Heart Expand Continued Access Protocol
Phase: NA
Conditions: Heart Transplant
Sponsor: TransMedics



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Table of Contents  
OCS™ HEART EXPAND CAP SYNOPSIS ....................................................................................... 5 
1. 
INTRODUCTION AND BACKGROUND INFORMATION ....................................................... 9 
1.1. Heart Transplantation and Current Clinical Challenges .................................................... 9 
2. 
SUMMARY OF PRIOR TESTING AND INVESTIGATIONS ................................................... 12 
2.1. OCS™ Heart Preclinical Testing ....................................................................................... 12 
2.2. OCS Heart EXPAND Trial .................................................................................................. 12 
2.2.1. Donor Heart Utilization ....................................................................................... 13 
2.2.2. OCS Heart EXPAND Trial –Subject Disposition .................................................... 14 
2.2.3. Donor Heart Utilization ....................................................................................... 14 
2.2.4. Donor Demographics........................................................................................... 15 
2.2.5. Recipient Demographics ..................................................................................... 15 
2.2.6. Heart EXPAND Trial Results – Patient Survival .................................................... 16 
2.2.7. Heart EXPAND Trial Results – Primary Graft Dysfunction (PGD) and Heart 
Graft-Related Serious Adverse Events (HGRSAEs) ..................................... 17 
2.2.8. Summary of Heart EXPAND Trial Results to Date ............................................... 17 
2.3. OCS Heart PROCEED II Trial ............................................................................................. 17 
2.3.1. Study Purpose ..................................................................................................... 18 
2.3.2. Primary Study Endpoint ...................................................................................... 18 
2.3.3. Secondary Study Endpoints ................................................................................. 18 
2.3.4. Subject Disposition .............................................................................................. 18 
2.3.5. Primary Study Endpoint Results .......................................................................... 18 
2.3.6. PROCEED II Secondary Endpoint Results – Cardiac-Graft Related Serious 
Adverse Events – Principal Safety Measure .............................................. 19 
2.3.7. Mechanical/Circulatory Support Following Transplant ...................................... 20 
2.3.8. Turned Down OCS Preserved Donor Hearts Based on OCS Assessment ............ 20 
2.3.9. Overall Adverse Events ........................................................................................ 20 
2.3.10. Summary Conclusions of PROCEED II Trial .......................................................... 20 
2.3.11. SRTR Database – Long Term Follow-up PROCEED II Patients ............................. 21 
2.4. Long term follow-up from OCS Heart Studies conducted in the UK and Germany ........ 24 
2.5. Discussion and Conclusions of the Long and Intermediate term Follow-up of OCS 
Heart System patients ......................................................................................... 26 
2.6. Differences between PROCEED II and Heart EXPAND Trials ........................................... 26 
2.7. Overall Summary of Clinical Data to Support Initiation of Heart EXPAND CAP .............. 27 
3. 
DEVICE DESCRIPTION .................................................................................................... 28 
3.1. Description of Major Components .................................................................................. 29 
3.1.1. OCS Heart Console .............................................................................................. 29 
3.1.2. Heart Perfusion Set (HPS) .................................................................................... 29 
3.1.3. OCS Heart Solution Set ........................................................................................ 30 
3.1.4. Mode of Action - Overview ................................................................................. 30 
4. 
TRIAL OBJECTIVES ......................................................................................................... 31 
4.1. Type of Trial ..................................................................................................................... 32 

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4.2. Trial Size and Subject Follow-up ...................................................................................... 32 
5. 
TRIAL ENDPOINTS ......................................................................................................... 32 
5.1. Primary Endpoint ............................................................................................................. 32 
5.2. Secondary Endpoints ....................................................................................................... 32 
5.3. Safety 33 
5.4. Other Endpoints .............................................................................................................. 33 
6. 
TRIAL POPULATION ....................................................................................................... 33 
6.1. Donor Eligibility Criteria .................................................................................................. 33 
6.2. Recipient Eligibility Criteria ............................................................................................. 34 
6.3. Subject Enrollment and Screen Failures ......................................................................... 34 
7. 
PRE-OPERATIVE TRIAL PROCEDURES ............................................................................. 35 
7.1. Subject Identification ...................................................................................................... 35 
7.2. Recipient Day of Transplant Assessment ........................................................................ 35 
7.3. Donor Screening and Acceptance ................................................................................... 36 
7.4. Donor Heart Retrieval and OCS Preservation and Assessment ...................................... 36 
7.4.1. Donor Heart Acceptance for Transplantation after OCS Preservation ............... 36 
7.4.2. Reject for Transplantation ................................................................................... 37 
8. 
TRANSPLANT, IMMEDIATE POST-OPERATIVE AND LONG TERM FOLLOW-UP ................ 37 
8.1. Transplant Details ............................................................................................................ 37 
8.2. Post Transplant Functional Assessments Day 0 – Day 30: .............................................. 37 
8.3. Long Term Follow-up: 6 and 12 months: ........................................................................ 38 
9. 
EVALUATION OF ADVERSE EVENTS ............................................................................... 39 
9.1. Serious Adverse Events (SAEs) ........................................................................................ 39 
9.2. Anticipated and Unanticipated Serious Adverse Events ................................................. 39 
9.3. Heart Graft Related SAEs ................................................................................................. 39 
9.4. Unanticipated Adverse Device Effect (UADE) ................................................................. 39 
9.5. Reporting of Adverse Events ........................................................................................... 41 
9.5.1. Relationship of an Adverse Events to OCS™ Heart ............................................. 41 
9.5.2. Severity ................................................................................................................ 42 
9.5.3. Pre-Existing Conditions ........................................................................................ 42 
10. 
STATISTICAL METHODS ................................................................................................. 42 
10.1. 
General ................................................................................................................ 42 
10.2. 
Analysis Populations ............................................................................................ 42 
10.2.1. Transplanted Recipient Population ..................................................................... 42 
10.2.2. OCS Heart Population .......................................................................................... 42 
10.3. 
Statistical Analysis ............................................................................................... 43 
10.3.1. Primary Endpoint ................................................................................................. 43 
10.3.2. Secondary Endpoints ........................................................................................... 43 
10.3.3. Other Endpoints .................................................................................................. 43 
10.4. 
Safety ................................................................................................................... 43 
10.4.1. Other Safety Analyses ......................................................................................... 43 

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10.5. 
Sample Size Determination ................................................................................. 44 
11. 
RISK ANALYSIS .............................................................................................................. 44 
11.1. 
Potential Risks ..................................................................................................... 44 
11.2. 
Manner in Which the Potential Risks Have Been Minimized .............................. 44 
11.3. 
Potential Benefits ................................................................................................ 45 
11.4. 
Risks Benefit Ratio ............................................................................................... 45 
12. 
DEVICE/SITE MANAGEMENT ......................................................................................... 45 
12.1. 
Packaging and Labeling ....................................................................................... 45 
12.2. 
Storage ................................................................................................................ 46 
12.3. 
Accountability ...................................................................................................... 46 
12.4. 
Device Complaints and Malfunctions .................................................................. 46 
13. 
REGULATORY/ETHICS .................................................................................................... 46 
13.1. 
Institutional Review Boards (IRB) ........................................................................ 46 
13.2. 
Informed Consent ................................................................................................ 46 
14. 
DATA COLLECTION/RECORDS/REPORTS ........................................................................ 47 
14.1. 
Investigator Records ............................................................................................ 47 
14.2. 
Investigator Reports ............................................................................................ 47 
14.3. 
Data Collection .................................................................................................... 48 
14.4. 
Source Documents .............................................................................................. 48 
14.5. 
Archiving of Records ............................................................................................ 48 
15. 
CLINICAL MONITORING ................................................................................................. 49 
15.1. 
Monitoring ........................................................................................................... 49 
15.2. 
Pre-Investigational (Initiation) Visit .................................................................... 49 
15.3. 
Periodic Monitoring Visits ................................................................................... 50 
15.4. 
Frequency of Monitoring Visits ........................................................................... 50 
15.5. 
Trial Completion Visit .......................................................................................... 50 
15.6. 
Protocol Deviations ............................................................................................. 50 
15.7. 
Medical Monitor .................................................................................................. 51 
15.8. 
Data Safety Monitoring Board & Stopping Rules ................................................ 51 
15.9. 
Investigator Training ........................................................................................... 52 
15.10. 
Confidentiality ..................................................................................................... 52 
15.11. 
Amendment Policy .............................................................................................. 52 
16. 
REFERENCES .................................................................................................................. 52 
APPENDIX 1. 
ISHLT CONSENSUS MANUSCRIPT HEART PRIMARY GRAFT DYSFUNCTION 
(PGD) (KOBASHIGAWA, ET AL. 2014) .................................................................... 55 
APPENDIX 2. 
SCHEDULE OF CLINICAL ASSESSMENTS .......................................................... 56 
APPENDIX 3. 
DRAFT PATIENT INFORMED CONSENT FORM TEMPLATE ............................... 57 
APPENDIX 4. 
DRAFT ELECTRONIC CASE REPORT FORMS .................................................... 58 

