Evaluating the Safety of Utilizing Donor Hearts From Donation After Circulatory Death (DCD) Donors Compared to Donor Hearts From Donation After Brain Death (DBD) Donors: A Single Center Pilot Study
Phase: NA
Conditions: Organ Transplant
Sponsor: Cedars-Sinai Medical Center

  
 
 
Evaluating the Safety of Utilizing Donor Hearts from 
Donation after Circulatory Death (DCD) Donors 
compared to Donor Hearts from Donation after Brain 
Death (DBD) Donors: A Single Center Pilot  
National Clinical Trial (NCT) Identified Number:  NCT05462041  
Sponsor - Investigator: Fardad Esmailian, MD 
Funded by:  Cedars Sinai Medical Center 
Version Number:  v.2.0 
 04 Aug 2022  
 

  
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schedule of Activities (SoA) ............................................................................................................... 3 
2 
INTRODUCTION ............................................................................................................................................ 4 
2.1 
Study Rationale .................................................................................................................................... 4 
2.2 
Background........................................................................................................................................... 4 
2.3 
Risk/Benefit Assessment .................................................................................................................... 5 
2.3.1 
Known Potential Risks ..................................................................................................... 5 
2.3.2 
Known Potential Benefits ................................................................................................ 6 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 6 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 6 
4 
STUDY DESIGN ............................................................................................................................................. 7 
4.1 
Overall Design ...................................................................................................................................... 7 
4.2 
Scientific Rationale for Study Design................................................................................................ 8 
4.3 
End of Study Definition ....................................................................................................................... 8 
5 
STUDY POPULATION .................................................................................................................................. 8 
5.1 
DCD Donor with NRP Eligibility Criteria ........................................................................................... 9 
5.2 
DCD Donor with DPP Eligibility Criteria ........................................................................................... 9 
5.3 
DBD Donor Eligibility Criteria ............................................................................................................. 9 
5.4 
Recipient Eligibility Criteria ............................................................................................................... 10 
5.5 
Screen Failures .................................................................................................................................. 10 
5.6 
Strategies for Recruitment and Retention ...................................................................................... 10 
6 
STUDY INTERVENTION ............................................................................................................................ 11 
6.1 
Study Intervention(s) Administration ............................................................................................... 11 
6.1.1 
Normothermic Regional Perfusion (NRP) Description ............................................. 11 
6.1.2 
Direct Procurement and Perfusion (DPP) Description ............................................. 12 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 15 
6.2.1 
Acquisition and accountability ...................................................................................... 15 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 15 
6.2.3 
Product Storage and Stability ....................................................................................... 16 
6.2.4 
Preparation ...................................................................................................................... 16 
6.3 
Study Intervention Compliance ........................................................................................................ 16 
6.4 
Concomitant Therapy ........................................................................................................................ 16 
7 
Study Stopping Rules and Participant Discontinuation/Withdrawal ...................................................... 16 
7.1 
Study Stopping Rules ........................................................................................................................ 17 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 17 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 17 
8.1 
Safety Assessments .......................................................................................................................... 17 
8.2 
Method for NRP - Normothermic Regional Perfusion (NRP) Procedures ................................. 18 
8.3 
Method for DPP - Direct Procurement and Perfusion (DPP) Procedures ................................. 20 
8.4 
Adverse Events and Serious Adverse Events ............................................................................... 24 
8.4.1 
Heart Graft-Related adverse events (HGRAE) .......................................................... 24 
8.4.2 
Definition of Serious Adverse Events (SAE) .............................................................. 24 
8.4.3 
Definition of Heart Graft-Related Serious Adverse Events (HGRSAE) ................. 24 
8.4.4 
Classification of an Adverse Event .............................................................................. 25 

  
8.4.5 
Time Period and Frequency for Event Assessment and Follow-Up ......................... 1 
8.4.6 
Adverse Event Reporting ................................................................................................ 1 
8.4.7 
Serious Adverse Event Reporting ................................................................................. 1 
8.4.8 
Events of Special Interest ............................................................................................... 1 
8.5 
Unanticipated Problems ...................................................................................................................... 1 
8.5.1 
Definition of Unanticipated Problems (UP) ................................................................... 1 
8.5.2 
Unanticipated Problem Reporting .................................................................................. 1 
9 
STATISTICAL CONSIDERATIONS ............................................................................................................ 2 
9.1 
Statistical Hypotheses ......................................................................................................................... 2 
9.2 
Sample Size Determination ................................................................................................................ 2 
9.3 
Populations for Analyses .................................................................................................................... 3 
9.4 
Statistical Analyses.............................................................................................................................. 3 
9.4.1 
General Approach ............................................................................................................ 3 
9.4.2 
Analysis of the Primary Endpoint(s) .............................................................................. 3 
9.4.3 
Analysis of the Secondary Endpoint(s) ......................................................................... 3 
9.4.4 
Baseline Descriptive Statistics ....................................................................................... 3 
9.4.5 
Planned Interim Analyses ............................................................................................... 3 
9.4.6 
Sub-Group Analyses ....................................................................................................... 4 
9.4.7 
Exploratory Analyses ....................................................................................................... 4 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ................................ 4 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ............................................................. 4 
10.1.1 
Informed Consent Process ............................................................................................. 4 
10.1.2 
Study Discontinuation and Closure ............................................................................... 5 
10.1.3 
Confidentiality and Privacy ............................................................................................. 5 
10.1.4 
Future Use of Stored Specimens and Data ................................................................. 6 
10.1.5 
Key Roles and Study Governance ................................................................................ 6 
10.1.6 
Safety Oversight ............................................................................................................... 6 
10.1.7 
Quality Assurance and Quality Control ......................................................................... 6 
10.1.8 
Data Handling and Record Keeping .............................................................................. 6 
10.1.9 
Protocol Deviations .......................................................................................................... 9 
10.1.10 
Publication and Data Sharing Policy ........................................................................... 10 
10.1.11 
Conflict of Interest Policy .............................................................................................. 10 
10.2 
Abbreviations ...................................................................................................................................... 11 
10.3 
Protocol Amendment History ........................................................................................................... 12 
11 
REFERENCES ............................................................................................................................................. 13 
 

Utilizing Donor Hearts from Donation after Circulatory Death (DCD) Donors compared to Donor Hearts from Donation after 
Brain Death (DBD) Donors: A Single Center Pilot  
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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and applicable United States (US) Code of Federal Regulations (CFR). The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from and documented approval from the Institutional Review Board (IRB), except where 
necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the 
conduct of this study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form, recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Evaluating the Safety of Utilizing Donor Hearts from Donation after 
Circulatory Death (DCD) Donors compared to Donor Hearts from Donation 
after Brain Death (DBD) Donors: A Single Center Pilot Study. 
Study Description: 
The purpose the research is to evaluate whether patients who receive a 
Donation after Circulatory Death (DCD) heart for cardiac transplantation 
using either normothermic regional perfusion (NRP) or direct procurement 
and perfusion (DPP) have similar outcomes as patients who receive 
Donation after Brain Death (DBD) heart using standard cold storage. The 
study will also evaluate whether DCD procured hearts have a meaningful 
impact on hearts available for transplantation at our center. 
 
Objectives: 
The primary objective of this proposed research is to evaluate the safety of 
utilizing DCD donor hearts as compared to DBD donor hearts for 
transplantation.  
 
The secondary objective is to assess the practical, financial, and logistical 
viability of using NRP vs. DPP for the procurement of DCD donor hearts. 
 
Endpoints: 
Primary Endpoints: 
Incidence of heart graft-related Serious Adverse Events (HGRSAEs) in the 
first 30 days post-heart transplantation in the DCD Heart Transplanted 
Recipient Population, defined as the following adverse events (at most one 
per type):  
• 
Moderate or Severe heart PGD (left or right ventricle) (not 
including rejection or cardiac tamponade) 
• 
Primary graft failure requiring retransplantation 
• 
Patient and graft survival at 30 days post-transplant 

Utilizing Donor Hearts from Donation after Circulatory Death (DCD) Donors compared to Donor Hearts from Donation after 
Brain Death (DBD) Donors: A Single Center Pilot  
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• 
Patient and graft survival at 30 days and initial hospital discharge, 
if later than 30 days 
• 
Use of post-transplant mechanical circulatory support (ECMO, 
LVAD, RVAD, BiVAD) for > 72 hours immediately post-transplant. 
 
