Verification of a Prediction Algorithm for Cardiopulmonary Patients Admitted to the Emergency Department (ED) (VPAC)
Conditions: Shortness of Breath Episode, Tachycardia, Bradycardia, Difficulty Breathing
Sponsor: Zoll Medical Corporation

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Verification of a Prediction Algorithm for Cardiopulmonary 
Patients Admitted to the Emergency Department  
 
Study Number - 5703 
Version: 2.0 
March 14, 2016 
 
269 Mill Road 
Chelmsford, MA 01824-4105 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Study Protocol 
 
 
CONFIDENTIAL 
This confidential document is the property of ZOLL Medical Corporation. No 
unpublished information contained herein may be disclosed without the prior written 
approval of ZOLL Medical Corporation. This study will be conducted in accordance with 
ISO14155. Essential documents will be archived by the sponsor. Dissemination may 
only be made with the express written permission of ZOLL Medical Corporation. 

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Sponsor 
 
Sponsor:  
 
Primary Contact: 
 
Address: 
 
 
Phone Number: 
Email: 
ZOLL Medical Corporation 
 
Marcia Hefner, Sr. Project Manager, Clinical 
Affairs 
 
269 Mill Road, Chelmsford, MA 01824 
 
951-217-1167 
mhefner@zoll.com 
 
 
 
 
Principle Investigator 
 
Investigator: 
 
Address: 
 
 
Phone Number: 
Email: 
Dr. Michael Kurz, MD, MS-HES, FACEP 
Assistant Professor 
Department of Emergency Medicine 
University of Alabama 
University of Alabama @ Birmingham 
OHB 251 
619 19th Street 
Birmingham, AL  35249-7013 
 
 
 
 

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List of Abbreviations 
 
   AE                     Adverse Event 
   AVPU                Alert, Voice, Pain, Unresponsive 
   CABG               Coronary Artery Bypass Surgery  
   CKMB               Creatinine Kinase-MB   
   CRF                  Case Report Form 
   eCRF                Electronic Case Report Form 
   ED                    Emergency Department 
   FDA                  Food and Drug Administration 
   GCP                 Good Clinical Practice 
   GCS                 Glascow Coma Score 
   HIPAA              Health Insurance Portability and Accountability Act 
   HRV                 Heart Rate Variability 
   IABP                Intra-aortic Balloon Pump 
   IB                     Investigator’s Brochure 
   ICU                  Intensive Care Unit 
   IRB                  Institutional Review Board 
   MEWS             Modified Early Warning Score 
   MI                    Myocardial infarction 
   NEWS             National Early Warning Score 
   PCI                  Percutaneous Coronary Intervention 
   PHI                  Protected Health Information 
   PI                     Principal Investigator 
   SAE                 Serious Adverse Event 
   SpO2               Oxygen Saturation 
   SOP                 Standard Operating Procedure 
   VT                    Ventricular Tachycardia 
    
 
 

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Table of Contents 
 
1 Introduction ................................................................................... 7 
1.1 
Background ............................................................................................. 7 
1.2 
Risks/Benefits .......................................................................................... 8 
1.2.1 
Risks ................................................................................................. 8 
1.2.2 
Benefits ............................................................................................. 8 
2 Study Protocol .............................................................................. 8 
2.1 
Study Design ........................................................................................... 8 
2.1.1 
Purpose ............................................................................................. 8 
2.1.2 
Scope and Duration........................................................................... 8 
2.1.3 
Sample Size ...................................................................................... 8 
2.1.4 
Study Objectives ............................................................................... 8 
2.1.5 
Primary Outcome Measure ............................................................... 9 
2.1.6 
Secondary Outcomes ........................................................................ 9 
2.2 
Subject Screening and Eligibility Criteria ................................................. 9 
2.2.1 
Subject Recruitment and Screening .................................................. 9 
2.2.2 
Inclusion Criteria ............................................................................. 10 
2.2.3 
Exclusion Criteria ............................................................................ 10 
2.3 
Study Procedures .................................................................................. 10 
2.3.1 
Subject Enrollment .......................................................................... 11 
2.3.2 
Evaluation Requirements ................................................................ 12 
2.3.3 
Case Report Forms and Evaluations............................................... 13 
2.4 
Classification of Adverse Events and Reporting of Adverse Events ...... 14 
2.4.1 
Adverse Event Reporting ................................................................ 14 
2.5 
Subject Withdrawal ................................................................................ 14 
2.6 
Protocol Deviations ................................................................................ 15 
3 Statistical Analysis ................................................................... 15 
3.1 
Introduction.......................................................................................... 15 
3.2 
Primary Outcome Measure ................................................................. 15 
3.3 
Secondary Outcome Measure ............................................................... 16 
3.4 
Randomization....................................................................................... 17 
3.5 
Blinding .................................................................................................. 17 
3.6 
Missing Data ........................................................................................ 17 
3.7 
Sample Size ......................................................................................... 17 
4 Monitoring Procedures ................................................................ 17 
4.1 
Monitoring .............................................................................................. 17 
4.2 
Investigator/Site Selection ..................................................................... 17 
4.3 
Case Report Form Review .................................................................... 18 
4.4 
Source Documents ................................................................................ 18 
4.5 
Interim On-site Monitoring ..................................................................... 18 
4.6 
Final Monitoring Visit ............................................................................. 18 
5 Study Administration ................................................................... 20 