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OCS™ HEART EXPAND CAP SYNOPSIS 
Protocol Title 
Continued Access Protocol to collect additional evidence to evaluate the Safety and Effectiveness 
of The Portable Organ Care System (OCS™) Heart for preserving, resuscitating and assessing 
Expanded Criteria Donor Hearts for Transplantation (Heart EXPAND CAP) 
Intended Use 
The OCS™ Heart will be used to preserve and assess donor hearts that do not meet current 
standard donor heart acceptance criteria for transplantation for one or more of the following 
reasons: 
• Expected total cross-clamp time of ≥4 hours; 
• Expected total cross-clamp time of ≥2 hours PLUS one or more of the following risk factors: 
− 
Donor age 45-55 years, inclusive, with no coronary catheterization data; or  
− 
Donor age ≥55 years; or 
− 
Left ventricular septal or posterior wall thickness of >12mm, but ≤16 mm; or 
− 
Reported down time of ≥20 min, with stable hemodynamics at time of final 
assessment; or 
− 
Left heart ejection fraction (EF) ≥40%, but ≤50% at time of acceptance of offer; or 
− 
Donor angiogram with luminal irregularities with no significant CAD (≤50%); or 
− 
History of carbon monoxide poisoning with good cardiac function at time of donor 
assessment; or 
− 
Social history of alcoholism with good cardiac function at time of donor assessment; or 
− 
History of diabetes without significant CAD (≤50%) on angiogram 
Objectives 
To provide additional data evaluating the safety and effectiveness of the OCS™ Heart System to 
preserve and assess donor hearts that do not meet current standard donor heart acceptance 
criteria (as identified above) for transplantation to potentially improve donor heart utilization for 
transplantation at a range of transplant centers in the U.S. and to permit patients and physicians 
access to the OCS Heart System while a PMA application is under preparation and review. 
Trial Design 
A prospective single-arm trial 
Trial Size 
A maximum of 8 participating sites with 75 transplanted heart recipients 
Screening and 
Treatment  
Donor hearts that are deemed acceptable for transplant will be screened for trial eligibility. Eligible 
donor hearts will be preserved and assessed with the Organ Care System (OCS). After OCS 
preservation and assessment, donor hearts will be evaluated for acceptability for transplantation 
according to prespecified criteria. 
 
Primary heart transplant candidates will be screened for trial eligibility. Every eligible candidate will 
be asked to participate. Eligible heart transplant candidates will receive OCS preserved donor 
hearts that have been deemed clinically acceptable for transplantation following preservation by 
the treating transplant clinical team according to specified criteria. 
Donor Heart 
Eligibility Criteria 
Inclusion 
At least one of the following: 
• 
Expected total cross-clamp time of ≥4 hours;  
• 
Expected total cross-clamp time of ≥2 hours PLUS one or more of the following risk 
factors: 
− 
Donor age 45-55 years, inclusive, with no coronary catheterization data; or  
− 
Donor age ≥55 years; or 
− 
Left ventricular septal or posterior wall thickness of >12 mm, but ≤16 mm; or 

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− 
Reported down time of ≥20 min, with stable hemodynamics at time of final 
assessment; or 
− 
Left heart ejection fraction (EF) ≥40%, but ≤50% at time of acceptance of offer; or 
− 
Donor angiogram with luminal irregularities with no significant CAD (≤50%); or 
− 
History of carbon monoxide poisoning with good cardiac function at time of donor 
assessment; or 
− 
Social history of alcoholism with good cardiac function at time of donor 
assessment; or 
− 
History of diabetes without significant CAD (≤50%) on angiogram.  
 Exclusion 
• 
CAD with >50% stenosis on angiogram, or  
• 
Cardiogenic shock or myocardial infarction, or  
• 
EF consistently <40%, or 
• 
Significant valve disease except for competent bicuspid aortic valve. 
Recipient 
Eligibility Criteria 
Inclusion 
• 
Registered primary heart transplant candidate 
• 
Age >18 years old 
• 
Written informed consent. 
Exclusion 
• 
Prior solid organ or bone marrow transplant 
• 
Chronic use of hemodialysis or renal replacement therapy for diagnosis of chronic renal 
insufficiency requiring dialysis 
• 
Multi-organ transplant. 
Donor Heart OCS 
Acceptance and 
Rejection Criteria  
Accept for Transplantation 
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). Parameters should be maintained within the following 
ranges for acceptance: 
• 
Final arterial perfusate lactate <5 mmol/L with stable lactate trend 
• 
Stability of OCS Heart Perfusion Parameter trends over time within the guidance ranges 
below: 
− 
Aortic Pressure (mean AOP): 40-100 mmHg 
− 
Coronary Flow (CF): 400-900 mL/min. 
Reject for Transplantation 
Donor hearts preserved on the OCS will be rejected for any of the following:  
• 
Transplanting surgeon and/or designee is clinically unsatisfied with donor heart 
condition/performance on the OCS Heart System at final evaluation, e.g., unstable and 
rising arterial lactate despite multiple maneuvers to optimize perfusion parameters 
(increasing AOP and/or CF) 
• 
Final arterial perfusate lactate ≥5 mmol/L 
 
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.  
Primary Endpoint 
• A composite of patient survival at Day 30 and absence of severe primary heart graft 
dysfunction (PGD) (LV or RV) in the first 24 hours post-transplantation according to ISHLT 
consensus manuscript (as defined in Appendix 1 of protocol) 

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Secondary 
Endpoints 
• Patient and graft survival at Day-30 post-transplant 
• Incidence of severe primary heart graft dysfunction (PGD) (LV or RV) in the first 24 hours 
post-transplantation according to ISHLT consensus manuscript (as defined in Appendix 1 of 
protocol) 
• Rate of donor heart utilization, defined as the proportion of eligible donor hearts that were 
successfully transplanted after preservation and assessment on the OCS Heart System. 
Other Endpoints 
• Patient survival at 6 and 12 months post-transplant 
• Incidence of primary graft failure requiring re-transplantation through 12 months post-
transplant 
• Duration of initial post-transplant ICU stay 
• Duration of initial post-transplant hospital stay.  
Safety 
Incidence of heart graft-related Serious Adverse Events (HGRSAEs) in the first 30 days post heart 
transplantation, defined as:  
• Moderate or Severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) according to ISHLT consensus manuscript (as 
defined in Appendix 1 of the protocol). 
• Primary graft failure requiring re-transplantation.  
Follow-up 
All patients will be followed for 12 months post-transplant (including post-market). 
Statistical 
Methods 
 
The transplanted recipient population will consist of all recipients who are transplanted according 
to this protocol. The analyses of all effectiveness and safety endpoints, except the rate of donor 
heart utilization, will be based on the transplanted recipient population.  
 
