DATA COLLECTION AND FOLLOW-UP 
Data collection will include: 
Donor: 
• Eligibility information 
• Demographics, Medical and Social Histories, Cause of Death 
• Liver assessment including warm ischemic time, cross clamp and flush times 
• OCS preservation parameters 
• OCS liver enzymes and lactate levels 
• Device malfunction (if applicable) 
• Non-transplant reason(s) (if applicable). 
Recipient: 
• Eligibility information 
• Demographics, Medical History and risk factors 
• Transplant details, including documentation of reconstruction of any accessory vessels 
or anatomical abnormalities prior to perfusion 
• Lab assessments: 
o AST – from ICU admission through Day 7 ± 1 day (for hospitalized patients only) 
o Bilirubin – Day 7 ± 1 day (for hospitalized patients only) 
o INR – Day 7 ± 1 day (for hospitalized patients only) 
• Subject and graft survival from Day 30 through Month 60.  Follow-up at these 
timepoints may be done via telephone and/or review of the subject’s medical record. 
• Presence/absence of ischemic cholangiopathy at 6 months 
• Liver graft-related serious adverse events up to 30 days post-transplant 
• Serious adverse events up to 30 days post-transplant 
• Protocol deviations (if applicable). 

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See the Schedule of Assessments in Appendix 1 for details and time windows for data collection 
parameters. 
7. 
EVALUATION OF ADVERSE EVENTS 
In this trial, only liver graft-related serious adverse events (LGRSAEs) as defined in Section 7.1 
below and serious adverse events (SAEs) will be collected through Day 30 post-transplant.  
7.1. 
Evaluation of Liver Graft-Related Serious Adverse Events 
Liver Graft-Related Serious Adverse Events are those which have any untoward effect on the 
health or safety of the patient and that are related to the transplanted liver (except for acute 
rejection).  LGRSAEs 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 and will consist only 
of the following events:  
• Primary non-function (defined as irreversible graft dysfunction requiring emergency 
liver re-transplantation or death, in the absence of immunologic or surgical causes); 
• Ischemic biliary complications (ischemic biliary strictures, and non-anastomotic bile duct 
leaks); 
• Vascular complications (non-surgical hepatic artery stenosis, hepatic artery thrombosis 
and portal vein thrombosis); 
• Liver allograft infections (liver abscess, cholangitis).   
• Liver graft-related coagulopathy. 
All LGRSAEs will be followed until resolution or stabilization of the event.  
7.2. 
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. 
 
 

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7.3. 
Anticipated Adverse Events 
Anticipated adverse events that are related to liver transplantation (and not specific to the OCS 
device) includes, but is not limited to:
• Acute rejection 
• Atrial and ventricular arrhythmias 
• Bleeding 
• Hemodynamic instability 
• Death 
• Fever 
• Early liver allograft dysfunction (EAD) 
• Respiratory failure 
• 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 
• Hyperammonemia 
• 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. 
 
 

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7.4. 
Unanticipated Adverse Device Effect (UADE)   
An UADE is 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. 
Unanticipated adverse device effects (UADE) should be reported to TransMedics, Inc., 
preferably within 48 hours of the time the investigator learns of the event, but in no case later 
than 5 working days.   
7.5. 
Recording and Reporting of Adverse Event 
All LGRSAEs and SAEs will be collected through 30 days post-transplant and should be entered 
as soon as possible into the study database.  For all LGRSAEs and SAEs, the investigator may be 
asked to supply any additional source documents that may be deemed necessary by the 
Sponsor.   
7.5.1. 
Relationship of an LGRSAE or SAE to OCS Liver  
The investigator will assess the relationship of the event to the OCS method of preservation.  
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 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 the adverse event. 
• Unlikely Related:  There is a temporal relationship with preservation with the OCS™ 
Liver 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 and the 
adverse event. 
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. 
7.6. 
Pre-Existing Conditions 
Pre-existing diseases or conditions will not be reported as adverse events. 