Secondary Endpoints:  
• 
Length of time on waiting list for DCD hearts (compared to time on 
waiting list for DBD heart for that patient, and compared to the 
median time for a patient matched for height and ABO group) 
• 
Utilization rates of heart offers, donors attended, and hearts 
explanted in DCD donors as compared to DBD donors. 
• 
Cost per DCD transplant and cost saving per DCD transplant 
(especially for in-patients/MCS patients)  
 
Study Population: 
Study subjects will be drawn from patients listed for heart transplant at 
Cedars-Sinai Medical Center. 
  
Phase: 
N/A 
Description of 
Sites/Facilities Enrolling 
Participants: 
This study is designed to be conducted as a single-center prospective pilot 
trial at Cedars Sinai Medical Center in Los Angeles, California. 
Description of Study 
Intervention: 
The primary research procedures are procurement and utilization of DCD 
donor hearts for transplantation and data collection/analysis. 
Study Duration: 
The total study duration is 18 months. 
Participant Duration: 
The study includes 7 research visits. Total subject participation is 30 Days 
 
 
 
 

Utilizing Donor Hearts from Donation after Circulatory Death (DCD) Donors compared to Donor Hearts from Donation after 
Brain Death (DBD) Donors: A Single Center Pilot  
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1.2 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
/Assessments 
Screening 
Visit 
Visit #1 
(Day 0 at 
Transplant) 
Visit #2 
(Day 7 
post-
transplant 
± 2 days) 
Visit #3 
(Day 14 
post-
transplant 
± 2 days) 
Visit #4 
(Day 21 
post-
transplant 
± 2 days) 
Visit #5 
(at 
hospital 
discharge) 
Visit #6 
(Day 30 
post-
transplant 
± 7 days) 
Eligibility & Informed Consent 
X 
 
 
 
 
 
 
Demographics/Characteristics 
X 
 
 
 
 
 
 
Medical & Cardiac History 
X 
 
 
 
 
 
 
Data Collection Donor 
Characteristics 
 
X 
 
 
 
 
 
Patient Visit (recipient) 
X 
X 
X 
X 
X 
X 
X 
Heart Transplantation 
 
X 
 
 
 
 
 
Data Collection Transplant 
Details 
 
X 
 
 
 
 
 
Data Collection PGD Scores 
 
X 
X 
 
 
 
X 
Data Collection Inotrope 
Support 
 
X 
X 
 
 
X 
X 
Right Heart Catheter Data 
 
X 
 
 
 
 
 
Data Collection Mechanical 
Circulatory Support 
 
X 
X 
 
 
X 
X 
Data Collection Invasive 
Ventilator Support 
 
X 
X 
 
 
 
 
Endomyocardial Biopsy 
(recipient) 
 
 
X 
X 
X 
 
X 
Data Collection Patient 
Survival 
 
 
 
 
 
 
X 
Data Collection Graft Survival 
 
 
 
 
 
 
X 
Data Collection Post-
Transplant Hemodynamics 
 
X 
X 
X 
X 
 
X 
Data Collection 
Immunosuppressive Meds & 
Induction (if applicable) 
 
X 
X 
X 
X 
X 
X 
Data Collection ICU & Hospital 
Stay 
 
 
 
 
 
X 
 
Data Collection Heart Graft-
Related AEs and SAEs 
 
X 
X 
X 
X 
X 
X 
Heart Transportation 
NRP/OCS1 
 
X 
 
 
 
 
 
 
1 DCD donor heart recipients only 
 
 
 
 
 
 
 

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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Heart transplantation remains the gold standard treatment for patients with end-stage heart failure. 
However, the shortage of suitable donor hearts is a major limitation to the widespread utilization of this 
life-saving procedure. The most recent report from the Organ Procurement and Transplantation 
Network/Scientific Registry of Transplant Recipients reported a 42.5% increase in the number of newly 
listed heart transplantation candidates from 2008 to 2019.  Unfortunately, the number of heart 
transplantations performed annually has remained steady over the past several years at 3000 to 4000. 
Until recently, beating hearts from donation after brain death (DBD) donors were the only heart donors 
used for transplantation worldwide.  The simple preservation method of cold storage became routinely 
used to transport DBD hearts between the donor and recipient hospitals and adequately preserves 
these ideal donor hearts. However, during the last 20 years, the number of suitable DBD donors has 
plateaued while the number of patients diagnosed with end stage organ failure continues to increase. As 
a result, the waiting list for organ transplantation has grown.  
With the increasing number of waitlisted patients, aggressive efforts to expand the donor pool of quality 
organs are necessary. The disparity between the supply of and demand for donor hearts has led to 
renewed interest in donation after circulatory death (DCD) in heart transplantation. Studies have 
estimated that DCD heart transplantation can increase the availability of donor hearts by up to 30%. 
 
 
2.2 
BACKGROUND  
 
Normothermic Regional Perfusion (NRP) 
 
Although DCD transplantation has been performed for other organs in the United States, programs for 
DCD heart transplantation have yet to be fully established. A primary concern is irreversible myocardial 
injury and organ damage from warm ischemia time (WIT) and reperfusion injury, to which the heart is 
particularly vulnerable given its high-energy requirements.   
 
Recent studies from DCD heart transplantation programs in the United Kingdom (UK) and Australia have 
reported 30-day and 1-year survival, graft function, and incidence of rejection comparable to those with 
conventional donation after brain death (DBD) heart transplant recipients.  Despite these encouraging 
results, the UK and Australian DCD approaches using ex situ perfusion devices have limitations in terms 
of cost and concern for primary graft dysfunction (PGD) necessitating extracorporeal membrane 
oxygenation (ECMO).   
 

Utilizing Donor Hearts from Donation after Circulatory Death (DCD) Donors compared to Donor Hearts from Donation after 
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To mitigate these factors, we propose a DCD heart transplantation protocol using cardiopulmonary 
bypass (CPB) for normothermic regional perfusion (NRP) based on established strategies for NRP DCD 
donor heart retrieval. The proposed benefits of this strategy include optimal myocardial protection, 
correction of metabolic abnormalities associated with circulatory arrest, and in situ functional 
assessment of the donor organ prior to transplant.  
 
Direct Procurement and Perfusion (DPP) utilizing the Organ Care System (OCS) 
 
For the past several decades there has been scientific and clinical interest in the development of ex-vivo 
heart perfusion (EVHP) with oxygenated and nutrient enriched blood to reduce ischemic injury to the 
donor heart and potentially enable ex-vivo assessment of metabolic and mechanical function. More 
recently, EVHP has been used to potentially expand the donor pool to include hearts from donation 
after circulatory death (DCD). 
 
However, due to potential damage of warm ischemia in the donor and the functional arrest of the heart 
that may never recover, DCD donors are not widely utilized for adult heart transplantation in the U.S. In 
contrast, international transplant centers have been successfully transplanting hearts from DCD donors, 
using the OCS Heart System for resuscitation, preservation and assessment of these hearts prior to 
transplantation. The OCS Heart System can minimize the detrimental effects of ischemia because it 
perfuses the donor heart with warm oxygenated blood. It enables the heart to be resuscitated to full 
beating state, and importantly enables the transplant team to assess metabolic (lactate production) and 
perfusion parameters of these hearts to determine their suitability for transplantation.  
 
Currently, the TransMedics’ OCS Heart technology is the only portable system available for ex-vivo 
maintenance of the donor heart in a metabolically active and beating state.  It is currently FDA approved 
for the procurement and transport of both DCD and DBD donor hearts. 
 
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
The main immediate potential risk to study participants is primary graft dysfunction (PGD). A DCD heart 
suffers a variable warm ischemic injury, circulatory stasis and imperfect subsequent (post-procurement) 
functional assessment which might increase this risk compared to a standard DBD heart transplant. 
However, DCD hearts do not suffer the catecholamine storm-induced injury of brain death and are 
typically procured from younger donors with less potential for so-existing conditions. The early results of 
several large series of DCD heart transplantation have been reported, and the PGD risk has not been any 
different from that for DBD heart transplantation. The operative risk of standard DBD heart 
transplantation varies according to recipient and donor factors, but is typically in the range of 5-10%. A 
similar risk has been observed in multiple reports of DCD transplantation performed in numerous 
different centers. Most of these centers have been new to the procedure.  

