Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest (EROCA)
Phase: NA
Conditions: Cardiac Arrest, Heart Arrest, Sudden Cardiac Arrest, Cardiopulmonary Arrest, Death, Sudden, Cardiac, Cardiopulmonary Resuscitation, CPR, Extracorporeal Cardiopulmonary Resuscitation, Extracorporeal Membrane Oxygenation
Sponsor: University of Michigan

ii 
 
Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest (EROCA) IDE 
Principal Investigator: Robert Neumar, MD, PhD I 
ND/IDE Sponsor: Robert Neumar, MD, PhD Funded by: NHLBI 
04/15/2019 
NCT03065647 
 
 

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Table of Contents 
LIST OF ABBREVIATIONS........................................................................................................................... 1 
STATEMENT OF COMPLIANCE ................................................................................................................. 2 
PROTOCOL SUMMARY ............................................................................................................................... 3 
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 5 
KEY ROLES .................................................................................................................................................. 6 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................... 7 
2.1 
Background Information ...................................................................................  …………….    7 
2.1.1 
CLINICAL SIGNIFICANCE .................................................................................... 7 
2.1.2 
RELEVANT CLINICAL RESEARCH ...................................................................... 8 
2.2 
Rationale .................................................................................................................................. 9 
2.3 
Potential Risks and Benefits .................................................................................................... 9 
2.3.1 
Known Potential Risks ........................................................................................... 9 
2.3.2 
Known Potential Benefits ..................................................................................... 10 
3 
OBJECTIVES AND PURPOSE ....................................................................................................... 10 
4 
STUDY DESIGN AND ENDPOINTS ............................................................................................... 11 
4.1 
Description of the Study Design ............................................................................................ 11 
4.2.2 
SAFETY Endpoints .............................................................................................. 11 
4.2.3 
Exploratory Endpoints .......................................................................................... 12 
5 
STUDY ENROLLMENT AND WITHDRAWAL ................................................................................. 12 
5.1 
Inclusion Criteria .................................................................................................................... 12 
5.1.1 Patient level INCLUSION ............................................................................................................ 12 
5.1.2 Included EMS AGENCIES / REGIONS / HOSPITALS ............................................................... 12 
5.2 
Participant Exclusion Criteria ................................................................................................. 13 
5.3 
Strategies for Recruitment and Retention .............................................................................. 13 
5.4 
Participant Withdrawal or termination .................................................................................... 15 
5.4.1 
Reasons for Withdrawal or Termination ............................................................... 15 
5.4.2 
Handling of Participant Withdrawals or termination ............................................. 15 
5.5 
Premature Termination or Suspension of Study .................................................................... 15 
6 
STUDY INTERVENTION ................................................................................................................. 16 
7 
STUDY PROCEDURES AND SCHEDULE ..................................................................................... 16 
7.1 
Study Procedures/Evaluations ............................................................................................... 16 
7.1.2 
Standard care study procedures .......................................................................... 17 
7.2 
Laboratory Procedures/Evaluations ....................................................................................... 18 
7.2.1 
Clinical Laboratory Evaluations ............................................................................ 18 
7.3 
Study Schedule ...................................................................................................................... 18 
7.3.1 
Screening ............................................................................................................. 18 
7.3.2 
Enrollment/Baseline ............................................................................................. 18 
7.3.3 
Follow-up .............................................................................................................. 21 
7.3.4 
Final Study Visit ................................................................................................... 21 
7.3.5 
Early Termination Visit ......................................................................................... 21 
7.3.7 
Schedule of Events Table .................................................................................... 21 
7.4 
Justification for Sensitive Procedures .................................................................................... 22 
7.5 
Concomitant Medications, Treatments, and Procedures ....................................................... 22 
8 
ASSESSMENT OF SAFETY ........................................................................................................... 22 
8.1 
Specification of Safety Parameters ........................................................................................ 22 
8.1.1 
Definition of Adverse Events (AE) ....................................................................... 23 

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8.1.2 
Definition of Serious Adverse Events (SAE) ........................................................ 23 
8.1.3 
Definition of Unanticipated Problems (UP) .......................................................... 23 
8.2 
Classification of an Adverse Event ........................................................................................ 24 
8.2.1 
Severity of Event .................................................................................................. 24 
8.2.2 
Relationship to Study Agent ................................................................................. 24 
8.2.3 
Expectedness ...................................................................................................... 26 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up ...................................... 26 
8.4 
Reporting Procedures ............................................................................................................ 26 
8.4.1 
Adverse Event Reporting ..................................................................................... 27 
8.4.2 
Serious Adverse Event Reporting ........................................................................ 27 
8.4.3 
Unanticipated Problem Reporting ........................................................................ 28 
8.4.4 
Events of Special Interest .................................................................................... 29 
8.4.5 
Reporting of Pregnancy ....................................................................................... 29 
8.5 
Study Halting Rules ............................................................................................................... 29 
8.6 
Safety Oversight .................................................................................................................... 29 
9 
CLINICAL MONITORING ................................................................................................................ 29 
10 
STATISTICAL CONSIDERATIONS ................................................................................................ 30 
10.1 
Statistical and Analytical Plans .............................................................................................. 30 
10.2 
Statistical Hypotheses ............................................................................................................ 30 
10.3 
Analysis Datasets .................................................................................................................. 30 
10.4 
Description of Statistical Methods .......................................................................................... 30 
10.4.1 
General Approach ................................................................................................ 31 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ....................................................... 31 
10.4.3 
Analysis of the Secondary Endpoint(s) ................................................................ 31 
10.4.4 
Safety Analyses ................................................................................................... 31 
10.4.5 
Adherence and Retention Analyses ..................................................................... 31 
10.4.6 
Baseline Descriptive Statistics ............................................................................. 32 
10.4.7 
Planned Interim Analyses .................................................................................... 32 
10.4.9 
Multiple Comparison/Multiplicity ........................................................................... 32 
10.4.10 
Tabulation of Individual Response Data .............................................................. 32 
10.4.11 
Exploratory Analyses ........................................................................................... 33 
10.5 
Sample Size ........................................................................................................................... 33 
10.6 
Measures to Minimize Bias .................................................................................................... 33 
10.6.1 
Enrollment/ Randomization/ Masking Procedures ............................................... 33 
10.6.2 
Evaluation of Success of Blinding ........................................................................ 33 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ............................... 34 
12 
QUALITY ASSURANCE AND QUALITY CONTROL ...................................................................... 34 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................................... 34 
13.1 
Ethical Standard AND JUSTIFICATION FOR EXCEPTION FROM INFORMED CONSENT34 
13.2 
Institutional Review Board ..................................................................................................... 36 
13.3 
Informed Consent Process .................................................................................................... 37 
13.3.1 
Consent/assent and Other Informational Documents Provided to Participants ... 37 
13.3.2 
Consent Procedures and Documentation ............................................................ 37 
13.4 
Participant and data Confidentiality ....................................................................................... 37 
13.4.1 
Research Use of Stored Human Samples,Specimens or Data ........................... 38 
13.5 
Future Use of Stored Specimens ........................................................................................... 38 
14 
DATA HANDLING AND RECORD KEEPING ................................................................................. 39 

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14.1 
Data Collection and Management Responsibilities ............................................................... 39 
14.2 
Study Records Retention ....................................................................................................... 39 
14.3 
Protocol Deviations ................................................................................................................ 40 
14.4 
Publication and Data Sharing Policy ...................................................................................... 40 
15 
STUDY ADMINISTRATION ................................................................................................... 41 
15.1 
Study Leadership ................................................................................................................... 41 
16 
CONFLICT OF INTEREST POLICY ...................................................................................... 41 
17 
LITERATURE REFERENCES ............................................................................................... 41 
Appendix A: EFIC PLAN .......................................................................................................................... 46 
Appendix B: UMHS ED ECPR GUIDELINES .......................................................................................... 60 
Appendix C: Washtenaw Livingston cardiac arrest guidelines .................................................... 63 

1 
 
 
LIST  OF ABBREVIATIONS 
AE 
Adverse Event 
ANCOVA Analysis of Covariance 
CC 
Coordinating Center 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Science 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Centers for Medicare and Medicaid Services 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good 
Clinical Practice: Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LSMEAN Least-squares Means 
MedDRA Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute & Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UM 
University of Michigan 
UP 
Unanticipated Problem 
US 
United States 

2 
 
  STATEMENT  OF COMPLIANCE 
 
 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on 
the Protection of Human Subjects (45 CFR Part 46), and the NHLBI Terms of Award. The 
Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the sponsor 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 Training. 
I agree to ensure that all staff members involved in the conduct of this study are informed 
about their obligations in meeting the above commitments. 
Principal Investigator: Robert W. Neumar, MD, PhD 
 
Signed:  
 
Date: 
 
Signature 

3 
 
  PROTOCOL SUMMARY 
 
 
Title: 
Extracorporeal  CPR for refractory out-of-hospital cardiac arrest 
(EROCA) 
Précis: 
EROCA is a prospective, randomized, open-label, clinical endpoint 
study comparing standard prehospital care to expedited transport of 
patients with refractory out-of-hospital cardiac arrest (OHCA) to a 
qualified emergency department capable of performing advanced 
resuscitation including extracorporeal cardiopulmonary 
resuscitation (ECPR). A maximum total of 30 patients will be 
randomized in the prehospital setting. The primary objectives are to 
determine the proportion of qualifying OHCA patients arriving to a 
qualified ED within 30 minutes of the initial 911 call and what 
proportion of patients can have ECPR initiated within 30 minutes of 
ED arrival. Patients arriving at the qualified ED will be treated under 
a standard institutional guideline and will be followed in the hospital 
for adverse events. In addition, patients will have follow up visits at 
90 days to determine functional and neuro-cognitive outcomes. 
Objectives: 
Co-Primary: Determine what proportion of patients with refractory 
OHCA can be reliably delivered to an ECPR-capable ED within 30 min 
of either the 911 call or prehospital provider witnessed first cardiac 
arrest (qualifying OHCA event). 
Co-Primary: Determine what proportion of patients with ongoing 
refractory cardiac arrest that have ECPR initiated within 30 minutes 
of ED arrival. 
Safety: To estimate frequency of adverse events associated with 
study interventions. 
Exploratory: Demonstrate the feasibility of field randomization of 
patients with refractory OHCA based on estimated time from 911 
call or EMS witnessed arrest to qualified ED arrival 
Exploratory: To provide preliminary estimates regarding 
neurological outcomes following this treatment. 
Endpoints 
Co-Primary : Time interval from 911 call or prehospital provider 
witnessed first cardiac arrest to qualified ED arrival in minutes 
Co-Primary : Time interval from qualified ED arrival to ECPR 
initiation in minutes 
Safety: Composite of major hemorrhage (requiring transfusion of 
over 4 units packed red blood cells per incident), arterial thrombosis 
(stroke, renal infarction, limb ischemia), venous thrombosis 
(pulmonary embolism or deep venous thrombosis), 
hemopericardium (requiring pericardiocentesis), 
pneumothorax(requiring thoracostomy tube placement), or vascular 
injury (causing complete occlusion and/or requiring vascular 

4 
 
procedure). 
Exploratory: Utility weighted modified Rankin Scale at 90 days 
Exploratory: Neuropsychological and cognitive testing using NIH 
toolbox 
Exploratory: Time to vascular access and time to ECPR cannulation 
Population: 
Out-of-hospital cardiac arrest patients who do not have return of 
spontaneous circulation after initial rhythm analysis by first- responders 
who can potentially arrive at a qualified ED in persistent cardiac arrest 
within 30 minutes of initial 911 call or EMS witnessed first cardiac 
arrest. 
Phase: 
2 
Number of Sites 
enrolling participants: 1 
Description of Study 
Interventions : 
Patients in the field will be randomized to either early transport to 
the hospital versus standard care (continued attempts at advanced 
cardiac life support in the field). Standard clinical procedures in the 
hospital will be followed for refractory cardiac arrest patients. 
Study Duration: 
30 months 
Participant Duration: 
Three months 

5 
 
 
 
 
*Return Of Spontaneous Circulation 
 
**Expedited transfer refers to immediately transferring a patient to the hospital while CPR is 
in progress, using mechanical chest compressions. 
SCHEMATIC  OF  STUDY DESIGN 

6 
 
  
KEY ROLES 
 
Robert W. Neumar, MD, PhD 
Principal Investigator 
Professor and Chair, Department of Emergency Medicine 
University of Michigan Health System 
B1-220 Taubman Center Dr. 
1500 E. Medical Center Dr. 
Ann Arbor, MI 48109-5301 
Phone: (734) 936-0253 
Email: neumar@med.umich.edu 
 
Robert Bartlett, M.D. 
Co-Principal Investigator 
Professor of Surgery, Active Emeritus 
Director, Extracorporeal Circulation Laboratory 
University of Michigan Health System 
B560B MSRB II, SPC 5686 
Ann Arbor, MI 48198-5686 
Phone: 734-649-3747 
Email: robbar@med.umich.edu 
 
William Meurer, MD, MS 
Assistant Professor, Department of Emergency Medicine 
University of Michigan Health System 
B1-220 Taubman Center Dr. 
1500 E. Medical Center Dr. 
Ann Arbor, MI 48109-5301 
Phone: (734) 615-2766 
Email: wmeurer@med.umich.edu 
 
Robert Silbergleit, M.D. 
Professor, Emergency Medicine 
24 Frank Lloyd Wright Dr. 
Suite H - 3100 
Ann Arbor, MI 48106-5700 
Phone: 734-232-2142 
Email: robie@med.umich.edu 
 
Kelley Kidwell, PhD 
Research Assistant Professor of Biostatistics 
1415 Washington Heights, SPH II M2525, Ann Arbor, MI 48104 
Ann Arbor, MI 48104 

7 
 
Phone: 734-764-6724 
kidwell@umich.edu 
 
Jennifer Fowler, RN BSN, CCRC 
Emergency Medicine Research Project Manager 
University of Michigan Health System 
B1-204 Taubman Center 
1500 E. Medical Center Dr. 
Ann Arbor, MI 48109-5301 
Phone: 734-647-0574 
Email: jenfow@umich.edu 
 
 
 