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8. 
STATISTICAL METHODS 
8.1. 
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 percentage. 
All statistical procedures will be performed using SAS Version 9.3 or higher. 
8.2. 
Analysis Populations 
Data analysis and summarization will be performed using the analysis populations defined 
below. 
8.2.1. 
Per Protocol Population 
The Per Protocol (PP) population will consist of all subjects who are transplanted in the study 
with a liver preserved on OCS Liver System and have no major protocol deviations.  The PP 
population will be used for primary analysis of effectiveness. 
8.2.2. 
Modified Intent-to-Treat Population 
The modified Intent-to-Treat (mITT) population will include subjects are who transplanted in 
the study with a liver preserved on OCS Liver System.  The mITT population will be used for the 
sensitivity analysis of effectiveness. The safety analysis will also be based on the mITT 
population. 
8.2.3. 
Donor Liver Population 
The Donor Liver Population will consist of all donor livers eligible for the study that were 
instrumented on the OCS. The Donor Liver Population will be used for rate of donor liver 
utilization after OCS Liver perfusion. 
8.3. 
Data Analysis 
The statistical analysis plan (SAP) provides 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. 
8.3.1. 
 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). 
8.3.2. 
 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), 

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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. 
8.3.3. 
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.  
8.3.4. 
Effectiveness Analysis 
8.3.4.1. 
Primary Endpoint 
The primary endpoint for this study is Liver Graft Survival through 6 months post-transplant, as 
defined per UNOS data collection criteria for Graft Status after liver transplantation*. 
* If patient dies and the death was a result of some other factor unrelated to graft 
failure, the graft will be considered functioning not failed (https://unos.org/wp-
content/uploads/unos/Adult_TRF_Liver.pdf. 
The primary effectiveness endpoint will show that the 6-month graft survival rate meets a 
performance goal defined as 0.765 (76.5%).  This OPG was determined based on the 2019 
SRTR/OPTN annual data report showing that 6-month graft survival for the recipients of DCD 
livers is 88.5%, with an 12% margin to allow for the fact that extended warm ischemia times 
and other risk factors are allowed and expected in this study.  As noted above, the UNOS 
statistic upon which the OPG is based does not include deaths that are unrelated to graft 
failure, and the primary effectiveness endpoint will be defined similarly to the UNOS national 
statistics. 
The formal statistical hypothesis test is as follows: 
H0:  πOCS liver ≤ 0.765, and 
H1:  πOCS liver > 0.765 
where πOCS liver is the 6-month graft survival rate for organs preserved on the OCS Liver 
System. 
The primary 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 
lower limit of confidence interval should be greater than 0.765 to reject the null hypothesis H0.  
If any patient has missing 6-month graft survival in the end of study, the Kaplan-Meier 
estimates will be used to test null hypothesis.  Subject not having 6-month graft survival will be 
censored at the date of last contact during the study.  The lower limit of Kaplan-Meier 
estimates of 95% confidence interval at 6 months should be greater than 0.765 to reject the 
null hypothesis H0.  Tipping point analysis will be provided for sensitivity analysis (Section 8.5). 

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8.3.4.2. 
Secondary Endpoints 
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, except the rate of donor liver utilization, will be 
analyzed using the PP population as primary analysis and using the mITT population as 
sensitivity analysis. 
8.3.4.3. 
 Other Endpoints 
The proportion of patient and graft survival at day 30, 6 months, 12 months, 24 months, 36 
months, 48 months and 60 months will be calculated with 95% confidence interval.  
The other endpoints will be analyzed with both PP population and mITT population. 
8.4. 
Safety Analysis 
The safety endpoint will be summarized using descriptive statistics.  A 95% confidence interval 
for the mean based on the t-distribution will be presented.  
8.5. 
 Treatment of Missing Data 
A tipping point analysis of the primary endpoint will be performed in the following manner for 
the PP population and mITT population.  Initially the analysis will be performed with all missing 
values for the primary endpoint defined to be successes (i.e., not graft failures).  If this analysis 
results in rejection of the null hypothesis, the analysis will continue by setting one missing value 
to be a graft failure and all of the other missing values to be successes.  This procedure will 
continue in the same manner, each time setting one additional missing value to be a failure, 
until the first time that the analysis does not result in rejection of the null hypothesis.  This 
point is referred to as the tipping point, the point at which conclusions change from being 
favorable to the treatment to being unfavorable. 
No other data imputation is planned for effectiveness and safety measures. 
8.6. 
Sample Size Determination 
Sample size calculations are based on the following specifications: 
• Comparison to Objective Performance Goal (OPG) 
• Endpoint is 6-month graft survival 
• One-sided, exact binomial confidence interval 
• Alpha = 0.025 
• Power = 80%   
• True proportion = 0.88 
• Objective Performance Goal = 0.765.  