The OCS heart population will consist of all donor hearts that are instrumented on the OCS Heart 
System. The analysis of the rate of donor heart utilization that were successfully transplanted after 
preservation and assessment on the OCS Heart System will be based on the OCS heart population. 
 
The primary endpoint will be summarized using counts and percentages and an exact 95% 
confidence interval for the true percentage based on the binomial distribution.  
 
Each secondary effectiveness endpoint will be summarized using counts and percentages and an 
exact 95% confidence interval for the true percentage based on the binomial distribution. The first 
two secondary effectiveness endpoints will be analyzed using the transplanted recipient 
population.  
 
The rate of donor hearts that were successfully transplanted after preservation and assessment on 
the OCS Heart System (i.e., donor heart utilization), will be analyzed using the OCS heart 
population. 
 
Safety will be analyzed principally by examination of the frequency of adverse events. In particular, 
the number of heart graft-related serious adverse events (HGRSAEs) up to the 30-day follow-up 
after transplantation per subject will be analyzed. This endpoint is defined to consist of the 
following adverse events (at most one per type), if they are serious adverse events: 
• Moderate or severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) according to ISHLT consensus manuscript (as 
defined in Appendix 1 of the protocol).  
• Primary graft failure requiring re-transplantation.  
 

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This endpoint will be summarized using descriptive statistics, specifically the mean, median, 
standard deviation, minimum, maximum, and a 95% confidence interval for the mean based on the 
t-distribution.  
Determination of 
Sample Size  
This is a continued access protocol and does not have a statistically determined sample size 
Trial Sponsor 
TransMedics, Inc. 
200 Minuteman Road, Suite 302 
Andover, MA, USA 01810 
 
 

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1. 
INTRODUCTION AND BACKGROUND INFORMATION 
1.1. 
Heart Transplantation and Current Clinical Challenges 
Heart transplantation is the gold standard and the most cost-effective treatment for end-stage heart 
failure (Hunt and Haddad 2008). While the demand for heart transplantation globally has increased 
significantly each year, the utilization or recovery of available donor hearts for transplantation has 
been limited. Based on the Organ Procurement and Transplantation Network (OPTN) 2014 report, 
4,323 (approximately 50%) consented, donor hearts in the US are not recovered annually, depriving 
thousands of patients the gift of new hearts to treat their end-stage heart disease (Israni, et al., 2016) 
(Figure 1). 
Figure 1: 
Heart Organ Use in the United States in 2014 (Figure DOD7.5 from OPTN/SRTR 
Annual Data Report 2014) (Israni, et al., 2016) 
 

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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 (so-called “Destination Therapy”) (Figure 2). 
Figure 2: 
MCS devices implanted in US 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 US 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 (see Table 1). Status 1A patient include 
those who were implanted with MCS devices while awaiting transplant. 
 
 
 
 

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• Assessing the adequacy of the perfusion and metabolic condition of the donor heart 
utilizing standard lactate levels to allow physicians to judge the suitability of the organ for 
transplantation using the standard criteria that physicians currently use when harvesting 
the organ from the donor, thus minimizing the risk of transplanting poorly functioning 
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 
utilizing extended criteria donors with the OCS Heart System has the potential to provide them 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. 
OCS Heart EXPAND Trial 
The Heart EXPAND trial (G140111) is an FDA-approved single arm study of extended criteria donor 
hearts, i.e., those that are currently not transplanted or are seldom transplanted in the U.S. due to 
challenging donor characteristics/medical history, or projected extended ischemia times (possibly due 
to procurement or complicated recipient explantation issues due to VADs).  
The Heart EXPAND trial was designed to enroll 75 subjects at a maximum of 20 U.S. sites. The primary 
endpoint is a composite of patient survival at Day 30 post-transplant and absence of severe primary 
graft dysfunction (PGD) at 24 hours post-transplant. Secondary Endpoints included: donor heart 
utilization rate (i.e., how many of these non-standard hearts were actually transplanted after OCS 
Heart System preservation and assessment), 30-day patient survival and freedom from severe 
primary graft dysfunction (PGD) at 24 hours after transplant.  
The 75th subject was enrolled on March 25, 2018, and the trial has reached its enrollment limit. The 
trial data are still being entered, cleaned and adjudicated, and patient follow-up is on-going. The 
sections below summarize the available data to date. 

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2.2.1. 
Donor Heart Utilization 
The Heart EXPAND trial was designed for 75 subjects at 20 US sites. The primary effectiveness 
endpoint is a composite of patient survival at Day 30 post-transplant and freedom from severe 
primary graft dysfunction (PGD) at 24 hours post-transplant. Secondary endpoints include: donor 
heart utilization rate (i.e., how many of these non-standard hearts were actually transplanted after 
OCS Heart System preservation and assessment), 30-day survival and freedom from severe PGD at 24 
hours after transplant. The primary hypothesis for this trial is that the true proportion of transplanted 
recipients with the composite of patient survival at Day 30 post-transplantation and freedom from 
severe PGD in the first 24 hours post-transplantation is greater than the Performance Goal value of 
0.65 (65%). This performance goal is based on literature and statistics for standard criteria heart 
transplants. Prior to the Heart EXPAND trial, there were no data available on post-transplant 
outcomes of extended criteria donor hearts.  
The safety endpoint is the number of heart graft-related serious adverse events (HGRSAEs) up to the 
30-day follow-up after transplantation per subject. The endpoint is defined to consist of the following 
adverse events (at most one per type) if they are serious adverse events: 
• Moderate or severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) as defined in Appendix 2 of the protocol, according 
to the ISHLT consensus manuscript. 
• Primary graft failure requiring re-transplantation 
The Heart EXPAND trial is a single arm study of extended criteria donor hearts, i.e., those that are 
currently not transplanted or are seldom transplanted in the US. To be included in this study, donor 
hearts had to have met one or more of the following inclusion criteria: 
• Expected total cross-clamp time of ≥ 4 hours 
• Expected total cross-clamp time of ≥ 2 hours PLUS one or more of the following risk 
factors: 
− Donor age 45-55 years old with no coronary catheterization data, or 
− Donor age ≥ 55 years old; or 
− Left ventricular septal or posterior wall thickness of >12 ≤ 16 mm; or 
− Reported down time of ≥20 min, with stable hemodynamics at time of final 
assessment; or 
− Left heart ejection fraction (EF) ≥ 40 ≤ 50%; or 
− Donor angiogram with luminal irregularities with no significant CAD 
− History of Carbon monoxide poisoning with good cardiac function at time of donor 
assessment 
− Social history of alcoholism with good cardiac function at time of donor assessment; or 
− History of diabetes combined with negative coronary angiogram for coronary artery 
disease (CAD). 