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5.1 
Study Sponsor ....................................................................................... 20 
5.2 
Applicable Regulations .......................................................................... 20 
5.2.1 
Institutional Review Board ............................................................... 20 
5.2.2 
Informed Consent ............................................................................ 20 
5.2.3 
Investigator Records ....................................................................... 20 
5.2.4 
Sponsor Records ............................................................................ 21 
5.3 
Publications ........................................................................................... 22 
5.4 
Study Discontinuation ............................................................................ 22 
5.5 
Use of Study Findings ........................................................................... 23 
5.5.1 
Subject Confidentiality ..................................................................... 23 
5.5.2 
Ownership of Study Data ................................................................ 23 
6 Appendices ................................................................................. 24 
ZOLL Tablet App ........................................................................... 30 
Description..................................................................................................... 30 
Usage ............................................................................................................. 30 
Connection Screen .................................................................................... 30 
ZAP Main Screen ....................................................................................... 30 
Data Retrieval ............................................................................................. 31 
7 References ................................................................................. 32 
 
 
 

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Protocol Summary 
 
Title 
Verification of a Prediction Algorithm for Cardiopulmonary 
Patients Admitted to the Emergency Department  
Short Title 
Verification of Prediction Algorithm 
Study Design 
Prospective observational clinical study 
Study 
Duration 
Estimated duration: 18 Months 
Study Site(s) 
3 Sites 
Objective(s) 
Verify existing prediction algorithm of cardiopulmonary events. 
 
Assess the prediction algorithm with regard to the frequency 
of cardiopulmonary events 
Primary 
Analysis 
Regression analysis 
Number of 
Subjects 
760 subjects 
Subject 
Eligibility 
Criteria 
Inclusion Criteria 
Candidates for this study must meet all of the following 
Inclusion criteria: 
1. 18 years of age or older 
2. Admission to emergency department requiring 
immediate medical attention due to presumed 
cardiac or pulmonary cause(s) and considered 
2nd or 3rd tier priority in triage system. 
Exclusion Criteria 
Candidates will be excluded from the study if any of the 
following conditions are present: 
1. Pregnant or suspected pregnancy 
2. Significant trauma 
3. Do Not Resuscitate order 
4. Known as ward of the state 
 
 

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1 
Introduction 
1.1 Background 
The best method by which to triage patients presenting to the emergency 
department (ED) has yet to be established. The key objective of the process of 
triage is to determine which patient is at the highest risk because that patient 
will require the greatest amount of resources and attention to determine the 
most appropriate treatment.  Risk stratification is a necessary method for 
triaging patients, particularly in the ED, as the number of patients presenting to 
the ED and the availability of staff is never equally matched requiring a method 
to determine the order and urgency in which patients are treated. 
 
Recent scoring systems to determine risk of significant clinical deterioration in 
patient health, such as the Modified Early Warning Score (MEWS), utilize vital 
signs (i.e., heart rate, respiration rate, blood pressure, temperature, pulse 
oximetry) and a subjective measure of the patient’s mental status (i.e., AVPU 
score: alert, reacts to voice, reacts to pain, or unconscious). Elevated MEWS 
values has been shown to be related to mortality.1 In the United Kingdom, a 
national early warning score (NEWS) has been implemented nationwide and 
been shown to discriminate patients at risk of the combined outcome of cardiac 
arrest, unanticipated intensive care unit (ICU) admission, or death within 24 
hours.2 
 
