Clinical Trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System (OCS™) Heart For Resuscitation, Preservation and Assessment of Hearts From Donors After Circulatory Death (DCD Heart Trial)
Phase: NA
Conditions: Heart Transplant
Sponsor: TransMedics

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OCS Heart DCD Revision 3.0 
 
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INVESTIGATIONAL PLAN/PROTOCOL 
 
Clinical Trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System (OCS™) 
Heart For Resuscitation, Preservation and Assessment of Hearts from Donors after Circulatory 
Death (DCD Heart Trial) 
 
 
 
 
 
Number OCS-CAR-03202019 
 
 
 
April 8, 2020 
Revision 3.0 
 
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 
20-March-2019 
2.0 
18-December-2019 
3.0 
8-April-2020  
(updated 19-May-2020) 

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TABLE OF CONTENTS 
OCS™ DCD HEART SYNOPSIS ...................................................................................................... 5 
1. 
INTRODUCTION AND BACKGROUND INFORMATION ..................................................... 10 
1.1. 
Heart Transplantation and Current Clinical Challenges: ....................................... 10 
2. 
SUMMARY OF PRIOR TESTING AND INVESTIGATIONS ................................................... 14 
2.1. 
OCS Heart Preclinical Testing ............................................................................... 14 
2.2. 
Preclinical Animal Testing of OCS Heart System for DCD hearts ........................... 14 
2.2.1. 
Iyer, et al., 2015 ..................................................................................... 14 
2.2.2. 
García Sáez, et al., 2015 ......................................................................... 15 
2.3. 
OCS Heart Clinical Testing for DCD Hearts Outside the U.S. .................................. 16 
2.3.1. 
Messer, et al., 2017................................................................................ 16 
2.3.2. 
Dhital, et al. (2015 and 2017) ................................................................. 17 
2.3.3. 
García Sáez, et al. (2016, 2017) .............................................................. 18 
2.4. 
Additional Clinical Studies of the OCS Heart System for Standard Criteria and 
Extended Criteria Donor Hearts ........................................................................... 18 
2.5. 
Overall Summary of Clinical Data to Support Initiation of OCS Heart DCD Trial .... 19 
3. 
DEVICE DESCRIPTION ...................................................................................................... 20 
3.1. 
Description of Major Components ....................................................................... 20 
3.1.1. 
OCS Heart Console ................................................................................. 20 
3.1.2. 
Heart Perfusion Set (HPS)....................................................................... 20 
3.1.3. 
OCS Heart Solution Set ........................................................................... 21 
3.1.4. 
Mode of Action - Overview .................................................................... 21 
4. 
TRIAL OBJECTIVES ........................................................................................................... 22 
4.1. 
Trial Design .......................................................................................................... 22 
4.2. 
Trial Size and Subject Follow-up ........................................................................... 23 
5. 
TRIAL ENDPOINTS ........................................................................................................... 23 
5.1. 
Primary Endpoint ................................................................................................. 23 
5.2. 
Secondary Endpoint ............................................................................................. 23 
5.3. 
Safety .................................................................................................................. 24 
5.4. 
Other Endpoints .................................................................................................. 24 
6. 
TRIAL POPULATION ........................................................................................................ 24 
6.1. 
DCD Donor Eligibility Criteria ............................................................................... 24 
6.2. 
Standard of Care Donor Eligibility Criteria ............................................................ 25 
6.3. 
Recipient Eligibility Criteria .................................................................................. 25 
6.4. 
Screening and Treatment ..................................................................................... 25 
6.5. 
DCD Heart Subject Enrollment and Screen Failures .............................................. 26 
7. 
PRE-OPERATIVE TRIAL PROCEDURES .............................................................................. 27 
7.1. 
Subject Identification ........................................................................................... 27 

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7.2. 
Recipient Day of Transplant Assessment .............................................................. 27 
7.3. 
Donor Screening and Acceptance for SOC Hearts ................................................. 27 
7.4. 
Donor Screening and Acceptance for DCD Hearts ................................................ 27 
7.5. 
DCD Donor Heart Retrieval and OCS Preservation and Assessment ..................... 28 
7.5.1. 
Donor Heart Acceptance/Rejection for Transplantation after OCS 
Preservation .......................................................................................... 28 
8. 
TRANSPLANT, IMMEDIATE POST-OPERATIVE AND LONG-TERM FOLLOW-UP FOR DCD 
HEART TRANSPLANTED RECIPIENTS ONLY............................................................. 28 
8.1. 
Transplant Details ................................................................................................ 28 
8.2. 
Post-transplant Functional Assessments Day 0 – Day 30 ...................................... 29 
8.3. 
Long-term Follow-up: 6 and 12 months ............................................................... 29 
8.4. 
Evaluation of Adverse Events for DCD Heart Recipients Only ............................... 29 
8.4.1. 
Serious Adverse Events (SAEs) ............................................................... 29 
8.4.2. 
Heart Graft-Related SAEs (HGRSAEs) ...................................................... 30 
8.4.3. 
Unanticipated Adverse Device Effect (UADE) ......................................... 30 
8.4.4. 
Anticipated SAEs .................................................................................... 30 
8.4.5. 
Reporting of Adverse Events .................................................................. 31 
8.4.6. 
Relationship of an SAE or HGRSAE to OCS Heart System ........................ 31 
8.4.7. 
Severity .................................................................................................. 32 
8.4.8. 
Pre-Existing Conditions .......................................................................... 32 
9. 
OCS HEART TRAINING RUNS ........................................................................................... 32 
10. 
STATISTICAL METHODS ................................................................................................... 32 
10.1. General 32 
10.2. Analysis Populations ............................................................................................ 33 
10.2.1. DCD Heart Transplanted Recipient Population ....................................... 33 
10.2.2. OCS Heart Population ............................................................................ 33 
10.2.3. SOC Heart Transplanted Recipient Population ....................................... 33 
10.3. Statistical Analysis................................................................................................ 33 
10.3.1. Primary Endpoint ................................................................................... 33 
10.3.2. Secondary and Other Endpoints ............................................................. 34 
10.4. Safety (DCD Heart Transplanted Recipient Population Only) ................................ 35 
10.5. Sample Size Determination .................................................................................. 35 
11. 
RISK ANALYSIS ................................................................................................................ 36 
11.1. Potential Risks ..................................................................................................... 36 
11.2. Manner in Which the Potential Risks Have Been Minimized ................................ 37 
11.3. Potential Benefits ................................................................................................ 38 
11.4. Risks Benefit Ratio ............................................................................................... 38 
12. 
DEVICE/SITE MANAGEMENT .......................................................................................... 38 
12.1. Packaging and Labeling ........................................................................................ 38 
12.2. Storage 38 
12.3. Accountability ...................................................................................................... 38 
12.4. Device Complaints and Malfunctions ................................................................... 39 

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13. 
REGULATORY/ETHICS ..................................................................................................... 39 
13.1. Institutional Review Boards (IRB) ......................................................................... 39 
13.2. Informed Consent ................................................................................................ 39 
14. 
DATA COLLECTION/RECORDS/REPORTS ......................................................................... 39 
14.1. Investigator Records ............................................................................................ 39 
14.2. Investigator Reports ............................................................................................ 40 
14.3. Data Collection .................................................................................................... 41 
14.4. Source Documents ............................................................................................... 41 
14.5. Archiving of Records ............................................................................................ 41 
15. 
CLINICAL MONITORING .................................................................................................. 41 
15.1. Monitoring .......................................................................................................... 41 
15.2. Site Initiation Visit ................................................................................................ 42 
15.3. Periodic Monitoring Visits .................................................................................... 42 
15.4. Frequency of Monitoring Visits ............................................................................ 42 
15.5. Study Close-out Visit ............................................................................................ 43 
15.6. Protocol Deviations.............................................................................................. 43 
15.7. Clinical Events Committee (CEC) .......................................................................... 43 
15.8. Data Safety Monitoring Board & Stopping Rules .................................................. 43 
15.9. Investigator Training ............................................................................................ 44 
16. 
CONFIDENTIALITY ........................................................................................................... 44 
17. 
AMENDMENT POLICY ..................................................................................................... 44 
18. 
REFERENCES .................................................................................................................... 45 
APPENDIX 1. 
ISHLT CONSENSUS MANUSCRIPT HEART PRIMARY GRAFT DYSFUNCTION 
(PGD) (KOBASHIGAWA, ET AL., 2014) .................................................................... 47 
APPENDIX 2. 
SCHEDULE OF CLINICAL ASSESSMENTS ................................................. 48 
APPENDIX 3. 
DRAFT PATIENT INFORMED CONSENT FORM TEMPLATE ...................... 49 
APPENDIX 4. 
DRAFT ELECTRONIC CASE REPORT FORMS ............................................ 50 
 

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OCS™ DCD HEART SYNOPSIS 
 
Protocol Title 
Trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System (OCS™) Heart for 
Resuscitating, Preserving and Assessing Hearts Donated after Circulatory Death (OCS™ Heart U.S. DCD 
Heart Trial) 
Objectives 
To evaluate the effectiveness of the OCS Heart System to resuscitate, preserve and assess hearts donated 
after circulatory death for transplantation to increase the pool of donor hearts available for 
transplantation. 
Trial Design 
A prospective, randomized and concurrent controlled, non-inferiority pivotal trial in which subjects who 
receive a DCD donor heart transplant will be compared to subjects who receive a standard criteria donor 
heart transplant (SOC1 and SOC2 - from both randomized and concurrent control groups), adjusting for 
differences in risk factors. 
 Trial Size 
A maximum of 25 participating sites with 90 transplanted DCD heart recipients and 90 standard of care 
heart transplant recipients. Follow-up data for the SOC recipients will be obtained from UNOS/OPTN 
database for U.S. heart transplant recipients. 
Screening and 
Treatment  
Primary heart transplant candidates will be screened for trial eligibility. Every eligible candidate will be 
asked to participate. Subjects will be randomized into two groups: DCD Heart Possible and SOC Heart 
Only. Subjects who are randomized into the SOC Heart Only group will have no possibility for a DCD 
Heart transplant. Subjects randomized into the DCD Heart Possible group have the possibility of receiving 
either a DCD heart preserved on OCS or an SOC donor heart, depending upon the donor match. In order 
to obtain enough subjects with DCD donor heart transplants, subjects will be randomized 3:1 to the DCD 
Heart Possible and SOC Heart Only arms, respectively. Follow-up survival data for transplanted subjects 
in the SOC Heart Transplanted Recipient (SOC1) group will be obtained from the UNOS/OPTN standard 
database for transplant recipients. Upon receiving a donor heart match and after confirmation of 
eligibility, SOC Heart transplanted recipients will have demographic information collected and will then 
exit the study and undergo standard heart transplantation according to the institution’s standard of care. 
 