 
Approximately 200,000 people are treated for out-of-hospital cardiac arrest (OHCA) each year 
in the United States. The modest improvement in survival rates over the past decade have 
been primarily attributed to better implementation of cardiopulmonary resuscitation (CPR), 
advanced cardiac life support (ACLS), and post-cardiac arrest care. However, no new therapies 
have been proven effective in more than a decade. The result is a plateauing of overall 
survival rates at approximately 10% [Mozaffarian 2015]. Extracorporeal cardiopulmonary 
resuscitation (ECPR) using percutaneous veno-arterial extracorporeal circulation (VA-ECMO) is 
emerging as a feasible and potentially effective resuscitation strategy for non-traumatic OHCA 
patients who fail standard therapy. In published case series, survival rates range from 4-33%, 
and organ donation as a secondary outcome occurs in 5-15% of patients. Despite the promise 
of this emerging therapy, a fundamental barrier to widespread implementation is the fact that 
efficacy of ECPR for OHCA has yet to be proven in a prospective randomized clinical trial. In 
October of 2015, the International Liaison Committee on Resuscitation (ILCOR) Consensus on 
Science and Treatment Recommendation made the following treatment recommendation: 
We suggest ECPR is a reasonable rescue therapy for selected patients with cardiac arrest when 
initial conventional CPR is failing in settings where this can be implemented (weak 
recommendation, very-low-quality evidence) [Callaway 2015]. The primary knowledge gap 
listed was: Controlled clinical trials are needed to assess the effect of ECPR versus traditional 
CPR on clinical outcomes in patients with cardiac arrest. The new AHA guidelines for CPR and 
Emergency Cardiovascular Care published in October 2015 state: There is insufficient evidence 
to recommend the routine use of ECPR for patients with cardiac arrest. In settings where it can 
be rapidly implemented, ECPR may be considered for select cardiac arrest patients for whom 
the suspected etiology of the cardiac arrest is potentially reversible during a limited period of 
2 
INTRODUCTION: BAC KGROUND INFORMATION  AND SCIENTIFIC RATIONALE 
2.1.1   CLINICAL SIGNIFICANCE 
2.1 
BACKGROUND INFORMATION 

8 
 
mechanical cardiorespiratory support (Class IIb, LOE C-LD) [Link 2015]. Thus, the most recent 
consensus of the world’s experts in the field is a call for more evidence in the form of a 
prospective randomized clinical trial. 
 
 
Almost all published case series of successful ECPR for OHCA initiate ECPR in the emergency 
department [Chen 2008, Kagawa 2010, Nagao 2000 and 2010, LeGuen 2011, Morimura 2011, 
Avali 2012, Bellezzo 2012, Johnson 2014, Sakamoto 2014, Stub 2014], The reason for this 
strategy is that the shorter the interval from cardiac arrest onset to initiation of ECPR, the 
better the chance for a favorable outcome. Figure 3 illustrates this relationship in recent 
OHCA studies (published after 2010) that specifically reported the collapse to ECPR interval 
and survival with good neurologic function for the entire study population. These and similar 
reports are the basis for our initial targeting of a 911 call to ECPR interval <60 min in the 
EROCA trial. In many countries where ECPR is used to treat OHCA, the ED is routinely staffed 
by physician specialists in anesthesia or cardiology with more formal training and experience 
in ECMO than emergency medicine physicians in the U.S. Institutions in the U.S. that perform 
ECPR for OHCA typically rely on cardiac surgery or cardiology consultants to come to the ED to 
place ECMO catheters and initiate ECPR [Johnson 2014]. However, the model has many 
logistical limitations that make it challenging to initiate ECPR within the therapeutic window, 
and if maintained will be a persistent barrier to widespread implementation. 
One example of a program that has incorporated emergency medicine physicians into the 
ECPR team that includes cardiologist and cardiothoracic surgeons Sharp Memorial Hospital in 
San Diego [Bellezzo 2012]. In their published case series, 8 out of 18 OHCA patients that met 
inclusion/exclusion had ECPR successfully initiated in the ED, and 3/18 had spontaneous ROSC 
before ECPR could be initiation. Of the 8 patients successfully treated with ECPR, 5 survived 
with good neurologic function (63%). However ECPR catheters could not be placed in 4 
patients, and two other patients were reported to have fatal complications of catheter 
placement (aortic dissection and bifemoral vein cannulation). Although these results 
demonstrate feasibility in a US ED, they also emphasize the importance of validated training 
and maintenance of competency for both clinical trial participation and widespread 
implementation. 
2.1.2   RELEVANT  CLINICAL RESEARCH 

9 
 
 
 
Relationship between collapse to ECPR interval and survival with good neurologic function in 
refractory OHCA cardiac arrest  1) Maekawa 2013; 2) Kagawa 2012; 3) Fagnoul 2013; 4) 
Haneya 2012; 5) Nagao 2010; 6) Avali 2012; 7) Le Guen 2011. Diamonds represent median 
intervals from collapse to ECPR and lines represents range. (Adapted from Fagnoul 2014 table 
2.) 
 
  2.2 
RATIONALE 
 
 
Currently available evidence suggests that ECPR for OHCA should be initiated within 60 
minutes of cardiac arrest onset to maximize the potential therapeutic benefit. Therefore, in 
addition to delivering patients to the ED within 30 minutes, it is essential that our system of 
care is able to initiate ECPR within ≤30 minutes of ED arrival. In a recently published study of 
ED-initiated ECPR, the median time from ECPR team arrival to initiation of ECPR was 20 
minutes [IQR 15-30 minutes] [Stub 2014]. The goal is to achieve <30-minute arrival to 
cannulation for all patients meeting inclusion/exclusion criteria for ECPR therapy. 
 
  2.3 
POTENTIAL RISKS  AND BENEFITS 
 
 
 
Risks of mechanical or traditional CPR: bruising and soreness of the chest is common after 
mechanical or traditional CPR. Pneumothorax and hemopericardium are also possible risks. 
Rib fractures and solid organ injuries (liver and spleen) are additional potential risks. 
Risk of EMS (early transport): motor vehicle crash during transport to the hospital. 
 
Alternatives to early transport with mechanical CPR: Continued BLS and ACLS at the scene 
with manual or mechanical CPR until ROSC is achieved or resuscitation efforts are terminated 
(current practice). 
2.3.1   KNOWN  POTENTIAL RISKS 

10 
 
Risks of ECPR (standard care procedure in hospital): vascular injury, limb ischemia, major 
hemorrhage, venous thromboembolism, stroke, renal failure, and infection. 
Alternatives to ECPR for refractory cardiac arrest: An option is to transport patients to the 
interventional cardiology laboratory with ongoing CPR for coronary angiography and PCI if 
indicated. The rationale for this approach is that an acute coronary occlusion is the cause of 
the cardiac arrest and treating that occlusion could result in ROSC. At this time there is less 
evidence to support this approach compared to ED-initiated ECPR followed by coronary 
angiography and PCI following initiation of ECPR if indicated. 
Risks of research: improper disclosure or release of personal or medical information. 
 
 
 
The potential benefit of the research to the research subjects in an improved chance of 
survival with good neurologic function. The current practice for patients with refractory OHCA 
is for EMS providers to cease resuscitation efforts in the field and pronounce the patients 
dead.  Early transport to an ED capable of advanced resuscitation strategies and ECPR has 
been reported to result in 4-33% survival with good neurologic function. The potential benefit 
to society is an improved system of care of OHCA that could double overall survival rates and 
with widespread implementation save thousands of lives each year in the United States. 
Reported risks for ECPR include hemorrhage, renal replacement therapy for acute kidney 
injury, vascular damage, thromboembolism, thromboembolism, stroke, and infection. Relative 
to the potential benefit of survival with good neurologic function, these risks seem 
reasonable. 
 
 
 
 
Co-Primary: To determine what proportion of patients with refractory OHCA can be delivered 
to an ECPR-capable ED within 30 min of the 911 call or prehospital provider witnessed first 
cardiac arrest (qualifying OHCA event). This is to establish the feasibility of the early transport 
protocol. 
Co-Primary: To determine what proportion of patients can have ECPR initiated within 30 
minutes of ED arrival for patients with ongoing refractory OHCA. This is to establish the 
feasibility of the ED advanced resuscitation protocol in situations where prenotification of the 
team has occurred by qualified prehospital providers. 
Safety: To estimate frequency of adverse events associated with study interventions. This 
early phase trial is not adequately sized to provide meaningful comparative estimates. The 
2.3.2   KNOWN  POTENTIAL BENEFITS 
3 
OBJECTIVES  AND PURPOSE 

11 
 
population of OHCA survivors is at high risk for death and adverse experiences under routine 
clinical care. 
Exploratory: Demonstrate the feasibility of field randomization of patients with refractory 
OHCA. This study is using a novel procedure to determine eligibility based on timing and 
location. 
Exploratory: We will collect ECPR process measures including time to confirmed vascular 
access and confirmed ECPR cannulation. These measures are collected as part of routine 
clinical care on all patients undergoing ECPR for cardiac arrest at the qualified emergency 
department(s). 
Exploratory: To provide preliminary estimates regarding neurological outcomes following this 
treatment. This study is not adequately sized to provide meaningful comparative data on 
neurological outcomes. This aim will provide insight into the proportion of patients with 
excellent outcomes, along with the proportion of patients with neurologically unsatisfactory 
outcomes. 
 
 
  4.1 
DESCRIPTION OF THE STUDY DESIGN 
 
 
4.2.1 Primary Endpoints 
 
Co-Primary Endpoint: Time interval from 911 call or prehospital witnessed first cardiac arrest 
(qualifying OHCA event) to ED arrival in minutes. 
The primary endpoint was selected because the goal of the study is to demonstrate the 
feasibility of transporting patients with refractory OHCA to an ECPR-capable ED within 30 
minutes of the 911 call or EMS witnessed arrest. 
Co-Primary Endpoint: Time interval from ED arrival to ECPR initiation in minutes 
 
This time interval was chosen because the apparent therapeutic window for OHCA ECPR is 60 
minutes and time from ED arrival to ECPR flow is estimated to be 30 minutes. 
 
 
Composite safety endpoint of hemorrhage requiring blood transfusion, pneumothorax 
requiring thoracostomy, hemopericardium requiring pericardiocentesis. 
Composite safety endpoint of, hemorrhage requiring blood transfusion (greater than 4 units 
packed red blood cells per incident), vessel damage requiring vascular procedure or leading to 
occlusion, venous/arterial thromboembolism, stroke, renal failure and infection 
4 
STUDY DESIGN AND  ENDPOINTS 
4.2.2   SAFETY ENDPOINTS 

12 
 
 
 
Additional safety outcomes: Splenic injury, liver injury, and all individual components of the 
composite endpoints listed in 4.2.2 
All participants: Utility weighted modified Rankin Scale and cerebral performance category at 
hospital discharge and 90 days. 
Randomization feasibility: Number of attempted uses of randomization app versus successful 
enrollments 
Patient reported outcomes: Neuro-QOL 
Cognitive functioning outcomes: NIH-Toolbox 
 
 
  5.1 
INCLUSION CRITERIA 
 
 
All adult out-of-hospital cardiac arrest patients, receiving emergency treatment by local Fire 
Department First Responders capable of using mechanical chest compression devices and 
Huron Valley Ambulance (HVA) paramedics will be evaluated for this study. This may include 
ethnic minorities, disabled, and economically challenged populations. 
 
 
• Present with out-of-hospital cardiac arrest, presumed non-traumatic etiology, 
requiring CPR 
• Age presumed or known to be 18 through 70 years old  (prior to 71st birthday) 
• Predicted arrival time at ECPR-capable hospital within timeframe specified 
• Initial shockable rhythm (ventricular tachycardia or ventricular fibrillation) or 
witnessed pulseless electrical activity or asystole 
• Persistent cardiac arrest after initial cardiac rhythm analysis and shock (if shock is 
indicated) 
Participants will be enrolled in the study if they meet initial inclusion criteria at the time of 
their cardiac arrest. 
                                                                                                                                                                                    
4.2.3   EXPLORATORY ENDPOINTS 
5 
STUDY ENROLLMENT AND  WITHDRAWAL 
5.1.1 PATIENT LEVEL INCLUSION 
5.1.2 INCLUDED EMS  AGENCIES /  REGIONS /  HOSPITALS 

13 
 
 
• Local Fire Department First Responders using mechanical chest compression devices 
including:  
•  Ann Arbor Fire Department First Responders  
• Ann Arbor Township Fire Department First Responders 
• Saline Area Fire Department 
• Scio Township Fire Department First Responders 
• Huron Valley Ambulance Paramedics 
• Michigan Medicine, University of Michigan  
 
  5.2 
PARTICIPANT EXCLUSION CRITERIA 
Exclusion criteria include: 
• Sustained return of spontaneous circulation (ROSC) 
• DNAR or DNI advanced directive 
• Preexisting evidence of opting out of study 
• Prisoner 
• Pregnant (obvious or known) 
• ECPR capable ED is not at the destination hospital as determined by EMS 
• LAR/Family member aware of study and refuses study participation at the scene 
 
 
 
There is no participant “recruitment” for this study as it is not possible to prospectively 
identify victims of out-of-hospital sudden cardiac arrest and obtain informed consent. 
Participants will be included in the study if they meet enrollment criteria at the time of their 
cardiac arrest. Based on historical data, we anticipate randomizing 30 refractory OHCA 
patients over 18 months. This clinical trial will be conducted under exception from informed 
consent (further details in Section 13). 
Patients will be screened and assigned a randomization group at the time of dispatch. Study 
eligibility and randomization will be further determined with the aid of an algorithm or 
expected time to eligible hospital map where a 911 dispatch operator will input eligibility data 
points and receive one of 3 responses. This is pre-enrollment treatment group assignment. 
Despite assignment to one of these three groups, the patient will not be considered 
randomized until they have met the inclusion criteria (including the refractory nature of the 
cardiac arrest.) 
1. Not eligible continue usual resuscitative care (stay in place until ROSC or resuscitation 
5.3 
STRATEGIES  FOR  RECRUITMENT AND RETENTION 

14 
 
meets termination criteria) 
2. Eligible, randomized to usual care (operationally same as 1 for paramedics) 
3. Eligible, randomized to early transport 
 
After an initial rhythm assessment and shock delivery (if indicated), patients who do not have 
ROSC will be considered randomized. Based on the assignment given at the time the 
prehospital providers were dispatched, they will either continue usual care (stay in place until 
ROSC) if assigned to that group (control), or undergo expedited transport with mechanical CPR 
device in place (experimental group). Patients who do not meet inclusion criteria or have 
exclusion criteria will not be considered randomized or enrolled, since no experimental 
procedures will occur to them (standard procedure is for patients to be transported after 
ROSC). If ROSC is achieved during transport or in the emergency department (experimental 
group), they will be included in the primary analysis of the expedited transport group. All 
patients will be followed for clinical outcomes. 
All Emergency Medical Services (EMS) personnel (engaged sites) will be trained by a member 
of the study team to the study protocol including randomization, eligibility, study procedures, 
exception from informed consent, and opting-out mechanisms. Training records will be 
maintained with the site coordinator. 
In accordance with the FDA’s Regulations, the investigator must attempt to notify all 
participants that they have been enrolled in a study. If the participant is unable to comprehend 
this due to loss of consciousness or dies, the investigator must attempt to notify their legally 
authorized representative. 
Study participants who die in the field or the hospital emergency department, attempts will be 
made to notify their family/LAR, by using EMS and hospital records contact information. Initial 
contact will be made by a letter requiring a signature/receipt for receipt confirmation. With 
respect for the grieving process, a letter will be sent 2-4 weeks after the death of the patient. 
These records will also be reviewed and data abstracted, in addition to reviewing for any 
potential adverse events. Letters returned to sender or knowledge initial letter was not 
received, a telephone call will be made, up to 2 times for notification. This will be done by a 
trained research team member, experienced with discussing sensitive topics such as the death 
of a loved one.   A communication tracking log will be kept. 
Study Participants who survive to hospital admission or their LAR/family member will be 
approached to notify them of being in the research study and invited to continue study 
participation, as soon as feasible after hospital admission. The person obtaining consent will 
first discuss the study with the participant’s physician or nurse to assess their condition and 
best timing for discussion with them or their LAR/family member. Once signed, a copy of this 
form is provided to the participant/LAR, in the medical record, and the original will be placed 

15 
 
in their research record. 
We will conduct education and training of engaged agencies and hospitals to maximize 
recruitment. Screening logs will be reviewed regularly with engaged agencies. 
 