A novel algorithm for determining risk of acute cardiac complications, including 
cardiac arrest, for patients presenting to the ED has recently been reported. 
Unlike prior risk stratification tools that relied on basic vital sign data, this 
algorithm utilizes multiple metrics of heart rate variability (HRV) as well as a 
machine learning approach to solve the risk classification problem. The 
algorithm requires the collection of vital sign data, patient mental status, and at 
least 5 minutes of continuous electrocardiography (to calculate HRV metrics). 
It was shown to be more accurate than MEWS in predicting cardiac arrest 
within 72 hours of admission to hospital.3 Furthermore, the algorithm has been 
used to predict serious complications (mortality, cardiac arrest, ventricular 
tachycardia, hypotension requiring inotropes or intra-aortic balloon pump 
(IABP) insertion, intubation or mechanical ventilation, complete heart block, 
bradycardia 
requiring 
pacing, 
and 
recurrent 
ischemia 
requiring 
revascularization) within 72 hours in patients presenting to the ED with chest 
pain. In this patient population, a score of 4 or higher from the algorithm had a 
sensitivity of 0.880, specificity of 0.680, positive predictive value of 0.195, and 
a negative predictive value of 0.985 which was better than using ST 
elevation/depression and troponin in predicting complications within 72 hours.4 
The primary limitation of the algorithm is that it has been developed and tested 
in Singaporean patients. Verification of the results of the studies using this 
algorithm in other patient cohorts is required. As such, the proposed study will 
investigate the sensitivity and specificity of the algorithm. 

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1.2 Risks/Benefits 
1.2.1 Risks 
This is an observational study. The only risk is a breach of the patient’s 
protected health information. 
If a patient or LAR is unwilling or unable to sign Informed Consent the data 
will be removed from the database and not be considered in the final analysis.  
These patients not participating will be replaced to ensure that the number of 
patients approved for this study is met. 
 
1.2.2 Benefits 
 
There is no benefit to an individual enrolled in this study. The benefit of this 
study is the verification of the algorithm.  
 
2 
Study Protocol 
2.1 Study Design 
2.1.1 Purpose 
The purpose of this study is to verify an existing algorithm used to predict 
cardiopulmonary events in patients presenting to the emergency department. 
2.1.2 Scope and Duration 
This is a prospective, multi-center, observational study. 
 
Enrollment in this study is expected to take approximately 18 months.  
Subjects are enrolled upon arrival to the emergency department and followed 
for 72 hours. 
2.1.3 Sample Size 
Approximately 760 subjects will be enrolled in this study. 
 
2.1.4 Study Objectives 
2.1.4.1 Primary Objective 
The primary objective is to verify an existing prediction algorithm of 
cardiopulmonary events.  
 

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2.1.4.2 Secondary Objective 
The secondary objective is to assess the prediction algorithm with regard to 
the frequency of cardiopulmonary events. 
2.1.5 Primary Outcome Measure 
2.1.5.1 Cardiopulmonary events 
Cardiopulmonary events will be measured as the occurrence of any 
cardiopulmonary event, not limited to: 
 
 
Cardiac arrest 
Sustained ventricular tachycardia (VT) 
Hypotension requiring inotropes or intra-aortic balloon pump (IABP) insertion 
Intubation or mechanical ventilation  
Complete heart block 
Bradycardia requiring insertion of a pacing wire or external pacing, and  
Percutaneous coronary intervention (PCI) or coronary artery bypass surgery 
(CABG),  
*all within 72 hours of presentation to the ED 
2.1.6 Secondary Outcomes 
2.1.6.1 Frequency of Cardiopulmonary Events 
The number of cardiac events will be measured as the occurrence of any 
cardiac and cardiac-related events, not limited to: 
 
 
1. In-hospital Death 
2. In-hospital Cardiac Arrest 
3. Composite cardiovascular outcome or intervention (Lethal Arrhythmias , 
Acute Pulmonary Edema, Cardiogenic Shock, Myocardial Infarction, 
Percutaneous Coronary Intervention, Coronary artery Bypass Surgery , 
New or Recurrent MI, Recurrent Ischemia requiring Revascularization)  
*all within 72 hours of presentation to the ED 
2.1.6.2 Cardiac Arrest 
Cardiac arrest will be defined as the event of developing ventricular 
fibrillation, having a sudden unexpected death, or having a resuscitation event 
requiring cardiopulmonary assistance (chest compressions and/or 
defibrillation). 
2.2 Subject Screening and Eligibility Criteria 
2.2.1 Subject Recruitment and Screening 
Subjects aged 18 years or older who meet the following inclusion and 
exclusion criteria. 