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As far as long-term risks, studies have reported follow-up to 5 years which is equivalent to standard 
heart transplantation. There is no data beyond this, and so no comment regarding the potential for a 
different rate of coronary vasculopathy can be made, however, there is no signal of this from the 
medium-term series. 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
The potential benefits to the patients are of an earlier heart transplant with a better-quality donor 
heart. Access to DCD heart transplants is one of the most effective ways of increasing the donor pool for 
any patient. This applies as much to urgent status patients who are at high priority for a standard donor 
heart, as it does to low status patients who typically have very long waits for suitable donor organs. 
Patients who are of large size, ABO blood group O and with durable LVAD implants suffer particularly 
long waits for appropriate donor hearts, and are therefore subject to a higher waiting list mortality. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
Based on the above, the benefits of using DCD donated hearts to expand the donor pool for cardiac 
transplantation outweigh the potential risks to trial subjects. 
 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR ENDPOINTS 
Primary 
 
 
The primary objective of this 
proposed research is to evaluate 
the safety of utilizing DCD donor 
hearts as compared to DBD donor 
hearts for transplantation. 
Incidence of heart graft-related 
Serious Adverse Events (HGRSAEs) in 
the first 30 days post-heart 
transplantation in the DCD Heart 
Transplanted Recipient Population, 
defined as the following adverse 
events (at most one per type):  
- Moderate or Severe heart PGD (left 
or right ventricle) (not including 
rejection or cardiac tamponade) 
- Primary graft failure requiring 
retransplantation 
- Patient and graft survival at 30 days 
post-transplant 
- Patient and graft survival at 30 days 
and initial hospital discharge, if later 
than 30 days 
- Use of post-transplant mechanical 
circulatory support (ECMO, LVAD, 
The primary objective 
of the study is to 
evaluate the safety of 
utilizing DCD donor 
hearts compared to 
DBD hearts for 
transplantation. 
Therefore, outcomes 
which evidence the 
function of the 
transplanted heart have 
been selected as 
primary endpoints. 
Each of the endpoints 
listed represents, or 
could represent, failure 
of the transplanted 
heart to adequately 
support the patient. 
 

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RVAD, BiVAD) for > 72 hours 
immediately post-transplant. 
Secondary 
 
 
The secondary objective is to 
assess the practical, financial and 
logistical viability of using NRP vs. 
DPP for the procurement of DCD 
donor hearts. 
- Length of time on waiting list for 
DCD hearts (compared to time on 
waiting list for DBD heart for that 
patient, and compared to the median 
time for a patient matched for height 
and ABO group) 
- Utilization rates of heart offers, 
donors attended, and hearts explanted 
in DCD donors as compared to DBD 
donors. 
 
- Cost per DCD transplant and cost 
saving per DCD transplant (especially 
for in-patients/MCS patients) 
 
The secondary 
objectives of the study 
concern the feasibility 
of the technique to 
usefully augment the 
number of patients to 
whom we can offer 
heart transplantation. 
Therefore, outcomes 
which evidence the use 
of resources required 
for each additional 
transplant have been 
selected as secondary 
endpoints. By bringing 
forward patients’ 
transplants, DCD heart 
transplantation may 
also reduce overall 
costs for heart 
transplant patients and 
therefore this endpoint 
is also considered. 
These outcomes will 
also be used to set the 
budget going forward. 
 
 
 
4 
STUDY DESIGN  
 
 
4.1 
OVERALL DESIGN 
 
The proposed study will evaluate two strategies for the retrieval of heart from donors after circulatory 
death (DCD):  Normothermic Regional Perfusion and Direct Procurement and Perfusion with the OCS 
Heart System. Currently, DCD hearts are  approved for use for transplantation (outside of a research 
protocol) in the US by using the Direct Procurement and Perfusion (DPP) with the OCS Heart System.  
In the U.S., heart donation occurs after a person has been declared brain dead and is called a donor 
after brain death (DBD). In these patients, the heart continues to beat and pump blood throughout the 
body. After life support is withdrawn, organs are retrieved immediately for transplantation. This study 
will use hearts from donors after circulatory death (DCD) donors. DCD donors are those whose hearts 
have stopped beating and no longer pump blood.  DCD hearts are not used as often for transplantation 

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today in the U.S. because they may be further injured during traditional cold storage. In the US, donor 
hearts are currently mostly obtained from donors after brain death (DBD), although DCD donors are 
used for other donated organs, such as: lungs, kidneys, and livers.  
This study will evaluate whether patients who receive a DCD heart transplant using either NRP or DPP 
have similar outcomes as patients who receive DBD hearts using standard cold storage. The study will 
also evaluate whether DCD procured hearts have a meaningful impact on hearts available for 
transplantation at our center. Ten (10) DCD donor heart recipients will be enrolled into the study 
intervention group, and approximately 30 DBD donor heart recipients will be enrolled into the control 
group.  
The primary objective of this proposed research is to evaluate the safety of utilizing DCD donor hearts as 
compared to DBD donor hearts for transplantation.  The secondary objective is to assess the practical, 
financial and logistical viability of using NRP vs. DPP for the procurement of DCD donor hearts. 
In order to assess the secondary objective, a total of 8 (± 1) DCD hearts will be procured utilizing NRP 
and 2 (± 1) DCD hearts will be procured with DPP. Should the NRP target number of eight be met prior to 
reaching the enrollment goal of 10 DCD donor heart recipients, DPP methods will be utilized for the 
remaining two DCD heart transplants, as clinically feasible.  
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The study is designed to evaluate the local implementation of a novel (to this institution) technique of 
donor heart procurement. The scientific and clinical value of DCD heart transplantation has already been 
established in several large series from expert centers and is accepted in consensus statements from the 
main societies representing heart transplantation. Therefore, a relatively small number of patients will 
be recruited, with limited statistical power, common in such a “learning curve” analysis. 
 
4.3 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.2. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. 
 
5 
STUDY POPULATION 
 
Donor Heart Screening 
Donor hearts will be screened for eligibility based on current standard of care criteria.   
 

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5.1 
DCD DONOR WITH NRP ELIGIBILITY CRITERIA 
 
DCD Donor with NRP Inclusion Criteria 
 
1. Age 18-45 years 
2. Weight ≥ 50Kg 
3. TTE showing good cardiac function (LVEF ≥ 50%) 
4. If there are risk factors for coronary artery disease a coronary angiogram may be requested and 
if not performed this should be factored into the acceptability of the organ 
 
DCD Donor with NRP Exclusion Criteria 
 
NRP Donor hearts will not be selected if they meet any of the following criteria: 
1. Prior chest surgery 
2. Cardiac Disease on TTE or on coronary angiogram 
3. NRP contraindicated or not supported by donor hospital 
 
 
5.2 
DCD DONOR WITH DPP ELIGIBILITY CRITERIA 
 
DCD Donor with DPP Inclusion Criteria 
1. Age 18-45 
2. Weight ≥ 50Kg 
3. TTE showing good cardiac function (LVEF ≥ 50%) 
4. If there are risk factors for coronary artery disease a coronary angiogram may be requested and 
if not performed this should be factored into the acceptability of the organ (coronary arteries 
should then be assessed later by direct visualization and palpation of the OCS) 
 
DCD Donor with DPP Exclusion Criteria 
 
DPP Donor hearts will not be selected if they meet any of the following criteria: 
1. Prior chest surgery 
2. Cardiac Disease on TTE or on coronary angiogram 
 
 
5.3 
DBD DONOR ELIGIBILITY CRITERIA 
 
DBD donor hearts will be screened and determined to be eligible for transplant according to the 
standard of care of the institution. DBD donor hearts that are eligible for transplantation will be 
procured using standard cold storage.   

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5.4 
RECIPIENT ELIGIBILITY CRITERIA 
 
Recipient Inclusion Criteria 
To be eligible to participate in this study, an individual must meet all the following criteria: 
 
1. Subjects must be willing and be capable of understanding the purpose and risks of the study and 
must sign a statement of informed consent OR consent of a legally authorized representative of 
a cognitively impaired individual will be obtained before the cognitively impaired individual may 
be included in research. 
2. Signed: 1) written informed consent document and 2) authorization to use and disclose 
protected health information  
3. Male or female, aged 18 years of age or older listed for primary heart transplant 
 
Recipient Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Prior history of cardiac transplantation 
2. Multi-organ transplant 
3. Current or planned participation in another interventional trial 
4. Recipient has any condition that, in the opinion of the Investigator, would make study 
participation unsafe or would interfere with the objectives of the study 
 
 
5.5 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently entered in the study.  
When a subject is matched with and accepts any donor heart (either from a DCD Donor or a DBD 
Donor), the recipient inclusion and exclusion criteria will be re-verified by the study team.  If the 
recipient is no longer eligible for the trial, they will be considered a screen failure and will exit the study. 
Trial data will not be collected for subjects who are screen failures.    
A subject will be considered a screen failure under any of the following conditions: 
• 
The patient does not meet eligibility criteria at the time of transplant 
• 
The patient becomes unsuitable for transplantation by any technique 
• 
Standard cold storage is not utilized in DBD Donor Heart transportation 
• 
The patient does not receive a heart transplant or is still on the waiting list at the conclusion of 
this trial 
 
5.6 
STRATEGIES FOR RECRUITMENT AND RETENTION 

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All patients on the heart transplant waiting list at Cedars-Sinai will be identified by trial investigators and 
screened for trial eligibility. Those patients who initially appear eligible for the trial will have the trial 
thoroughly explained to them by a trial investigator, be invited to participate, and will be asked to sign an 
informed consent. Consent of a legally authorized representative of a cognitively impaired individual will 
be obtained before the cognitively impaired individual may be included in research.  
Consented transplant candidates will be eligible to receive DCD donor hearts that have been deemed 
clinically acceptable for transplantation by the treating transplant clinical team. Patients who consent to 
this study and receive a heart transplant will subsequently be entered into this study. Subjects who 
receive a standard of care DBD donor heart transplant will enter the control arm, while those who 
receive a DCD donor heart will enter the study arm.  
 