  5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
 
 
 
A study participant has the right to withdraw from the study at any time without 
consequence. Reasons for withdrawal may include not wanting to complete the 90-day 
follow-up visit, becoming tired with the follow-up surveys and requesting to stop, or deciding 
to no longer participate. 
 
 
 
FDA regulations require investigators to prepare and maintain adequate study files recording 
all observations and other pertinent information relative to the clinical trial and when a 
participant or LAR/family member withdrawals further participation, the data already 
collected, remains with the study database. 
If a study participant or LAR/family member declines further study participation, then no 
further data collection will occur. Since this is an observational study after randomization, 
the participant can safely withdraw and will not be at risk of injury. 
In the case of participant withdrawal, data about their death is contained in public vital 
statistics records and will be queried. Access to public records is not subject to restriction 
under 21CFR or other FDA regulations. 
 
  5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
 
 
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 the investigator, 
funding agency, the IND/IDE sponsor and regulatory authorities. If the study is prematurely 
terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) 
for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
5.4.1   REASONS FOR WITHDRAWAL OR TERMINATION 
5.4.2   HANDLING OF  PARTICIPANT WITHDRAWALS OR  TERMINATION 

16 
 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
Study may resume once concerns about safety, protocol compliance, data quality is addressed 
and satisfy the sponsor, IRB and/or FDA. 
 
 
This study is a comparison of two treatment strategies for refractory out-of-hospital cardiac 
arrest (OHCA): continued standard care in the field (control) versus expedited transport with 
ongoing mechanical CPR to a hospital capable of initiating extracorporeal cardiopulmonary 
resuscitation (ECPR) in the emergency department (experimental). ECPR is defined as 
percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) initiated during 
cardiac arrest. The duration of ECPR is typically 72 hours to allow the patient’s heart function 
to recover prior to weaning. Many devices make up an ECMO circuit (cannulas, conduit, 
reservoir, pump, oxygenator, heat exchanger, monitors, sweep gas controller, bubble traps, 
blood filters, positive and negative pressure monitors and controls). The devices used for 
ECMO are FDA-approved for up to 6 hours for the indication of cardiopulmonary bypass. 
However, ECPR for the treatment of refractory cardiac arrest is not a FDA approved or cleared 
indication for ECMO devices, and thus is considered investigational in this study. Current 
American Heart Association Guidelines state that “ In settings where it can be rapidly 
implemented, ECPR may be considered for select cardiac arrest patients for whom the 
suspected etiology of the cardiac arrest is potentially reversible during a limited period of 
mechanical cardiorespiratory support (Class IIb, LOE C-LD)”. ECPR is currently performed in the 
University of Michigan University Hospital ED for selected patients with refractory cardiac 
arrest as part of our standard practice. Examples of local guidelines for EMS and ED care are 
given as appendices B and C. 
 
 
 
  7.1 
STUDY  PROCEDURES/EVALUATIONS 
 
 
7.1.1 Study specific procedures 
Consent Process 
Participants or their legally authorized representative (LAR) or family member will be 
approached within a reasonable timeframe and will be requested for consent to continue in 
the study. The availability and emotional state of LAR/family members will be taken into 
account, and anticipate a longer timeframe in these situations. The progress of obtaining 
written informed consent will be documented in the medical record. For participants who do 
not survive to hospital admission, a letter will be sent as notification. 
6 
STUDY INTERVENTION 
7 
STUDY  PROCEDURES AND SCHEDULE 

17 
 
Review of Medical Records 
 
FDA’s regulations require clinical investigators to prepare and maintain adequate and 
accurate case histories (21 CFR 312.62(b) and 812.140(a). In general, the investigator should 
arrange to have access to all records that are generated and maintained from enrollment until 
discharge or death, unless the participant or their LAR/family member discontinues the 
participant’s participation in the study. Medical records will be reviewed by a member of the 
research team up until this time and if the participant or LAR or family member discontinues 
participation, the data already collected will remain with the study. 
 
Prehospital Medical Records 
 
BLS and ACLS run reports will be reviewed on all study participants by the study team and 
study specific data abstracted. Run reports become part of the medical record when patients 
are brought to the emergency department and for cardiac arrests pronounced dead in the 
field, will be sent to the study team securely (i.e. by fax). 
The following scales will be performed by a member of the research team at hospital 
discharge and Day 90, in participants who survive. 
Modified Rankin Scale (mRS) 
 
 
The mRS is commonly used for measuring the degree of disability or dependence in the daily 
activities of people who have suffered a neurological disability. mRS score is widely used in 
stroke research. 
Cerebral Performance Categories Scale (CPC) 
 
CPC score is widely used in cardiac arrest research to assess neurologic outcome. 
NIH Toolbox 
The NIH toolbox includes several cognitive, motor, and psychological tests. It can be 
administered via an iPad. 
 
 
 
 
Standard care for the treatment of OHCA will include cardiac defibrillators, mechanical CPR, 
intravenous (IV) therapy, arterial blood pressure monitoring, central line monitoring, 
intubation, mechanical ventilation, heart monitoring, cardiac catheterization, hypothermic 
7.1.2   STANDARD CARE  STUDY PROCEDURES 

18 
 
targeted temperature management, and continuous EEG monitoring. Standard procedures for 
engaged prehospital providers/agencies and qualified emergency departments will be 
followed. Examples of prehospital and in-hospital standard care protocols are given as 
appendices B and C. 
 
 
 
No biological materials, including blood samples, will be obtained as part of this study 
protocol. 
 
 
Screening  (Day 0, Field Baseline) 
 
Screening will be done by prehospital providers in all out-of-hospital cardiac arrests in the 
engaged agencies area. All out-of-hospital cardiac arrests, meeting inclusion criteria will be 
considered for the study. 
 
 
Pre Enrollment – Treatment Group Assignment / Randomization 
 
At the time of dispatch of EMS, the dispatcher will enter the address of the arrest, age of the 
patient, and time of 911 call into a web form. The form will use an application to determine 
whether the patient is within the travel distance to arrive at the hospital within the pre- 
specified interval.  They will immediately receive one of the following messages: 
1) Not eligible, continue usual resuscitative care (patient may be out of geographic time 
area, may be over 71 years old) 
2) Eligible, randomized to usual care 
3) Eligible, randomized to early transport. 
If the dispatcher is unable to access the assignment/randomization website, there will be a 
study team member, with access rights to the website available by telephone at all times. 
 
 
Pre-hospital run sheet(s) will be reviewed for study eligibility and enrollment criteria. The 
emergency department and hospital electronic medical record will be reviewed for continued 
inclusion criteria, including time intervals from 911 call to randomization and 911 call to 
7.2.1   CLINICAL  LABORATORY EVALUATIONS 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
7.3.1   SCREENING 
7.3 
STUDY SCHEDULE 
7.3.2   ENROLLMENT/BASELINE 

19 
 
emergency department admission, if applicable. Until hospital discharge, all data collected 
will come from previously collected medical records. 
Initial Enrollment/Field Baseline  (Day 0) 
 
Patients will be enrolled and randomized if they meet the inclusion criteria, namely, the 
presence of refractory cardiac arrest (defined as no ROSC after initial rhythm analysis and 
shock if indicated). The treatment group was pre-assigned during the screening phase, but 
patients with immediate ROSC are considered screened out of the study as no experimental 
intervention will occur to them. 
Patients with persistent cardiac arrest in the field who are randomized will be followed for 
clinical outcomes per the protocol whether or not they have ECPR. 
Due to the sudden and urgent nature of cardiac arrest, treatment must occur immediately. 
Enrollment will occur at the time of randomization by the prehospital providers at the scene 
of the out-of-hospital cardiac arrest. Patients will be enrolled under the exception from 
informed consent (EFIC) process. 
 Prehospital Medical Records 
 
Prehospital run reports is where Basic Life Support (BLS) and Advanced Life Support (ALS) 
document the events of the 911 call and often become part of the medical record when 
patients are brought to the emergency department. Any run reports not found in the medical 
record and for participants who dies prior to the emergency department will be collected 
directly from the agencies. 
 
EMS medical records will be reviewed and the following data abstracted: 
• Date and time of 911 call 
• Time of index cardiac arrest 
• Status of witnessed arrest 
• Status of Bystander CPR 
• Time of collapse 
• Time CPR initiated 
• Duration of EMS CPR 
• Initial recorded cardiac arrest rhythm 
• Use of Impedance-threshold device 
• Use and type of advanced airway 
• Location of cardiac arrest (home, public place, parking lot, street, etc.) 
• Date and time of ED arrival 
 
Index Cardiac Arrest/Emergency Department  (Day 0) 

20 
 
Emergency Department (ED) medical records will be reviewed and the following data 
abstracted: 
• Date and time of ED arrival 
• Status and timing  of ROSC 
• Demographic information 
• Physician progress note(s) 
• Past medical history; known comorbidities 
• Nurses notes 
• Tests performed and their results 
• Procedures performed and their outcome 
• Status of ECPR procedure 
o Time of confirmed placement of arterial and venous ECMO catheters 
o Time of initiation of ECPR 
• ED Discharge diagnosis 
• ED disposition 
 
Survival to Hospital Admission (Day 0- Hospital Discharge or Death) 
 
Attempt to notify the participant, LAR, or family member of study participation and seek 
permission to continue in the study, using the written IRB approved  informed consent form. 
 
Hospital medical records will be reviewed and the following data abstracted: 
• Date and time of Hospital admission 
• Status of ROSC 
• Use of therapeutic hypothermia 
• Neurologic status 
• Physician progress note(s) 
• Nurses notes 
• Tests performed and their results 
• Procedures performed and their outcome 
• Assess for serious adverse events 
 
Hospital Discharge 
Hospital medical records will be reviewed and the following data abstracted: 
• Date and time of Hospital discharge 
• Survival status 
• Assess for serious adverse events 
• Discharge disposition 
 
The following assessments will be performed by a member of the study team: 
• CPC 
• mRS 
• NIH Toolbox Cognitive Testing 

21 
 
 Assess for Serious Adverse Events (SAE’s) 
Prehospital and hospital records will be reviewed for serious adverse events. 
 
 
Follow-up Visit (Day 90 +/- 15 days) 
The following assessments will be performed by a member of the study team: 
• CPC 
• mRS 
• NIH Toolbox Cognitive Testing 
• Quality of Life Survey 
 
 
Final study visit is the Day 90 visit described above in section 7.3.3. The study participant will 
be contacted by telephone to set up a follow up appointment. Reasonable costs such as 
parking, bus fare, or mileage will be covered by the study. 
 
 
 
Prehospital patients in cardiac arrest will not have the ability to notify prehospital providers of 
their choice to participate or not. If a LAR/family member is aware of the study and objects to 
their participation, prehospital providers will not enroll the patient. 
If the participant survives to hospital admission, a member of the study team will attempt to 
contact the participant or LAR/family member to notify them of study participation and obtain 
informed consent for continued participation in the study. The participant or LAR or family 
member has the right to decline study participation at any time before or after informed 
consent is obtained. A participant, however may not withdraw use of the data already 
collected.  At the point of termination, the medical record will no longer be reviewed However, 
data about a participant’s death is contained in public vital statistics records. Access to public 
records is not subject to restriction under 21 CFR 50.24 or other FDA regulations. 
 
 
 
 
 
 
 
7.3.3   FOLLOW-UP 
7.3.4   FINAL  STUDY VISIT 
7.3.5   EARLY  TERMINATION VISIT 

22 
 
7.3.7   SCHEDULE OF  EVENTS TABLE 
 
 
Procedures 
Index Cardiac 
Arrest (Field 
Emergency 
Department 
Survival to Hospital 
Admission 
Hospital  Course 
Hospital Discharge 
End of Study/Day 90 
Screening 
x 
Enrollment 
x 
Randomization 
x 
ROSC 
x 
x 
Survival Status 
x 
x 
x 
x 
x 
x 
Review of pre-hospital medical 
x 
Review of medical record 
x 
x 
x 
x 
x 
x 
Informed Consent Process 
x 
x 
CPC 
x 
x 
mRS 
x 
x 
NIH Toolbox 
x 
x 
Quality of Life Survey 
x 
Monitor Serious Adverse Events 
x 
x 
x 
x 
x 
x 
ROSC – Return of Spontaneous Circulation 
CPC – Cerebral Performance Category 
mRS – Modified Rankin Scale 
 
 
  7.4 
JUSTIFICATION FOR SENSITIVE PROCEDURES 
 
 
Not applicable. 
 