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standard donor hearts preserved on OCS were non-inferior to the outcomes of heart transplant 
recipients whose donor hearts were preserved using standard of care cold storage.  
TransMedics received full approval for the PROCEED II trial protocol under IDE G060127/S024 on July 
22, 2008. The results have been published in the Lancet (Ardehali, et al. 2015). 
2.3.1. 
Study Purpose 
The purpose of this trial was to compare the safety and effectiveness of the OCS Heart System to the 
standard of care cold storage (Control) for the preservation of standard donor hearts. The clinical trial 
and planned statistical analyses were a non-inferiority design intended to show that the OCS Heart 
System (OCS) was as safe and effective as cold storage for standard criteria heart preservation for 
transplantation.  
2.3.2. 
Primary Study Endpoint 
The primary study endpoint was 30-day patient survival following transplantation with the originally 
transplanted heart and no mechanical circulatory assist device at Day 30.  
2.3.3. 
Secondary Study Endpoints 
The secondary study endpoints were:  
• Incidence of serious cardiac (graft) related adverse events, defined as those which are 
attributed to preservation injury of the donor heart in the first 30 days post-transplant: 
right ventricular dysfunction; left ventricular dysfunction; graft failure and myocardial 
infarction.  
• Incidence of biopsy proven ISHLT grade 2R (moderate) or 3R (severe) acute rejection on 
any of the surveillance endomyocardial biopsies as determined by the core pathology 
laboratory or clinically symptomatic rejection requiring augmentation of 
immunosuppressive therapy during the 30-day follow-up period; and 
• Length of intensive care unit (ICU) stay. 
2.3.4. 
Subject Disposition 
Of the 143 initially screened and randomized patients, 13 patients failed secondary 
screening/eligibility. Thus, 130 patients comprised the ITT Population, with 67 patients randomly 
assigned to the OCS Group and 63 patients randomly assigned to the standard cold storage group 
(Control Group). The As-Treated Population consisted of 128 randomized patients who received an 
OCS or Control donor heart, regardless of whether or not there was conformance with the 
randomization assignment, with 62 in the OCS Group and 66 is the Control group. The Per-Protocol 
Population comprised 121 randomized subjects who received a donor heart in conformance with the 
randomization assignment and had no major protocol violations, with 60 in the OCS Group and 61 in 
the Control Group.  
2.3.5. 
Primary Study Endpoint Results 
The study met its primary endpoint for all study populations, demonstrating that the OCS is non-
inferior to Control preservation (Table 6).  

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measure of post-transplantation graft function and directly reflects the quality of the 
preservation of the donor heart.   
• During the conduct of the PROCEED II trial, five donor hearts designated for four randomized 
patients (1 patient with 2 donor hearts offered) were deemed not acceptable for 
transplantation while on the OCS and were declined for transplantation. The four patients 
(that these hearts were assigned to) were subsequently transplanted with another donor 
heart offer and their outcomes were included in the analysis of this trial. Four (4) of the 5 
donor hearts were declined due to rising perfusate lactate levels during the OCS preservation 
session, indicating persistent myocardial ischemia despite attempts of optimization of 
myocardial perfusion and 1 heart was declined due to friable aortic tissue that was difficult to 
support the aorta cannula for OCS perfusion. The ex-vivo metabolic assessment afforded by 
OCS is a new capability that enables some biomarker data to be assessed by the transplant 
team up to the point of transplantation, which cannot be achieved with cold storage.  
2.3.11. 
SRTR Database – Long Term Follow-up PROCEED II Patients 
Although the PROCEED II trial was designed with a maximum 30-day follow-up, FDA requested longer 
term survival data and TransMedics obtained data for the PROCEED II subjects from the Scientific 
Registry of Transplant Recipients (SRTR) voluntary registry. The SRTR voluntary registry 
(http://www.srtr.org/) manages the collection of U.S. national transplant data and conducts research 
on solid-organ transplantation in the U.S.1 In addition, TransMedics contacted its international sites 
to obtain long term follow-up on the 10 international patients who participated in the PROCEED II 
Trial since the SRTR patient registry includes only US patients. Finally, two US patients in the 
PROCEED II Trial were not included in the registry data set provided by SRTR (one due to transcription 
error in the UNOS ID number and one for unknown reasons). TransMedics contacted the US 
investigational sites and obtained follow-up status on these two US patients and survival status was 
confirmed. By aggregating the SRTR and site data, long-term follow-up information was available for 
patients ranging from 1 year up to 5 years post-transplantation.  
Post-hoc observational survival analyses for the PROCEED II trial patients were performed with 
Kaplan-Meier survival estimates calculated separately for the OCS and standard of care (SOC) Groups. 
These analyses considered all-cause mortality from the time of transplantation through 3 years and 3 
months, and included 130 patients (118 from the SRTR registry data set and 12 from TransMedics 
data collection directly from the investigational sites).  
Figure 6 below shows the post-hoc observational Kaplan-Meier survival analyses for All-Cause 
Mortality, which included 16 deaths in the OCS Group and 8 deaths in the SOC Group from heart 
transplantation (Day 0) through the follow-up period (3 years and 3 months). There was an apparent 
decrease in survival for the OCS subjects compared to the SOC patients. 
                                                 
1The study used data from the SRTR. The SRTR data system includes data on all donor, wait-listed candidates and 
transplant recipients in the U.S., submitted by the members of the Organ Procurement and Transplantation Network 
(OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services 
provides oversight to the activities of the OPTN and SRTR contractors. The data reported here have been supplied by the 
Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients 
(SRTR). The interpretation and reporting of these data are the responsibility of the sponsor and in no way should be seen 
as an official policy of or interpretation by the SRTR or the U.S. Government. 

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2.5. 
Discussion and Conclusions of the Long and Intermediate term Follow-up of 
OCS Heart System patients 
When including long-term follow-up from SRTR and other sources, there were 16 deaths in the OCS 
Group and 8 deaths in the SOC Group in PROCEED II patients from Day 0 through the follow-up period 
(3 years and 3 months). There was an apparent decrease in survival for OCS patients compared to the 
SOC patients. 
However, mirroring the short-term results of the PROCEED II trial, the SRTR long term data showed 
that the number of patients whose cause of death was due to PGF was similar between the two 
groups. The European data were consistent with this finding. Graft related mortality is the primary 
focus for assessing the impact of heart preservation technology such as the OCS Heart System.  
All other causes of mortality observed were consistent with the SRTR reported long-term causes of 
deaths for adult heart transplant recipients in the U.S. and are likely related to the 
immunosuppressed condition and other clinical factors of the recipient.  
2.6. 
Differences between PROCEED II and Heart EXPAND Trials 
When considering the totality of the evidence supporting the safety of the OCS Heart System, it is 
important to recognize that the two previous IDE trials of the OCS Heart System present a number of 
key differences: 
1. Differences in Donors: PROCEED II is a study of standard criteria donor hearts, while the Heart 
EXPAND trial is a study of extended criteria donor hearts, i.e., those that are seldom 
transplanted in clinical practice today. 
2. Differences in Recipients: Subjects were enrolled in PROCEED II using different 
inclusion/exclusion criteria than Heart EXPAND. PROCEED II was designed in 2006, based on 
the publication of the pivotal clinical trial for Celsior, which was the only new device 
technology for donor heart preservation at that time (Vega, et al., 2001). Heart EXPAND, on 
the other hand, was designed in 2014 and reflects the current clinical practices in the 
treatment of heart failure (use of VADs) as well as contemporary practices in heart 
transplantation. 
3. Observed Cross Clamp Time vs Expected Cross Clamp Time: Although expected cross clamp 
time > 4 hours was the inclusion criteria for 37% of the donors in Heart EXPAND, and 
extended cross-clamp times were also observed in PROCEED II, there are fundamental 
differences between the donor hearts in PROCEED II that had observed cross-clamp times > 4 
hours compared to the donor hearts in the Heart EXPAND trial that had expected cross clamp 
times > 4 hours. 
4. Differences in Practices for Cardioplegia and Myocardial Protection Protocols for Pre & Post-
OCS Heart Perfusion: PROCEED II was the first pivotal trial conducted of the OCS Heart System 
and at the time that the protocol was designed and approved by the FDA, TransMedics and 
the trial investigators did not fully appreciate the importance of standardizing and controlling 
various aspects of the clinical use model, including cardioplegia and myocardial protection 
following OCS Heart perfusion. These aspects of the clinical use model were standardized 
across all investigational sites in the OCS Heart EXPAND trial. 