In the DCD Heart Possible arm, if a screened and eligible subject is matched with an SOC donor heart 
before an eligible DCD donor heart becomes available and is transplanted, these subjects will form a 
second SOC Heart Transplanted Recipient group (SOC2). Follow-up survival data for subjects in the SOC2 
group will be obtained from the UNOS/OPTN standard database for transplant recipients. Upon receiving 
a donor heart match and after confirmation of eligibility, SOC Heart transplanted recipients will have 
demographic information collected and will then exit the study and undergo standard heart 
transplantation according to the institution’s standard of care. 
 
Data will be collected according to this protocol for subjects in the DCD Heart Possible arm who receive a 
DCD Heart match and are transplanted with the DCD heart as outlined in this protocol (DCD Heart 
Transplanted Recipient group). 
DCD Donor Heart 
Eligibility Criteria 
Inclusion 
• 
Maastricht Category III DCD donor, defined as expected death after the withdrawal of life- 
supportive therapy (WLST) 
• 
Donor age 18-49 years old inclusive 
• 
Warm ischemic time (WIT) ≤ 30 mins, with warm ischemic time defined as: Time from when 
mean systolic blood pressure (SBP) is < 50 mmHg or peripheral saturation < 70% to aortic cross-
clamp and administration of cold cardioplegia in the donor. 
 Exclusion 
• 
Previous cardiac surgery; 
• 
Known coronary artery disease; 
• 
Cardiogenic shock or myocardial infarction;  
• 
Sustained terminal EF of ≤ 50%; or  
• 
Significant valve disease except for competent bicuspid aortic valve. 
Standard Criteria 
(SOC) Donor Hearts 
Standard criteria donor hearts will be screened and determined to be eligible for transplant according to 
the standard of care at each institution  

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Recipient 
Eligibility Criteria  
Inclusion 
• 
Primary heart transplant candidates 
• 
Age ≥ 18 years old 
• 
Signed: (1) written informed consent document; (2) authorization to use and disclose protected 
health information; and (3) consent to TransMedics’ use of recipients’ UNOS/OPTN data and 
recipients’ INTERMACS data.  
Exclusion 
• 
Prior solid organ or bone marrow transplant 
• 
Chronic use of hemodialysis or diagnosis of chronic renal insufficiency 
• 
Multi-organ transplant 
• 
Investigator unwilling to randomize to either arm. 
DCD Donor Heart on 
OCS Transplant 
Criteria 
Accept for Transplantation 
Donor hearts preserved on the OCS Heart System to be maintained within the following target ranges: 
• 
Stable or downward trending lactate after initial adjustments of the OCS Heart perfusion 
parameters to achieve adequate perfusion to the donor heart 
• 
Stability of OCS Heart perfusion parameters within range: 
o AOP 40-100 mmHg 
• 
Transplanting surgeon and/or heart failure cardiologist must clinically accept the OCS perfused 
donor heart for transplant. 
 
Reject for Transplantation 
• 
Transplanting surgeon and/or heart failure cardiologist clinically unsatisfied with donor heart 
condition/performance on the OCS Heart System at final evaluation  
• 
Unstable and rising arterial lactate despite maneuvers to optimize perfusion parameters.  
 
Note: Certain donor hearts may require perfusion with parameters outside of these guidance ranges. 
Acceptance for transplantation should be primarily based on an acceptable lactate trend. 
Primary Endpoint 
• 
A non-inferiority comparison of patient survival at 6 months post-transplant between recipients of 
DCD donor hearts preserved on the OCS Heart System and recipients of standard criteria donor 
hearts preserved using cold storage (SOC1 + SOC2), adjusting for risk factors. 
Secondary Endpoint  
• 
Utilization Rate, defined as the number of eligible DCD donor hearts that met the warm ischemic 
time limit above and were instrumented on the OCS Heart System that meet the acceptance criteria 
for transplantation after OCS Heart preservation divided by the total number of eligible DCD donor 
hearts that met the warm ischemic time limit above and were instrumented on the OCS Heart 
System.  
Other Endpoints 
(Calculated for DCD 
Transplanted 
Recipients only) 
• 
Patient and graft survival at 30 days post-transplant 
• 
Patient and graft survival at 30 days and initial hospital discharge, if later than 30 days 
• 
Severe heart primary graft dysfunction (PGD) (left or right ventricle) (not including rejection or 
cardiac tamponade) according to ISHLT consensus manuscript (as defined in Appendix 1 of this 
protocol) 
• 
Use of post-transplant mechanical circulatory support (LVAD, RVAD, BiVAD) for > 72 hours 
immediately post-transplant. 
Safety Endpoint 
(Calculated for DCD 
Transplanted 
Recipients only) 
The safety endpoint is defined as the incidence of heart graft-related Serious Adverse Events (HGRSAEs) 
in the first 30 days post-heart transplantation in the DCD Heart Transplanted Recipient Population, 
defined as the following adverse events (at most one per type):  
• 
Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac 
tamponade) according to ISHLT consensus manuscript (as defined in Appendix 1 of this 
protocol). 
• 
Primary graft failure requiring retransplantation 
This endpoint is calculated for the DCD Heart Recipient population only. 
Other endpoints  
• 
Patient survival at 1 year after transplant (collected post-approval); comparison of DCD Transplanted 
recipients and standard of care recipients (SOC1 + SOC2) through UNOS/OPTN database. 

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Follow-up 
• 
All patients will be followed for 6 months pre-market. 1 year follow-up will be post-market. 
Statistical Methods 
 
The DCD Heart Transplanted Recipient Population will consist of all eligible recipients who are 
transplanted with an eligible DCD donor heart that met the warm ischemic time limit defined above, 
preserved on OCS and met the transplantability criteria. The analyses of all effectiveness and safety 
endpoints, except the utilization rate, will be based on the DCD Heart Transplanted Recipient Population.  
The OCS Heart Population will consist of all eligible donor hearts that met the warm ischemic time limit 
above and were instrumented on the OCS Heart System. The analysis of utilization rate will be based on 
the OCS Heart population. 
 
The SOC Heart Transplanted Recipient Population will consist of all recipients who received a standard 
criteria donor heart (SOC1 + SOC2 as defined in Section 6.4). 
 
The analyses of the primary endpoint and of patient survival at one year after transplant will be based on 
the DCD Heart Transplanted Recipient Population and the SOC Heart Transplanted Recipient Population.  
 
The analyses of: (1) patient and graft survival at 30 days post-transplant; (2) patient and graft survival at 
30 days and at initial hospital discharge if longer than 30 days; (3) the use of post-transplant mechanical 
circulatory support (LVAD, RVAD, and BiVAD) for > 72 hours immediately post-transplant; (4) Severe heart 
PGD (left or right ventricle) (not including rejection or cardiac tamponade) according to ISHLT consensus 
manuscript (as defined in Appendix 1 of this protocol); and (5) HGRSAEs and SAEs will be based on the 
DCD Heart Transplanted Recipient Population.  
 
Statistical Analysis  
The primary endpoint is a comparison of survival at 6 months for DCD heart transplanted recipients and 
standard criteria heart transplanted recipients (SOC1 + SOC2 as defined in Section 6.4), adjusting for 
differences in risk factors. This is a non-inferiority study.  
 
Risk Factors 
We will adjust for the known donor and recipient risk factors for mortality shown in the list below1: 
Donor Variables: 
• 
Donor Age ≥ 55 years 
• 
Gender mismatch (female donor to male recipient). 
Recipient Variables: 
• 
Age ≥ 65 
• 
LVAD, ECMO or IABP prior to transplant 
 
For continuous baseline characteristics, two-sided, two-sample t-tests will be used to test for a difference 
in means between treatment groups. For categorical baseline characteristics, the chi-square test will be 
used to test for a difference in proportions between treatment groups. We will adjust the analysis of the 
primary endpoint for any of these baseline characteristics for which there is a statistically significant 
difference (p-value < 0.15) between the treatment groups. 
 
The null and alternative hypotheses for the primary endpoint are as follows: 
H0: pSOC – pDCD ≥ 0.20 
 vs. 
H1: pSOC – pDCD < 0.20 
                                                        
1 Cardiac Donor Risk Factors Predictive of Short-Term Heart Transplant Recipient Mortality: An Analysis of the United 
Network for Organ Sharing Database. Trans Proc. 2015 Dec; 47(10): 2944-2951., Heart Transplant Survival based on 
Recipient and Donor Risk Scoring: A UNOS Database Analysis, ASAIO J., 2016; 62:297-301. Report from the American 
Society of Transplantation Conference on Donor Heart Selection in Adult Cardiac Transplantation in the United States. 
Am.J.Transplant, 2017; 17:2559-2566 

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where pDCD and pSOC represent the true survival proportions at 6 months for DCD and SOC heart 
transplant patients, respectively.  
 