 
Clinical care is at the discretion of the clinical team. No concomitant medications, treatments 
or procedures are required or prohibited by the research protocol. 
 
 
  8.1 
SPECIFICATION  OF  SAFETY PARAMETERS 
 
 
Predefined safety clinical events are outlined in the endpoints sections 4.2.2 and 4.2.3. Since 
the study intervention is early transport versus continued resuscitation in the field, and all 
interventions occurring after this intervention represent standard care, safety endpoints will 
provide a qualitative assessment of the strategies given the limited sample size. Summaries of 
7.5 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES 
8 
ASSESSMENT  OF SAFETY 

23 
 
events by group will be provided to all relevant monitoring bodies. Given the severity of 
cardiac arrest, most patients will experience one or more SAEs as part of routine clinical care. 
 
 
An adverse event (AE) is any unfavorable and unintended sign (including a clinically significant 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medical treatment or procedure regardless of whether it is considered related to the medical 
treatment or procedure (attribution of unrelated, unlikely, possible, probable, or definite). 
Each AE is a unique representation of a specific event used for medical documentation and 
scientific analysis. 
 
 
A serious adverse event (SAE) is an AE that is fatal or life threatening, is permanently or 
substantially disabling, requires or prolongs hospitalization, results in a congenital anomaly, 
requires intervention to prevent permanent impairment or damage, or any event that the 
treating clinician or internal medical monitor judges to be a significant hazard, 
contraindication, side effect, or precaution. Reporting serious adverse events (SAEs) are 
based on the guidelines of the International Conference on Harmonization (ICH). 
 
 
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 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. 
This study will use the OHRP definition of UP. 
 
This definition could include an unanticipated adverse device effect, any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or associated 
with, a device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the investigational plan or application, or any other 
8.1.1   DEFINITION OF  ADVERSE EVENTS (AE) 
8.1.2   DEFINITION OF  SERIOUS ADVERSE EVENTS (SAE) 
8.1.3   DEFINITION OF  UNANTICIPATED PROBLEMS (UP) 

24 
 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects (21 CFR 812.3(s)). 
 
  8.2 
CLASSIFICATION OF AN  ADVERSE EVENT 
 
 
 
‘Severity’ is not the same as ‘serious.’ Serious is based on patient/event outcome or action 
criteria usually associated with events that pose a threat to a patient’s life or health. The term 
‘severe’ is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache). Seriousness (not severity) serves as a guide 
for defining regulatory reporting obligations. Most AEs include clinical criteria that describe 
patient/event outcomes or indicated interventions to more clearly substantiate seriousness. 
All adverse events occurring within 24 hours of study enrollment and all serious adverse 
events occurring during study participation will be documented on the AE case report form. 
Adverse events will be documented using the NCI Common Terminology Criteria for Adverse 
Events Version 3.0 (CTCAE). The CTCAE provides descriptive terminology that will be used for 
recording and reporting adverse events that occur in the EROCA trial. The CTCAE provides a 
grading (severity) scale for each AE term and AEs are listed alphabetically within categories 
based on anatomy or pathophysiology. The CTCAE (v 3.0) displays Grades 1-5 with unique 
clinical descriptions of severity for each AE based on this general guidance: 
Grade 1: 
Mild AE 
Grade 2: 
Moderate AE 
Grade 3: 
Severe AE 
Grade 4: 
Life-Threatening or Disabling AE 
Grade 5: 
Death related to AE 
Note: Severity is not equivalent to seriousness. A serious adverse event (SAE) would be any 
event in category 4 or 5, and any event in category 3 that required or prolonged 
hospitalization. 
Not all grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than five 
options for Grade Selection i.e., Grade 5 (Death) is not appropriate for some AEs and 
therefore is not an option.  A version of the CTCAE is available in the MoP 
 
8.2.1   SEVERITY  OF EVENT 
8.2.2   RELATIONSHIP TO  STUDY AGENT 

25 
 
The site principal investigator is responsible for designating, at the time an AE is reported, 
how likely it is that the AE is caused by the study intervention. This determination requires 
clinical judgement, but for purposes of this study an algorithm is used to help the investigator 
provide reporting that is as objective as possible and consistent with reporting across the trial. 
Modified for EROCA, based upon: Adverse Events Reporting Requirements SOP. NIH-NIAID. 
http://www.niaid.nih.gov/ncn/sop/adverseevents.htm , accessed 11-30-04. 
 
Not related: The temporal relationship between treatment exposure and the adverse event is 
unreasonable or incompatible and/or adverse event is clearly due to extraneous causes (e.g., 
underlying disease, environment) 
Unlikely: May have reasonable or only tenuous temporal relationship to intervention. Must 
meet both of the following conditions: 
• Could readily have been produced by the subject’s clinical state, or environmental 
or other interventions. 
• Does not follow known pattern of response to intervention. 
Possibly:  Must meet any 2 of the 3 following conditions 
 
• Has a reasonable temporal relationship to intervention. 
• Could not readily have been produced by the subject’s clinical state or 
environmental or other interventions. 
• Follows a known pattern of response to intervention. 
Probably:  Must meet all 3 of the following conditions 
 
• Has a reasonable temporal relationship to intervention. 
• Could not readily have been produced by the subject’s clinical state or have been 
due to environmental or other interventions. 
• Follows a known pattern of response to intervention. 
Definitely:  Must meet all 3 of the following conditions 
 
• Has a reasonable temporal relationship to intervention. 
• Could not possibly have been produced by the subject’s clinical state or have been 
due to environmental or other interventions. 
• Follows a known pattern of response to intervention. 

26 
 
 
 
The site principal investigator will be responsible for determining whether an AE is expected 
or unexpected. An AE will be considered unexpected if the nature, severity, or frequency of 
the event is not consistent with the risk information previously described for the study agent. 
 
  8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT  AND  FOLLOW-UP 
 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review by a 
study monitor. All AEs including local and systemic reactions not meeting the criteria for SAEs 
will be captured on the appropriate RF. Information to be collected includes event description, 
time of onset, clinician’s assessment of severity, relationship to study product (assessed only 
by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. UPs will be 
recorded in the data collection system throughout the study. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The PI or designated research staff will record all reportable events with start dates occurring 
any time after study enrollment until 24 hours (for non-serious AEs) or 90 days or last day of 
study participation (for SAE’s). At each study visit, the investigator or study coordinator will 
inquire about the occurrence of SAEs since the last visit. Events will be followed for outcome 
information until resolution or stabilization. 
 
  8.4 
REPORTING PROCEDURES 
 
 
An adverse event (AE) is any unfavorable and unintended sign (including a clinically significant 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medical treatment or procedure regardless of whether it is considered related to the medical 
treatment or procedure (attribution of unrelated, unlikely, possible, probable, or definite). 
Each AE is a unique representation of a specific event used for medical documentation and 
scientific analysis. 
8.2.3   EXPECTEDNESS 

27 
 
A serious adverse event (SAE) is an AE that is fatal or life threatening, is permanently or 
substantially disabling, requires or prolongs hospitalization, results in a congenital anomaly, 
requires intervention to prevent permanent impairment or damage, or any event that the 
treating clinician or internal medical monitor judges to be a significant hazard, 
contraindication, side effect, or precaution. Reporting serious adverse events (SAEs) are 
based on the guidelines of the International Conference on Harmonization (ICH). 
 
 
 
All AEs occurring within 24 hours of study participation and all serious adverse events (SAEs) 
occurring up until 90 days or last day of study participation are recorded on the online AE case 
report form (CRF) through the study database. The Site PI or Study Coordinator or designee is 
responsible for entering any and all AEs and SAEs into the database as soon as he/she 
becomes aware of the event and updating the information (e.g., date of resolution, action 
taken) in a timely manner. All non-serious AEs must be recorded on the electronic AE CRF 
within 5 days from the time it was discovered by the site study personnel. (All non-serious AEs 
during hospitalization must be entered within 5 days of discharge or end of study for that 
subject.) For SAEs, the data entry must take place within 24 hours of discovery of the event. 
The Site PI is responsible for the monitoring and follow-up of AEs until resolution (or end of 
study for that subject) and appropriate documentation in the subject research record. In 
addition to performing protocol-specified follow up, the participating PI must review all 
previously reported ongoing AEs to evaluate the current status. If an AE that was previously 
reported on the Adverse Event CRF fully resolves and then recurs at a later date, the second 
occurrence is considered a new AE and a new Adverse Event CRF must be completed. 
Likewise, if an SAE that was previously reported and subsequently fully resolved later recurs at 
a level requiring expedited reporting, the SAE must be reported as a new SAE on the Adverse 
Event CRF. 
Upon completion of the study protocol by the subject, premature withdrawal from the study 
by the subject, or subject’s death, all information regarding each AE must be completed, if not 
done so earlier. 
 
 
The study clinician will complete a SAE Form within the following timelines: 
 
All Serious Adverse Events (SAEs) occurring during a subject’s study participation will be 
recorded up until 90 days or last day of study participation. All SAEs must be entered into 
the database system within 24 hours of first 
8.4.1   ADVERSE EVENT REPORTING 
8.4.2   SERIOUS ADVERSE EVENT  REPORTING 

28 
 
knowledge of the SAE. Additionally, all current study data for that particular subject must be 
entered to allow for timely review. 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and 
submit to the study sponsor and to the reviewing IRB as soon as possible, but in no event later 
than 10 working days after the investigator first learns of the effect. The study sponsor 
contact information is provided in Section 1, Key Roles. The study sponsor is responsible for 
conducting an evaluation of an unanticipated adverse device effect and shall report the 
results of such evaluation to FDA and to all reviewing IRBs and participating investigators 
within 10 working days after the sponsor first receives notice of the effect. Thereafter the 
sponsor shall submit such additional reports concerning the effect as FDA requests. 
 
 
 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion 
of an UP report form. It is the site investigator’s responsibility to report UPs to their IRB and to 
the DCC/study sponsor. The UP report will include the following information: 
• 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 SAEs will be reported to the IRB and to the DCC/study sponsor within 7 days of 
the investigator becoming aware of the event. 
Any other UP will be reported to the IRB and to the DCC/study sponsor within 7 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 OHRP within 7 
days of the IR ’s receipt of the report of the problem from the investigator. 
An investigator shall submit to the sponsor and to the reviewing IRB a report of any 
unanticipated adverse device effect occurring during an investigation as soon as possible, but 
in no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)), A sponsor who conducts an evaluation of an unanticipated adverse device 
8.4.3   UNANTICIPATED  PROBLEM REPORTING 

29 
 
effect under 812.46(b) shall report the results of such evaluation to FDA and to all reviewing 
IRB's and participating investigators within 10 working days after the sponsor first receives 
notice of the effect. Thereafter the sponsor shall submit such additional reports concerning 
the effect as FDA requests (21 CFR 812.150(b)(1)). 
 
 
Not applicable 
 
 
Patients who are obviously pregnant will not be enrolled. If pregnancy is discovered, the team 
will request permission to follow pregnant women to pregnancy outcome. As the intervention 
(early transport with mechanical CPR) occurs prior to laboratory testing, no additional 
treatment is possible under this protocol after the discovery of pregnancy and patients are 
only on the protocol for the collection of outcomes. 
 
  8.5 
STUDY  HALTING RULES 
 
 
No formal quantitative stopping rules are in place for EROCA. The study may be modified or 
discontinued at any time by the IRB, the NHLBI, the sponsor, the OHRP, the FDA, or other 
government agencies as part of their duties to ensure that research subjects are protected. 
 
  8.6 
SAFETY OVERSIGHT 
 
 
Safety oversight will be under the direction of an independent DSMB composed of individuals 
with the appropriate expertise, including emergency medicine. The DSMB will meet at least 
semiannually to assess safety and efficacy data on each arm of the study. The DMSB will 
operate under the rules of an approved charter that will be written and reviewed at the 
organizational meeting of the DSMB. At this time, each data element that the DSMB needs to 
assess will be clearly defined. The DSMB will provide its input to NIH. We will provide tables 
providing all SAEs by group, along with clinical outcomes, and a listing of SAEs by individual 
enrolled (given the small sample size of EROCA), as part of reporting to DSMB. 
 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human 
subjects are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with applicable regulatory requirement(s). 
• 
Designated study staff not involved with the enrollment will conduct monitoring. This 
will occur throughout the study, and will involve targeted or review of certain data (primary 
8.4.4   EVENTS OF  SPECIAL INTEREST 
8.4.5   REPORTING  OF PREGNANCY 
9 
CLINICAL MONITORING 

30 
 
endpoints, safety endpoints, consent forms). Monitoring reports will be distributed to the PI 
or site PIs if applicable. 
• 
Independent audits will not be conducted. 
 
• 
Each clinical site will perform internal quality management of study conduct, data 
collection, documentation and completion. As necessary, individualized quality management 
plans will be developed to describe a site’s quality management. 
 
 
  10.1 
STATISTICAL  AND  ANALYTICAL PLANS 
 
 
This is a pilot trial, designed to demonstrate proof of feasibility prior to a larger scale trial that 
will be powered to improve patient outcomes. The primary endpoints target process 
measures, namely the delivery of randomized patients to the qualified ED within 30 minutes 
of qualifying event. 
 
  10.2 
STATISTICAL HYPOT HESES 
 
• 
Co-Primary Endpoint(s): Arrival to qualified ED within 30 minutes 
 
We hypothesize that the proportion of patients randomized to early transport arriving at the 
hospital within 30 minutes will be greater than the historical proportion of 38.7%. 
• 
Co-Primary Endpoint(s): Initiation of ECPR within 30 minutes of ED arrival 
 
We hypothesize that greater than or equal to 80% of patients will have ECPR (qualifying ED 
standard care process) initiated within 30 minutes of ED arrival. 
 
  10.3 
ANALYSIS DATASETS 
 
 
The analytic datasets will use a modified per-protocol population. Patients who are assigned 
to early transport and do not have ROSC after initial rhythm analysis (and shock if indicated) 
and have the early transport initiated will be considered the primary analytic population for 
the ED arrival endpoint. Patients who are randomized to early transport and remain in cardiac 
arrest for at least 10 minutes after ED arrival and have the institutional standard care ECPR 
process initiated are considered the primary analytic population for the ECPR initiation 
endpoint. Exploratory clinical and safety endpoints will be collected on the entire population 
of refractory OHCA patients enrolled/randomized to either early transport or usual care. 
 