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Based on the above specifications, a sample size of 101 transplanted subjects with DCD donor 
liver preserved on OCS Liver System is required.  The sample size will be increased to 130 to 
allow for a sufficient number of subjects in the per protocol population. 
8.7. 
Stopping Rule 
The following stopping rules are to be used in the study: 
1. Stop the study if and when there are 4 deaths before Day 30 or initial hospital discharge 
post-transplant (whichever is later) among the first 10 recipients; or 
2. Stop the study if and when there are 4 incidences of primary non-function within the 
first 7 days post-transplant among the first 10 recipients; or 
3. Stop the study if and when there are 7 deaths before Day 30 or initial hospital discharge 
post-transplant (whichever is later) among the first 20 recipients; or 
4. Stop the study if and when there are 7 incidences of primary non-function within the 
first 7 days post-transplant among the first 20 recipients. 
This rule is based on the following:  Let p denote the true proportion of recipients transplanted 
with an OCS-preserved liver for whom the recipient does not survive until Day 30 or initial 
hospital discharge post-transplant (whichever is later) or let p denote the true proportion of 
recipients transplanted with an OCS-preserved liver for whom the recipient experiences 
primary non-function of the graft within the first 7 days post-transplant.  Stop the study (based 
on 10 or 20 recipients) if there is statistical evidence that the true value of p exceeds 0.12, i.e., 
if the  exact 97.5% lower confidence bound for p  exceeds 0.12 (12%). The above statistical 
stopping rules would be applied to all combinations of number of deaths and incidences of PNF 
and number of recipients that were observed in the study.  
 
 
TransMedics will be responsible for implementing the stopping rule and will notify the DSMB as 
if the stopping rules are met.  In addition, the DSMB will review the rules at the scheduled 
DSMB meetings. 
9. 
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.  
9.1. 
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 

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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.  However, since this study includes donor livers 
currently seldom utilized for transplantation, the potential additional chance for a liver 
is an added benefit.  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.  This trial is designed to utilize livers 
that are seldom accepted for transplantation using cold storage preservation.  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. 
9.2. 
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 and studies of the OCS Liver System outside the U.S., 
have demonstrated the safety of the device. 
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.  

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• 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, this will be the second IDE trial involving the OCS Liver System.  The first study, the OCS 
Liver PROTECT study (G140192) has not raised any questions regarding safety of the device. 
9.2.1. 
Potential Benefits 
The low utilization of donor livers from DCD donors has contributed to the severe shortage of 
donor livers.  The OPTN/SRTR Annual Report indicates that, 12 months after listing, 21% of 
patients will die or become delisted and only 42% of subjects listed will receive a transplant 
(Kim, et al., 2019). 
The OCS Liver System’s preservation and assessment capabilities could potentially increase the 
rate of utilization of DCD donor livers that are seldom used due to the limitations of cold 
storage techniques.  Utilization of these donor livers could improve the chances of waiting list 
recipients to receive a lifesaving liver transplant 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. 
9.2.2. 
Risk: Benefit Ratio 
Based on the above, the benefits of using OCS Liver System technology to preserve and assess 
DCD livers to ensure their suitability for liver transplantation outweigh the potential risks to trial 
subjects.  
10. 
DEVICE/SITE MANAGEMENT 
10.1. 
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. 
10.2. 
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.   