The analysis of this endpoint will be performed using a linear probability model, with the following terms 
in the model: (1) treatment; (2) all of the known donor and recipient risk factors listed previously; and (3) 
any of the potential risk factors listed above for which there is a statistically significant difference 
between treatment groups. The p-value for the test of the null hypothesis will be obtained based on a 
statistic for the difference (SOC - DCD) in least squares means (actually proportions rather than means) 
for each treatment minus the non-inferiority margin of 0.20 all divided by the standard error of the 
difference in the least squares means and assuming an approximate normal distribution. The test will be 
conducted at the 0.05 level of significance.  
 
Secondary and Other Endpoints  
Secondary Endpoint: 
Utilization Rate, defined in Section 5.2  
 
Other Endpoints: 
DCD Heart Transplanted Recipients only: 
• 
Patient and graft survival at 30 days post-transplant  
• 
Patient and graft survival at 30 days post-transplant and at initial hospital discharge, if later 
than 30 days 
• 
Severe heart PGD (left or right ventricle) (not including rejection or cardiac tamponade) 
according to ISHLT consensus manuscript (as defined in Appendix 1 of this protocol) 
• 
Use of post-transplant mechanical circulatory support (LVAD, RVAD, BiVAD) for > 72 hours 
immediately post-transplant. 
 
DCD Heart Transplanted Recipients and SOC Heart Transplanted Recipients: 
• 
Patient survival at one year after transplant (collected post-approval and collected from 
UNOS for SOC Heart Transplanted Recipients). 
 
Each endpoint will be summarized using counts and percentages and an exact (Clopper-Pearson) 95% 
confidence interval for the true percentage based on the binomial distribution. Patient survival at one 
year after transplant will be summarized for both the DCD Heart Transplanted Recipient and SOC Heart 
Transplanted (SOC1 + SOC2 as defined in Section 6.4) Recipient populations. 
 
Comparisons of recipient demographics and baseline characteristics and of patient survival at 6 months 
will be performed for the following treatment groups (as defined in Section 6.4): 
• 
SOC1 vs SOC2 
• 
DCD Heart vs SOC1 
• 
DCD Heart vs SOC2 
 
Continuous demographic and baseline characteristics will be summarized by treatment group using 
descriptive statistics (mean, standard deviation, median, minimum, and maximum). Categorical 
demographic and baseline characteristics and patient survival at 6 months will be summarized by 
treatment group using counts and percentages. For continuous variables, comparisons of treatment 
groups will be performed using two-sided, two-sample t-tests. For categorical variables, comparisons will 
be performed using Fisher's Exact Test.  
 
Safety (DCD Heart Transplanted Recipient Population Only) 
Serious Adverse Events (SAEs) and Heart Graft-related Serious Adverse Events (HGRSAEs) will be collected 
within the first 30 days post-transplant and the mean number of HGRSAEs per subject will be summarized 
using descriptive statistics. HGRSAEs are defined as the following adverse events (at most one per type): 
Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac tamponade) 

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according to ISHLT consensus manuscript (as defined in Appendix 1 of this protocol) and primary graft 
failure requiring retransplantation. 
 
SAEs and HGRSAEs will also be tabulated using counts and percentages alone and in regards to the 
relationship of the HGRSAE to the device, and the severity of the HGRSAE.  
 
Sample Size Determination 
We have assumed that transplantation of a DCD donor heart will occur at the same ratio as SOC heart 
transplants, despite the 3:1 randomization of DCD Heart Possible to SOC Heart Only. The sample size 
calculations are based on the following specifications: 
• 
Non-inferiority study with comparison of DCD heart transplanted recipients to SOC heart 
transplanted recipients 
• 
Primary endpoint is patient survival at 6 months post-transplant 
• 
One-sided normal approximation test 
• 
Alpha = 0.05  
• 
Power = 80%  
• 
Assume 1:1 occurrence of SOC heart transplants (SOC1 and SOC2) and DCD heart 
transplants 
• 
True SOC survival percentage = 93% 
• 
True DCD survival percentage = 85% 
• 
Non-inferiority margin = 20%.  
 
Based on these assumptions, a sample size of 84 DCD heart transplanted recipients and at least 84 SOC 
heart transplanted recipients will provide at least 80% power. This sample size was increased to 90 per 
group to reflect potential enrollment of subjects who are lost to follow-up, withdraw or do not meet 
eligibility criteria. 
Trial Sponsor 
TransMedics, Inc. 
200 Minuteman Road, Suite 302 
Andover, MA, USA 01810 
 

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The donor organ shortage has also led to an increasing utilization of Mechanical Circulatory Support 
(MCS) devices, which are being used as either a “Bridge to Transplant” or as a replacement for organ 
transplantation (“Destination Therapy”) (Figure 2). 
Figure 2: 
MCS devices implanted in U.S. patients, 2006-September 2017. From INTERMACS Quarterly 
Statistical Report, 2017. (Kirklin, et al., 2017) 
 
 
MCS devices are being implanted in patients who are candidates for heart transplant (so-called Bridge 
to Transplant (BTT) indication) solely as a result of the donor organ shortage. The American Heart 
Association, ISHLT, The American Transplant Society and investigators in the U.S. and worldwide 
recognize heart transplant as the “gold standard” treatment and the only curative therapy for end 
stage heart failure. (Peura, et al., 2012; Katz, et al., 2015; Wilhelm, 2015; Mancini, 2010; 
Kobashigawa, et al., 2017). In fact, this shortage of donor organs results in approximately 16% of the 
Status 1A patients listed on the national waiting list for heart transplantation dying or deteriorating 
so much that they were removed from the waiting list at 12 months (Table 1). Status 1A patients 
include those who were implanted with MCS devices while awaiting transplant. 
 
 

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the organ from the donor, thus substantially minimizing the risk of transplanting poor 
hearts into recipients. 
In summary, patients listed for heart transplantation due to their end stage heart disease are 
suffering from a terminal, life-threatening condition. Increasing the number of heart transplants by 
preserving extended criteria donors and DCD hearts with the OCS Heart System has the potential to 
provide patients with end stage heart failure with the gold-standard, life-saving treatment. 
2. 
SUMMARY OF PRIOR TESTING AND INVESTIGATIONS 
2.1. 
OCS Heart Preclinical Testing  
The OCS Heart System is CE marked and has undergone extensive preclinical testing to demonstrate 
its safety, effectiveness, and readiness for clinical use. The Heart Perfusion Set has also been 
evaluated and tested in accordance with ISO-10993 “Biological Evaluation of Medical Devices,” 
including evaluations for acute toxicity, irritation, sensitization, cytotoxicity, hemolysis, genotoxicity 
and pyrogenicity. These test results demonstrated that the device and its materials are biocompatible 
and suitable for their intended use. The Heart Perfusion Set will be provided sterile using validated 
methods, and is appropriately packaged to maintain sterility. The OCS 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 meets its expected performance specifications and is safe and suitable for 
clinical use. 
2.2. 
Preclinical Animal Testing of OCS Heart System for DCD hearts 
Two preclinical animal studies have been published that evaluated the use of the OCS Heart System 
to preserve DCD hearts in animal models. 
2.2.1. 
Iyer, et al., 2015 
This study evaluated the use of the OCS Heart System to preserve DCD hearts in a porcine orthotopic 
heart transplant model. DCD hearts preserved with the OCS Heart System were compared to DCD 
hearts preserved using standard cold storage for 4 hours.  
All donor hearts were exposed to 30 minutes of warm ischemia in a DCD asphyxia model prior to 
being flushed with cardioplegia. The comparison of the experimental timeline for the two groups is 
shown in Figure 4 below. Orthotopic transplantation into recipient animals was then performed. 

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maximum warm ischemic time of 30 min. Donor heart warm ischemic times were 28 min, 25 min, and 
22 min, with OCS Heart perfusion times of 257 min, 260 min, and 245 min, respectively. Two patients 
needed temporary mechanical support. All three recipients had normal cardiac function within a 
week of transplantation, and, at the time of the report, were alive and recovering well at 176, 91, and 
77 days after transplantation. 
The second report, published in 2017, described the experience of using the OCS Heart System to 
preserve DCD hearts at St. Vincent’s Hospital in Sydney, Australia. The donors were Maastricht 
Category III donors, < 40 years of age, no history of cardiac disease or cardiac risk factors, minimal 
inotropes and an expected warm ischemia time of 30 minutes. All donor hearts were perfused with 
the OCS Lung System. Time from withdrawal of therapy to cessation of circulation was 4 to 25 
minutes (median 14 minutes). Total warm ischemic time was 14 to 28 minutes (median 25 minutes), 
with the time on OCS from 210 to 410 minutes (mean 302 minutes). Results for 12 patients have been 
reported. One patient needed mechanical support with IABP and 4 patients required ECMO support. 
There has been no mortality and all patients have normal biventricular function at 25 to 829 days 
post-transplant at the time of the report. The authors concluded that excellent graft and recipient 
survival can be achieved from transplantation with DCD hearts using the OCS Heart System. 
2.3.3. 
García Sáez, et al. (2016, 2017) 
García Sáez, et al. (2016) reported on the outcomes of 2 recipients with long-term left ventricular 
assist device (LVAD) support who were successfully transplanted with DCD hearts preserved on the 
OCS Heart System despite the adverse donor/recipient risk profile. The authors noted “The ability to 
assess graft viability is of particular importance in DCD HTx, where, in contrast to the DBD setting, the 
donor organ has invariably been subjected to a sustained ischemic insult before procurement. We 
deliberately prolonged OCS support duration to allow comprehensive graft assessment and to 
achieve surgical preparedness in technically demanding recipients with LVADs in situ.” In this report, 
the two patients were alive and well 290 and 291 days after transplantation. 
This same author followed up with a report of 5 high-risk recipients (García Sáez, et al., 2017). This 
included three recipients with LVADs and one subject who was undergoing a second heart 
transplantation. All patients received DCD heart transplants preserved on OCS. Following transplant, 
two patients developed primary graft dysfunction requiring mechanical support. One patient died 
within the first 30 days post-transplant (the patient who had undergone a second heart transplant). 
The remaining 4 patients are well and alive at a mean 324 days post-transplant (range 18-496 days).  
2.4. 
Additional Clinical Studies of the OCS Heart System for Standard Criteria 
and Extended Criteria Donor Hearts 
TransMedics has conducted two previous IDE studies of the OCS Heart System in Standard Criteria 
and Extended Criteria Donor Hearts. These studies provide supporting evidence for the safety of the 
OCS Heart System for this investigation and are briefly described below. 
• The OCS Heart EXPAND trial was a prospective, single arm study of 75 heart transplant 
recipients who received hearts preserved on the OCS. These hearts were from extended 
criteria donors, i.e., those that are seldom transplanted in transplant institutions today 
without the OCS. The results demonstrated: 