  10.4 
DESCRIPTION  OF  STATISTICAL METHODS 
 
10 
STATISTICAL CONSIDERATIONS 

31 
 
 
 
The primary goal of this study is to establish that a high proportion of patients with refractory 
OHCA can be expeditiously transported to the hospital for initiation of advanced resuscitation. 
Randomization is not intended to create comparable groups, but instead is being used to 
demonstrate the feasibility of using a position sensitive randomization procedure in the field. 
Randomization in this protocol includes two currently used approaches to OHCA: expedited 
transport to the hospital after initial attempts at resuscitation versus continued resuscitation 
efforts in the field until ROSC. 
Descriptive statistics for study groups will be presented as medians, and interquartile ranges 
for continuous data; categorical data will be reported as proportions. 
Patients randomized to the test arm and achieve ROSC prior to initiation of ECPR will be included in the 
primary analysis of the expedited transport group. 
 
 
Co-Primary Endpoint(s): Arrival to qualified ED within 30 minutes 
 
The proportion of qualifying episodes to arrive at the ED within 30 minutes will be compared 
to our historical data point estimate of 38.7% using a one sample exact test of binomial 
proportions at the 0.05 two-sided significance level. 
Co-Primary Endpoint(s): Initiation of ECPR within 30 minutes of ED arrival 
 
Using the modified intention to treat population with ongoing cardiac arrest in the qualified 
ED, we will declare the analysis of this objective successful if 80% or more of patients have 
ECPR (qualifying ED standard care process) initiated within 30 minutes of ED arrival. No formal 
hypothesis test will be conducted. 
 
 
This study does not have any powered secondary endpoints. All clinical and other process 
endpoints are exploratory. 
 
 
This is a small clinical trial. We will summarize SAEs by study group (early transport versus 
usual care) and provide a listing of all SAEs for each of the patients in the intent to treat 
population. 
 
10.4.1 GENERAL APPROACH 
10.4.2 ANALYSIS OF  THE  PRIMARY EFFICACY ENDPOINT(S) 
10.4.3 ANALYSIS OF THE  SECONDARY ENDPOINT( S) 
10.4.4 SAFETY ANALYSES 
10.4.5 ADHERENCE AND RETENTION  ANALYSES 

32 
 
We will qualitatively summarize the reasons that patients were randomized but that the 
assigned early transport or usual care pathways were not followed. We will qualitatively 
summarize reasons for participant withdrawal. 
 
 
We will provide descriptive statistics including demographic variables by study group (early 
transport versus usual care). As the patients are randomized in the field, no baseline 
laboratory variables are available. No hypothesis testing will be used to compare the groups 
due to the small sample size. 
 
 
 
 
The DSMB will review safety data as per their charter. The main listed safety endpoints will be 
reviewed. No formal statistical boundaries will be used to determine stopping for safety 
concerns. 
 
 
We will not employ formal stopping rules for efficacy or futility given the small sample size of 
the study 
 
 
We will pre-specify subgroup analyses of the primary endpoints by gender, age (less than 50 
versus 51-70), diabetes, prior cardiac disease, and race/ethnicity. These subgroup analyses 
will be presented graphically and in tables. Given the small sample size formal hypothesis 
testing will not be performed. In addition, we will also categorize the defined safety endpoints 
by each of the subgroups mentioned above, graphically and in tables. 
 
 
We are employing two primary endpoints, but no adjustment for multiplicity will be 
performed as the process endpoint is a threshold. 
 
 
Individual participant data for the primary endpoints will be summarized in tabular form. We 
will also include exploratory endpoint data (mRS and CPC) in these tables. 
10.4.6 
BASELINE  DESCRIPTIVE STATISTICS 
10.4.7 PLANNED  INTERIM ANALYSES 
10.4.7.1 
SAFETY REVIEW 
10.4.7.2 
EFFICACY REVIEW 
10.4.8 ADDITIONAL  SUB-GROUP ANALYSES 
10.4.9 MULTIPLE COMPARISON/MULTIPLICITY 
10.4.10 
TABULATION  OF  INDIVIDUAL RESPONSE DATA 

33 
 
 
 
Each of the exploratory endpoints will be summarized using appropriate techniques based on 
the distribution (for continuous variables) or event rates (for categorical variables). Group 
(early transport versus usual care) comparisons will be presented in graphical, or tabular form 
for the exploratory endpoints. Formal hypothesis testing will be avoided given the small 
sample size. 
 
  10.5 
SAMPLE SIZE 
 
 
Based on 2014 data, we expect approximately 20 unique visits in one year to qualify, thus in 18 
months we expect 30 patients to qualify with the protocol used on at least 24 (80%) of these. 
With 24 patients, if we find that 19/24 (79.2%) of cases meet time limit we have 98% power to 
find that the proportion of patients arriving at the ED within 30 minutes is significantly 
different than in 2014. The protocol will be deemed optimal if ≥19/24 patients are transported 
to the ED within 30 minutes (95% CI lower bound 62.6%). 
 
  10.6 
MEASURES TO MINIM IZE BIAS 
 
 
 
The website will be used to randomize subjects. As different dispatchers will likely be 
attending to the care of subsequent cardiac arrest patients. we believe that there is limited 
chance that they will be able to predict the next treatment assignment, and as such, the risk 
of bias is low. 
Randomization will occur in blocks of 5. We will use an urn method. Randomization will not be 
stratified by any clinical variable or by enrolling prehospital provider. The blocking is intended 
to maintain balance. The randomization ratio is 4:1 with the expedited transport group 
favored. Since the main study goals involve the expedited transport of patients to the hospital 
and since randomization has been introduced mainly to evaluate the effectiveness of the 
randomization procedure we believe the 4:1 ratio is justified. In addition, expedited versus 
delayed transport are both currently used treatment strategies for OHCA across North 
America and there is equipoise about assignment into either of these groups. In situations 
where the dispatcher uses the website and gives a treatment group assignment, but the 
patient is not enrolled/randomized in the study because they did not have refractory cardiac 
arrest, that treatment group assignment will be returned to the urn. 
 
 
This study is unblinded. 
10.4.11 
EXPLORATORY ANALYSES 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING  PROCEDURES 
10.6.2 EVALUATION OF  SUCCESS OF BLINDING 

34 
 
 
 
The entire study will be conducted using an electronic data acquisition method where all 
clinical data on enrolled subjects will be data entered (single-keyed) by the site personnel into 
a web-based data management system. In order to provide user-friendly and easy-to-navigate 
interfaces, the data capture screens are designed based upon individual CRFs. Prior to study 
start, the system is validated to ensure the data entry screens mirror the CRFs and that the 
pre-programmed data rules appropriately detect incorrect data. The data will be managed 
after data entry via data queries from the Coordinating Center at UM. 
The latest version of each CRF will be available for use as worksheets and source documents 
by study personnel. This process facilitates version control of these study related documents, 
particularly since documents may evolve over the course of the study. This user friendly web- 
based database system, developed by the coordinating center, will be used for data entry, 
data validation, project progress monitoring, subject tracking, tracking, user customizable 
report generation and secure data transfer. 
 
 
QC procedures will be implemented beginning with the data entry system and data QC checks 
that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated, documented (recorded), and reported in compliance with the protocol, GCP, and 
the applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and 
inspection by local and regulatory authorities. 
 
 
 
 
 
The investigator will ensure that this study is conducted in full conformity with Regulations 
for the Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
21 CFR Part 56, and/or the ICH E6. Additional details regarding EFIC are provided in appendix 
A . Below when referring to the participant or individual, it is highly likely that the legally 
11 
SOURCE  DOCUMENTS AND ACCESS TO  SOURCE  DATA/DOCUMENTS 
12 
QUALITY ASSURANCE AND QUALITY  CONTROL 
13 
ETHICS/PROTECTION  OF  HUMAN SUBJECTS 
13.1 
ETHICAL STANDARD  AND  JUSTIFICATION FOR EXCEPTION FROM INFORMED 
CONSENT 

35 
 
authorized representative for the subject will be providing consent as the patients will likely 
remain comatose in the early emergency department care. 
1. Subjects are in a life-threatening situation, available treatments are unproven or 
unsatisfactory, and the collection of valid scientific evidence is necessary to determine 
the safety and effectiveness of a particular intervention. 
 
a. Cardio-pulmonary resuscitation (CPR) is the first line of treatment for a cardiac 
arrest, a life-threatening situation, and must be initiated immediately. This 
study will enroll patients not responding to standard basic life support (BLS) 
and advanced cardiovascular life support (ACLS) and no other alternative 
treatments are proven effective when the arrest is refractory to standard 
therapy. 
b. The vast majority of people who suffer an out of hospital cardiac arrest (OHCA) 
die, despite the expertise of highly-trained emergency medical service (EMS) 
providers.  It is unknown whether standard CPR can be improved. 
c. Based on the CARES registry data for Washtenaw/Livingston Medical Control 
Authority (MCA), 408 OHCA patients were treated in 2014, 133 (33%) achieved 
sustained return of spontaneous circulation and only 30 survived to hospital 
discharge (7.4%) with only 24 (5.9%) having good neurologic function at 
hospital discharge. This is well below the national survival rate of 8-10%. 
d. Clinical trials are needed. No prospective, randomized clinical trial has 
compared standard CPR to ECPR. Almost all published case series of successful 
ECPR from OHCA initiate ECPR in the emergency department [Chen 2008, 
Kagawa 2010, Nagao 2000 and 2010, LeGuen 2011, Morimura 2011, Avali 2012, 
Bellezzo 2012, Johnson 2014, Sakamoto 2014, Stub 2014]. The reason for this 
strategy is that the shorter the interval from cardiac arrest onset to initiation of 
ECPR is. The better the chance for a favorable outcome. Scientific evaluation is 
necessary in order to further test the efficacy of the proposed intervention, 
transport to an ED for higher level of care and ECPR. 
2. Obtaining informed consent is not feasible because: 
 
a. Patients who are in cardiac arrest are unresponsive and unable to 
communicate. It is unreasonable and impractical for first responders to 
identify, verify, and obtain consent from a legally authorized representative. 
b. The optimal therapeutic window for initiating interventions and ECPR is within 
60 minutes of the cardiac arrest onset. 

36 
 
c. OHCA patients cannot be identified prospectively 
 
3. Participation in the research holds out the prospect of direct benefit to the subjects 
because: 
 
a. Patients are in a life-threatening situation 
 
b. Published case series where initiating ECPR in the emergency department have 
reported survival rates with good neurologic function ranging from 4-33% 
c. Potential risk of complications of transport with mechanical CPR (rib fractures, 
pneumothorax, internal organ laceration or motor vehicle crash) or ED initiated 
ECPR (hemorrhage, vascular injury, deep venous thrombosis, pulmonary 
embolism, stroke, lime ischemia, infection) are balanced by the anticipated 
benefit of survival with good neurologic function. 
4. The clinical investigation could not be practicably be carried out without the waiver 
 
a. Time to treatment for cardiac arrest needs to begin immediately. Since these 
patients are unable to consent for themselves and there is not time to identify, 
inform, and consent a legally authorized representative, all patients must be 
enrolled under EFIC. Additionally, informed consent requires the LAR to have 
time to understand the consent material, be able to ask questions, and 
decipher what the patient would want. This is not possible to do in a few 
minutes and during such a stressful time. Inability to obtain informed consent 
can limit the ability to discover new treatments for such a critical and life- 
threatening event like sudden cardiac arrest. 
5. Length of the potential therapeutic window and contact a legally authorized 
representative. 
 
a. The optimal therapeutic window is immediate or non-existent. Randomization 
into the study must be done immediately, at the time of initiating CPR. 
Every effort will be made to identify, inform, and determine consent to continue in the study 
from a legally authorized representative, in a reasonable amount of time. 
Participants who regain good neurologic function and are able, will be informed and consent 
will be attempted. 
 
  13.2 
INSTITUTIONAL  REVIEW BOARD 
 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the IRB for review and approval. Approval of both the protocol and the 

37 
 
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 previously consented participants need to be re-consented. 
 
 
Initial enrollment is initiated under and exception from informed consent as the patient is 
unconscious in cardiac arrest. Enrollments will not occur until after EFIC plan and protocol 
approval by the relevant IRB(s). 
Consent forms describing in detail the study agent, study procedures, and risks are given to 
the participant and written documentation of informed consent is required prior to continuing 
study procedures. The following consent materials are submitted with this protocol: informed 
consent to continue participation, notification letters. 
 
 
Informed consent is a process that is initiated prior to the participant or the individual’s legally 
authorized representative agreeing to continue to participate in the study and continues 
throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of continued participation will be provided to the participants and their families along 
with a description of what has occurred so far given initial enrollment under EFIC. Consent 
forms will be 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. All participants will receive a verbal explanation in terms suited to 
their 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 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. The participants may withdraw consent at any time 
throughout the course of the trial. A copy of the informed consent document will be given to 
the participants for their records. 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 continue to participate in this study. 
 
  13.4 
PARTICIPANT  AND  DATA CONFIDENTIALITY 
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
13.3 
INFORMED CONSENT PRO CESS 
13.3.2 CONSENT  PROCEDURES AND DOCUMENTATION 

38 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, 
and the sponsor(s) and their agents. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition 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. 
The study monitor, other authorized representatives of the sponsor or representatives of the 
IRB may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records 
for the participants in this study. The clinical study site will permit access to such records. 
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 local IRB and Institutional regulations. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the Coordinating Center at University of 
Michigan. This will not include the participant’s contact or identifying information. Rather, 
individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used by clinical 
sites and by Coordinating 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 the Coordinating 
Center. 
 
 
 
 
 
 
Intended Use: Samples and data collected under this protocol may be used to study cardiac 
arrest. No genetic testing will be performed. 
Storage: Samples and data will be stored using codes assigned by the investigators. Data will 
be kept in password-protected computers. Only investigators will have access to the samples 
and data. 
 