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5. Differences in OCS Device Design: Following completion of PROCEED II, two major device 
modifications were made to standardize practices and increase the ease of use of the OCS 
Heart System, which were implemented in the Heart EXPAND trial. One of these device 
modifications was the replacement of the infusion pump used for solution administration 
from an off-the-shelf model (Alaris) to a fully integrated console subsystem (i.e., the Ex-Vivo 
Solution Delivery Subsystem (SDS)) that led to more consistent adherence with the use model. 
The second modification was a change in the oxygenator from the Novalung oxygenator (PN 
100001800) to the Maquet Quadrox-i oxygenator (PN 100004194) to allow the user to follow 
a mechanical cooling procedure of the OCS-preserved heart for improved myocardial 
protection post-OCS. Both of these changes were approved by FDA. 
For these reasons, it is appropriate to consider the PROCEED II results independently from the results 
for Heart EXPAND trial. The PROCEED II trial is supportive evidence and should not be considered as a 
primary data set when evaluating the OCS Heart System for the EXPAND indication. 
2.7. 
Overall Summary of Clinical Data to Support Initiation of Heart EXPAND CAP 
In summary, there have been two US IDE trials and numerous published OUS studies of the OCS Heart 
System. The existing clinical data support the initiation of this CAP. Specifically: 
In summary, there have been two U.S. IDE trials and numerous published OUS studies of the OCS 
Heart System. The existing clinical data support the initiation of this CAP. Specifically: 
• The OCS Heart EXPAND trial: This is the most clinically relevant data to support the CAP 
given that the donor hearts used were non-standard donor hearts that would mostly go 
unutilized for transplantation and have the identical eligibility critera proposed in this CAP. 
OCS Heart EXPAND Trial is 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. Although the data for the Heart EXPAND trial are still being collected, monitored 
and adjudicated, the preliminary results are very encouraging, demonstrating: 
− Utilization rate of 80.6% of donor hearts that are seldom used for transplantation 
today. These donor hearts were refused by other, non-EXPAND trial centers an 
average of 65.6 times but were able to be preserved and 80.6% were successfully 
transplanted in this study. 
− The incidence of ISHLT severe PGD was 10.7%, and the incidence of ISHLT moderate or 
severe PGD was 12.0%. These rates compare favorably with or are lower than 
contemporary literature reporting PGD rates post-heart transplantation from standard 
criteria donor hearts and based on ISHLT PGD criteria. 
− Survival at 30 days and 6 months was 94.7% and 88%, respectively, with 12-month 
follow-up still on-going. The deaths have been reviewed and adjudicated by the 
medical monitor. Four of the deaths are heart graft related with the remainder due to 
pre-existing conditions or other causes. 
• PROCEED II Trial was the first pivotal study of the OCS Heart System. This trial was 
designed in 2006 and it studied categorically different donor hearts and recipient profiles 
compared to OCS Heart EXPAND trial. Specifically, PROCEED II studied routine standard 

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donor hearts that were being used for transplantation at the time. The PROCEED II trial 
was a randomized study of the OCS Heart System compared to standard of care cold 
storage, and it enrolled routine standard criteria donor hearts that were transplanted into 
comparatively lower risk heart transplant recipients. 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).  
• Real life clinical experience of the OCS Heart System for preservation of standard criteria 
donor hearts conducted outside the U.S. at hospitals in Germany and the United Kingdom 
showed improved rates of survival and lower rates of PGD for OCS compared to standard 
of care cold storage. 
• Real life clinical experience of extended criteria donors, including numerous heart 
transplants from DCD donors, have been conducted outside the U.S. and the results for 
utilization and patient survival are very encouraging. 
In conclusion, this application includes a substantial body of evidence to support the safety and 
effectiveness of the OCS Heart System. In particular, the Heart EXPAND trial shows high utilization 
rate, with good clinical outcomes, demonstrating the ability of the OCS Heart System to expand the 
potential pool of donor organs. These data provide strong support for the initiation of the proposed 
CAP. 
3. 
DEVICE DESCRIPTION 
The OCS Heart System is an integrated portable platform designed to maintain donor hearts in a near 
physiologic, normothermic perfusion state. The OCS Heart System consists of: 
• OCS Heart Console 
• OCS Heart Perfusion Set – comprised of Heart Perfusion Module (HPM) and Accessories 
• OCS Heart Solution Set.  
These major components are shown in Figure 8 below.  

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Figure 8: 
Figures of the OCS Heart System 
 
3.1. 
Description of Major Components 
3.1.1. 
OCS Heart Console 
The OCS Heart Console is the reusable, non-sterile portable enclosure incorporating the electronics, 
software, fluid pumping systems, monitoring systems, power supply, batteries, gas cylinder, mobile 
base and Wireless Monitor. The Wireless Monitor displays information and allows the user to adjust 
certain settings.  
The OCS Heart Console provides a rigid compartment to house and securely connect to the HPM 
during transport. The OCS Heart Console connects to a mobile base with locking wheels. 
3.1.2. 
Heart Perfusion Set (HPS) 
The Heart Perfusion Set (HPS) consists of the Heart Perfusion Module (HPM) and Disposable 
Accessories. The HPM provides a closed circulatory system to protect, maintain and support the 
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 

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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 
Figure 9 below. The OCS contains a pulsatile pump that directs flow through the gas exchanger, to be 
oxygenated, and then through the blood warmer and then to the aorta of the donor heart. An 
additional perfusate component, known as the TransMedics Maintenance Solution, is infused into 
this circuit. The heart consumes oxygen and nutrients as the blood travels from the aorta through the 
coronary arteries and returns blood to the circuit through its pulmonary artery. The OCS maintains 
the blood at a constant temperature, oxygenates the perfusate at a constant rate, and provides 
perfusate in a pulsatile flow at a constant rate.  

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Figure 9: 
Schematic of the OCS Heart System Fluid Flow 
 
4. 
TRIAL OBJECTIVES 
The objective of Heart EXPAND CAP is to provide additional data evaluating the safety and 
effectiveness of the OCS Heart System to preserve and assess donor hearts that do not meet current 
standard donor heart acceptance criteria for transplantation to potentially improve donor heart 
utilization for transplantation at a range of transplant centers in the U.S. and to permit patients and 
physicians access to the OCS Heart System while a PMA application is under preparation and review. 
The donor hearts to be evaluated in this trial do not meet current standard donor heart acceptance 
criteria for one or more of the following reasons: 
• Expected total cross-clamp time of ≥ 4 hours  
• Expected total cross-clamp time of ≥ 2 hours PLUS one or more of the following risk 
factors: 
− Donor age 45-55 years inclusive, with no coronary catheterization data; or 
− Donor age ≥55 years; or 

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− Left ventricular septal or posterior wall thickness of >12 mm, but ≤16 mm; or 
− Reported down time of ≥ 20 min, with stable hemodynamics at time of final 
assessment; or 
− Left heart ejection fraction (EF) ≥40%, but ≤50% at time of acceptance of offer; or 
− Donor angiogram with luminal irregularities with no significant CAD (≤50%); or 
− History of carbon monoxide poisoning with good cardiac function at time of donor 
assessment; or 
− Social history of alcoholism with good cardiac function at time of donor assessment; or 
− History of diabetes without significant CAD (≤50%) on angiogram. 
4.1. 
Type of Trial 
The Heart EXPAND CAP is a prospective, single-arm continuation protocol. The CAP seeks to provide 
additional data on the safety and effectiveness of the OCS™ Heart System for donor hearts that today 
may not be transplanted due to the limitations associated with cold storage technique due to the 
impact of ischemia injury. The CAP permits patients and physicians access to the OCS Heart System 
while a PMA application is under preparation and review.  
4.2. 
Trial Size and Subject Follow-up 
This trial will be conducted at up to 8 institutions, in the United States and will include 75 
transplanted heart recipients. The number of subjects was determined based on the enrollment rate 
for Heart EXPAND and following FDA guidelines for CAPs.  
Subjects will be followed for 12 months from the date of transplantation (some of which will be post-
market). The summary of follow-up assessments are is summarized in Appendix 2: 
• All subjects will be followed from transplant to discharge. 
• Patient and graft survival will be documented at Day-30 post transplant.  
• Subjects will be followed at 6 and 12 months post-transplant as summarized in Appendix 
2. 
5. 
TRIAL ENDPOINTS 
5.1. 
Primary Endpoint 
A composite of patient survival at Day 30 and absence of severe primary heart graft dysfunction 
(PGD) (LV or RV) in the first 24 hours post-transplantation according to ISHLT consensus manuscript 
(as defined in Appendix 1). 
5.2. 
Secondary Endpoints 
• Patient survival and graft survival at Day-30 post transplantation 