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- Utilization rate of 80.6% of donor hearts that are rarely used for transplantation today. 
These donor hearts were refused by other (non-EXPAND) centers an average of 65.6 
times but were able to be preserved and 80.6% were transplanted successfully in this 
study. 
- The incidence of ISHLT severe PGD was 10.7%, and the incidence of ISHLT moderate or 
severe PGD was 14.7%. These rates compare favorably with contemporary literature 
reporting PGD rates post-heart transplantation using the ISHLT criteria. 
- Survival at 30 days, 6 months, and 12 months was 95%, 88%, and 84%, respectively.  
• The FDA also approved a Continued Access Protocol (CAP) for EXPAND called the EXPAND 
CAP. The study is on-going and data are still being collected, but based on the available 
data the results show: 
- 38 donor hearts were preserved and assessed on the OCS Heart System. 
- The utilization rate is 89.5%, with 34 of 38 extended criteria donor hearts successfully 
transplanted.  
- The first 20 transplanted patients have reached a minimum of 30-day follow-up and all 
survived (100% survival at 30-days). 
- No severe LV or RV ISHLT PGD has been reported among the first 20 subjects 
transplanted. 
• PROCEED II was the first pivotal study of the OCS Heart System. It was a randomized study 
of the OCS Heart System compared to standard of care cold storage, and it enrolled 
standard criteria donor hearts. The study met its primary endpoint and non-inferiority was 
shown in 30-day survival, as well as in the secondary endpoint, i.e., cardiac graft-related 
SAEs. Longer-term data, obtained from the SRTR database, showed lower survival rates for 
the OCS group at 2-3 years of follow-up; however, the incidence of cardiac graft-related 
deaths was similar and other deaths were typical for heart transplant recipients (late 
infection, malignancy, multi-organ failure). The results of this study were published in the 
Lancet (Ardehali, et al., 2015). 
• Studies of the OCS Heart System for preservation of standard criteria donor hearts 
conducted outside the U.S. at hospitals in Germany and the UK showed improved rates of 
survival and lower rates of PGD for OCS compared to standard of care cold storage 
(Koerner, et al., 2014). 
2.5. 
Overall Summary of Clinical Data to Support Initiation of OCS Heart DCD 
Trial 
In summary, studies of the OCS Heart System for the preservation of DCD hearts have been 
performed outside of the U.S. These studies have shown 77.8 - 86.7% utilization rate, with 90-day and 
1-year survival comparable to outcomes obtained with standard criteria donor hearts preserved using 
cold storage standard of care.  
In addition, the OCS Heart EXPAND trial, the OCS Heart EXPAND CAP and studies of the use of OCS to 
preserve extended criteria hearts performed outside the U.S. shows high utilization rate, with good 

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heart. It uses a physical conduit to connect to the heart, incorporates various sensors, and interfaces 
with the OCS Heart Console to oxygenate, warm and circulate the perfusate.  
The accessories are intended to:  
• Collect and process the donor blood 
• Prime and then infuse the OCS Heart Solution to the HPM  
• Connect the heart to the HPM circuit 
• Facilitate monitoring of the heart operation  
• Infuse cardioplegia to terminate the preservation. 
The HPM provides the sterile blood circuit and protected environment for a heart within the OCS. It is 
designed as a single-use, pre-assembled module that mounts into the OCS. The heart is instrumented 
within the heart chamber of the HPM. The Wireless Monitor displays measurements made within the 
HPM. The HPM includes: 
• Dual lid heart-specific heart chamber 
• Integrated and easily accessible blood sampling and de-airing manifold 
• Integrated pulsatile pump head interface 
• Integrated low shear titanium blood warmer 
• Integrated blood oxygenator (or gas exchanger) 
• Integrated sensors (pressure and temperature) and circuitry to communicate with the 
Console. 
3.1.3. 
OCS Heart Solution Set 
The OCS Heart Solution Set consists of two proprietary heart preservation solutions, a Priming 
Solution and a Maintenance Solution, to replenish the nutrients and hormones (adenosine) that the 
metabolically active donor heart requires. The solutions are packaged in a three-chamber bag 
(nominal volume of 500 ml per chamber). At the time of use, the Priming Solution (500 ml) is 
dispensed into the HPM. The Maintenance Solution is manufactured as two component solutions 
(500 ml each) that are individually manufactured and then mixed immediately before infusion into 
the HPM. Additives are required at the time of use. The additives are not supplied by TransMedics, 
and are added by user. 
The OCS Heart Solution Set is not intended to be administered directly to the donor or the recipient. 
The donor heart is arrested prior to removal using a standard cardioplegia solution. Prior to 
transplantation into the recipient, the donor heart is arrested on the OCS through the use of a 
standard cardioplegia solution, at which time the perfusate (including the donor blood, Priming 
Solution and Maintenance Solution) are flushed from the donor heart.  
3.1.4. 
Mode of Action - Overview 
The OCS Heart System preserves the heart in a near-physiological, beating state by perfusing the 
heart with a warmed, donor-blood based perfusate that is supplemented with nutrients and oxygen 
in a controlled and protected environment referred to as the circuit. The circuit is illustrated in 

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transplantation after OCS Heart preservation divided by the total number of eligible DCD donor 
hearts that met the warm ischemic time limit above and were instrumented on the OCS Heart 
System. 
5.3. 
Safety  
The safety endpoint is defined as the incidence of Heart Graft-related Serious Adverse Events 
(HGRSAEs) in the first 30 days post-heart transplantation in the DCD Heart Transplanted Recipient 
Population, defined as the following adverse events (at most one per type): 
• Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac 
tamponade) according to ISHLT consensus manuscript (as defined in Appendix 1 of this 
protocol). 
• Primary graft failure requiring retransplantation. 
This endpoint is calculated for the DCD Heart Transplanted Recipient Population only. 
5.4. 
Other Endpoints  
Other endpoints collected for the DCD Heart Transplanted Recipient Population include: 
• Patient and graft survival at 30 days post-transplant 
• Patient and graft survival at 30 days and initial hospital discharge, if later than 30 days 
• Severe PGD (left or right ventricle) (not including rejection or cardiac tamponade) 
according to ISHLT consensus manuscript (as defined in Appendix 1 of this protocol) 
• Use of post-transplant mechanical circulatory support (LVAD, RVAD, BiVAD) for > 72 hours 
immediately post-transplant. 
Other endpoints calculated for both the DCD Heart Transplanted Recipients and the SOC Heart 
Transplanted Recipients (SOC1+SOC2) include: 
• Patient survival at 1 year after transplant (collected post-approval); comparison of DCD 
Heart Transplanted Recipients and SOC Heart Transplant Recipients (SOC1 + SOC2) 
through UNOS/OPTN database. 
6. 
TRIAL POPULATION  
The trial will include heart transplant recipients, aged 18 to 49 years, inclusive, at up to 25 
investigational sites in the U.S. Medicare beneficiaries with a clinical need for transplantation will be 
treated in the same manner as patients not covered by a Medicare plan. The rules of participation 
and results of the study apply to Medicare and non-Medicare covered patients in the same manner.  
6.1. 
DCD Donor Eligibility Criteria 
Donor Inclusion Criteria 
• Maastricht Category III DCD donor, defined as expected death after the withdrawal of life- 
supportive therapy (WLST) 

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• Donor age 18-49 years old inclusive 
• Warm ischemic time (WIT) ≤ 30 mins, with warm ischemic time defined as: Time from 
when mean systolic blood pressure (SBP) is < 50 mmHg or peripheral saturation < 70% to 
aortic cross-clamp and administration of cold cardioplegia in the donor. 
Donor Exclusion Criteria 
Donor hearts will be excluded if they meet any of the following criteria: 
• Previous cardiac surgery; 
• Known coronary artery disease; 
• Cardiogenic shock or myocardial infarction; 
• Sustained terminal EF of ≤ 50%; or 
• Significant valve disease except for competent bicuspid aortic valve. 
6.2. 
Standard of Care Donor Eligibility Criteria 
Standard criteria donor hearts will be screened and determined to be eligible for transplant according 
to the standard of care at each institution. Standard of care donor hearts that are eligible for 
transplantation will be preserved according to the standard practices at each institution. 
6.3. 
Recipient Eligibility Criteria 
Recipient Inclusion Criteria 
• Primary heart transplant candidates 
• Age ≥ 18 years old 
• Signed: (1) written informed consent document; (2) authorization to use and disclose 
protected health information; and (3) consent to TransMedics’ use of recipients’ 
UNOS/OPTN data and consent to TransMedics’ use of recipients’ INTERMACS data. 
Recipient Exclusion Criteria 
• Prior solid organ or bone marrow transplant 
• Chronic use of hemodialysis or diagnosis of chronic renal insufficiency 
• Multi-organ transplant 
• Investigator unwilling to randomize to either arm. 
6.4. 
Screening and Treatment 
Primary heart transplant candidates will be screened for trial eligibility. Every eligible candidate will 
be asked to participate. Subjects will be randomized into two groups: DCD Heart Possible and SOC 
Heart Only. Subjects who are randomized into the SOC Heart Only group will have no possibility for a 
DCD Heart transplant. Subjects randomized into the DCD Heart Possible group have the possibility of 
receiving either a DCD heart or an SOC donor heart, depending upon the donor match. In order to 
obtain enough subjects with DCD donor heart transplants, subjects will be randomized 3:1 to the DCD 