All subjects will be patients of the principal investigator and co-investigators, managed as part of the 
Cedars-Sinai Advanced Heart Failure/Heart Transplant Program.  Subjects will be approached in person 
during clinic visits or upon hospital admission by investigators or study coordinators after confirming 
eligibility.  No advertising will be used for recruitment purposes. 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
The study intervention of DCD donor cardiac transplantation will be compared to a control group of 
standard of care DBD donor heart transplantations. Due to the in-situ functional arrest of the DCD heart, 
reperfusion of the organ is performed to resuscitate the heart to a full beating state prior to 
transplantation. In this study, the two different strategies utilized for DCD heart retrieval are established 
methods of procuring solid organs. Normothermic Regional Perfusion (NRP) procedures will be used to 
procure all DCD hearts unless contraindicated or prohibited by the donor hospital. In the event the 
donor hospital does not allow NRP for cardiac organ procurement, or the target number of eight DCD 
transplants with NRP has been achieved, Direct Procurement and Perfusion (DPP) with the Organ Care 
System (OCS) should be utilized (for NRP and DPP methods, see Section 8).  
Regardless of perfusion strategy, all DCD donor hearts will undergo standard of care functionality 
assessments and will only be utilized if they are deemed clinically acceptable for transplantation.   
 
6.1.1 NORMOTHERMIC REGIONAL PERFUSION (NRP) DESCRIPTION 
The NRP method uses the Affinity CP Centrifugal Blood Pump (AP40) coupled with the CAPIOX FX 
Advance Oxygenator and Hardshell Reservoir for extracorporeal circulation of the donor heart prior to 
harvest. This method will utilize: 
• 
Affinity CP Centrifugal Blood Pump (AP40) 
• 
External Drive Motor Model 560A 
• 
Medtronic pump speed controller 
• 
CAPIOX FX25 Advance Oxygenator with Integrated Arterial Filter and Hardshell Reservoir 

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Description of Major Components 
Affinity CP Centrifugal Blood Pump 
The Affinity CP Centrifugal Blood Pump is used to pump blood through the extracorporeal bypass circuit 
for extracorporeal circulatory support for periods appropriate to cardiopulmonary bypass (up to 6 
hours). The pump is designed to move blood by centrifugal force generated by a combination of a 
smooth rating cone and low-profile impeller fins.  Energy is transferred from the pump in the form of 
pressure and velocity as the blood is driven toward the outlet port of the pump. To limit friction and 
heat generation, the Affinity CP Centrifugal Blood Pump utilizes a pivot-bearing design on a dual ceramic 
pivot. It has been sterilized using ethylene oxide. 
The Affinity CP Centrifugal Blood Pump couples to a remote magnetic drive unit called the External Drive 
Motor Model 560A, which interfaces with a Medtronic pump speed controller. It also couples with the 
Emergency Handcrank Model HC150A in the event of controller or power failure. Additional information 
about the external drive motor and the emergency handcrank is located in the appropriate Medtronic 
pump speed controller operator’s manual. 
 
CAPIOX FX25 Advance Oxygenator and Hardshell Reservoir 
The CAPIOX FX is a membrane oxygenator with microporous polypropylene hollow fibers, to be used as 
an extracorporeal gas exchange device in which the blood flows on the outside of the fibers and with 
the ventilating gas flowing through the fibers.  
The CAPIOX FX consists of:  
• 
A module for gas exchange with an integrated heat exchanger and arterial filter 
• 
Hardshell reservoir with an integrated cardiotomy filter  
The integrated heat exchanger is used to warm or cool blood and/or perfusion fluid as it flows through 
the device. The hardshell reservoir is used to store blood during extra-corporeal circulation from the 
venous line and the cardiotomy line. The reservoir contains a venous section that is comprised of a filter 
and defoamer to facilitate air bubble removal. The cardiotomy section of the reservoir contains a filter 
to remove particulate matter and a defoamer to facilitate air bubble removal. 
All blood contacting surfaces are coated with Xcoating Surface Coating, which is a bio-compatible 
material that is applied on the blood-contacting surfaces of the device to reduce the adhesion of 
platelets to the device.  
Normothermic Regional Perfusion procedures will be conducted per Cedars-Sinai’s institutional standard 
of care.  
 
 
 
6.1.2 DIRECT PROCUREMENT AND PERFUSION (DPP) DESCRIPTION 

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Direct Procurement and Perfusion Description 
The DPP method will utilize the Organ Care System (OCS Heart System), which 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 
The OCS system is commercially available and approved for use in transportation of donor hearts for 
cardiac transplantation.  
These major components are shown in Figure 1 below. 
Figure 1: Figures of the OCS Heart System 
 
 
Description of Major Components 
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. 
Heart Perfusion Set (HPS) 

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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 
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. 
 
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 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. 
 
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 2 
below. The OCS contains a pulsatile pump that directs flow through the gas exchanger, to be 

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oxygenated, and then through the blood warmer and then to the aorta of the donor heart. An additional 
perfusate component, known as the 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. 
 
Figure 2: Schematic of the OCS Heart System Fluid Flow 
 
 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
The investigator or designee will maintain a record of OCS Heart System devices received, used, or 
discarded under this protocol.  
 
All device components and supplies utilized for Normothermic Regional Perfusion will be supplied per 
standard institutional guidelines.  
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 

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The Affinity CP Centrifugal Blood Pump and Medtronic External Drive Motor Model 560A are 
manufactured by Medtronic.  The CAPIOX FX Advance Oxygenator with Integrated Arterial Filter and 
Hardshell Reservoir is manufactured by Terumo. Refer to the appropriate device brochure and 
instructions for use for additional product information. 
 
The OCS Heart Perfusion Set and accessories and the Perfusion Solution will be supplied sterile and are 
intended and labeled for single use only.  The OCS and its components will be clearly labeled with 
instructions for use for the device. The OCS Heart System utilized in this protocol is manufactured by 
TransMedics. 
 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
The Affinity CP Centrifugal Blood Pump should be stored at temperatures between -30°C and 57°C, and 
ambient humidity from 20-85%, no condensing. Do not store the CAPIOX FX at extreme temperatures 
and humidity; avoid direct sunlight.  
 
The Organ Care System (OCS) devices will be stored in a secure location. Access should be strictly limited 
to the investigators and their designees. 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%). 
 
 
6.2.4 PREPARATION 
 
See Method for NRP (Section 8.2) and Method for DPP (Section 8.3). 
 
 
6.3 
STUDY INTERVENTION COMPLIANCE 
 
Not Applicable. 
 
6.4 
CONCOMITANT THERAPY 
 
For this protocol, inotropic medication, immunosuppressive medication and induction therapies will be 
collected at timepoints specified in the Schedule of Activities (Section 1.2). Inotropic medication doses 
will be collected at ICU admission T0, T12, T24, T48 and T72 hours after ICU admission post-heart 
transplantation. In addition, medications used to treat all serious heart graft-related serious adverse 
events (SAEs) will be recorded. 
 