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2.2.2 Inclusion Criteria 
Candidates for this study must meet all of the following Inclusion criteria: 
1. 18 years of age or older; 
2. Admission to emergency department requiring immediate medical 
attention which is presumed to be cardiac or cardiopulmonary related 
and considered 2nd or 3rd tier priority in triage system. Symptoms 
including: 
Shortness of breath 
Skin pallor consistent with cardiopulmonary complications 
Chest pain 
Rapid or irregular heartbeat 
 
And any symptoms considered to be cardiac or cardiopulmonary-
related by the investigator 
2.2.3 Exclusion Criteria 
Candidates will be excluded from the study if any of the following conditions 
are present: 
1. Pregnant or suspected pregnancy; 
2. Significant trauma 
3. Do Not Resuscitate order 
4. Known as ward of the state 
2.3 Study Procedures 
 
Schedule of Events 
Hospital Stay Status 
Admit 
During 
Discharge/ 
Withdrawal 
Inclusion/Exclusion Criteria 
X 
  
  
Informed Consent 
X1 
  
  
Study Evaluations 
Demographics (date of birth/age, gender and 
ethnicity) 
X 
  
  
Smoking status 
X 
  
  
ED diagnosis (primary) 
X 
  
  
Final diagnosis (primary) 
  
  
X 
Medications including beta-blockers, 
combined alpha and beta-blockers, digitalis, 
calcium channel blocker, bronchodilators, 
amiodarone, other anti-arrhythmics 
X 
X 
X 

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2.3.2 Evaluation Requirements 
2.3.2.1 Assessments 
The following data points will be recorded: 
• Inclusion/Exclusion Criteria 
• Demographics (date of birth/age, gender and ethnicity) 
• Smoking status 
• ED diagnosis (primary) 
• Final diagnosis (primary) 
• Medications including beta-blockers, combined alpha and beta-blockers, 
digitalis, calcium channel blocker, bronchodilators, amiodarone, other anti-
arrhythmics 

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2.3.3.2 Protocol Deviation CRF 
This form will be used to document any protocol deviations in the study.  
Please see Section 2.6 and Protocol Deviation CRF for additional information 
regarding Protocol Deviations.   
2.3.3.3 Subject Discontinuation CRF 
This form will be used to document a subject’s reason for exiting the study. 
Please see Section 2.5 for additional information regarding Subject 
Discontinuation.   
2.3.3.4 Adverse Event CRF 
All adverse events and complications will be recorded and reported on the 
Adverse Event CRF. Serious adverse events must be reported to the Sponsor 
within 24 hours, but no later than 10 days after made aware of the event. 
2.4 Classification of Adverse Events and Reporting of Adverse Events 
Serious adverse events must be reported to the Sponsor within 24 hours of 
becoming aware of the event, but no later than 10 days after the event. The 
Investigator is responsible for reporting adverse events to their individual 
IRBs. 
 
Serious adverse event is defined as:  
• Death 
• A serious deterioration in the health of the patient that results in a life-
threatening illness or injury  
• A permanent impairment of a body structure of body function  
• In-patient hospitalization or prolongation of existing hospitalization 
• Medical or surgical intervention to prevent permanent impairment to 
body structure or function  
• Fetal distress, fetal death or congenital abnormality or birth defect. 
 
 
2.4.1 Adverse Event Reporting 
Adverse event reporting will comply with the regulations of the local IRB. 
 
2.5 Subject Withdrawal 
An enrolled subject is considered ‘withdrawn’ from the study if their 
participation in the study is discontinued for any reason after enrollment.  
Possible reasons for withdrawal include: 
 
• Eligibility Criteria not met 
• Investigator judgment 

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If a subject withdraws from the study, a Subject Discontinuation CRF will be 
completed.   
2.6 Protocol Deviations 
An Investigator shall notify the sponsor and reviewing IRB of any deviations 
from the study protocol that are done to protect the life or physical well-being 
of a subject.  Such notice shall be given as soon as possible, but no later than 
5 working days after the deviation occurred.   
 
A protocol deviation is defined as a deviation from the study protocol.  
 
Protocol deviations will be documented on a Protocol Deviation CRF.  
3 Statistical Analysis 
3.1 Introduction 
The primary objective is to verify an existing prediction algorithm of 
cardiopulmonary events.  The secondary objective is to assess the prediction 
algorithm with regard to the frequency of cardiopulmonary events. 
 