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Heart Possible and SOC Heart Only arms, respectively. Follow-up survival data for transplanted 
subjects in the SOC Heart Transplanted Recipient (SOC1) group will be obtained from the 
UNOS/OPTN standard database for transplant recipients. Upon receiving a donor heart match and 
after confirmation of eligibility, SOC Heart transplanted recipients will have demographic information 
collected and will then exit the study and undergo standard heart transplantation according to the 
institution’s standard of care. 
In the DCD Heart Possible arm, if a screened and eligible subject is matched with an SOC donor heart 
before an eligible DCD donor heart becomes available and is transplanted, these subjects will form a 
second SOC Heart Transplanted Recipient group (SOC2). Follow-up survival data for subjects in the 
SOC2 group will be obtained from the UNOS/OPTN standard database for transplant recipients. Upon 
receiving a donor heart match and after confirmation of eligibility, SOC Heart transplanted recipients 
will have demographic information collected and will then exit the study and undergo standard heart 
transplantation according to the institution’s standard of care. 
Data will be collected according to this protocol for subjects in the DCD Heart Possible arm who 
receive a DCD Heart match and are transplanted with the DCD heart as outlined in this protocol (DCD 
Heart Transplanted Recipient group). 
6.5. 
DCD Heart Subject Enrollment and Screen Failures 
As part of the screening process for subjects in the DCD Heart Transplanted Recipient population, the 
following must occur:  
• Recipient must be matched with a donor heart that meets eligibility criteria for DCD Heart 
Trial; 
• Recipient must meet eligibility criteria for this DCD Heart Trial; 
• The matched DCD donor heart must be accepted for transplantation in the donor chest by 
the transplant surgeon or designee (including meeting the Warm Ischemic Time limit 
outlined in this protocol); 
• The matched donor heart must be instrumented on the OCS; 
• The donor heart matched to this recipient must meet transplantability criteria per Section 
7.5.1 of the protocol following OCS Heart System instrumentation; and 
• The recipient must be transplanted with the DCD heart instrumented on OCS. 
A subject will be considered a screen failure under any of the following conditions: 
• The matched DCD donor heart is not accepted for transplantation in the donor chest by 
the transplant surgeon or designee (including meeting the Warm Ischemic Time limit 
outlined in this protocol). 
• The matched DCD donor heart is not instrumented on the OCS. 
• The donor heart matched to this recipient fails to meet transplantability criteria per 
Section 7.5.1 of the protocol following OCS Heart System instrumentation (i.e., donor 
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• The recipient fails to meet inclusion/exclusion criteria on the day of the potential 
transplant after an eligible DCD donor heart is instrumented on the OCS Heart System and 
accepted for transplantation following OCS preservation. 
• Logistical reasons prevent transplantation of DCD donor heart instrumented on the OCS 
Heart System that meets acceptance criteria for transplant following OCS preservation 
(e.g., transplant center or OPO issues, transportation or allocation issues, surgeons or ORs 
are unavailable). 
A subject will be considered enrolled in the DCD Heart arm when the subject is transplanted with 
the OCS-instrumented organ. Trial data will be collected only for those subjects considered enrolled 
in the trial.  
Subjects who are screen failures that remain eligible for the study will return to the waiting list for 
another heart transplant. Since these are subjects in the DCD Heart Possible arm, depending on the 
donor match, this next transplant may be either a DCD Heart or an SOC heart.  
7. 
PRE-OPERATIVE TRIAL PROCEDURES 
7.1. 
Subject Identification  
Those patients who initially appear eligible for the trial will have the trial explained to them, be 
invited to participate, and will be asked to sign an informed consent. Subjects will then be 
randomized to either SOC Heart Only or DCD Heart Possible arms as described above. When a 
matching eligible donor heart becomes available, the inclusion and exclusion criteria for the recipient 
will be re-verified. If the recipient is no longer eligible for the trial, they will be considered a screen 
failure and they will exit the study, and no information will be collected for these subjects. 
7.2. 
Recipient Day of Transplant Assessment 
The purpose is to conduct a final assessment of whether the potential recipient still meets the 
eligibility criteria. Specific data to be collected can be found in the Schedule of Assessments in 
Appendix 2.  
7.3. 
Donor Screening and Acceptance for SOC Hearts 
The investigator or a member of her/his transplant team will evaluate the donor and the quality and 
suitability of the heart for transplantation, according to his or her standard practice. If the donor 
heart does not meet criteria for transplantation it will be considered a “dry run” and no information 
on this donor heart will be collected. 
7.4. 
Donor Screening and Acceptance for DCD Hearts 
The investigator or a member of her/his transplant team will evaluate the donor and the quality and 
suitability of the DCD heart for: (1) transplantation, according to his or her clinical judgement and (2) 
eligibility for the DCD Heart arm of this study, including meeting the warm ischemic time limit 
outlined in this protocol. If the donor heart does not meet the above criteria, it will be considered a 
“dry run” and no information on this donor heart will be collected. 

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If the donor heart meets the above criteria and is preserved on OCS, baseline characteristics, 
demographics and other donor information will be collected at this visit. Parameters to be collected 
can be found in the Schedule of Assessments in Appendix 2. 
7.5. 
 DCD Donor Heart Retrieval and OCS Preservation and Assessment 
Upon acceptance into the trial, the investigators will retrieve and preserve the donor heart according 
to the OCS Heart Instructions for Use (IFU). 
7.5.1. 
Donor Heart Acceptance/Rejection for Transplantation after OCS Preservation 
Donor hearts preserved on the OCS should have stable parameters throughout perfusion after initial 
stabilization period (defined as the time period during which perfusion is initiated and primary 
parameter adjustments are made). 
Accept for Transplantation 
Donor hearts preserved on the OCS Heart System to be maintained within the following target 
ranges: 
• Stable or downward trending lactate after initial adjustments of the OCS Heart perfusion 
parameters to achieve adequate perfusion to the donor heart 
• Stability of OCS Heart Perfusion Parameters within range: 
- AOP 40-100 mmHg. 
• Transplanting surgeon and/or heart failure cardiologist must clinically accept the OCS 
perfused donor heart for transplantation. 
Reject for Transplantation 
• Transplanting surgeon and/or heart failure cardiologist clinically unsatisfied with donor 
heart condition/performance on the OCS Heart System at final evaluation. 
• Unstable and rising arterial lactate despite maneuvers to optimize perfusion parameters. 
Note: certain donor hearts may require perfusion with parameters outside of these guidance ranges. 
Acceptance for transplantation should be primarily based on an acceptable lactate trend. 
Any decision to turndown hearts after preservation and assessment on OCS Heart System should be 
documented on the appropriate CRF. Samples should be sent to the central core lab for assessment 
of any inherent cardiac pathology that was not diagnosed at retrieval of the donor heart.  
8. 
TRANSPLANT, IMMEDIATE POST-OPERATIVE AND LONG-TERM FOLLOW-UP 
FOR DCD HEART TRANSPLANTED RECIPIENTS ONLY 
8.1. 
Transplant Details 
The following information concerning the transplant procedure will be collected: 
• The organ recipient unique post-transplant patient identifier 
• Warm ischemic time as defined in this protocol 

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• Total cross clamp duration in minutes (from donor cross-clamp application to removal of 
cross-clamp in the recipient) 
• Pre-OCS cold ischemia time (time from donor cross clamp until start of perfusion on OCS) 
• Post-OCS cold ischemia time (time from heart flush on OCS until aortic cross-clamp 
removal in the recipient) 
• Any surgical complications encountered during surgery. 
8.2. 
Post-transplant Functional Assessments Day 0 – Day 30 
• Heart PGD Surveillance in the first 24 hours 
• Initial use of Mechanical Circulatory Support in the first 72 hours 
• Inotropic Support for first 24 hours from T0 to T24 hours after ICU admission 
• Echocardiogram results within the first 24 hours post-transplant (if available) starting from 
ICU admission 
• Right Heart Catheter Data (not required; data collected only if performed as part of 
institution’s standard of care) 
• Initial Post-Transplant ICU Stay 
• Initial Post-Transplant Hospital Stay 
• Patient and Graft Survival at Day 30 will be assessed. 
• Serious Adverse Events: All SAEs will be collected for the first 30 days post-transplant. SAEs 
will be followed until the investigator designates the event to be either resolved or its 
effect on the patient’s condition stabilized. 
8.3. 
Long-term Follow-up: 6 and 12 months 
Follow-up data collection will be conducted at 6 months (± 30 days) and 12 months (± 60 days) post-
transplant to evaluate patient survival, graft survival and diagnosis of cardiac allograft vasculopathy. 
These follow-ups may be performed by phone. 
8.4. 
Evaluation of Adverse Events for DCD Heart Recipients Only 
Only serious adverse events (SAEs) and Heart Graft-Related SAE’s (HGRSAEs) will be captured in this 
study (DCD Heart Transplanted Recipients only). 
8.4.1. 
Serious Adverse Events (SAEs) 
Serious adverse events will be collected only through Day 30 post-transplant. 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 