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• Incidence of severe primary heart graft dysfunction (PGD) (LV or RV) in the first 24 hours 
post-transplantation according to ISHLT consensus manuscript (as defined in Appendix 1) 
• Rate of donor heart utilization, defined as the proportion of eligible donor hearts that 
were successfully transplanted after preservation and assessment 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, defined as:  
• Moderate or Severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) according to ISHLT consensus manuscript.  
• Primary graft failure requiring re-transplantation.  
5.4. 
Other Endpoints 
• Patient survival at 6 and 12 months post-transplant 
• Incidence of primary graft failure requiring re-transplantation through 12 months post-
transplant 
• Duration of initial post-transplant ICU stay 
• Duration of initial post-transplant hospital stay. 
6. 
TRIAL POPULATION  
The trial will consist of 75 heart transplant recipients, aged >18 years, at up to 8 investigational sites 
in the US. 
6.1. 
Donor Eligibility Criteria 
Donor Inclusion Criteria 
Donor hearts are required to meet at least one of the following inclusion criteria: 
• Expected total cross-clamp time of ≥4 hours; or 
• Expected total cross-clamp time of ≥2 hours PLUS one of the following risk factors: 
− Donor age 45-55 years, inclusive, with no coronary catheterization data; or 
− Donor age ≥55 years; or 
− Left ventricular septal or posterior wall thickness of >12 mm, but ≤16 mm; or 
− Reported down time of ≥20 min, with stable hemodynamics at time of final 
assessment; or 
− Left heart ejection fraction (EF) ≥40%, but ≤50% at time of acceptance of offer; or 
− Donor angiogram with luminal irregularities with no significant CAD (≤50%); or 

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− History of carbon monoxide poisoning with good cardiac function at time of donor 
assessment; or 
− Social history of alcoholism with good cardiac function at time of donor assessment; or 
− History of diabetes without significant CAD on angiogram (≤50%). 
Donor Exclusion Criteria 
Donor hearts will be excluded if they meet any of the following criteria: 
• CAD with >50% stenosis on angiogram, or  
• Cardiogenic shock or myocardial infarction, or  
• EF consistently <40%, or 
• Significant valve disease except for competent bicuspid aortic valve. 
6.2. 
Recipient Eligibility Criteria 
Recipient Inclusion Criteria 
Recipients are required to meet all the following criteria on the day of transplant: 
• Registered primary heart transplant candidate 
• Age ≥18 years old 
• Written informed consent.  
Recipient Exclusion Criteria 
Recipients will be excluded if they meet any of the following criteria on the day of transplant: 
• Prior solid organ or bone marrow transplant 
• Chronic use of hemodialysis or renal replacement therapy for diagnosis of chronic renal 
insufficiency requiring dialysis 
• Multi-organ transplant. 
6.3. 
Subject Enrollment and Screen Failures 
As part of the screening process, the following must occur:  
• Subject must be matched with a donor heart that meets eligibility criteria for Heart 
EXPAND CAP; and  
• Subject must meet eligibility criteria for Heart EXPAND CAP; and 
• The matched donor heart must be accepted for transplantation in the donor chest by the 
transplant surgeon or designee; and  
• The matched donor heart must be instrumented on the OCS. 
A subject will be considered a screen failure under the following conditions: 

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• The donor heart matched to this recipient fails to meet transplantability criteria per 
Section 7.4 of the protocol following OCS Heart System instrumentation (i.e., donor heart 
turndown). 
• The recipient fails to meet inclusion/exclusion criteria on the day of the potential 
transplant after an eligible donor heart is instrumented on the OCS™ Heart System and 
accepted for transplantation following OCS instrumentation preservation. 
• Logistical reasons prevent transplantation of 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 when the subject is transplanted with the OCS-instrumented 
organ. 
Subjects who are screen failures that remain eligible for the study will return to the waiting list for 
another heart transplant. Depending on the donor match, this next transplant may be either in the 
Heart EXPAND CAP or the subject may be transplanted using standard cold storage and will not be 
enrolled in this study.  
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.  
7. 
PRE-OPERATIVE TRIAL PROCEDURES 
7.1. 
Subject Identification  
All patients on the transplant waiting list, or in the process of listing on the transplant waiting list, 
who are approached by trial investigators for consent for this trial will be identified in a “screening 
log.” 
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 for participation in the trial prior 
to treatment. When a matching eligible donor heart becomes available, the inclusion and exclusion 
criteria for the recipient will be re-verified. 
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. The following information will be verified on the day of transplant:  
• Eligibility: Investigator will review and confirm that the potential recipient is still a 
candidate for heart transplantation and continues to meet all inclusion criteria and no 
exclusion criteria for this study. 
• Demographics/Characteristics  
• Recipient Risk Factors & Medical History  

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7.3. 
Donor Screening and Acceptance 
The investigator or a member of her/his transplant team will evaluate the donor and the quality and 
suitability of the heart for: (1) transplantation, according to his or her standard practice and (2) 
eligibility for the Heart EXPAND CAP. The following evaluations will be conducted: 
• Organ Donor Identification Number and Type of Registry (e.g., UNOS ID) 
• Donor Demographics  
• Donor Characteristics  
• Donor’s Cause of Death  
• Donor Medical History  
• Donor Social History  
• Donor Heart Assessment: An EF is required to determine subject eligibility. The donor 
heart can be assessed prior to procurement and acceptance using one or more of the 
following methods: 
− Angiogram findings (if available) 
− Echocardiogram findings (if available) 
− Final inspection and palpation prior to acceptance in the chest 
• Donor Eligibility: The donor will be evaluated to document whether the eligibility criteria 
for Heart EXPAND CAP are met.  
7.4. 
Donor Heart Retrieval and OCS Preservation and Assessment 
After final evaluation of the donor heart in the donor’s chest and after a decision is made to procure 
the organ for transplantation, donor eligibility for Heart EXPAND CAP will be reviewed. Upon 
acceptance into the trial, the investigators will retrieve and preserve the donor heart according to the 
OCS Heart Instructions for use (IFU). 
7.4.1. 
Donor Heart Acceptance 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). Parameters should be maintained within the following ranges for 
acceptance: 
• Final arterial perfusate lactate < 5 mmol/L with stable lactate trend 
• Stability of OCS Heart Perfusion parameter trends over time within the guidance ranges 
below: 
− Aortic Pressure (mean AOP): 40-100 mmHg 
− Coronary Flow (CF): 400-900 mL/min. 