Standard summary statistics will be calculated for relevant study variables.  For 
continuous variables, summary statistics will include means, medians, standard 
deviations and 95% confidence intervals around the means.  Categorical variables 
will be summarized using counts and percentages.  Statistical analyses will be 
conducted in SAS version 9.1 or above (SAS Institute, Cary, N.C.) or another 
statistical analysis package. 
3.2 
Primary Outcome Measure 
The primary outcome measure is the occurrence of cardiopulmonary events. It 
will be measured as the occurrence of any cardiopulmonary event, within 72 
hours of presentation to the ED, including: 
 
Cardiac arrest 
Sustained ventricular tachycardia (VT) 
Hypotension requiring inotropes or intraaortic balloon pump (IABP) insertion 
Intubation or mechanical ventilation  
Complete heart block 
Bradycardia requiring insertion of a pacing wire or external pacing, and  
Percutaneous coronary intervention (PCI) or coronary artery bypass surgery 
(CABG). 
 
For the primary outcome measure of occurrence of cardiopulmonary events, binary 
logistic regression will be used to estimate the probability that a cardiopulmonary 

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event has occurred given the values of explanatory variables, given by the 
following equation: 
 
 
Y is the primary outcome measure 
Yi = 1 if a cardiopulmonary event has occurred 
Yi = 0 if there is no cardiopulmonary event 
 
πi = the probability of a cardiopulmonary event 
 
X = (X1, X2, ..., Xk) being the set of explanatory variables  
 
Model: 
 
logit(πi)=β0+β1xi1+…+βkxik 
 
A Receiver Operating Characteristic Curve will be constructed and the area 
under the curve will be calculated to assess the model sensitivity. 
 
3.3 Secondary Outcome Measure 
 
The secondary outcome measure of the frequency of any cardiac event will be 
measured as the occurrence of any cardiac and cardiac-related events, not 
limited to: 
 
 
1. In-hospital Death 
2. In-hospital Cardiac Arrest 
3. Composite cardiovascular outcome or intervention (Lethal Arrhythmias , 
Acute Pulmonary Edema, Cardiogenic Shock, Myocardial Infarction, 
Percutaneous Coronary Intervention, Coronary artery Bypass Surgery , 
New or Recurrent MI, Recurrent Ischemia requiring Revascularization)  
 
For the secondary outcome measure of frequency of any cardiopulmonary event, 
multiple linear regression will be used to estimate the probability that an increase 
in the number of cardiopulmonary events given the values of explanatory variables, 
given by the following equation: 
 
 
Yi is the number of cardiopulmonary events 
 
πi = the probability of a cardiopulmonary event 
 
X = (X1, X2, ..., Xi) be the set of explanatory variables  
 
p=number of β coefficients in the model (including the intercept) 
 
Model: 
 
yi=β0+β1xi,1+βp−1xi,p−1+ϵi 

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3.4 Randomization 
This study is observational and no randomization of subjects will occur. 
 
3.5 Blinding 
This study is observational and no blinding will occur. 
 
3.6 Missing Data 
The primary analysis will be based on the data as observed.  Two additional 
sensitivity analyses will be performed where subjects with missing data are (1) 
assumed to have no cardiopulmonary events and (2) assumed to have a 
cardiopulmonary event. 
3.7 Sample Size 
Approximately 760 subjects are planned to be enrolled in the study to provide 634 
subjects in the final analysis. 
 
When the sample size is 634, the logistic regression test of β=0 (α = 0.050 two-
sided) will have 80% power to detect a β of 0.747 (an odds ratio of 2.111); this 
assumes that one normally distributed covariate x is being added to the model 
after adjustment for prior covariates, that its multiple correlation with covariates 
already in the model is 0.500 and, that the proportion of successes at the mean 
of x is 0.050. 
4 Monitoring Procedures 
4.1 Monitoring 
This study will be monitored according to appropriate regulations and SOPs.  
The Investigator will allocate adequate time for such monitoring activities.  
The Investigator will also ensure that the monitor is given access to all the 
study-related documents and related facilities, and has adequate space to 
conduct the monitoring visit. 
4.2 Investigator/Site Selection 
The following documents must be received prior to site initiation and 
maintained at the site and Sponsor: 
• Signed Clinical Study Agreement; 
• Current Medical License; 
• Current Curriculum Vitae (CV) for Primary Investigator(s) – dated and 
signed 

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• IRB/EC Approval Letter; and 
• IRB Membership List and/or Accreditation Statement 
 