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• 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. 
8.4.2. 
Heart Graft-Related SAEs (HGRSAEs) 
Heart Graft-related SAEs (HGRSAEs) are defined as: 
• Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac 
tamponade) according to ISHLT consensus manuscript as defined in Appendix 1 of this 
protocol.  
• Primary graft failure requiring re-transplantation. 
HGRSAEs will be collected from the time a subject is transplanted with the OCS DCD Heart until the 
completion of the 30-day follow-up evaluation. A HGRSAE will be followed until resolution or 
stabilization of the event. 
8.4.3. 
Unanticipated Adverse Device Effect (UADE) 
The investigator will assess each serious adverse event for whether it is anticipated or unanticipated 
using the list specified in Section 8.4.4 below. 
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. 
8.4.4. 
Anticipated SAEs 
Anticipated SAEs that are associated with heart transplant procedures within the first 30 days after 
heart transplant includes, but is not limited to:
• Acute rejection 
• Atrial and ventricular arrhythmias 
• Bleeding (major) 
• Hemodynamic instability 
• Death 
• Fever 
• Infection 
• Primary Graft Dysfunction  
• Respiratory failure 
• Graft failure 
• Sepsis 
• Renal dysfunction 
• Hyperammonaemia 
• Malignancy (post-transplant 
lymphoproliferative disorder (PTLD) 
• Multiple organ failure 

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• Myocardial infarction 
• Neurological dysfunction 
• Hepatic dysfunction 
• Diabetes due to steroid and anti-
rejection medications 
• Gall stones 
• GI bleeding 
• Pancreatitis 
• Peptic ulceration 
• Gastritis 
• Gastro esophageal reflux disease (GERD) 
• Aspiration  
• Cardiac tamponade 
• Pneumo-mediastinum 
• Pneumothorax 
• Hemothorax 
• Pleural bleeding 
• Pleural effusion 
• Venous thromboembolism (deep venous 
thrombosis [DVT]) 
• Pulmonary embolism (PE) 
• Sternal wound dehiscence 
• Organ deemed not transplantable after 
retrieval 
• Stroke 
• Psychosis 
• Cerebrovascular accident 
• Peripheral vascular clotting or occlusion 
due insertion of mechanical support 
• Limb gangrene due to vascular occlusion 
due insertion of mechanical support 
• Use of mechanical circulatory support 
• Coagulopathy 
• Hyperacute rejection 
• Anastomotic site complications; 
narrowing, bleeding or occlusion 
• Delayed sternal wound closure due to 
compromised cardiac function or 
excessive bleeding or both 
• Bowel thromboembolic complications 
and gangrene 
• Protamine and other anti-heparin 
medication reaction 
• Heparin induced thrombocytopenia 
 
8.4.5. 
Reporting of Adverse Events 
Unanticipated adverse device effects (UADE) should be reported to TransMedics, Inc., within 48 hours 
of the time the investigator learns of the event, but in no case later than 5 working days after learning 
of the event. 
All SAE information will only be collected from transplant through day 30. SAEs should be entered 
into the study database as soon as possible. SAE will be followed until the investigator designates the 
event to be either resolved or its effect on the patient’s condition stabilized. Details related to 
treatment of the SAE will also be collected. 
8.4.6. 
Relationship of an SAE or HGRSAE to OCS Heart System 
The investigator will assess the relationship of the HGRSAE to the OCS Heart System. The relationship 
will be assessed using the following categories:  

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• Definitely Related: There is a reasonable causal and temporal relationship between 
preservation with the OCS Heart and the adverse event. 
• Possibly Related: There is a reasonable relationship with preservation with the OCS Heart 
and the adverse event, but the causal relationship is unclear or lacking. 
• Unlikely Related: There is a temporal relationship with preservation with the OCS Heart 
and the adverse event, but there is not a reasonable causal relationship between the OCS 
Heart and the event. 
• Unrelated: There is no relationship between preservation with the OCS Heart and the 
adverse event. 
8.4.7. 
Severity 
The investigator will rate the severity of the serious 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. 
8.4.8. 
Pre-Existing Conditions 
Pre-existing diseases or conditions will not be reported as adverse events. 
9. 
OCS HEART TRAINING RUNS 
Prior to transplanting any DCD hearts in this study, all investigators will complete one or two training 
runs. The purpose of these training runs is to allow the investigator and the surgical team to become 
familiar with the procurement of DCD hearts, specifically, the warm ischemia inclusion criteria, and to 
obtain experience in instrumenting and resuscitating DCD hearts on the OCS Heart System. The donor 
organs procured and instrumented in the training runs are not intended for transplantation. The 
results of the training runs will not be included in any data analyses, including the calculation of the 
utilization rate. 
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.  

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10.2. 
Analysis Populations 
10.2.1. 
DCD Heart Transplanted Recipient Population 
The DCD Heart Transplanted Recipient Population will consist of all eligible recipients who are 
transplanted with an eligible DCD donor heart that met the warm ischemic time limit defined above, 
preserved on OCS and met the transplantability criteria. The analyses of all effectiveness and safety 
endpoints, except the utilization rate, will be based on the DCD Heart Transplanted Recipient 
Population. 
10.2.2. 
OCS Heart Population 
The OCS Heart Population will consist of all eligible donor hearts that met the warm ischemic time 
limit above and were instrumented on the OCS Heart System. The analysis of utilization rate will be 
based on the OCS Heart population. 
10.2.3. 
SOC Heart Transplanted Recipient Population 
The SOC Heart Transplanted Recipient Population will consist of all recipients who received a 
standard criteria donor heart (SOC1 + SOC2 as defined in Section 6.4). 
The analyses of the primary endpoint and of patient survival at one year after transplant will be based 
on the DCD Heart Transplanted Recipient Population and the SOC Heart Transplanted Recipient 
Population.  
The analyses of: (1) patient and graft survival at 30 days post-transplant; (2) patient and graft survival 
at 30 days and at initial hospital discharge if longer than 30 days; (3) the use of post-transplant 
mechanical circulatory support (LVAD, RVAD, and BiVAD) for > 72 hours immediately post-transplant; 
(4) Severe heart PGD (left or right ventricle) (not including rejection or cardiac tamponade) according 
to ISHLT consensus manuscript (as defined in Appendix 1 of this protocol); and (5) HGRSAEs and SAEs 
will be based on the DCD Heart Transplanted Recipient Population. 
10.3. 
Statistical Analysis 
10.3.1. 
Primary Endpoint 
The primary endpoint is a comparison of survival at 6 months for DCD heart transplanted recipients 
and standard criteria heart transplanted recipients (SOC1 + SOC2 as defined in Section 6.4), adjusting 
for differences in risk factors. This is a non-inferiority study. 
Risk Factors 
We will adjust for the known donor and recipient risk factors for mortality shown in the list below2: 
 
 
                                                        
2 Cardiac Donor Risk Factors Predictive of Short-Term Heart Transplant Recipient Mortality: An Analysis of the United 
Network for Organ Sharing Database. Trans Proc. 2015 Dec; 47(10): 2944-2951., Heart Transplant Survival based on 
Recipient and Donor Risk Scoring: A UNOS Database Analysis, ASAIO J., 2016; 62:297-301. Report from the American 
Society of Transplantation Conference on Donor Heart Selection in Adult Cardiac Transplantation in the United States. 
Am.J.Transplant, 2017; 17:2559-2566 

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Donor Variables: 
• Donor Age ≥ 55 years 
• Gender mismatch (female donor to male recipient). 
Recipient Variables: 
• Age ≥ 65 
• LVAD, ECMO or IABP prior to transplant 
For continuous baseline characteristics, two-sided, two-sample t-tests will be used to test for a 
difference in means between treatment groups. For categorical baseline characteristics, the chi-
square test will be used to test for a difference in proportions between treatment groups. We will 
adjust the analysis of the primary endpoint for any of these baseline characteristics for which there is 
a statistically significant difference (p-value < 0.15) between the treatment groups. 
The null and alternative hypotheses for the primary endpoint are as follows: 
H0: pSOC – pDCD ≥ 0.20 
 vs. 
H1: pSOC – pDCD < 0.20 
where pDCD and pSOC represent the true survival proportions at 6 months for DCD and SOC 
heart transplant patients, respectively.  
The analysis of this endpoint will be performed using a linear probability model, with the following 
terms in the model: (1) treatment; (2) all of the known donor and recipient risk factors listed 
previously; and (3) any of the potential risk factors listed above for which there is a statistically 
significant difference between treatment groups. The p-value for the test of the null hypothesis will 
be obtained based on a statistic for the difference (SOC - DCD) in least squares means (actually 
proportions rather than means) for each treatment minus the non-inferiority margin of 0.20 all 
divided by the standard error of the difference in the least squares means and assuming an 
approximate normal distribution. The test will be conducted at the 0.05 level of significance.  
10.3.2. 
Secondary and Other Endpoints  
Secondary Endpoint: 
Utilization Rate, defined in Section 5.2  
Other Endpoints: 
DCD Heart Transplanted Recipients only: 
• Patient and graft survival at 30 days post-transplant  
• Patient and graft survival at 30 days post-transplant and at initial hospital discharge, if 
later than 30 days 
• Severe heart PGD (left or right ventricle) (not including rejection or cardiac tamponade) 
according to ISHLT consensus manuscript (as defined in Appendix 1) 