7 
STUDY STOPPING RULES AND PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 

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7.1 
STUDY STOPPING RULES 
The criteria below provide guidance for suspending trial enrollment/DCD donor heart utilization until 
review by the Data and Safety Monitoring Board (DSMB) (Section 10.1.6).  
Selected serious adverse events (SAEs) of concern and their thresholds are: 
• 
Two (2) episodes of severe primary graft dysfunction (PGD) per ISHLT grading criteria (left or 
right ventricle, not including rejection or cardiac tamponade) requiring extracorporeal 
membrane oxygenation (ECMO) within 24 hours after transplant in subjects who received DCD 
donors. 
• 
Two (2) deaths occur in subjects who received DCD donors within 7 days after transplant 
It is the responsibility of the Principal Investigator to report all of the above SAEs to the DSMB within 24 
hours of discovering the event. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Subjects will be considered screen failures if they require a multi-organ transplant or become unsuitable 
for transplantation by any technique. A subject will be considered enrolled in the study if they undergo a 
heart transplant (either DCD or DBD) that meets the eligibility criteria as described in Section 5. 
Participants are free to withdraw from participation in the study at any time upon request. 
Since the outcomes are all fairly immediate to the transplant procedure itself, it is unlikely that there 
would be scope for withdrawal from the study after the procedure has taken place.  
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
SAFETY ASSESSMENTS  
 
All data collection as outlined in the Schedule of Activities (Section 1.2) will be evaluated to assess the 
safety of utilizing DCD donor hearts as compared to DBD donor hearts for transplantation: 
• 
Donor Characteristics 
• 
Transplant Details 
• 
PGD Scores 
• 
Inotrope Support 
• 
Right Heart Catheter Data 
• 
Mechanical Circulatory Support Data 
• 
Invasive Ventilator Support Data 
• 
Patient Survival 
• 
Graft Survival 
• 
Post-Transplant Hemodynamics 
• 
Immunosuppressive Medications & Induction (if applicable) 
• 
ICU & Hospital Stay 
• 
Heart Graft-Related AEs and SAEs 

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Procedures that will be completed during the study as part of regular standard of clinical care: 
• 
Demographics/Characteristics 
• 
Medical & Cardiac History 
• 
Patient Visits 
• 
Endomyocardial Biopsy (recipient) 
 
8.2 
METHOD FOR NRP - NORMOTHERMIC REGIONAL PERFUSION (NRP) PROCEDURES 
 
1. NRP Donor Heart Selection 
NRP Donor heart selection will occur as deemed clinically acceptable for transplantation per eligibility 
criteria outlined in Section 5.1 
2. DCD Donor Withdrawal of Life Sustaining Treatment 
- 
The location of WLST should be agreed in advance, and a spacious OR is reserved for the donor 
procedure 
- 
The donor hematocrit should be > 30% and transfusion to this level may be required 
- 
Heparin 30000 IU is administered at the time of WLST 
- 
The local team are clear that mechanical asystole (not electrical asystole) represents circulatory 
arrest 
- 
The pulmonary team agrees for the main PA to be transected immediately and therefore to perform 
the antegrade flush through a Y-type cannula 
- 
Once WLST has occurred, communication regarding the donor’s vitals between OPO and the organ 
procurement teams is essential. 
- 
Functional warm ischemic time begins when the systolic blood pressure is less than or equal to 
50mmHg. If the patient does not suffer circulatory arrest within 25 minutes of this time, then the 
heart will be declined. If the blood pressure rises above 50mmHg, then this clock is reset. 
- 
The team will wait for 90 minutes from WLST. If circulatory arrest has not occurred in this time then 
the heart will be declined. 
 
3. Surgical Protocol  
The team comprises at a minimum two surgeons, two procurement technicians and one perfusionist.  
Pre-Withdrawal of Support 
- 
The ECMO circuit should be prepared including the Medtronic Affinity CP Blood Pump device and 
the CAPIOX FX25 Advance Oxygenator with Integrated Arterial Filter and Hardshell Reservoir.  
Prime solution: 
o 4 units packed red cells (approx. 1200mL) 
o 1.5 litre Plasmalyte 
o 50,000 units heparin 
o 1mmol/kg sodium bicarbonate (1mL/kg 8.4% solution)  

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- 
If a heat-exchanger is available, set the perfusate temperature to 37ºC 
- 
Set up Mayo stand (surgeon side, on patient right) 
o Scalpel  
o Sternal saw (test to ensure working) 
o 2nd Sternal Saw Battery (test to ensure working) 
o Retractor 
o Metzenbaum scissors x2 
o Forceps x2 
o Tube clamps x2 
o Arterial cannula and 2-stage venous cannula 
o Bulb syringe with saline 
- 
Set up second Mayo stand (assistant side, on patient left) 
o Metzenbaum scissors 
o Forceps x2 
o Angled vascular clamps x3 
o Cardioplegia needle  
- 
Ensure suction available/ adequate (ideally 3, two for chest, one for abdomen) 
- 
Discuss roles/plan with all teams and OR staff 
When the donor suffers circulatory arrest, or death is clearly imminent, the surgeons should do their 
final scrub. 
Retrieval Procedure 
- 
Patient is positioned, prepped, and draped   
- 
Incision made, sternum divided with saw 
- 
Pericardium widely opened with scissors 
- 
The surgeon pulls down on the aortic arch while the assistant clamps in turn the innominate artery, 
left carotid artery and left subclavian artery. 
- 
Arterial cannula inserted into the distal ascending aorta through a stab incision (the surgeon 
performs and the assistant holds this in place with their right hand). The surgeon clamps the cannula 
and connects to the red line of the ECMO circuit. Third scrubbed person fills the cannula/tubing with 
saline as the connection is made. 
- 
Venous cannula inserted to right atrium through a stab incision (the surgeon performs and the 
assistant hold this in place with their left hand). The surgeon clamps the cannula and connects to the 
blue line of the ECMO circuit. Third scrubbed person fills the cannula/tubing with saline as the 
connection is made. 
- 
The perfusionist starts the ECMO flow and records the time.  
- 
Flow rates of 2 L/min should be targeted initially, until the RA cannula is fixed in place to avoid 
entrainment of air. The air/O2 mixer should be set to deliver a gas flow of 2L/min with a starting 
FIO2 of 21%. Once the circuit is stable, the flow can be increased to 3-5L/min, aiming for an SVO2 
60-90%, pH 7.35-7.45, Hematocrit > 20% and pCO2 35-45mmHg, with a mean BP of 60-70mmHg. An 

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infusion of vasopressin may be required to support the BP. Field suction may augment the blood 
return to the venous reservoir. 
- 
At this point all the organs are perfused, and the donor situation is analogous to the DBD donor. The 
abdominal team can continue with their dissection and assessment. The thoracic teams should 
secure their cannulae and continue with their dissection and assessment including the lungs. The 
donor can be re-intubated at this point and bronchoscopy performed. 
- 
After a minimum of 20 minutes on ECMO, ventilation of the lungs can be fully resumed and the 
ECMO can be weaned with the heart taking over the circulation. 
- 
Heart function is assessed from systemic blood pressure, CVP and visual examination, and if deemed 
adequate, the recipient procedure can be triggered. 
- 
If the heart function is inadequate (or indeed the lung function is inadequate) it may be necessary to 
resume ECMO to support the abdominal organs. 
- 
Once all teams are ready, timing of cross-clamp, delivery of preservation solutions and explantation 
of the heart (and other organs) proceeds exactly as for DBD donors. 
- 
The heart is placed in cold storage for transport. 
 
Stepwise procedure 
Primary Surgeon 
Assistant Surgeon 
Skin incision 
Sternotomy  
Place sternal retractor 
Open pericardium 
Pass off suction  
Secure the ECMO tubing 
Pull down on the aortic arch and free the origins 
of the supra-aortic vessels  
Clamp each supra-aortic vessel 
Aortic cannulation, clamp and connect to red line 
Secure aortic cannula 
RA cannulation, clamp and connect to blue line  
Secure RA cannula 
Instructs perfusionist to commence ECMO 
 
Places purse-strings to secure the aortic and RA 
cannulae 
 
Manages the circulatory indices 
Places field suction 
 
 
8.3 
METHOD FOR DPP - DIRECT PROCUREMENT AND PERFUSION (DPP) PROCEDURES 
 
1. DPP Donor Heart Selection 
In the event that Normothermic Regional Perfusion (NRP) for organ procurement is contraindicated or 
prohibited by the donor hospital, Direct Procurement and Perfusion (DPP) methods will be utilized. DPP 
Donor heart selection will occur as deemed clinically acceptable for transplantation per eligibility criteria 
outlined in Section 5.2.  