Additional items that may be collected, are preferably collected prior to 
initiation, but not required at that time: 
• CV’s for Co-Investigator(s) – dated and signed; and 
• Site Personnel Training Record(s).   
4.3 Case Report Form Review 
A database that is compliant with 21 CFR Part 11 will be used. eCRFs 
received from the site will be documented with their date of receipt and 
entered into the study database. If there is missing, incomplete, unclear or 
discrepant information recorded on eCRFs, a Data Clarification Form (DCF) 
will be generated. The DCF will be sent to the Investigator for completion and 
signed by the appropriate site personnel. The DCF will then be sent back to 
the Sponsor to update the database. All common modules are demographics, 
screening, adverse events, labs, medical history, medications, procedures, 
treatment discontinuation, study completion, and signatures. 
4.4 Source Documents 
Source data is all information, original records of clinical findings, 
observations, or other activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Examples of source data include: 
Patient Medical Records, recorded data from automated instruments, and 
subject files involved in the clinical study. 
4.5 Interim On-site Monitoring 
The monitor will maintain personal contact with the Investigator and staff by 
fax, phone, mail, and on-site visits. The monitor will require access to all 
subjects’ records at each site visit.  These may include: 
• Patient Medical Records 
• Investigator Administrative Records 
• Subject Binders 
 
Monitoring will verify: 
• Protocol and regulatory compliance;  
• Verification of data recorded on Case Report Forms to source documents; 
and  
• Adequate subject enrollment. 
4.6 Final Monitoring Visit 
At the close of the study, the monitor will make a final on-site visit. The 
purpose of this visit is to: 
• Collect all outstanding study data; 

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• Insure that the Investigator’s files are accurate and complete; 
• Review record retention requirements with the Investigator;  
• Assure that all requirements are met for the closure of the study. 

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5 Study Administration 
5.1 Study Sponsor 
ZOLL Medical is the study sponsor and responsible for selecting qualified 
Investigators and providing them with the information they need to conduct 
the study properly, ensuring proper monitoring of the clinical site, ensuring 
that IRB review and approval are obtained, and ensuring that any reviewing 
IRBs are promptly informed of significant new information about the study. 
5.2 Applicable Regulations 
The following regulations were considered in developing/designing this study 
and apply to the ongoing conduct of the study: 
• ISO 14155 
5.2.1 Institutional Review Board 
Prior to participating in the study, the Investigator must forward written 
approval from the appropriate reviewing IRB. The Investigator is responsible 
for obtaining and maintaining IRB approval to participate in this study and 
forwarding evidence of IRB notification of approval, disapproval, or study 
termination to Sponsor. 
5.2.2 Informed Consent 
 
Patients will typically be unable to give informed consent at the time of enrollment 
based on the seriousness of their injuries or the process in which medical care is 
given. As this is an observational study and the data collected is only that of 
standard of care treatment this trial should be considered non-significant risk. 
Every effort will be made to ensure that consent is received from the patient or 
patient’s legally authorized representative (LAR) within 24 hours of patient 
enrollment.  
If a patient or LAR is unwilling or unable to sign Informed Consent the data 
will be removed from the database and not be considered in the final analysis.  
These patients not participating will be replaced to ensure that the number of 
patients approved for this study is met. 
 
Records and Reports 
5.2.3 Investigator Records 
The Investigator is responsible for the preparation (review and signature) and 
retention of the records cited below. Records are subject to inspection and 
must be retained for a period of at least two (2) years (or according to local 
regulatory requirements) after the study is terminated or the date that the 
records are no longer required for purposes of supporting publications. 
Records to be maintained by the Investigator include: 

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• 
Study protocol and all amendments 
• 
Signed Clinical Study Agreement 
• 
IRB approval letter, including informed consent 
• 
IRB membership list 
• 
Correspondence relating to the study 
• 
CVs for all Investigators  
• 
Site personnel signature list 
• 
Clinical monitor sign-in log 
• 
Blank set of CRFs and instructions for completion  
• 
Patient enrollment log 
•          Reports (includes annual reports, final reports from Investigator 
and Sponsor) 
 
The following records must be maintained for each subject enrolled in the 
study: 
• 
All data entered (e)CRF’s 
• 
Supporting documentation of any complications  
 
ZOLL reserves the right to secure data clarification and additional medical 
documentation on subjects enrolled in this study. 
5.2.4 Sponsor Records 
ZOLL Medical will maintain the following accurate, complete, and current 
records that are cited below. 
5.2.4.1 Sponsor Administrative Records 
• Enrolled Subject Identification Log 
• Site Training and Monitoring Log 
• Device Accountability Records 
• Non-Disclosure Agreement 
• Clinical Trial Agreement 
• Investigator Information 
o Current CV(s) 
o Current Medical License 
o Financial Disclosure Forms(s) 
• Monitoring  
o Monitoring Letter(s) 
o Monitoring Visit Report(s) 
o Site Visit Report(s) 
o Site Personnel Training Record(s) 
• IRB 
o IRB roster or letter of assurance 
o IRB Approval Letter(s) 