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• Use of post-transplant mechanical circulatory support (LVAD, RVAD, BiVAD) for > 72 hours 
immediately post-transplant. 
DCD Heart Transplanted Recipients and SOC Heart Transplanted Recipients: 
• Patient survival at one year after transplant (collected post-approval and collected from 
UNOS for SOC Heart Transplanted Recipients). 
Each endpoint will be summarized using counts and percentages and an exact (Clopper-Pearson) 95% 
confidence interval for the true percentage based on the binomial distribution. Patient survival at one 
year after transplant will be summarized for both the DCD Heart Transplanted Recipient and SOC 
Heart Transplanted (SOC1 + SOC2 as defined in Section 6.4) Recipient populations. 
Comparisons of recipient demographics and baseline characteristics and of patient survival at 6 
months will be performed for the following treatment groups (as defined in Section 6.4): 
• SOC1 vs SOC2 
• DCD Heart vs SOC1 
• DCD Heart vs SOC2. 
Continuous demographic and baseline characteristics will be summarized by treatment group using 
descriptive statistics (mean, standard deviation, median, minimum, and maximum). Categorical 
demographic and baseline characteristics and patient survival at 6 months will be summarized by 
treatment group using counts and percentages. For continuous variables, comparisons of treatment 
groups will be performed using two-sided, two-sample t-tests. For categorical variables, comparisons 
will be performed using Fisher's Exact Test.  
10.4. 
Safety (DCD Heart Transplanted Recipient Population Only) 
Serious Adverse Events (SAEs) and Heart Graft-related Serious Adverse Events (HGRSAEs) will be 
collected within the first 30 days post-transplant and the mean number of HGRSAEs per subject will 
be summarized using descriptive statistics. HGRSAEs are defined as the following adverse events (at 
most one per type): Moderate or Severe heart PGD (left or right ventricle) (not including rejection or 
cardiac tamponade) according to ISHLT consensus manuscript (as defined in Appendix 1) and primary 
graft failure requiring retransplantation. 
SAEs and HGRSAEs will also be tabulated using counts and percentages alone and in regards to the 
relationship of the HGRSAE to the device, and the severity of the HGRSAE. 
10.5. 
Sample Size Determination 
We have assumed that transplantation of a DCD donor heart will occur at the same ratio as SOC heart 
transplants, despite the 3:1 randomization of DCD Heart Possible to SOC Heart Only. The sample size 
calculations are based on the following specifications: 
• Non-inferiority study with comparison of DCD heart transplanted recipients to SOC heart 
transplanted recipients 
• Primary endpoint is patient survival at 6 months post-transplant 
• One-sided normal approximation test 

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• Alpha = 0.05  
• Power = 80%  
• Assume 1:1 occurrence of SOC heart transplants (SOC1 and SOC2) and DCD heart 
transplants 
• True SOC survival percentage = 93% 
• True DCD survival percentage = 85% 
• Non-inferiority margin = 20%.  
Based on these assumptions, a sample size of 84 DCD heart transplanted recipients and at least 84 
SOC heart transplanted recipients will provide at least 80% power. 
This sample size was increased to 90 per group to reflect subjects who are lost to follow-up, withdraw 
or do not meet eligibility criteria. 
To ensure timely completion of the trial, TransMedics proposes the following modification to the 
enrollment of SOC subjects: 
1. As soon as 90 DCD recipients are transplanted, the trial enrollment will stop, regardless of the 
number of SOC transplanted recipients. 
2. If, at the time the 90h DCD recipient is transplanted, the SOC enrollment is less than the 
proposed 90 subjects, the outcomes for the remaining subjects will be obtained from the 
UNOS registry by accessing patient and graft demographics and survival data for SOC subjects 
transplanted at the participating Heart DCD trial investigational sites over the previous 2 
years. The distribution of SOC subjects obtained from UNOS will reflect the distribution of 
enrollment in the Heart DCD among the various sites. 
3. The final SOC1 and SOC2 patient cohorts will include the subjects transplanted in the trial, 
supplemented with subjects obtained from UNOS at the same investigational sites, to reach 
the SOC sample size of 90 subjects. 
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. 
11.1. 
Potential Risks 
The potential risks to subjects from participation in this clinical trial include the following: 
• Potential Risks Associated with Heart Transplant Procedures: These risks include post-
operative complications not associated with the OCS Heart System 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. 

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• The Potential Risks Associated with OCS Heart System: Subjects have the risk of not 
receiving organs preserved with the OCS Heart System under certain conditions including: 
(1) the OCS Heart System may not work properly, or there may not be personnel available 
trained in the use of the Heart System or (2) the OCS Heart System may malfunction, or 
the medical staff may make an error which could lead to damage of the donor heart. If this 
occurs, the subject will have to wait for a new donor heart to become available. As with 
any medical device, there is always a risk of extremely rare or previously unknown side 
effects developing from the treatment. 
• Potential Risk of Using a Donor Heart that is Unsuitable for Transplantation: Regardless 
of the preservation system that is used, there is the risk that a patient can receive a heart 
that does not adequately function. This trial is designed to utilize hearts that would not be 
accepted for transplantation using cold storage preservation. There is the possibility that 
using such hearts may increase the risk of transplanting a heart that that does not function 
appropriately. It is also possible that the donor heart may not meet transplantability 
criteria after OCS preservation and would be turned down for transplant. In the EXPAND 
trial and in trials of DCD donors conducted outside the U.S., only 20% of the donor hearts 
were turned down following OCS preservation so the anticipated frequency of this event is 
low. 
11.2. 
Manner in Which the Potential Risks Have Been Minimized 
The Sponsor has relied upon a number of different means, including the device design, risk analysis 
and management process, preclinical testing, and the clinical protocol itself, to minimize the risks to 
subjects and to protect their safety and welfare. 
The OCS has undergone extensive preclinical and animal studies to demonstrate that the device 
performs as intended and all materials are biocompatible. Previous clinical studies, including the 
Heart EXPAND trial and studies of DCD hearts performed outside the U.S., have not indicated any 
safety signals that would preclude initiation of this study. 
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 heart acceptance criteria after OCS Heart perfusion and assessment are based 
on clinically relevant markers for perfusion of donor hearts on OCS and clinical standards 
of accepting conventional donor hearts for transplantation. Thus, the donor heart will be 
fully assessed based on the current standards of evaluating donor hearts before accepted 
for transplantation. The recipient should not be subjected to any surgical or medical 
procedures until the heart has been accepted for transplantation by the transplanting 
team. 
• As with any heart transplant procedure, subjects will be monitored before, during and 
after the operative procedure. The investigators have extensive experience with heart 
transplants and will be trained to use the OCS Heart 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. 

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11.3. 
Potential Benefits 
The low utilization of donor hearts has led to a severe shortage of donor hearts to meet the large and 
growing need for heart transplantation; the Scientific Registry for Transplant Recipients (SRTR) and 
Organ Procurement Transplant Network (OPTN) report that approximately 25% of the patients on the 
national waiting list have either died or their health deteriorated prior to a heart transplant 
procedure. 
The OCS Heart System’s preservation and assessment capabilities could potentially increase the rate 
of utilization of donor hearts that are not used due to the limitations of cold storage techniques. The 
previous Heart EXPAND study demonstrated an 80% utilization of these expanded criteria donor 
hearts, and studies of the OCS performed outside the U.S. observed 78 - 80% utilization of DCD 
hearts. This could improve the chances of waiting list recipients to receive a lifesaving heart 
transplant and reduce waiting list time and mortality. In addition, the OCS heart’s ability to assess 
donor hearts after removal allows for the assessment the function of the donor heart before it is 
transplanted. 
11.4. 
Risks Benefit Ratio 
Based on the above, the benefits of using OCS Heart technology to recruit, preserve and assess donor 
hearts to ensure their suitability for heart transplantation outweigh the potential risks to trial 
subjects. 
12. 
DEVICE/SITE MANAGEMENT 
12.1. 
Packaging and Labeling 
The OCS Heart Perfusion Set and accessories and the Perfusion Solution will be supplied sterile and 
are intended and labeled for single use only. 
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 will 
be provided to each investigational site. 
12.2. 
Storage 
The investigational devices will be stored in a secure location. 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. The OCS Heart Perfusion Set should 
be stored at temperatures between -20°C and 50°C, and ambient humidity from 10-95%, no 
condensing. 
Note: The OCS Heart Perfusion Set should be operated at ambient temperatures (10°C to 35°C), and 
ambient humidity (20%-90%). 
12.3. 
Accountability 
The investigator or designee will maintain a record of investigational devices received, used, 
discarded, or returned to the Sponsor. 

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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 Part 812), ISO Standard 14155, and in accordance with good 
clinical practices. 
13.1. 
Institutional Review Boards (IRB)  
Prior to initiation of any trial procedures, trial documents 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 or EC’s approval at the clinical site prior to the initiation of the trial at that particular site. 
13.2. 
Informed Consent 
The IRB 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. 
A copy of the proposed draft Informed Consent template is included in Appendix 3.  
14. 
DATA COLLECTION/RECORDS/REPORTS 
14.1. 
Investigator Records 
Prior to participation in the investigation, the investigators will provide the following documentation 
to the Sponsor: 
• Signed Investigator Agreement  
• Signed financial disclosure form 
• Curriculum Vitae (CV). 
Written approval of the protocol and informed consent document from the IRB; Investigators will be 
responsible to maintain on file the following records (Note that this is not the complete list of items 
to be maintained): 
• All relevant correspondences and required reports that pertain to the trial 
• Records of receipt, use or disposition of the investigational device 
• 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 

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• 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. 
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, preferably within 24 hours of learning of the subject’s 
death, but in no event later than 48 hours. The investigator will also notify the Sponsor 
immediately of a serious adverse event, preferably within 48 hours of learning of the 
serious adverse event, but in no event later than 5 working days. 
• The investigator will notify the Sponsor of any unanticipated adverse device effects 
(UADE) preferably within 48 hours after the investigator first learns of the effect, but in no 
event later than 5 working days. The investigator will notify its IRB of any unanticipated 
adverse device effects as soon as possible, but no later than 10 working days after the 
investigator first learns of the effect. 
• 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, but no later than 5 working days 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, but no later than 5 working days 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. 