  13.5 
FUTURE USE  OF  STORED SPECIMENS 
 
 
Data collected for this study will be analyzed and stored at the Coordinating Center (UM). 
After the study is completed, the de-identified, archived data will be transmitted to and 
stored at the institutional or NHLBI determined data repository, under the supervision of UM 
13.4.1 RESEARCH USE  OF  STORED HUMAN SAMPLES,SPECIMENS OR  DATA 

39 
 
and/or NHLBI, for use by other researchers including those outside of the study. Permission to 
transmit data to the UM institutional data repository will be included in the informed consent. 
When the study is completed, access to study data and/or samples will be provided through 
the UM institutional data repository. 
 
 
14 
DATA HANDLING AND RECORD  KEEPING 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Black ink is required to ensure clarity of reproduced copies. When 
making changes or corrections, cross out the original entry with a single line, and initial and 
date the change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE 
ORIGINAL. 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and 
maintained for recording data for each participant enrolled in the study. Data reported in the 
eCRF derived from source documents should be consistent with the source documents or the 
discrepancies should be explained and captured in a progress note and maintained in the 
participant’s official electronic study record. 
Clinical data (including AEs) and expected adverse reactions data) and clinical laboratory data 
will be entered into, a 21 CFR Part 11-compliant data capture system provided by the UM. The 
data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical 
data will be entered directly from the source documents. 
 
  14.2 
STUDY  RECORDS RETENTION 
 
 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by local regulations. No records 
will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when these documents no longer need 
to be retained. 

40 
 
  14.3 
PROTOCOL DEVIATIONS 
 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP 
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 E6: 
 
• 
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. 
 
It is the responsibility of the site 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. Protocol deviations must be sent to the local IRB per 
their guidelines. The site PI/study staff is responsible for knowing and adhering to their IRB 
requirements. Further details about the handling of protocol deviations will be included in the 
MOP. 
 
  14.4 
PUBLICATION  AND  DATA SHARING POLICY 
 
 
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final 
peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. 
The International Committee of Medical Journal Editors (ICMJE) member journals have 
adopted a clinical trials registration policy as a condition for publication. The ICMJE defines a 
clinical trial as any research project that prospectively assigns human subjects to intervention 
or concurrent comparison or control groups to study the cause-and-effect relationship 
between a medical intervention and a health outcome. Medical interventions include drugs, 
surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. 
Health outcomes include any biomedical or health-related measures obtained in patients or 
participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and 
the Section 801 of the Food and Drug Administration Amendments Act of 2007, requires that 
all clinical trials be registered in a public trials registry such as clinicaltrials.gov , which is 
sponsored by the National Library of Medicine. Other biomedical journals are considering 
adopting similar policies. For interventional clinical trials performed under NIH IC grants and 
cooperative agreements, it is the grantee’s responsibility to register the trial in an acceptable 

41 
 
registry, so the research results may be considered for publication in ICMJE member journals. 
The ICMJE does not review specific studies to determine whether registration is necessary; 
instead, the committee 
recommends that researchers who have questions about the need to register err on the 
side of registration or consult the editorial office of the journal in which they wish to 
publish. 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal 
investigator) register and report results of certain "applicable clinical trials": 
• 
Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase 
I investigations, of a product subject to FDA regulation; 
• 
Trials of Devices: Controlled trials with health outcomes of a product subject to FDA 
regulation (other than small feasibility studies) and pediatric postmarket surveillance 
studies. 
NIH grantees must take specific steps to ensure compliance with NIH implementation of 
FDAAA 
 
 
  15.1 
STUDY LEADERSHIP 
 
 
The Steering Committee will govern the conduct of the study. The Steering Committee will be 
composed of the Study Chairman, the PI of the Coordinating Center, representatives of 
NHLBI, the PI of the clinical sites, and the project manager. The Steering Committee will meet 
in person at least annually. 
 
 
 
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 trial. The study leadership in 
conjunction with the NHLBI has established policies and procedures for all study group 
members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
 
 
15 
STUDY ADMINISTRATION 
16 
CONFLICT  OF  INTEREST POLICY 
17 
LITERATURE REFERENCES 

42 
 
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Kagawa E, Dote K, Kato M, Sasaki S, Nakano Y, Kajikawa M, Higashi A, Itakura K, Sera A, Inoue 
I, Kawagoe T, Ishihara M, Shimatani Y, Kurisu S. Should we emergently revascularize occluded 
coronaries for cardiac arrest?: rapid-response extracorporeal membrane oxygenation and 
intra-arrest percutaneous coronary intervention. Circulation. 2012;1261605-13. PMID: 
22899771 
Lamhaut L, Jouffroy R, Soldan M, Phillipe P, Deluze T, Jaffry M, Dagron C, Vivien B, Spaulding 
C, An K, Carli P. Safety and feasibility of prehospital extra corporeal life support 
implementation by non-surgeons for out-of-hospital refractory cardiac arrest. Resuscitation. 
2013;84:1525-9. PMID: 23827888 
Le Guen M, Nicolas-Robin A, Carreira S, Raux M, Leprince P, Riou B, Langeron O. 
Extracorporeal life support following out-of-hospital refractory cardiac arrest. Crit Care. 
2011;15:R29. 
Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, 
Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: Adult Advanced 
Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for 
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18 
Suppl 2):S444-S4464. PMID: 26472995 
Maekawa K, Tanno K, Hase M, Mori K, Asai Y. Extracorporeal cardiopulmonary resuscitation 
for patients with out-of-hospital cardiac arrest of cardiac origin: a propensity-matched study 
and predictor analysis. Crit Care Med. 2013;41:1186-96. PMID: 23388518 
Meurer WJ1, Lewis RJ, Tagle D, Fetters MD, Legocki L, Berry S, Connor J, Durkalski V, Elm J, 
Zhao W, Frederiksen S, Silbergleit R, Palesch Y, Berry DA, Barsan WG. An overview of the 
adaptive designs accelerating promising trials into treatments (ADAPT-IT) project. Ann Emerg 
Med. 2012;60:451-457. PMID: 22424650 

44 
 
Morimura N, Sakamoto T, Nagao K, Asai Y, Yokota H, Tahara Y, Atsumi T, Nara S, Hase M. 
Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A review of 
the Japanese literature.  Resuscitation. 2011;82:10-14. PMID: 20934798 
Morrison LJ, LJ Kierzek G, Diekema DS, Sayre MR, Silvers SM, Idris AH, Mancini ME. Part 3: 
ethics: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and 
Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S665-75. PMID: 20956219 
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després 
JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, 
Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, 
Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, 
Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, 
Turner MB; American Heart Association Statistics Committee and Stroke Statistics 
Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American 
Heart Association. Circulation. 2015;131:e29-322. PMID: 25520374 
Nagao K, Hayashi N, Kanmatsuse K, et al. Cardiopulmonary cerebral resuscitation using 
emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in 
patients with cardiac arrest outside the hospital. J Am Coll Cardiol 2000;36:776–83.10. PMID: 
10987599 
Nagao K, Kikushima K, Watanabe K, Tachibana E, Tominaga Y, Tada K, Ishii M, Chiba N, Kasai 
A, Soga T, Matsuzaki M, Nishikawa K, Tateda Y, Ikeda H, Yagi T. Early induction of 
hypothermia during cardiac arrest improves neurological outcomes in patients with out-of- 
hospital cardiac arrest who undergo emergency cardiopulmonary bypass and percutaneous 
coronary intervention. Circ J. 2010;74:77-85. PMID: 19942784 
Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, Kudenchuk PJ, Ornato 
JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, Morrison 
LJ. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association 
Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. 
Circulation. 2010;122(18 Suppl 3):S729-S767. PMID: 20956224 
Rubertsson S, Lindgren E, Smekal D, Östlund O, Silfverstolpe J, Lichtveld RA, Boomars R, 
Ahlstedt B, Skoog G, Kastberg R, Halliwell D, Box M, Herlitz J, Karlsten R. Mechanical chest 
compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation 
in out-of-hospital cardiac arrest: the LINC randomized trial. JAMA. 2014;311(1):53-61. PMID: 
24240611 
Sakamoto T, Morimura N, Nagao K, Asai Y, Yokota H, Nara S, Hase M, Tahara Y, Atsumi T; 
SAVE-J Study Group. Extracorporeal cardiopulmonary resuscitation versus conventional 
cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective 
observational study. Resuscitation. 2014;85:762-8.  PMID: 24530251 

45 
 
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT 
Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N 
Engl J Med. 2012: 16;366:591-600. PMID: 22335736 
Spinelli E1, Davis RP, Ren X, Sheth PS, Tooley TR, Iyengar A, Sowell B, Owens GE, Bocks ML, 
Jacobs TL, Yang LJ, Stacey WC, Bartlett RH, Rojas-Peña A, Neumar RW. Thrombolytic- 
Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest. Crit 
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to prevent limb ischemia during veno-arterial ECMO using the femoral artery: the posterior 
tibial approach. Perfusion. 2012;27:141-5. PMID: 22143092 
Stub D, Bernard S, Pellegrino V, Smith K, Walker T, Sheldrake J, Hockings L, Shaw J, Duffy SJ, 
Burrell A, Cameron P, Smit DV, Kaye DM. Refractory cardiac arrest treated with mechanical 
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Wallmüller C, Sterz F, Testori C, Schober A, Stratil P, Hörburger D, Stöckl M, Weiser C, 
Kricanac D, Zimpfer D, Deckert Z, Holzer M. Emergency cardio-pulmonary bypass in cardiac 
arrest: seventeen years of experience. Resuscitation. 2013;84(3):326-30. PMID: 22800860 

46 
 
APPENDICES 
 
  APPENDIX A: Original EFIC PLAN 
 
Please see revised Community Consultation and Public Disclosure activities planned for the Saline, 
MI area expansion of the study, provided as a separate document.  
EROCA Trial 
 
Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest 
Exception From Informed Consent (EFIC) Plan 
Public Disclosure Sites: Ann Arbor, MI, Washtenaw County Plan Date Prepared: May 04, 2016 
Plan Revised Date 02/02/17 
Date of IRB approval: 9/22/16 
Introduction 
Learning how to provide better emergency care for patients with life-threatening conditions 
requires clinical research conducted in the earliest minutes and hours of treatment. Clinical 
trials of interventions for emergencies like cardiac arrest involve patients who are 
unresponsive and unable to communicate, and treatments that must be given so rapidly that 
it is impractical to identify and obtain consent on behalf of the patient from a surrogate 
decision maker (legally authorized representative). Such trials are therefore performed with 
an exception from informed consent (EFIC) for emergency research, and are governed by a 
special set of research regulations defined at 21 § CFR 50.24. We propose a clinical research 
project, EROCA, to be conducted using EFIC. This document will explain why the project 
qualifies for EFIC, and how the investigators propose to meet the Community Consultation 
and Public Disclosure requirements for EFIC. 
Research involving OHCA patients presents an ethical dilemma. The resulting delay in 
obtaining consent can significantly affect the efficacy of an intervention and limits patient 
eligibility for inclusion in such a time-critical study. Despite this difficulty, clinical trials to 
determine the best treatment for OHCA must be done. Failing to conduct research on 
potentially beneficial treatment for this population also poses harm. 
Applicability of EFIC to the EROCA Trial and Compliance with FDA Requirement, 21 CFR 
50.24 
Listed below are the FDA regulations that qualify use of the EFIC process in clinical research, 
followed by an explanation of how this study meets these requirements. 
1. Subjects are in a life-threatening situation, available treatments are unproven or 
unsatisfactory, and the collection of valid scientific evidence is necessary to determine 
the safety and effectiveness of a particular intervention. 

47 
 
a. Cardiopulmonary resuscitation (CPR) is the first line of treatment for a cardiac 
arrest, a life-threatening situation, and must be initiated immediately.  This 
study will enroll patients not responding to standard basic life support (BLS) and 
advanced cardiovascular life support (ACLS) and no other alternative treatments 
are proven effective  when the arrest is refractory to standard therapy. 
b. The vast majority of people who suffer an out of hospital cardiac arrest (OHCA) 
die, despite the expertise of highly-trained emergency medical service (EMS) 
providers.  It is unknown whether standard CPR can be improved. 
c. Based on the CARES registry data for Washtenaw/Livingston Medical Control 
Authority (MCA), 408 OHCA patients were treated in 2014, 133 (33%) achieved 
sustained return of spontaneous circulation and only 30 survived to hospital 
discharge (7.4%) with only 24 (5.9%) having good neurologic function at hospital 
discharge. This is well below the national survival rate of 8-10%. 
d. Clinical trials are needed. No prospective, randomized clinical trial has compared 
standard CPR to ECPR. Almost all published case series of successful ECPR from 
OHCA initiate ECPR in the emergency department [insert references].  The 
reason for this strategy is that the shorter the interval from cardiac arrest onset 
to initiation of ECPR is. The better the chance for a favorable outcome. 
Scientific evaluation is necessary in order to further test the efficacy of the 
proposed intervention, transport to an ED for higher level of care and ECPR. 
 
2. Obtaining informed consent is not feasibe because: 
a. Patients who are in cardiac arrest are unresponsive and unable to communicate. 
It is unreasonable and impractical for first responders to identify, verify, and 
obtain consent from a legally authorized representative. 
b. The optimal therapeutic window for initiating interventions and ECPR is within 
60 minutes of the cardiac arrest onset. 
c. OHCA patients cannot be identified prospectively 
 
3. Participation in the research holds out the prospect of direct benefit to the subjects 
because: 
a. Patients are in a life-threatening situation 
b. Published case series where initiating ECPR in the emergency department have 
reported survival rates with good neurologic function ranging from 4-33% 
c. Potential risk of complications of transport with mechanical CPR (rib fractures, 
pneumothorax, internal organ laceration or motor vehicle crash) or ED initiated 
ECPR (hemorrhage, vascular injury, deep venous thrombosis, pulmonary 
embolism, stroke, lime ischemia, infection) are balanced by the anticipated 
benefit of survival with good neurologic function. 

48 
 
4. The clinical investigation could not be practicably be carried out without the waiver 
a. Time to treatment for cardiac arrest needs to begin immediately. Since these 
patients are unable to consent for themselves and there is not time to identify, 
inform, and consent a legally authorized representative, all patients must be 
enrolled under EFIC. Additionally, informed consent requires the LAR to have 
time to understand the consent material, be able to ask questions, and decipher 
what the patient would want. This is not possible to do in a few minutes and 
during such a stressful time. Inability to obtain informed consent can limit the 
ability to discover new treatments for such a critical and life-threatening event 
like sudden cardiac arrest. 
 