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Note: certain expanded criteria donor hearts may require perfusion with parameters outside of these 
guidance ranges. Acceptance for transplantation should be primarily based on an acceptable lactate 
trend/value. 
7.4.2. 
Reject for Transplantation 
Donor hearts preserved on the OCS will be rejected for any of the following:  
• Transplanting surgeon and/or designee is clinically unsatisfied with donor heart 
condition/performance on the OCS Heart System at final evaluation, e.g., unstable and 
rising arterial lactate despite multiple maneuvers to optimize perfusion parameters 
(increasing AOP and/or CF) 
• Final arterial perfusate lactate ≥ 5 mmol/L. 
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 
8.1. 
Transplant Details  
The following information concerning the transplant procedure will be collected:  
• The organ recipient unique post-transplant patient identifier 
• 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 Primary Graft Dysfunction (PGD) Surveillance in the first 24 hours (see Appendix 1) 
• Initial use of Mechanical Circulatory Support  
• Inotropic Support for first 24 hours: the following inotropic medication doses, if available, 
will be collected at ICU admission T0 and T24 hours after ICU admission post-heart 
transplantation: 
− Dopamine – mcg/kg/min 
− Dobutamine – mcg/kg/min 
− Amiodarone – mcg/kg/min 
− Milrinone – mcg/kg/min 

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− Epinephrine – mcg/kg/min 
− Norepinephrine – mcg/kg/min 
• Echocardiogram results in the first 24 hours 
• Right Heart Catheter Data between ICU admission T0 and T24 hours after ICU admission 
post-heart transplantation (not required; collected only if performed as part of the 
institution’s standard of care): 
− Pulmonary Artery Pressures (PAP) 
− Pulmonary Capillary Wedge Pressure (PCWP) 
− Cardiac index (CI) 
− Right Atrial Pressure (RAP) 
− Initial Post-Transplant ICU Stay 
• Initial use of Mechanical Respiratory Support 
• Initial Post-Transplant Hospital Stay 
• Immunosuppression Medications 
• Trans-thoracic echocardiogram prior to Discharge 
• Patient and Graft Survival at Day 30 (+5 days), patient and graft survival 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 and 12 months post transplant. Although the follow-
up may be done via phone contact; medical records may be needed for additional information.  
• 6-Month Follow-Up: At 6 months post transplant (± 30 days), the patient will be evaluated 
for: 
− Patient and graft survival 
− Whether the patient was re-hospitalized after initial discharge, and, if so, the primary 
reason for the hospitalization and the length of stay 
− Information will also be collected on any diagnosis of cardiac dysfunction and, if so, the 
method of diagnosis and treatment.  
• 12-Month Follow-Up: At 12 months (± 30 days) post transplant, the patient will be 
evaluated for: 
− Patient and graft survival 
− Any diagnosis of cardiac allograft vasculopathy and, if so, the method of diagnosis 
(e.g., IVUS, coronary angio). 

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9. 
EVALUATION OF ADVERSE EVENTS  
Only serious adverse events (SAEs) will be captured in this study. 
9.1. 
Serious Adverse Events (SAEs) 
An adverse event will be classified as serious if it meets any of the following criteria: 
• Results in, leads to, or contributes to, a death; 
• Is life-threatening; 
• Results in permanent disability or incapacity (i.e., permanent impairment of a body 
function or permanent damage to a body structure); 
• Requires in-patient hospitalization or prolongs hospitalization; 
• Necessitates medical or surgical intervention to preclude a permanent disability or 
incapacity; 
• Results in fetal distress, fetal death or a congenital anomaly/birth defect. 
9.2. 
Anticipated and Unanticipated Serious Adverse Events 
The investigator will assess each serious adverse event for whether it is anticipated or unanticipated 
using the definitions below. 
9.3. 
Heart Graft Related SAEs 
Heart Graft Related SAEs (HGRSAEs) are defined as 
• Moderate or Severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) according to ISHLT consensus manuscript.  
• Primary graft failure requiring re-transplantation.  
Heart-graft related SAEs will be collected from the time a subject is transplanted with the OCS™ heart 
until the completion of the 30-day follow-up evaluation. A HGRSAE will be followed until resolution or 
stabilization of the event. 
9.4. 
Unanticipated Adverse Device Effect (UADE)  
An UADE means any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was not previously 
identified or encountered before at least once in standard clinical practice, in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
Anticipated serious adverse events are associated with heart transplant procedures and have been 
documented within the first 30 days after heart transplant The list of events includes, but is not 
limited to: 
• Acute rejection 

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• Atrial and ventricular arrhythmias 
• Bleeding (major) 
• Hemodynamic instability 
• Death 
• Fever 
• Primary Graft Dysfunction  
• Respiratory failure 
• Graft failure 
• Sepsis 
• Renal dysfunction 
• Hyperammonaemia 
• Malignancy (post-transplant lymphoproliferative disorder (PTLD) 
• Multiple organ failure 
• Myocardial infarction 
• Neurological dysfunction 
• Hepatic dysfunction 
• Diabetes due to steroid and anti-rejection medications 
• Gall stones 
• 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) 

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• 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. 
9.5. 
Reporting of Adverse Events 
All SAE information will only be collected from transplant through day 30. 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.  
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.  
9.5.1. 
Relationship of an Adverse Events to OCS™ Heart  
The investigator will assess the relationship of the serious adverse event to the OCS™ Heart System. 
The relationship will be assessed using the following categories:  
• Definitely Related: There is a reasonable causal and temporal relationship between 
preservation with the OCS™ Heart and the adverse event. 
• Probably Related: It is more likely than not that there is a reasonable causal relationship 
between preservation with the OCS™ Heart 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. 

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• 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. 
9.5.2. 
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. 
9.5.3. 
Pre-Existing Conditions 
Pre-existing diseases or conditions will not be reported as adverse events. 
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.  
10.2. 
Analysis Populations 
10.2.1. 
Transplanted Recipient Population 
The transplanted recipient population will consist of all recipients transplanted with OCS Heart-
preserved donor hearts. The analyses of all effectiveness and safety endpoints, except the rate of 
donor hearts utilization that were successfully transplanted after preservation and assessment on the 
OCS Heart System, will be based on the transplanted recipient population. 
10.2.2. 
OCS Heart Population 
The OCS heart population will consist of all donor hearts that are instrumented on the OCS. The 
analysis of the rate of donor hearts utilization that were successfully transplanted after preservation 
and assessment on the OCS Heart System will be based on the OCS heart population. 

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10.3. 
Statistical Analysis  
10.3.1. 
Primary Endpoint 
The primary endpoint will be summarized using counts and percentages and an exact 95% confidence 
interval for the true percentage based on the binomial distribution.  
10.3.2. 
Secondary Endpoints 
Each secondary effectiveness endpoint will be summarized using counts and percentages and an 
exact 95% confidence interval for the true percentage based on the binomial distribution. The first 
two secondary effectiveness endpoints will be analyzed using the transplanted recipient population.  
The rate of donor hearts that were successfully transplanted after preservation and assessment on 
the OCS Heart System (i.e., donor heart utilization), will be analyzed using the OCS heart population.  
10.3.3. 
Other Endpoints 
Other endpoints for this trial include: 
• Patient survival at 6 and 12 months post-transplant 
• Incidence of primary graft failure requiring re-transplantation through 12 months post-
transplant 
• Duration of initial post-transplant ICU stay 
• Duration of initial post-transplant hospital stay 
Each endpoint will be summarized using counts and percentages and an exact 95% confidence 
interval for the true percentage based on the binomial distribution.  
10.4. 
Safety  
Safety will be analyzed principally by examination of the frequency of adverse events. In particular, 
the number of heart graft-related serious adverse events (HGRSAEs) up to the 30-day follow-up after 
transplantation per subject will be analyzed. This endpoint is defined to consist of the following 
adverse events (at most one per type), if they are serious adverse events:  
• Moderate or severe primary heart graft dysfunction (PGD) (left or right ventricle) (not 
including rejection or cardiac tamponade) according to ISHLT consensus manuscript.  
• Primary graft failure requiring re-transplantation.  
This endpoint will be summarized using descriptive statistics, specifically the mean, median, standard 
deviation, minimum, maximum, and a 95% confidence interval for the mean based on the t-
distribution.  
10.4.1. 
Other Safety Analyses 
In addition, the numbers and percentages of subjects experiencing at least one (definitely or 
probably-related) serious device-related AE, at least one unanticipated SAE, and the number and 
percentage of deaths will all be tabulated. SAEs will also be tabulated using counts and percentages 
alone and in regards to the relationship of the SAE to the device, and the severity of the SAE.  

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10.5. 
Sample Size Determination 
This is a continued access protocol and the sample size was not determined using statistical methods. 
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 device such as graft failure, 
primary graft dysfunction, rejection, infection and other organs/systems complications, 
graft vessel disease (an expression of chronic rejection), infection, abnormal kidney 
function, diabetes, high level of cholesterol, high blood pressure, cancer and neurological 
complications. 
• 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, only 19.4% 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, have not indicated any safety signals that would preclude initiation of this study. 