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2. DCD Donor Withdrawal of Life Sustaining Treatment 
- 
The location of WLST should be agreed in advance, and a spacious OR is reserved for the donor 
procedure 
- 
The donor hematocrit should be > 30% and transfusion to this level may be required 
- 
Heparin 30,000 IU is administered at the time of WLST 
- 
The local team are clear that mechanical asystole (not electrical asystole) represents circulatory 
arrest 
- 
The liver team agrees to hold off perfusion until the cardiac team have drained enough donor blood 
for OCS priming (typically no more than 60 seconds) 
- 
The pulmonary team agrees for the main PA to be transected immediately and therefore to perform 
the antegrade flush through a Y-ed cannula  
- 
Once WLST has occurred, communication regarding the donor’s vitals between OPO and the organ 
procurement teams is essential. 
- 
Functional warm ischemic time begins when the systolic blood pressure is less than or equal to 
50mmHg. If the patient does not suffer circulatory arrest within 25 minutes of this time, then the 
heart will be declined. If the blood pressure rises above 50mmHg, then this clock is reset. 
- 
The team will wait for 90 minutes from WLST. If circulatory arrest has not occurred in this time, then 
the heart will be declined. 
- 
 
3. Surgical Protocol  
The team comprises at a minimum two surgeons and two procurement technicians, one of whom is 
the trained OCS operator, and one perfusionist. 
Pre-Withdrawal of Support 
- 
OCS system preparation: 
o The OCS disposable module should only be opened when the donor has met cardiac arrest, 
but several elements should be prepared in advance 
▪ 
The OCS operator should take charge of the blood collection bag (30,000 IU of 
heparin inside) as well as reservoir additions, maintenance solution, levothyroxine 
solution and epinephrine solution 
▪ 
The 2nd transplant practitioner should take charge of the Del Nido cardioplegia, 
connect defibrillator to OCS module and communication 
▪ 
The back table prep for OCS instrumentation should also be set up sterile in advance 
(aortic connectors, 4x pledgeted sutures and free pledgets, needle driver, scissors, 
cable ties and gun, purse string suture for PA, tie for PA, PA cannula, suture for LV 
vent, LV vent, suture to close RA vent, suture to close IVC, pacing wire) 
- 
Set up Mayo stand (surgeon side, on patient right) 
o Scalpel  
o Sternal saw (test to ensure working) 
o 2nd Sternal Saw Battery (test to ensure working) 
o Retractor 

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o Metzenbaum scissors x2 
o Forceps x2 
o 2-stage venous cannula connected to primed collection bag (for blood collection) 
- 
Set up second Mayo stand (assistant side, on patient left) 
o Metzenbaum scissors 
o Forceps x2 
o Cardioplegia needle  
- 
Ensure suction available/ adequate (ideally 3, two for chest, one for abdomen) 
- 
Discuss roles/plan with all teams and OR staff 
When the donor suffers circulatory arrest, or death is clearly imminent, the OCS operator can install the 
OCS disposable module; and the surgeons should do their final scrub 
Retrieval Procedure 
- 
Patient is positioned, prepped, and draped   
- 
Incision made, sternum divided with saw 
- 
Pericardium widely opened with scissors 
- 
Drainage cannula inserted to right atrium, collection bag dropped to patient right, and clamp 
removed 
o 1.2-1.5L of blood must be collected. It is essential that no preservation solution is given prior 
to blood collection. 
o Collection may be aided by placing the patient in Trendelenburg position 
o Communication with the abdominal team is key. Blood collection should take no more than 
60 seconds 
- 
While surgeon collects priming blood, the assistant places the cardioplegia needle and connects to 
the cardioplegia line 
- 
After blood collected, the heart is vented via the IVC and pulmonary veins, the aorta is clamped, and 
500ml del Nido cardioplegia is delivered 
- 
Heart is excised in the standard fashion 
- 
OCS setup as per standard 
OCS Medication Kit 
MEDICATION 
QTY  
IN KIT 
Levothyroxine 100mcg vial 
2 
Sodium chloride 0.9%, 100mL bag 
1 
Sodium bicarbonate 8.4%, 1mEq/mL (50mL vial) 
1 
(Solu-Medrol) Methylprednisolone 125mg vial 
2 
Epinephrine 1mg/1mL ampule 
1 
Ciprofloxacin 200mg/100mL bag  
1 
Cefazolin 1g vial 
1 

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Stepwise procedure 
Primary Surgeon 
Assistant Surgeon 
Skin incision 
Sternotomy  
Place sternal retractor 
Open pericardium 
Pass off cardioplegia line 
Pass off suction  
Open right atrial appendage and cannulate  
Grasp right atrial appendage and assist 
Secure cannula for blood collection, 
communication with abdominal team and 
procurement teams 
Assist with collection of blood 
Verify cardioplegia line is flushed 
Vent heart – IVC and pulmonary vein (or LAA if 
lungs also being procured)  
Assist with venting, suction placement 
Clamp aorta 
Place cardioplegia needle to ascending aorta 
(high as possible) 
Hold needle as cardioplegia given 
Connect cardioplegia line and verify flow 
Apply ice to heart 
Excision of heart  
Assist with heart excision 
Place heart on OCS 
Assist with OCS 
Heparin 3000 units/mL (10mL vial) 
1 
Dextrose 5% (500mL bag) 
1 
Calcium gluconate 10%, 100mg/1mL (10mL vial) 
1 
Sterile water for injection (10mL vial) 
3 
Albumin (Human) 25% (50mL vial) or (single 100mL vial if possible) 
2 
Lidocaine 1%, 10mg/mL (30mL vial) 
1 
Millex GV 0.22 Micron Filter Unit  
2 
5 micron 19G filter needle 
2 
Mannitol 25%, 12.5g/50mL (50mL vial) 
1 
Potassium Chloride 2mEq/mL (10mL vial) 
1 
Infuvite Adult multivitamin 2x5mL vials 
1 
Humulin R (regular insulin) 100 units/mL (3mL vial) 
1 
Del Nido Solution (1030 mL bag) 
1 
Glyceryl Trinitrate (50 mg) 
1 
Erythropoietin (2500 IU) 
1 

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The decision to use the heart will depend on the appearance, flow/pressure parameters and lactate 
profile observed during perfusion. The recipient operation should be triggered following consideration 
of these factors and the travel time. 
 
 
 
   
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
Only Serious Adverse Events (SAEs) and Heart Graft-Related Adverse Events (HGRAEs) will be captured in 
this study. 
 
8.4.1 HEART GRAFT-RELATED ADVERSE EVENTS (HGRAE) 
 
All heart graft-related adverse events (HGRAEs) are to be recorded on the electronic case report forms 
until post-transplant day 30 or through hospital discharge if longer than 30 days. The description of the 
adverse event will include: the date of onset, duration, severity, seriousness, the relationship of the 
event to the trial treatment, anticipated or not, and any treatment required. The principal investigator is 
responsible for the classification and reporting of heart graft-related adverse events to the appropriate 
regulatory authorities. 
 
 
8.4.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
 
Serious adverse events will be collected only through Day 30 post-transplant. An adverse event will be 
classified as serious if it meets any of the following criteria:  
• 
Results in, leads to, or contributes to, a death  
• 
Is life-threatening  
• 
Results in permanent disability or incapacity (i.e., permanent impairment of a body function or 
permanent damage to a body structure)  
• 
Requires in-patient hospitalization or prolongs hospitalization  
• 
Necessitates medical or surgical intervention to preclude a permanent disability or incapacity  
• 
Results in fetal distress, fetal death or a congenital anomaly/birth defect 
 
 
8.4.3 DEFINITION OF HEART GRAFT-RELATED SERIOUS ADVERSE EVENTS (HGRSAE)  
 
Heart Graft-Related SAEs are defined as: 
• 
Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac 
tamponade) according to ISHLT consensus manuscript 
• 
Primary graft failure requiring re-transplantation 
• 
Use of post-transplant mechanical circulatory support (ECMO, LVAD, RVAD, BiVAD) for > 72 
hours immediately post-transplant 

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• 
Lack of patient and/or graft survival at 30 days post-transplant 
• 
Lack of patient and/or graft survival at initial hospital discharge, if later than 30 days post-
transplant 
 
HGRSAEs will be collected from the time a subject is transplanted until the completion of the 30-day 
follow-up evaluation. A HGRSAE will be followed until resolution or stabilization of the event.  
 
8.4.4 CLASSIFICATION OF AN ADVERSE EVENT 
8.4.4.1 SEVERITY OF EVENT 
The investigator will rate the severity of the adverse event using the following categories  
 
• 
Mild – The adverse event is transient and/or easily tolerated by the subject  
• 
Moderate – The adverse event causes the subject discomfort and interrupts the subject's usual 
activities 
• 
Severe – The adverse event causes considerable interference with the subject's usual activities 
 
 
8.4.4.2 RELATIONSHIP TO STUDY INTERVENTION 
The investigator will assess the relationship of the AE to the utilization of a DCD donor heart. The 
relationship will be assessed using the following categories: 
 
• 
Definitely Related – There is a reasonable causal and temporal relationship between utilization 
of a DCD donor heart and the adverse event  
• 
Probably Related – It is more likely than not that there is a reasonable causal relationship 
between utilization of a DCD donor heart and the adverse event 
• 
Possibly Related – The There is a reasonable relationship with the utilization of a DCD donor 
heart and the adverse event, but the causal relationship is unclear or lacking 
• 
Unlikely Related – There is a temporal relationship with the utilization of a DCD donor heart and 
the adverse event, but there is not a reasonable causal relationship between the trial device and 
the event   
• 
Unrelated – There is no relationship between the utilization of a DCD donor heart and the 
adverse event 
 
8.4.4.3 EXPECTEDNESS  
 
The investigator will be responsible for determining whether an adverse event (AE) or serious adverse 
event (SAE) is expected or unexpected.   
 