5. Length of the potential therapeutic window and contact a legally authorized 
representative. 
The optimal therapeutic window is immediate or non-existent. Randomization 
into   the study must be done immediately, at the time of initiating CPR. 
 
Every effort will be made to identify, inform, and determine consent to 
continue in the study from a legally authorized representative, in a reasonable 
amount of time. 
Participants who regain good neurologic function and are able, will be informed 
and consent will be attempted. 
 
Additional Protections 
Additional protections of the rights and welfare of the participants will be provided, 
including: 
1. Community Consultation 
2. Public Disclosure before the study starts, including opt-out and decline 
participation options 
3. Public Disclosure following completion of the study; providing sufficient 
information, including demographic characteristics and study results. 
4. Establishment of an independent Data Safety Monitoring Board (DSMB) to 
exercise oversight of the study. 
5. Plan to contact the legally authorized representative (LAR) or family 
member to seek informed consent for the patient’s participation in the 
study within the therapeutic window if feasible or after enrollment as soon 
as possible when feasible. If a patient dies prior to hospital admission, all 
attempts will be made to notify their LAR or family member of the study 

49 
 
and patient’s participation, if feasible. If a patient regains consciousness 
and is capable, informed consent will be attempted as soon as feasible. 
 
 
The federal requirements of 21 § CFR 50.24 include consulting with the community of patients 
that could potentially be enrolled in the proposed research project, and public disclosure that 
a research project will be done that will involve members of the local population. 
If community consultation were viewed as community consent, this would imply that the 
input came from a large proportion or essentially all the members of the community as 
opposed to representatives of the community. The process is meant to solicit input from the 
community regarding the study. The IRB makes the final determination as to study approval 
based on information obtained from the community consultation. For the purposes of EFIC, 
the definition of community includes “the community in which research will take place” and 
the “community from which subjects will be drawn.” In other words the community includes 
the geographical area from which patients will be drawn and the group of patients with, or at 
risk for, the disease of interest. 
The content of community consultation will inform the community participants that informed 
consent will not be obtained for any research subjects prior to enrollment. Specifically, the 
goal will be to: 
• Inform the community about relevant aspects of the study including its 
risks and expected benefits 
• Hear the perspective of the community on the proposed research 
• Provide information about ways in which individuals wishing to be 
excluded may indicate this preference 
 
The type and frequency of community consultation will: 
 
• Provide opportunities for broad community discussion 
• Ensure that representatives from the communities involved in the 
research participate in the consultation process 
• Use the most appropriate ways to provide for effective community 
consultation 
• Be based on numerous factors, including the size of the communities, 
the languages spoken within those communities, the targeted research 
population and the heterogeneity of the population 
Community Consultation 

50 
 
Based on our interpretation of the regulations and their proposed ethical basis, we have 
prepared a list of recommendations for implementation of the commonly used methods for 
community consultation. 
A schedule of community consultation activities will be prepared and communicated to the 
IRB at the outset of the process. Representatives of the IRB are invited and encouraged to 
attend any of the activities. Any additions, cancellations, or changes to the schedule will be 
communicated to the IRB. At community consultation activities, investigators will describe 
the need for EFIC and why prospective consent is not possible, inform the community about 
the relevant aspects of the study, including its risks and benefits. 
Questions and concerns will be solicited from the community participants and documented. 
Participants will also be given the opportunity to answer a survey to share their views. 
Our 
goals for community consultation are to learn about the values and feelings of participants as 
they apply to the proposed research, rather than to have the community deliberate or vote on 
the project per se. People are experts on themselves rather than on research, so we primarily 
ask people to tell us about themselves and how they feel about what they have heard. 
 
 
 
The consultation will encompass the following three major forms: 
 
1. Visits to existing community groups at regularly scheduled meetings. Anticipate 
attending 3-5 meetings, depending on response from committee chairs. 
We feel that the best way to show respect for the community is to go out and meet people 
where they are already gathering. It also minimizes the risk of low turn-out at meetings 
scheduled de novo and increases the investigators’ exposure to a variety of comments. 
In this method of community consultation, members of the study team, sometimes 
accompanied by representatives of their participating Institutional Review Boards, ask to 
present and discuss the study at a regularly scheduled meeting of a relevant community 
group. 
For each group, we propose the following: 
 
• A study team member will be present to answer questions from the community. 
• Presentation will be clear, use of video/handouts depending on the venue, and be 
brief 
• If a presentation is longer than 15 minutes, it will be interactive. 
• We will consider who the best person is to present to each group. 
Community Consultation Activities 

51 
 
• Study team will be available for at least 30 minutes depending on how much time we 
are allocated (10 minutes to present, 15 minutes for discussion, and 5 minutes to 
hand-out and get back evaluation surveys). 
• Study team will probe for discussion using open-end questions. 
• Study team will ensure that the discussion includes feedback from the participants on 
EFIC. 
• No monetary incentive to participants will be offered 
 
A survey for group participants to indicate their thoughts, feelings, and opinions about 
the EFIC regulations and the study, anonymously, will be handed out and collected 
back at the end of the event. Study staff should allow at least five minutes at the end 
of the event for attendees to complete the 
 
We propose to contact the following groups by telephone and/or mail about presenting at 
their meetings, with the goal of holding 3-5 events total: 
• Ann Arbor Community Foundation 
• Ann Arbor City Council 
• Business groups 
• Ann Arbor Police Officers 
• Ann Arbor YMCA 
• Faith-based organizations 
• Neighborhood Residential Associations 
• Retiree groups 
• UMHS Groups/Programs 
o Support group meeting for patients and families at the Frankel 
Cardiovascular Center 
o Patient and Family Centered Care (PFCC) 
 
2. Survey Methods 
Based on our experience with other EFIC research studies, we believe an interview 
style, two-way dialogue discussion and address any questions, followed by a well- 
designed structured survey is an effective method of communication. Our experience 
revealed that respondents are more apt to understand complex research concepts, 
such as randomization, informed consent, EFIC, surrogate, etc, when specific examples 
are given.   We also believe this method can be used to reach large numbers and a 
wide variety of respondents including, individuals at risk of cardiac arrest. 
A member of the research team will provide ample information to the survey 
respondent, and the survey will provide detailed information about EFIC regulation 
and the EROCA study.   We anticipate conducting 50-75 surveys. 

52 
 
We propose visiting the following: 
 
A. Cardiology Clinic – community at risk 
We will approach adult patients and family members in the UMHS clinic to 
participate in our survey. If the participant agrees, verbal consent will be obtained 
and proceed with the interview. We will ensure that their participation does not 
interfere with patient care. Each survey will be take approximately 7-10 minutes to 
complete and will be initiated by a trained clinical research coordinator (CRC) 
delegated by the PI. 
B. Emergency Department – community at risk, geographic location, at risk 
population. Adult stable patients in the UMHS emergency department and their 
family members will be approached. 
 
Completing a survey will suffice as implied consent. We will ensure that their 
participation does not interfere with patient care. Each survey will be take 
approximately 7-10 minutes to complete and will be initiated by a trained clinical 
research coordinator (CRC) delegated by the PI. Members of the study team will 
identify potential participants from the ED electronic tracking board. A study team 
member or research coordinator will approach the patient and/or family member 
for their willingness to complete the survey. If the participant agrees, verbal 
consent will be obtained and proceed with the interview. 
 
C. Set up EFIC/EROCA table if feasible at one or more events in Ann Arbor so 
community members can learn about the study and complete a survey if they 
choose.  Examples of events include: 
a. Health Fairs 
b. Sporting events 
c. Concerts and performing arts events 
d. Festivals and Art Fairs 
 
3. Use of a study website that has capacity to solicit and receive comments 
Included could be  a  streamed generic emergency research video from the NETT 
 
https://nett.umich.edu/patients-communities/community-videos 
 
4. Opt-Out Mechanism 
Prior to and throughout the duration of the clinical trial, patients and their families will 
have various methods through which they can refuse participation in the trial. We will 
include this information at the community consultation meetings and on the brochures 
and posters for public disclosure. We will provide “File of Life” magnets, driver’s license 

53 
 
stickers, and cards at community events and have a link on our website to mail if 
requested. If a medical bracelet (wrist band) is preferred, one will be provided with 
instructions that it must be worn throughout the study duration. 
EMS providers are accustomed to looking for medical information, typically in a “File of 
Life” posted to the refrigerator or the back of the door and if outside their home, their 
wallet is searched for identification and any medical history. We will provide “File of Life” 
magnets, stickers, wrist bands, and cards at community events and have a link on our 
website to mail if requested. 
If a family member is instructed about the study and declines, the patient will not be 
included in the study and standard CPR protocols will be followed. This will be carefully 
covered in EMS training. 
Community Consultation Mechanics 
Once community consultation meetings are scheduled, IRB will be notified and 
members are encouraged to attend the meetings, if available. 
 
All attendees, interviewees, and those who access the website will be asked to 
complete an attendance record, including their demographics. Only IRB approved 
handouts will be available to all attendees and should be in provided in an 
understandable language. Opt out procedures will be documented and included in 
the handout. 
 
Responses from the three forms of community consultation will be compiled in one 
report and submitted to IRB for consideration. 
 
Presentation Materials 
All presentation materials, including scripts, survey, and educational materials 
presented in this plan have been developed with input from members of the 
Neurological Emergencies Treatment Trials (NETT) , who have quite a bit of experience 
conducting community consultation and public disclosure. 
 
 
 
All community consultation activities will be reported to the IRB, including the 
responses required written survey questions. Proposed timeframe to complete the 
community consultation activities is 4 months. 
A summary of the community consultation will include information about: the 
participants, the presentation, community questions and comments, and responses to 
closed- and open-ended questions. 
Reporting Community Consultation 

54 
 
Catchment area information will be collected as per the IRB. This information will allow 
the research team to concentrate its consultation and announcement efforts on the 
appropriate communities. 
 
Public Disclosure requirement of the Exception from Informed Consent (EFIC) regulations (21 
CFR 50.24) for emergency research, states: 
21 CFR 50.24 
(a)(7)Additional protections of the rights and welfare of subjects will be provided, 
including at least: 
 
(ii) Public disclosure to the communities in which the clinical investigation will be 
conducted and from which the subjects will be drawn, prior to initiation of the clinical 
investigation, of plans for the investigation and its risks and expected benefits; 
(iii) Public disclosure of sufficient information following completion of the clinical 
investigation to apprise the community and researchers of the study, including the 
demographic characteristics of the research population, and its results; 
Public disclosure will be done prior to enrollment and continue throughout the study period 
and after the study has completed. The study team will provide updates prior to and during 
the study period, and after the study has completed. The study results will be distributed 
locally and nationally through peer-reviewed journals, and presentations at national meetings. 
Public disclosure is defined as the “dissemination of information about the research sufficient 
to allow a reasonable assumption that communities are aware of the plans for the 
investigation, its risks and expected benefits and the fact that the study will be conducted”. It 
also includes “dissemination of information after the investigation is completed so that 
communities and scientific researchers are aware of the study’s results”. 
Appropriate public disclosure includes: 
 
• Clear statement that informed consent will not be obtained for any subjects 
• Information about the study medications use including a balanced description of the 
risks and benefits 
• Synopsis of the research protocol and study design 
• How potential study subjects will be identified 
• Participating sites/institutions 
• Description of the attempts to contact a LAR 
• Suggestions for opting out of the study 
PUBLIC DISCLOSURE 

55 
 
 
 
 
 
Using several different channels of communication for public disclosure increases the 
likelihood of reaching more of the intended audiences. It also can increase repetition of the 
message, improving the chance that intended audiences will be exposed to it often enough to 
absorb it.  For these reasons, we will use a combination of channels. 
Our plans for implementation include: 
 
1. In-hospital Activities 
We will post brochures and posters across Michigan Medicine Clinics, to include, the 
Emergency Department, Cardiology Clinics, employee areas, and any other are 
identified as relevant, before and during the trial. We will also utilize email messaging, 
to include  M Headlines, M Research, The University Record, etc. These materials will 
provide a description of the study, local contact information, study website address, 
and opt-out information.  All materials will be reviewed by IRB prior to use. 
2. Community Activities 
Obtain a booth/table at various local community events and hand out brochures 
and/or flyers describing study with contact information and talk with members of the 
community. We will target groups that appear to have interest in healthcare and/or 
cardiac disease, such as health fairs, American Heart Association (Ann Arbor), and 
organized walk/runs in the area as well as any other event where community members 
may gather in large numbers, such as libraries, sports facilities, concerts, fairs and 
festivals. 
 
 
3. Electronic Resources 
Electronic-based education is a passive approach to disseminating information that has 
benefits and challenges. There is no way to accurately measure whether how much of the 
community is reached by these methods. Access may be limited to those segments of the 
population with regular computer access. Despite these problems, electronic study education 
is inexpensive to develop and maintain and offers continuous and anonymous input from the 
public. 
In collaboration with UMHS Department of Communication, we propose to advertise EROCA 
and EFIC in local appropriate websites and via paid social media advertising. 
Public Disclosure Planned 

56 
 
A copy of the press release or another IRB approved document will be submitted to 
neighborhood associations, requesting the information be shared. There are many on-line 
neighborhood associations who can reach hundreds of their neighbors through electronic 
means. 
A copy of the press release or another IRB approved document will be submitted to City of 
Ann Arbor Communications Director requesting it be placed in their monthly newsletter that 
reaches all City of AA employees and approximately 500 community members on their mailing 
list. 
 
 
 
  2.  BROADCAST AND PRI NT MEDIA 
 
 
Purchased advertising in broadcast and print media ensures dissemination of accurate 
materials to a wide audience. We plan to advertise in the paper and electronic versions of the 
local news papers. 
 
In collaboration with UMHS Department of Communication, a news release will be written and 
IRB approved prior to distribution to any media. 
 
Printed materials, including advertisements for publication in newspapers and magazines, brochures, 
and flyers will be reviewed and approved by the IRB . Advertisements will be purchased in both English 
language and foreign language newspapers as appropriate. All printed advertisements will provide a 
general description of the study, the national and/or local website address, as well as site contact 
information. 
 
We also plan to contact local radio stations, who may be interested in covering the study and EFIC. 
Investigator appearances on local, radio, television, or call-in talk shows can bridge the line between 
public disclosure and community consultation. 
 