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In addition, this clinical protocol incorporates several procedures to minimize the risks to subjects and 
to ensure the benefits of the clinical trial outweigh its potential risks. 
• The donor 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 device 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. 
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 80.6% utilization of these extended criteria 
donor 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. 

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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.  
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 
Written informed consent will be obtained from all subjects before any trial-specific procedures are 
performed.  
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 as Appendix 3.  

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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 
• 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 

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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. 
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. 

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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.  
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 
is 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.  
The Sponsor has ethical, legal and scientific obligations to carefully follow this trial in a detailed and 
orderly manner in accordance with established research principles. As part of a concerted effort to 
fulfill these obligations (maintain current personal knowledge of the progress of the trial), the 
Sponsor's monitors will visit the center during the trial in addition to maintaining frequent telephone 
and written communications. The following guidelines are provided to describe the Sponsor’s 
procedures for monitoring the clinical studies. If the investigator is not complying with the signed 
Investigator Agreement, the protocol, or any condition of the trial, (e.g., incomplete data forms) the 
Sponsor has the right to terminate the investigator’s participation in the trial. The Sponsor is 
responsible for selecting trial monitors qualified by training and experience to conduct monitoring of 
the trial and for ensuring the quality of the trial monitoring visits by the monitor. The Sponsor’s 
general monitoring procedures for investigational studies are described below. 
15.2. 
Pre-Investigational (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 nature 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 review and 
approval of the clinical investigation before it is initiated and to ensure continuing review 
of the study by the Institutional Review Board, and to keep the sponsor informed of 
all Institutional Review Board actions concerning the study  

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• Has adequate facilities and access to an adequate number of suitable subjects to conduct 
the investigation. 
15.3. 
Periodic Monitoring Visits 
Monitoring visits will be conducted as scheduled by the sponsor. The monitor should visit each site as 
needed to ensure the following: 
• Facilities continue to be adequate and acceptable. 
• Informed consent has been obtained. 
• The protocol is being properly followed. 
• 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.  
15.5. 
Trial Completion Visit 
The trial termination visit may be combined with a monitoring visit. The following tasks will be 
completed at the last visit by the monitor. 
• 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 submitting a protocol deviation form. 
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. 
Sites must notify their IRB of protocol deviations in accordance with local IRB requirements. 

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15.9. 
Investigator Training 
Device, protocol and electronic database training will be provided to the appropriate personnel prior 
to patient enrollment in the trial. Device training will be conducted at the TransMedics clinical 
training facility or equivalent training facility. Protocol training will include a thorough review of this 
protocol. Electronic database training will consist of an explanation of the structure of the database, 
the data elements to be collected, simulated use of the database, error handling, and instructions 
regarding the handling of queries. 
15.10. 
Confidentiality 
All information generated in this trial will be considered highly confidential and must not be disclosed 
to any persons not directly concerned with the trial without written prior permission from the 
Sponsor. Authorized regulatory officials and Sponsor personnel (or their representatives) will be 
allowed full access to inspect and copy the records. All investigational devices, subject bodily fluids, 
and/or other materials collected shall be used solely in accordance with this protocol, unless 
otherwise agreed to in writing by the Sponsor. Subjects will be identified only by initials and unique 
subject numbers on the case report forms. If necessary, their full names may be made known to the 
Sponsor, a regulatory agency, or other authorized officials. 
15.11. 
Amendment Policy 
The investigator will not make any changes to this protocol without prior written consent from the 
Sponsor and subsequent approval by the IRB or EC, except if the deviation from the protocol is 
necessary to protect the life and physical well being of a subject in an emergency. Such protocol 
deviations will be reported to the Sponsor and the reviewing IRB or EC as soon as possible, but no 
later than 5 working days after the emergency occurred. Protocol amendments will be submitted to 
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).  
16. 
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. Colvin, et al. OPTN/SRTR 2016 Annual Data Report: Heart. Am. J. Transplant., 2018, 
https://doi.org/10.1111/ajt.14561. 
3. D’Alessandro et al. Predictive Risk Factors for Primary Graft Failure Requiring Temporary 
Extra-Corporeal Membrane Oxygenation Support After Cardiac Transplantation in Adults. 
European Journal of Cardio-thoracic Surgery; 2011; 40: 962- 970.  
4. Dronavalli et al. Primary Graft Dysfunction Following Heart Transplantation; Validity of a 
Pragmatic Self-Reporting Definition. J. Heart Lung Transplant.; 2013: S213-214. 
5. Hunt, SA, Haddad F. The changing face of heart transplantation. J. Am. Coll. Cardiol.; 2008; 
52:587-598. 

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6. 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. 
7. Katz, et al. Advanced Therapies for End-Stage Heart Failure. Current Cardiology Reviews; 2015, 
11:63-72. 
8. Kirklin, et al. Eighth Annual INTERMACS Report: Special focus on framing the Impact of 
Adverse Events. J. Heart Lung Transplant.; 2017, 36: 1080-1086. 
9. Kobashigawa, et al. Report from a Consensus Conference on Primary Graft Dysfunction after 
Cardiac Transplantation. J. Heart Lung Transplant.; 2014; 33: 327-340. 
10. 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. 
11. Koerner, M. et al. Normothermic Ex Vivo Allograft Blood Perfusion in Clinical Heart 
Transplantation. Heart Surgery Forum. 2014. 17(3): E144-145. 
12. Lima et al. Marginal Cardiac Allografts Do Not Have Increased Primary Graft Dysfunction in 
Alternative List Transplantation. Circulation; 2006; 114: 127-32. 
13. Mancini, D. and Lietz, K. Selection of Cardiac Transplantation Candidates in 2010. Circulation; 
2010; 122:173-183. 
14. Nicoara, et al. Primary Graft Dysfunction after Heart Transplantation: Incidence, Trends and 
Associated Risk Factors. Am. J. Transplant.; 2018; 18:1461-1470. 
15. 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. 
16. Sabatino, et al. Clinical relevance of the International Society for Heart and Lung 
Transplantation Consensus Classification of Primary Graft Dysfunction after Heart 
Transplantation: Epidemiology, Risk Factors and Outcomes. J. Heart Lung Transplant.; 2017, 
36(11):1217-1225. 
17. Singh, et al. ISHLT Primary Graft Dysfunction Incidence, Risk Factors and Outcome: A UK 
National Study. Transplantation; 2018 May 1. doi: 10.1097/TP.0000000000002220. 
18. Sorabella, et al. Cardiac Donor Risk Factors Predictive of Short-Term Heart Transplant 
Recipient Mortality: An Analysis of the United Network for Organ Sharing Database. 
Transplant. Proc. 2015 Dec; 47(10): 2944-2951. 
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. Trivedi, et al. Heart Transplant Survival Based on Recipient and Donor Risk Scoring: A UNOS 
Database Analysis. ASAIO J. 2016; 62:297-301. 
21. Tsui, S., Private communication, 2015. 

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22. Vega, J.D., et al. A multicenter, randomized, controlled trial of Celsior for flush and 
hypothermic storage of cardiac allografts. Ann. Thorac. Surg. 2001 May 7(15):1442-1447. 
23. 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 Medical Monitor. 
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, 2018; Squiers, 2018). If 
hemodynamic data are not collected, the Medical Monitor will use available clinical data to 
adjudicate PGD severity grading. 

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APPENDIX 3. 
DRAFT PATIENT INFORMED CONSENT FORM TEMPLATE 
 
(This Page is Intentionally Left Clear)  
 

TransMedics Confidential 
 
Heart EXPAND CAP Ver 3.0 22-Sep-2020 
 
Page 58 of 58 
APPENDIX 4. 
DRAFT ELECTRONIC CASE REPORT FORMS 
 
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