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10.3. 
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. 
10.4. 
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. 
11. 
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. 
11.1. 
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.  
11.2. 
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.   
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. 

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12. 
DATA COLLECTION/RECORDS/REPORTS 
12.1. 
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. 
12.2. 
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.   

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• 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. 
12.3. 
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.  
12.4. 
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. 
13. 
CLINICAL MONITORING 
13.1. 
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 

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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. 
13.2. 
Pre-Trial Monitoring Procedures 
13.2.1. 
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. 
13.2.2. 
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.  
13.3. 
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. 

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• 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. 
13.4. 
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.   
13.5. 
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. 
13.6. 
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. 
13.7. 
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 
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.  
 

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13.8. 
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. 
13.9. 
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.  
13.10. 
Investigator Device Training 
Device training will be provided to all new investigators and support staff that have no 
experience with the OCS Liver device 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.  
13.11. 
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.   
13.12. 
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.  
14. 
REFERENCES 
1. Eren, et al. Donations After Circulatory Death in Liver Transplant. Exp Clin Transplant; 2016 
October; 14(5); 463-470. 
2. Israni, et al. OPTN/SRTR 2017 Annual Data Report: Deceased Organ Donation. Scientific 
Registry of Transplant Recipients; 2019. 
3. Jadlowiec and Taner. Liver transplantation: Current status and challenges. World J 
Gastroenterol; 2016 May 14; 22(18): 4438-4445. 

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4. Kim, et al., OPTN/SRTR 2017 Annual Data Report: Liver. Scientific Registry of Transplant 
Recipients; 2019. 
5. Mateo, et al. Risk Factors for Graft Survival After Liver Transplantation from Donation After 
Cardiac Death Donors: An Analysis of OPTN/UNOS Data. American Journal of 
Transplantation; 2006; 6: 791–796. 
6. Mathur, et al. Donation after Cardiac Death Liver Transplantation: Predictors of Outcome. 
American Journal of Transplantation; 2010; 10: 2512–2519. 

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APPENDIX 1. 
SCHEDULE OF CLINICAL ASSESSMENTS 
 
Donor Data Collection Overview 
Eligibility & ID 
X 
Demographics/Characteristics 
X 
Donor Cause of Death 
X 
Donor Medical & Social History 
X 
Warm Ischemic Time 
X 
Donor Liver Assessment 
X 
Donor Cross Clamp Time and Flush Detail 
X 
OCS Preservation Parameters 
X 
OCS Liver Enzymes & Lactate Levels 
X 
Device Malfunction (if applicable) 
X 
Non-transplant Reason(s) (if applicable) 
X 
 
 
 

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Recipients Data Collection Overview 
 
Day 01  
Day 1-62 
Day 7 
Day 30 
± 7 days 
Month 6 
± 1  
Month 12 
± 1  
Month 24 
± 2 
Month 36 
± 2  
Month 48 
± 2  
Month 60 
± 2  
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
 
 
Demographics and 
Medical Hx 
X 
 
 
 
 
 
 
 
 
 
Tx Details 
X 
 
 
 
 
 
 
 
 
 
AST 
X 
X3 
X3 
 
 
 
 
 
 
 
Bilirubin 
 
 
X3 
 
 
 
 
 
 
 
INR 
 
 
X3 
 
 
 
 
 
 
 
Patient survival 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Graft survival 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Ischemic 
cholangiopathy 
surveillance 
 
 
 
 
X 
 
 
 
 
 
LGRSAEs 
X 
X 
X 
X 
 
 
 
 
 
 
SAEs 
X 
X 
X 
X 
 
 
 
 
 
 
ICU Stay 
X 
X 
X 
X 
 
 
 
 
 
 
Initial Hospital 
Admission 
X 
X 
X 
X 
 
 
 
 
 
 
1 Day 0 is defined as date of transplant and ICU admission immediately post-liver transplantation. 
2 Day 1 starts 24 hours after ICU admission date and time. 
3 Only if subject is still hospitalized post-transplant. All discharged patients will not be required to have these labs collected.