Any local flyers or brochures distributed will reference EROCA study website as an additional resource 
for patients, families, and healthcare providers to get information as well as ask questions about 
EROCA. 
 
 
 
 
 
All Public Disclosure activities will be summarized into a report and submitted to IRBMED for 
review. 
Timeline for Community Consultation and Public Disclosure Activities 
Reporting Public Disclosure 

57 
 
We anticipate beginning community consultation and public disclosure activities as soon as 
possible after IRB review and approval of our EFIC plan, with a goal of completion by Janurary, 
2017.  The community consultation activities will occur over the course of about 5 months. 
Public disclosure will begin prior to study enrollment, will continue throughout study 
enrollment, and conclude with dissemination of study results after the study has concluded. 
We plan to initiate public disclosure activities at least 2-weeks prior to the start of the 
proposed trial. Public disclosure will continue beyond the end of study enrollment and 
through disclosure of study results, and anticipate a 1-3 year timeframe. 
Analysis and Presentation of Results From Community Consultation and Public Disclosure 
 
Reporting of community consultation results will be provided by the study team to the IRB. 
Summaries of the data will be reported to the FDA. 
Data collected regarding CC and PD will include the following elements: 
• 
Consultation methodology used 
• 
Community type: geographic or condition-specific 
• 
Participants involved: number and demographics 
• 
Duration, content, format of information presented 
• 
Free text log of comments, questions, and responses to open-ended questions 
• 
Log of pre-determined closed-ended survey questions and responses 
 
The study team will review survey responses and group meetings in summary form, and 
general themes will be summarized. The results of all local community consultation efforts will 
be summarized and submitted to IRBMED for review. If appointed and if present at the focus 
group discussions, an IRB liaison will provide an in-depth review of the discussions and 
additional feedback to the IRB as needed. Summaries of public disclosure will be reported to 
the IRB prior to approval, and then at least annually or upon request from the IRB. 
A provision of the protocol has been made to allow participants who learn of the trial through 
community consultation or public disclosure or other means, and who would not want to 
participate if treated for a cardiac arrest, to opt-out of trial prior to such an event. Opt-out 
forms will be available on the Huron Valley Ambulance (HVA) and all community consultation 
interactions. 
Contacting Legally Authorized Representatives (LAR) or family members 
The federal regulations for contact of a Legally Authorized Representative (21 CFR 50.24) 
state: 
(a)(7)Additional protections of the rights and welfare of the subjects will be provided, 
including, at least: 
(v) If obtaining informed consent is not feasible and a legally authorized 
representative is not reasonably available, the investigator has committed, if 

58 
 
feasible, to attempting to contact within the therapeutic window the subject's 
family member who is not a legally authorized representative, and asking whether 
he or she objects to the subject's participation in the clinical investigation. The 
investigator will summarize efforts made to contact family members and make this 
information available to the IRB at the time of continuing review. 
 
(b) The IRB is responsible for ensuring that procedures are in place to inform, at the 
earliest feasible opportunity, each subject, or if the subject remains incapacitated, a 
legally authorized representative of the subject, or if such a representative is not 
reasonably available, a family member, of the subject's inclusion in the clinical 
investigation, the details of the investigation and other information contained in the 
informed consent document. The IRB shall also ensure that there is a procedure to 
inform the subject, or if the subject remains incapacitated, a legally authorized 
representative of the subject, or if such a representative is not reasonably available, 
a family member, that he or she may discontinue the subject's participation at any 
time without penalty or loss of benefits to which the subject is otherwise entitled. If 
a legally authorized representative or family member is told about the clinical 
investigation and the subject's condition improves, the subject is also to be informed 
as soon as feasible. If a subject is entered into a clinical investigation with waived 
consent and the subject dies before a legally authorized representative or family 
member can be contacted, information about the clinical investigation is to be 
provided to the subject's legally authorized representative or family member, if 
feasible. 
 
A procedure for prospective informed consent will be developed as is required by 21 CFR 
50.24, in the unlikely event that a LAR can be identified within the presumed short 
therapeutic time window for the intervention and is able to provide a meaningful prospective 
surrogate consent for patient enrollment. However, it is highly unlikely consent will be 
obtained prospectively in this EROCA trial for the reasons summarized in the scientific 
protocol, to delay treatment of the patient in sudden cardiac arrest long enough to identify 
and contact either an LAR or other family members. In circumstances in which is it impossible 
to identify a LAR within the therapeutic time frame, EFIC will be applied. 
Participants enrolled in EROCA under EFIC procedures and unable to consent, their LAR or 
family member(s) will be informed of the clinical investigation, including inclusion criteria at 
the earliest possible opportunity. 
Participants enrolled in EROCA with EFIC, or their LAR/family member(s), will be informed of 
study enrollment in the clinical investigation at the earliest possible opportunity. 
Participants admitted to the hospital will be approached in person. A study team member will 
speak with the senior clinician to determine the stability of the participant and the 
appropriate time for speaking with the participant, or if not alert and capable of making 
informed decisions, a LAR or family member. The study team member will approach the 
participant(or LAR/family) to notify them about the participant’s enrollment under EFIC, 
provide information about the study, including continued enrollment. 

59 
 
Participant’s rights, the responsibilities of the investigators, and answer any questions about 
the study. At that time, the patient or the LAR will be asked to provide consent for continued 
participation in the study. A written informed consent document will be used to document the 
decision to either continue in the study or to not participate any further. A copy of this form 
will be provided to the participant and another copy will be placed in the research record. 
Participants who do not wish to continue to participate will be excluded from all further 
aspects of the study except for the collection of data required by the FDA and permitted by 
the IRB to determine safety and efficacy. If informed consent is provided by a LAR or family 
member, we will approach the subject at the earliest possible opportunity to seek 
prospective, written informed consent for continuing participation in the study, should they 
become capable of doing so. 
It is anticipated that the notification of participants of LAR/family member(s) will commonly 
take place in the hospital within 12-24 hours of their cardiac arrest. If the participant remains 
unable to participate in this process and family members or another legally authorized 
representative are not present, continued attempts will be made to contact an LAR. Attempts 
to notify the participant or an LAR will be repeated three times after the patient has been 
initially enrolled. All notification attempts will be recorded on the subject’s case report form. 
Reports of these logs will be included in annual reports to the IRB. 
If a participant is enrolled into EROCA and dies before a legally authorized representative or 
family member can be contacted, the investigators will send a letter with basic information 
about the clinical investigation, the subject’s inclusion, and contact information to obtain 
more information or to answer questions if desired. 
Due to the high mortality rate with sudden cardiac arrest, we expect many participants will 
die prior to coming to the hospital and a letter will be sent to their LAR and/or family 
member(s). If no contact members are identified in prehospital and hospital records, 
attempts will be made to locate one through an obituary search for a next of kin listing and if 
found, their contact information will be sought using on-line address sites. 
For participants enrolled, who die prior to hospitalization, a letter will be sent to the 
participant’s LAR/family member. The letter will include information about the study, their 
enrollment under EFIC, information collected, no further participation, contact information if 
they have questions. 
Description of Refusal of Participation Procedures (Opt-Out) 
Prior to and throughout the duration of the clinical trial, patients and their families will have 
various methods through which they can refuse participation in the trial. We will include this 
information at the community consultation meetings and on the brochures and posters for 
public disclosure. We will provide “File of Life” magnets, stickers, and cards at community 
events and have a link on our website to mail if requested. 

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  APPENDIX B:  UMHS ED  ECPR GUIDELINES 
 
 
Extracorporeal cardiopulmonary resuscitation (ECPR) is standard practice in the University of 
Michigan Hospital Emergency Department. ECPR utilizes a venous-arterial extracorporeal 
membrane oxygenation (VA-ECMO) circuit built from several components including. These 
510K cleared devices may change based on the institutional practice of the hospital and are 
provided here as an example of the types of devices used. 
QUADROX-iD Adult diffusion membrane Oxygenator 
CentriMag Primary Console 
CentriMag Back-up Console 
CentriMag Motor 
CardioHelp System 
 
Inclusion/Exclusion criteria for ECPR 
Inclusion Criteria: 
- Age 18-70 
- -Initial shockable (ventricular tachycardia or ventricular fibrillation) or witnessed pulseless 
electrical activity or witnessed asystole 
- Anticipated interval from cardiac arrest onset (or 911 call) to establishing ECMO flow </= 60 
minutes 
- Potentially reversible cause of cardiac arrest 1 
 
Exclusion Criteria: 
-Sustained return of spontaneous circulation (ROSC) 
 
-DNAR or DNI advanced directive 
 
- Goals of care exclude ECPR (DNAR/DNI, advanced directive, or family discussion) 
- Contraindication to anticoagulation 2 
- Estimated BMI >40 
- Advanced or life-limiting comorbidity 3 
- Unable to independently perform ADLs at baseline 
- Treating physician and/or ECMO consultant feels that ECPR is futile 4 
 
(1) Potentially reversible causes of cardiac arrest include: ACS, refractory 
arrhythmia, myocarditis, massive PE, severe hypothermia, drug overdose 
 
(2) Contraindications to anticoagulation include: Suspected or known intracranial 
hemorrhage, traumatic arrest, significant active bleeding 

61 
 
(3) Advanced or life-limiting co-morbidities include: Stroke or CNS lesion with significant 
neurologic or cognitive impairment, liver cirrhosis including ESLD, ESRD, advanced 
COPD or other chronic lung disease, advanced or metastatic malignancy 
 
(4) Indications of futility are subject to the gestault of the treating physician and/or ECMO 
surgeon, but may include: Septic shock multiorgan failure, hypoxemic arrest, metabolic 
acidosis with pH <7.0, Lactate >15, ETCO2 <10 despite optimal ACLS, poor candidate 
for destination LVAD, artificial heart, or transplant 
 
 
 
 
UMHS AES ECPR Protocol 
 
 
 
 
(1) Inclusion/Exclusion criteria per Appendix 1 
(2) Necessary resources will be determined case-by-case, with necessary available 
resources including: ECMO specialist or ECMO credentialed emergency department RN 
dedicated to sitting pump until transfer to CVC; CVC bed to be made available ASAP; 
ED and EC3 staffing/volume/capacity to care for ECPR patient; Availability of EC3 
Intensivist by phone or in person 

62 
 
(3) Initiation of ECPR includes femoral veno-arterial cannulation by an ECMO surgeon or 
an emergency physician credentialed for the procedure, as well as circuit and pump 
management by an ECMO specialist or ECMO-credentialed emergency department RN 
(4) Potential disposition destinations include: Cardiavascular center ICU; cardiac 
catheterization lab; and/or EC3, if EC3 intensivist and ECMO credentialed RN available 
 
Standard data collected on cardiac arrest patients in UMHS AES 
For internal review, quality improvement, and education, the following data elements are 
among those routinely obtained in patients with cardiac arrest and post-cardiac arrest care 
delivered in AES: 
 
1. Time intervals, including time of arrest or 911 call, transport time, time of ED arrival, 
down-time, duration of CPR, time of return of circulation or initiation of ECPR 
2. Drugs and shocks administered 
3. Method(s) and device(s) used for CPR 
4. Method(s) and device(s) used for airway management 
5. End-Tidal CO2 measurements 
6. Vital sign trends, with attention to diastolic blood pressure measurements when 
obtained invasively 
7. Ventilator parameters, including settings and dynamic measurements 
8. Blood gas results 
9. Cerebral blood flow index via “C-Flow” device 
10. Method(s) of therapeutic hypothermia, when utilized 
11. Initial and subsequent cardiac rhythms 
12. Return of circulation ECG interpretations 
13. Bedside echocardiography images and interpretations 
14. Cardiac catheterization results 
15. ED, ICU, and hospital length of stay 
16. EEG and neuro-prognostication results, including head CT, MRI, SSEP, NSE level, 
Neurology consultation documentation 
17. Cerebral performance category upon discharge 

63 
 
  APPENDIX  C:  WASHTENAW LIVINGSTON  CARDIAC ARREST GUIDELINES 
 
 
Cardiac Arrest – General 
This protocol should be followed for all adult cardiac arrests. Medical cardiac arrest patients 
undergoing attempted resuscitation should not be transported unless return of spontaneous 
circulation (ROSC) is achieved or transport is ordered by medical control or otherwise specified in 
protocol. 
If an arrest is of a known traumatic origin refer to the Dead on Scene Protocol. 
If it is unknown whether the arrest is traumatic or medical, continue with this protocol. 
Patients displaying a Do Not Resuscitate order or bracelet – follow DNR Protocol. 
When an ALS unit is present, follow this general cardiac arrest protocol in conjunction with the 
protocol that addresses the indentified rhythm. 
Once arrest is confirmed, emphasis should be on avoiding interruptions in CPR. 
CPR should be done in accordance with current guidelines established by the American Heart 
Association. 
 
Pre-Medical Control MFR/EMT/SPECIALIST 
1. Confirm Arrest 
A. Assess for signs of normal breathing. 
B. Check a carotid pulse for not more than 10 seconds. 
2. Initiate CPR or continue CPR if already in progress and apply and use AED as soon as available. 
3. Ensure CPR quality 
A. Compressions at least 2” in depth for adults. 
B. Compression rate at least 100 per minute (An FDA approved mechanical CPR device operating 
at the manufacturer pre-set rate meets this rate requirement). 
C. Avoid excessive ventilation (volume and rate). 
4. Continue CPR with minimal interruptions, changing the rescuer doing compressions every 2 
minutes, when possible. 
5. Initiate ALS response if available. 
6. Establish a patent airway, maintaining C-Spine precaution if indicated, using appropriate airway 
adjuncts and high flow oxygen. See Emergency Airway Procedure. 
 
EMT 
7. Establish a patent airway with a supraglottic airway. After insertion, provide continuous CPR 
without pauses for ventilation. Ventilations should be 
EROCA – IDE Protocol Version 0.03 
73 

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delivered at 8-10 breaths per minute or 1 breath every 5 to 6 seconds. See Emergency Airway 
Procedure. 
8. Verify CPR quality frequently and anytime the rescuer providing compressions or ventilations 
changes. 
9. If Return of Spontaneous Circulation (ROSC) has not been achieved after three, two minute 
cycles of CPR and ALS is not available or delayed, contact medical control, initiate transport.