Anticipated SAEs that are associated with heart transplant procedures within the first 30 days after 
heart transplant includes, but is not limited to: 
 
• 
Acute rejection  
• 
Atrial and ventricular arrhythmias  

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• 
Bleeding (major)  
• 
Hemodynamic instability  
• 
Death  
• 
Fever  
• 
Infection  
• 
Primary Graft Dysfunction  
• 
Respiratory failure  
• 
Graft failure  
• 
Sepsis  
• 
Renal dysfunction  
• 
Hyperammonaemia  
• 
Malignancy (post-transplant 
lymphoproliferative disorder (PTLD)  
• 
Multiple organ failure  
• 
Myocardial infarction  
• 
Neurological dysfunction  
• 
Hepatic dysfunction  
• 
Diabetes due to steroid and anti-
rejection medications  
• 
Gall stones  
• 
GI bleeding  
• 
Pancreatitis  
• 
Peptic ulceration  
• 
Gastritis  
• 
Gastro esophageal reflux disease 
(GERD)  
• 
Pneumo-mediastinum  
• 
Pneumothorax  
• 
Hemothorax  
• 
Pleural bleeding  
• 
Pleural effusion  
• 
Venous thromboembolism (deep 
venous thrombosis [DVT])  
• 
Pulmonary embolism (PE)  
• 
Sternal wound dehiscence  
• 
Organ deemed not transplantable after 
retrieval  
• 
Stroke  
• 
Psychosis  
• 
Cerebrovascular accident  
• 
Peripheral vascular clotting or occlusion 
due insertion of mechanical support  
• 
Limb gangrene due to vascular 
occlusion due insertion of mechanical 
support  
• 
Use of mechanical circulatory support  
• 
Coagulopathy  
• 
Hyperacute rejection  
• 
Anastomotic site complications; 
narrowing, bleeding or occlusion  
• 
Delayed sternal wound closure due to 
compromised cardiac function or 
excessive bleeding or both  
• 
Bowel thromboembolic complications 
and gangrene  
 
8.4.5 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
Subjects will be monitored before, during and after the operative procedure to help ensure their safety. 
The investigators are members of transplant teams who have extensive experience with heart 
transplantation. Subjects in the trial will undergo frequent visits and routine monitoring to help detect 
any abnormal changes and to provide appropriate treatment as necessary. 
 
All heart graft-related events and any heart graft-related serious adverse events will be followed and 
documented until the investigator designates the event to be either resolved or its effect on the 
patient’s condition is stabilized. 
 

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All heart graft-related adverse events and serious adverse events are to be recorded on the electronic 
case report forms until post-transplant day 30. The description of the adverse event will include: the 
date of onset, duration, severity, seriousness, the relationship of the event to the trial treatment, 
anticipated or not, and any treatment required. All serious adverse events occurring during the course 
of the first 30 days post-transplant will be documented on the appropriate electronic case report form(s) 
in REDCap. Heart graft-related AEs will be recorded up to the 30-day follow-up or through hospital 
discharge if longer than 30 days. The principal investigator is responsible for the classification and 
reporting of heart graft-related adverse events to the appropriate regulatory authorities. 
 
8.4.6 ADVERSE EVENT REPORTING  
 
All AEs captured throughout the duration of the study will be reported to the DSMB on a quarterly basis. 
 
8.4.7 SERIOUS ADVERSE EVENT REPORTING  
   
All SAEs captured throughout the duration of the study will be reported to the DSMB on a quarterly 
basis.  It is the responsibility of the Principal Investigator to report all serious adverse events (SAEs) of 
concern (as defined in Section 7.1) to the DSMB within 24 hours of discovering the event. 
 
8.4.8 EVENTS OF SPECIAL INTEREST  
Not Applicable. 
 
8.5 
UNANTICIPATED PROBLEMS 
 
8.5.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
8.5.2  UNANTICIPATED PROBLEM REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data and Safety Monitoring Board (DSMB). The UP report will include the following 
information: 

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• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DSMB as soon 
as possible, but no later than 10 business days from the investigator’s or study team’s 
awareness of the event, incident, information or outcome.     
• 
Any other UP will be reported to the IRB and to the DSMB within 10 business days of the 
investigator becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) as required. 
 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
Primary Endpoint 
• 
Comparison of the incidence of Heart Graft-related Serious Adverse Events (HGRSAEs) in the 
first 30 days post-heart transplantation for DCD heart transplanted recipients and DBD heart 
transplanted recipients. 
 
Secondary Endpoints 
• 
Comparison of length of time on waiting list for DCD hearts to:  
o Time on waiting list for DBD heart for that patient 
o Median time for a DBD heart transplant recipient matched for height and ABO group 
• 
Utilization rates of heart offers, donors attended, and hearts explanted in DCD donors as 
compared to DBD donors 
• 
Cost per DCD transplant and cost saving per DCD transplant (especially for in-patients/MCS 
patients) 
 
 
9.2 
SAMPLE SIZE DETERMINATION 
The study is intended to serve as a proof-of-concept study. Comparative analyses will be primarily 
descriptive due to a small sample size. 
 

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9.3 
POPULATIONS FOR ANALYSES 
 
All heart transplanted recipients during the study period (both DCD recipients and DBD recipients) will 
be included in analyses. 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
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. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
Safety Analysis 
Serious Adverse Events (SAEs) and Heart Graft-related Serious Adverse Events (HGRSAEs) will be 
collected within the first 30 days post-transplant and the mean number of HGRSAEs per subject will be 
summarized using descriptive statistics. HGRSAEs are defined as the following adverse events (at most 
one per type):  
• 
Moderate or Severe heart PGD (left or right ventricle) (not including rejection or cardiac 
tamponade) 
• 
Primary graft failure requiring re-transplantation 
• 
Patient and graft survival at 30 days post-transplant 
• 
Patient and graft survival at 30 days and initial hospital discharge, if later than 30 days 
• 
Use of post-transplant mechanical circulatory support (ECMO, LVAD, RVAD, BiVAD) for > 72 
hours immediately post-transplant. 
SAEs and HGRSAEs will also be tabulated using counts and percentages alone and in regards to the 
relationship of the HGRSAE to the study intervention, and the severity of the HGRSAE. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary endpoints will be analyzed in a manner analogous to the primary endpoint, inclusive of 
transplant recipients who receive a DCD or DBD heart during the study period. 
 
9.4.4 BASELINE DESCRIPTIVE STATISTICS 
Baseline descriptive statistics will apply to demographic and clinical descriptions of the study cohort. 
 
9.4.5 PLANNED INTERIM ANALYSES  

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Not Applicable. See section 10.1.6 for description of DSMB safety oversight and study stopping rules.  
9.4.6 SUB-GROUP ANALYSES 
 
Not Applicable. 
 