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• All study conduct related correspondence with an IRB or FDA 
• All study conduct correspondence with Site 
• Required reports (reference Table 5) 
• Documents Received Tracking Log 
• Study protocol and previous revisions 
5.2.4.2 Subject Records 
• Original completed CRFs 
• Copies of all completed logs and other subject specific forms (originals are 
maintained at site until the end of the study) 
• Original subject specific protocol deviations 
• Adverse event supporting data (e.g. EMS reports, medical records) 
• Original completed Data Clarification Forms (DCFs) 
5.3 Publications 
All publications and strategy will be reviewed and approved by the Sponsor. 
In general, publications using study data will be managed as follows: 
 
 
Authorship Selection 
Authors will be selected based on the following criteria: 
• Investigator’s participation in the study design process; or 
• Investigators participation in the study analysis process; and 
• Providing substantive contributions to the writing and development of the 
resulting publication. 
 
Confidentiality 
The Sponsor and authors will assure that no information, which would reveal 
a subject’s identity, is used in any publication. Information, which could be 
used to establish a subject’s identity, should not be provided to the Sponsor. 
Authors and the Sponsor will take every reasonable precaution to protect the 
identity of subjects enrolled in the study. 
 
Review of Communication Guidelines 
Investigators will receive a communication regarding the authorship selection, 
the publication co-authors and to which scientific platform the publication will 
be submitted. 
5.4 Study Discontinuation 
Sponsor will notify the Investigator of the completion or termination of the 
study or of the Investigator’s participation in the study. The Sponsor will 
provide a summary to the reviewing IRB of the study within 6 months of study 
termination. 

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5.5 Use of Study Findings 
5.5.1 Subject Confidentiality 
In conducting the study, the investigational site will comply with all applicable 
laws and regulations relating to the confidentiality and security of individually 
identifiable medical information including but not limited to the requirements of 
the Health Insurance Portability and Accountability Act (HIPAA).   
 
In the event that a subject revokes authorization to collect or use PHI, the 
Investigator, by regulation, retains the ability to use all information collected 
prior to the revocation of subject authorization.  For subjects that have 
revoked authorization to collect or use PHI, attempts should be made to 
obtain permission to collect at least vital status (i.e. the subject is alive and 
well) at the end of their scheduled study period. 
 
All personal information pertaining to subjects will be kept confidential. 
Subjects will be identified only by their Subject ID Number.  Clinical study 
documents and hospital and clinic medical records pertaining to subjects may 
be reviewed by Sponsor personnel or their representatives. 
 
Information obtained in the course of executing this study, including still and 
motion photography, may be presented for regulatory, clinical or educational 
purposes as long as no subject is identified.  
 
5.5.2 Ownership of Study Data 
The cumulative set of data collected by ZOLL Medical from the Investigator is 
considered ZOLL’s data.   
 
 
 
 
 

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6 
Appendices 
ECG Monitoring 
The X Series is intended for use to monitor and/or record 3-, 5-, or 12-lead ECG 
waveform and heart rate, and to alarm when heart rate is above or below limits 
set by the operator.  
Each site will receive 3 X-series monitors to be used on subjects enrolled in the 
study.  These devices will be on loan and will be returned to the sponsor at the 
completion of the study. 
The patient’s ECG is monitored by connecting the patient to the unit via a 3-, 5-, 
or 12-lead patient cable or hands-free therapy electrodes. The ECG waveform is 
presented on the display along with the following information:   
• averaged heart rate, derived by measuring R to R intervals 
• lead selection - I, II, III, aVR, aVL, aVF, V1, V2, V3, V4, V5, V6 (with ECG 
cable), PADDLES, or PADS. 
• ECG size - 0.125, 0.25, 0.50, 1.0, 2.0, 4.0 cm/mV, AUTO 
• status messages 
The ECG bandwidth is user selectable. 
IMPORTANT:  FOR PURPOSES OF THIS STUDY WE ARE REQUIRING THE 
RECORDING OF A 3-LEAD, CONTINUOUS ECG OF AT LEAST 5 MINUTES. 
Continuous Waveform Recording 
Continuous waveform recording allows you to record continuous waveforms to a 
full disclosure case log for the patient being monitored. This feature needs to be 
enabled by a supervisor. The supervisor can access this feature by pressing the 
Setup quick access key ( ), and then selecting Supervisor>Log>Waveform 
Recording. In this menu, the following settings can be customized: 
• Record Displayed Waveforms – Record only the top waveform that is 
displayed or record all     waveforms that are displayed. 
• Record Additional Waveforms – Always record the CO2 waveform or 
always record the IBP and the CO2 waveforms. 
Note: When Continuous waveform recording is disabled, no waveforms (except 
snapshots) are recorded. 
The full disclosure case can, at a minimum, concurrently store the following 
information: 