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14.3. 
Data Collection 
All data required by the trial protocol will be entered into the trial database by the investigator or his 
or her designate. A copy of draft eCRFs is provided in Appendix 4. 
14.4. 
Source Documents 
Original documentation supporting the data recorded on the CRFs must be maintained, and may 
include clinical charts, medical records, laboratory reports, physician referral or consultation letters, 
x-ray reports, etc. Adverse events which are managed at a health care facility other than the study 
site must be reported on the case report form and every attempt must be made to obtain source 
documentation from that facility. 
During monitoring visits, source documents will be reviewed to ensure accuracy and validity of data 
recorded on the CRFs. Source document verification will be performed by TransMedics or its 
designee, with due regard to subject confidentiality. 
14.5. 
 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. 
15. 
CLINICAL MONITORING 
15.1. 
Monitoring 
The trial will be monitored by TransMedics. All monitors will be qualified by education, training, and 
experience. After the study has been initiated, TransMedics or its designee will perform periodic 
monitoring visits to assess study progress, perform device accountability, assess the adequacy of 
records, and to ensure adherence to the study protocol. Monitoring visits could be done live or via 
webconference. 
A summary of the monitoring visit, including documentation of completed previous action items 
and/or new or outstanding action items, and/or significant findings will be provided to the 
Investigator. 
In addition to periodic monitoring visits, TransMedics may perform remote monitoring to ensure data 
are submitted in a timely manner. Ongoing communication with investigators and study staff will be 
performed through written correspondence and telephone conversations. 
Details related to site monitoring will be documented in the Sponsor’s study-specific monitoring plan. 
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’s general monitoring procedures for 
investigational studies are described below. 

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15.2. 
Site Initiation Visit  
TransMedics or its designee will be responsible for determining and documenting that each 
investigator clearly understands and accepts the responsibilities and obligations incurred in 
conducting a clinical study. The sponsor or its designee will ensure, prior to study initiation, that the 
investigator:  
• Understands the requirements for device accountability  
• Understands the requirements of the clinical protocol  
• Understands reporting obligations  
• Understands and accepts the obligations to obtain informed consent  
• Understands and accepts the obligation to obtain Institutional Review Board approval of 
the protocol and informed consent form prior to the enrollment of the first subject.  
• Has adequate facilities to conduct the investigation. 
Site initiation could be done via webconference. 
15.3. 
Periodic Monitoring Visits 
Monitoring visits will be conducted as scheduled by the sponsor. The monitor should visit (or conduct 
the visit via webconference) with 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. 
• 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 
supporting documentation. 
• 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. 
• The appropriate staff is carrying out trial activities. 
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. 

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15.5. 
Study Close-out Visit 
The study close-out visit may be combined with a monitoring visit. The following tasks will be 
completed at close-out visit. 
• Ensure that all required CRFs have been completed/submitted. 
• Ensure final disposition of investigational devices. 
• Remind the investigator of the obligation to retain the records in accordance with local 
country requirements, and prepare a final report for the sponsor and Institutional Review 
Board. 
15.6. 
Protocol Deviations 
The study should be conducted as described in this protocol. All deviations from the protocol should 
be reported to the Sponsor by entering a protocol deviation form into the study database. 
For sites who demonstrate repeated deviations that may affect the safety of subjects, and/or the 
integrity of the data, corrective measures will be instituted such as re-training. Continued protocol 
deviations may result in the site’s termination from the trial. 
15.7. 
Clinical Events Committee (CEC) 
The Sponsor will utilize an independent Clinical Events Committee (CEC) to provide individual serious 
adverse event adjudication for the trial. It is anticipated that the CEC will meet with the Sponsor on a 
periodic basis, or as needed, depending on the rate of patient accrual. The CEC will be guided by the 
CEC Charter; however, the primary responsibilities of the CEC are to: 
• Review reportable serious adverse events, including PGD, that occur over the course of 
the trial and the subsequent classification of these adverse events as related to the device. 
• Provide recommendations to extend the length of follow-up past 30 days post-transplant 
for a subject experiencing a serious adverse event. 
15.8. 
Data Safety Monitoring Board & Stopping Rules 
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 efficacy and safety 
endpoints. The DSMB will make recommendations to the Sponsor regarding continuation, 
modification or termination of the clinical trial. The DSMB will review all data submitted to them by 
the Sponsor and may request additional information to assist in their decision process. They will 
attend scheduled meetings and issue written minutes of their meetings; furthermore, the appointed 
Chair will be responsible for issuing final written recommendations. 
The following stopping rule is to be used in the study: 
• Stopping Rule: Let p denote the true proportion of recipients transplanted with an OCS-
treated heart for whom the recipient does not survive until Day 30. Whenever a recipient 
dies within 30 days post-transplant, calculate a 97.5% lower confidence bound for p. Stop 
the study if this lower confidence bound exceeds 0.15 (15%). 

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the chairman of the IRB responsible for reviewing amendments. Except for “administrative letters,” 
investigators will await IRB approval of protocol amendments before implementing the change(s). 
18. 
REFERENCES 
1. Ardehali, et al. Ex-vivo perfusion of donor hearts for human transplantation (PROCEED II): a 
prospective, open-label, multicenter, randomised non-inferiority trial. Lancet. 2015 Jun 
27;385(9987):2577-84.  
2. Dhital, et al. Adult heart transplantation with distant procurement and ex-vivo preservation of 
donor hearts after circulatory death: a case series. The Lancet, 2015, 385(9987), 2585-2591. 
3. Dhital, et al. Rapid Retrieval and Ex-Situ Portable Machine Perfusion allows Successful Cardiac 
Transplantation with Donor Hearts from Controlled Donation after Circulatory Death. J. Heart 
Lung Transplant; 2017. 
4. García Saéz, et al., Ex vivo heart perfusion after cardiocirculatory death; a porcine model. J. 
Surg. Res., 2015 May 1; 95(1):311-314, doi: 10.1016/j.jss.2014.12.039. Epub 2014 Dec 23. 
5. García Saéz, et al. Heart Transplantation after donor circulatory death in patients bridged to 
transplant with implantable left ventricular assist devices. J. Heart Lung Transplant.; 2016, 
35(10): 1255-1260. 
6. García Saéz, et al. Donor Circulatory Death Heart Transplantation with Adverse Donor and 
Recipient Risk Profile. J. Heart Lung Transplant.; 2017, 36(45): S16. 
7. Hunt, SA, Haddad F. The changing face of heart transplantation. J. Am. Coll. Cardiol.; 2008; 
52:587-598. 
8. Israni, et al. OPTN & SRTR Annual Data Report 2014. American Journal of Transplantation; 
Volume 16, Issue S2, pages 195-215, 11 JAN 2016 DOI: 10.1111/ajt.13673. 
9. Iyer, et al., Normothermic Ex Vivo Perfusion provides superior organ preservation and enables 
viability of hearts from DCD donors. Am J. Transplant., 2015, 15:371-380. 
10. Katz, et al. Advanced Therapies for End-Stage Heart Failure. Current Cardiology Reviews; 2015, 
11:63-72. 
11. Kirklin, et al. Eighth Annual INTERMACS Report: Special focus on framing the Impact of 
Adverse Events. J. Heart Lung Transplant.; 2017, 36: 1080-1086. 
12. Kobashigawa, et al. Report from a Consensus Conference on Primary Graft Dysfunction after 
Cardiac Transplantation. J. Heart Lung Transplant.; 2014; 33: 327-340. 
13. Kobashigawa, et al. Report from the American Society of Transplantation Conference on 
Donor Heart Selection in Adult Cardiac Transplantation in the United States. Am J. 
Transplantation; 2017; 17:2559-2566. 
14. Koerner, M. et al. Normothermic Ex Vivo Allograft Blood Perfusion in Clinical Heart 
Transplantation. Heart Surgery Forum. 2014. 17(3): E144-145. 
15. Mancini, D. and Lietz, K. Selection of Cardiac Transplantation Candidates in 2010. Circulation; 
2010; 122:173-183. 

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16. Messer, et al. Outcome after Heart Transplantation from Donation after Circulatory-
determined Death Donors. J. Heart. Lung Transplant; 2017, 36(12):1311-1312. 
17. Nicoara, et al. Primary Graft Dysfunction after Heart Transplantation: Incidence, Trends and 
Associated Risk Factors. Am. J. Transplant.; 2018; 18:1461-1470. 
18. Peura, et al. on behalf of the American Heart Association Heart Failure and Transplantation 
Committee, Recommendations for the Use of Mechanical Circulatory Support: Device 
Strategies and Patient Selection: A Scientific Statement from the American Heart Association. 
Circulation; 2012; 126:2648-2667. 
19. Squiers, et al. Application of the International Society for Heart and Lung Transplantation 
(ISHLT) criteria for Primary Graft Dysfunction after Cardiac Transplantation: Outcomes from a 
High-Volume Centre. Euro. J. Cardio-Thoracic Surg; 2017, 51:263-270. 
20. Wilhelm, M.J. Long term outcome following heart transplantation: Current Perspective. J. 
Thoracic Dis.; 2015; 7(3):549-551. 

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APPENDIX 1. 
ISHLT CONSENSUS MANUSCRIPT HEART PRIMARY GRAFT 
DYSFUNCTION (PGD) (KOBASHIGAWA, ET AL., 2014) 
 
 
 
Note: All incidences of PGD will be adjudicated by the CEC. 
Hemodynamic data will be used in the assessment of PGD severity only if collected by centers as 
clinically indicated, per the institution’s standard of care. This approach is consistent with 
contemporary U.S. publications on PGD using ISHLT criteria (Nicoara, et al., 2018; Squiers, et al., 
2018). If hemodynamic data are not collected, the CEC will use available clinical data to adjudicate 
PGD severity grading. 
 

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APPENDIX 3. 
DRAFT PATIENT INFORMED CONSENT FORM TEMPLATE 
 
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APPENDIX 4. 
DRAFT ELECTRONIC CASE REPORT FORMS 
 
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