9.4.7 EXPLORATORY ANALYSES 
 
Not Applicable. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.   
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
 
All patients on the heart transplant waiting list at Cedars-Sinai will be identified by trial investigators and 
screened for trial eligibility. Those patients who initially appear eligible for the trial will have the trial 

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thoroughly explained to them by a trial investigator, be invited to participate, and will be asked to sign 
an informed consent. Consent of a legally authorized representative of a cognitively impaired individual 
will be obtained before the cognitively impaired individual may be included in research. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, investigator, and regulatory 
authorities.  If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and will provide the reason(s) 
for the termination or suspension.  Study participants will be contacted, as applicable, and be informed 
of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
DSMB extermination of unexpected, significant, or unacceptable risk to participants or meeting 
one of the stopping rules. 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the DSMB. 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators and their 
staff. This confidentiality is extended to the clinical information relating to participants. Therefore, the 
study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized third 
party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at Cedars Sinai Medical Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be 

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identified by a unique study identification number. The study data entry and study management 
systems used by clinical sites and by Cedars Sinai Medical Center research staff will be secured and 
password protected. At the end of the study, all study databases will be de-identified and archived at 
Cedars Sinai Medical Center. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Not applicable. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
 
Principal Investigator 
Fardad Esmailian, MD  
Surgical Director, Heart Transplantation and Mechanical Circulatory Support 
Clinical Chief, Department of Cardiac Surgery  
Cedars-Sinai Heart Institute 
127 S. San Vicente Blvd., Suite A3103, Los Angeles CA 90048 
 
 
 
10.1.6 SAFETY OVERSIGHT 
An independent Data and Safety Monitoring Board (DSMB), comprised of expert physicians in the 
related field who are not participating in the trial, will perform monitoring activities 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.  The DSMB will have a formal meeting at least once annually. Frequency of the meetings 
may be changed by the DSMB in consultation with the Principal Investigator based on need. An ad hoc 
meeting may be called at any time by the DSMB Chairperson or by the PI and research staff should 
ethical or patient safety issues arise. 
A status update will also be provided to the DSMB on a quarterly basis via email correspondence by the 
DSMB Coordinator. 
Section 7.1 outlines criteria for suspension of enrollment/DCD donor heart utilization until review by the 
DSMB. It is the responsibility of the Principal Investigator to report all of the above SAEs to the DSMB 
within 24 hours of discovering the event. 
 
10.1.7 QUALITY ASSURANCE AND QUALITY CONTROL 
An internal auditor will regularly review the conduct of the trial, verify adherence to the protocol, and 
confirm the completeness, consistency, and accuracy of all documented data. 
 
10.1.8 DATA HANDLING AND RECORD KEEPING  

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10.1.8.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff under the supervision of the site investigator. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. 
 
All data collected will already exist in the medical record under standard of care.  
 
Data will be reviewed from between the dates of 3/01/2022 to 9/01/2023. Data will be collected from 
the following timepoints: post-heart transplant Day 0, Day 7, Day 14, Day 30 and at hospital discharge.  
Data will be collected prospectively and retrospectively. 
 
The following data points/variables will be collected: 
• 
Incidence of primary graft dysfunction 
• 
Initial use of mechanical circulator support: The use of ECMO, intra-aortic balloon, LVAD, RVAD 
or biVAD 
• 
Number of inotropes/pressors at 24 hours post-transplant 
• 
Inotropic support for first 72 hours:  The following inotropic medication doses will be collected 
at ICU admission T0, T12, T24, T48, and T72 hours after ICU admission post-heart 
transplantation:  
o Dopamine – mcg/kg/min  
o Dobutamine – mcg/kg/min  
o Amrinone – mcg/kg/min  
o Milrinone – mcg/kg/min  
o Epinephrine – mcg/kg/min  
o Norepinephrine – mcg/kg/min  
• 
Initial use of mechanical respiratory support: Duration of initial post-transplant invasive 
ventilator support from time of initial admission to ICU post heart transplant until extubation 
• 
Immunosuppression Medications (at day 7 and at time of discharge) 
• 
Incidence of reperfusion injury on endomyocardial biopsy 
• 
Cardiac index 
• 
Cardiac output 
• 
Blood pressure 
• 
Mean arterial pressure 
• 
Pulmonary artery pressure 
• 
Pulmonary capillary wedge pressure 
• 
Left atrial pressure 
• 
Right atrial pressure 
• 
Right ventricular pressure 
• 
Stroke volume 
• 
Ejection fraction 

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• 
BUN and Creatinine 
• 
Liver function tests 
• 
Cellular rejection 
• 
Antibody mediated rejection 
• 
Graft related serious adverse events 
• 
Mitochondrial function 
• 
Age at transplant 
• 
Sex 
• 
Donor characteristics 
• 
Total cross clamp duration in minutes 
• 
Ischemic time 
• 
Surgical complications 
• 
Total length of stay 
• 
ICU length of stay 
• 
Total blood products used 
• 
Trans-thoracic echocardiogram results prior to discharge: 
o Ejection Fraction (EF%) 
o Wall motion assessment 
o LV Septal and posterior wall thickness 
o Any valve abnormalities 
• 
Patient and graft survival at day 30 
• 
Incidence of acute cellular rejection in the first 30 days post heart transplant 
• 
Incidence of antibody mediated rejection in the first 30 days post heart transplant 
• 
Adverse events:  All heart graft-related serious adverse events and any heart graft-related 
adverse events will be followed and documented until the investigator designates the event to 
be either resolved or its effect on the patient’s condition stabilized. 
• 
Medications: Medications used to treat all serious heart graft-related adverse event (SAE)-
related until the SAE is resolved. 
• 
Financial data related to transplant procedure 
• 
Donor heart utilization rates 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.  Source documents are defined as the results of original observations and activities of a clinical 
investigation.  Source documents will include, but are not limited to, progress notes, electronic data, 
computer printouts, screening logs, and recorded data from automated instruments.  All source 
documents pertaining to this trial will be maintained by the investigators and made available for 
inspection by authorized persons. 
 
During each subject assessment, an investigator participating in the trial will record progress notes to 
document all significant observations. In addition, any contact with the subject via telephone or other 
means that provides significant clinical information will also be documented in the progress notes.  

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All data required by the trial protocol will be completely and accurately entered into the REDCap 
database by the investigator or his or her designate, identifying subjects by subject number. Essential 
trial documents must be maintained by the Investigator for at least 7 years.  
 
Storage of Physical Records: Physical records will be maintained for this study at a secure location where 
access is limited to approved personnel. The records will not be removed from Cedars-Sinai premises. 
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into REDCap a 21 CFR Part 11-compliant data capture 
system provided by Cedars Sinai Medical Center. Clinical data will be entered directly from the source 
documents. 
 
Secure storage: Data will be housed in a HIPAA-compliant secure storage system, like REDCap or Box, 
within the Cedars-Sinai network with access restricted to approved members of the research team.  
 
Limited Access: Private identifiable information, will be accessible only to IRB approved study team 
members with current IRB training. 
 
Unique ID Numbers: Each patient will be assigned a unique ID number, which will be used to code data 
and specimens 
 
10.1.8.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 2 years after the conclusion of the study. 
 
10.1.9 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or institutional regulatory requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 

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It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10 working days 
of the scheduled protocol-required activity. Any protocol deviations made in order to eliminate 
apparent immediate hazard to a research subject must be reported to the IRB within 5 business days.  
All deviations must be addressed in study source documents. The site investigator is responsible for 
knowing and adhering to the reviewing IRB requirements and reporting timelines of deviations.  
 
10.1.10 
PUBLICATION AND DATA SHARING POLICY 
 
This study will comply with Clinical Trials Registration and Results Information Submission rule. As such, 
this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted 
to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.  
Data from this study may be requested from other researchers 2 years after the completion of the 
primary endpoint by contacting the Principal Investigator.  
 
 
10.1.11 
CONFLICT OF INTEREST POLICY 
 
Any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or 
any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial.   
 
 
 

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10.2 ABBREVIATIONS 
 
AE 
Adverse Event 
BP 
Blood Pressure 
CFR 
Code of Federal Regulations 
CPB 
Cardiopulmonary bypass 
CRF 
Case Report Form 
CVP 
Central Venous Pressure 
DBD 
Donation after Brain Death 
DCD 
Donation after Circulatory Death 
DSMB 
Data Safety Monitoring Board 
DPP 
Direct Procurement and Perfusion 
ECMO 
Extracorporeal Membrane Oxygenation 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FIO2 
Fraction of Inspired Oxygen 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
HGRAE 
Heart Graft-Related Adverse Event 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Conference on Harmonisation  
IRB 
Institutional Review Board 
ISHLT 
International Society for Heart and Lung Transplantation 
IU 
International Unit 
IVC 
Inferior Vena Cava 
LV 
Left Ventricle 
LVEF 
Left Ventricular Ejection Fraction 
NCT 
National Clinical Trial 
NRP 
Normothermic Regional Perfusion 
OCS 
Organ Care System 
OHRP 
Office for Human Research Protections 
OPO 
Organ Procurement Organization 
PA 
Pulmonary Artery 
pCO2 
Partial Pressure of Carbon Dioxide 
PGD 
Primary Graft Dysfunction 
PI 
Principal Investigator 
RA 
Right Atrium 
SAE 
Serious Adverse Event 
SOA 
Schedule of Activities 
SVO2 
Mixed Venous Oxygen Saturation 
TTE 
Transthoracic Echocardiogram 
UP 
Unanticipated Problem 
US 
United States 
WLST 
Withdrawal of Life Sustaining Treatment 
 
 
 

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10.3 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
V 1.0 
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- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
 
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