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• 32 monitor snapshots 
• 500 non-ECG events 
• 24 hours of continuous ECG (4 waveforms), Capnography, IBP (3 
channels), and Pads Impedance 
The actual information that is stored depends on usage. Also, the specific 
combination of stored continuous waveform data depends on how the waveform 
recording settings are configured in the Supervisor menu. 
ECG Monitoring Setup 
The proper application and placement of electrodes is essential for high quality 
ECG monitoring. Good contact between the electrode and skin minimizes motion 
artifact and signal interference. 
The following procedure describes how to monitor a patient’s ECG using 3- and 
5-Lead ECG cables.  
To monitor a patient’s ECG using 3- and 5-Lead ECG cables, perform the 
following steps: 
1. Prepare the patient's skin for electrode application: 
2. Apply the electrode pads to the patient. 
3. Connect each lead of the ECG cable to the appropriate electrode. 
4. Insert the patient cable plug into the ECG input connector on the X Series unit. 
5. Select the ECG waveforms to be displayed on the waveform trace display 
screen. 
6. Observe the patient‘s electrocardiogram on the display, and adjust size of the 
ECG waveform trace, as necessary. 
Preparing the Patient for Electrode Application 
The proper application of electrodes is essential for high quality ECG monitoring. 
Good contact between the electrode and skin minimizes motion artifact and 
signal interference. 
Before applying electrodes, prepare the patient’s skin, as necessary: 
• Shave or clip excess hair at electrode site. 
• Clean oily skin with an alcohol pad. 
• Rub site briskly to dry. 

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Applying Electrodes to the Patient 
The following sections show where to place electrodes when using 3- and 5-Lead 
cables to perform ECG monitoring. For 3-Lead ECG cables, apply electrodes as 
in Figure 4-1, 3-Lead Electrode Placement. For 5-Lead ECG cables, apply 
electrodes as in Figure 4-2, 5-Lead Electrode Placement. 
Avoid placing electrodes over tendons and major muscle masses. 
Make sure that the ECG electrodes are placed to allow defibrillation, if 
necessary. 
3-Lead Electrode Placement 
Depending upon local usage, the ECG leads are marked either RA, LA, and LL 
(or R, L, and F). The following table shows the markings and color codes for the 
different lead sets. 
 
 
AHA Color Coding 
IEC Color 
Coding  
Placement of Electrodes  
RA/White Electrode 
R/Red 
Electrode 
Place near patient’s right mid-
clavicular line, directly below 
clavicle  
LA/Black Electrode  
L/Yellow 
Electrode  
Place near patient’s left mid-
clavicular line, directly below 
clavicle.  
LL/Red Electrode  
F/Green 
Electrode  
Place between 6th and 7th 
intercostal space on patient’s left 
mid-clavicular line.   

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7 
References 
 
1. Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified 
Early Warning Score in medical admissions. QJM. 2001 Oct;94(10):521-6. 
 
2. Smith GB, Prytherch DR, Meredith P, Schmidt PE, Featherstone PI. The 
ability of the National Early Warning Score (NEWS) to discriminate 
patients at risk of early cardiac arrest, unanticipated intensive care unit 
admission, and death. Resuscitation. 2013 Apr;84(4):465-70. 
 
3. Ong ME, Lee Ng CH, Goh K, Liu N, Koh ZX, Shahidah N, Zhang TT, 
Fook-Chong S, Lin Z. Prediction of cardiac arrest in critically ill patients 
presenting to the emergency department using a machine learning score 
incorporating heart rate variability compared with the modified early 
warning score. Crit Care. 2012 Jun 21;16(3):R108. doi: 10.1186/cc11396. 
 
4. Ong ME, Goh K, Fook-Chong S, Haaland B, Wai KL, Koh ZX, Shahidah 
N, Lin Z. Heart rate variability risk score for prediction of acute cardiac 
complications in ED patients with chest pain. Am J Emerg Med. 2013 
Aug;31(8):1201-7.