Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac Arrest
Phase: NA
Conditions: Cardiac Arrest
Sponsor: University of Alabama at Birmingham

 
 
 
 
 
 
 
Pragmatic Trial of Airway Management  
in Out-of-Hospital Cardiac Arrest 
 
(Pragmatic Airway Resuscitation Trial) 
 
Clinical Trial Protocol 
 
 
Version 5.0 February 19, 2015 –revised and approved protocol 
 
Version 5.1 April 1, 2015 –Minor changes to DSMB revised and approved protocol 
 
Version 6.0 July 13, 2016 – Minor updates 
 
Version 7.0 November 29, 2016 – Revisions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This trial protocol is adapted with permission from the ROC CCC Trial protocol. 
This protocol may not be used or reproduced without permission.
PRAGMATIC AIRWAY
RESUSCITATION TRIAL

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Clinical Trial Protocol  
 
 
 
  
TABLE OF CONTENTS 
1. 
Key Study Information ........................................................................................................ 5 
 
Clinical Trial Registration .................................................................................................... 5 
1.1
 
Funding and Support .......................................................................................................... 5 
1.2
 
Study Leadership and Key Personnel ................................................................................. 5 
1.3
 
Principal Investigator, Lead Facilitator ..........................................................................5 
1.3.1
 
Co-Investigators ...........................................................................................................5 
1.3.2
2. 
Acronyms and Abbreviations ............................................................................................. 6 
3. 
SUMMARY - Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac Arrest 
(Pragmatic Airway Resuscitation Trial) ............................................................................. 8 
4. 
Study Objective ................................................................................................................. 11 
5. 
Background ....................................................................................................................... 11 
 
Conceptual Framework .................................................................................................... 11 
5.1
6. 
Pertinent Existing Evidence on Endotracheal and Laryngeal Tubes............................. 14 
 
Animal .............................................................................................................................. 14 
6.1
 
Human.............................................................................................................................. 14 
6.2
 
Observational Studies ................................................................................................. 14 
6.2.1
 
Randomized Controlled Trials ..................................................................................... 16 
6.2.2
7. 
Existing EMS Airway Practices ........................................................................................ 16 
8. 
Overview of Trial Design ................................................................................................... 17 
9. 
Inclusion Criteria ............................................................................................................... 17 
10. 
Exclusion Criteria .............................................................................................................. 17 
11. 
Trial Setting ....................................................................................................................... 18 
12. 
Interventions ...................................................................................................................... 19 
 EMS Personnel Training Levels........................................................................................ 19 
12.1
 Primary Endotracheal Intubation (Control Arm) ................................................................ 19 
12.2
 ETI Device and Technique .......................................................................................... 19 
12.2.1
 ETI Techniques Permitted in the Trial ......................................................................... 20 
12.2.2
 Primary Laryngeal Tube Insertion (Intervention Arm) ........................................................ 20 
12.3
 LT Device and Technique ........................................................................................... 20 
12.3.1
 Limitation of the Trial Intervention Arm to the Laryngeal Tube .................................... 21 
12.3.2
 Research Procedures ....................................................................................................... 21 
12.4
 Protocol Considerations ................................................................................................... 22 
12.5
 Number of Airway Insertion Attempts .......................................................................... 22 
12.5.1
 Unsuccessful Airway Insertion and Rescue Interventions ........................................... 23 
12.5.2
 Confirmation of Airway Placement .............................................................................. 23 
12.5.3
 Use of Neuromuscular Blocking Agents ...................................................................... 24 
12.5.4
 Absence of a Bag-Valve-Mask-Only Arm .................................................................... 24 
12.5.5
 Emergency Department Management of the EMS Airway Device ............................... 24 
12.5.6
 EMS Personnel Airway Management Experience ....................................................... 25 
12.5.7
 Post-Arrest Care ......................................................................................................... 25 
12.5.8
13. 
Random Allocation and Blinding ..................................................................................... 26 
 Random Allocation Method ............................................................................................... 26 
13.1

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 Rationale for Cluster Randomization ................................................................................ 27 
13.2
 Blinding of Treatment Assignment .................................................................................... 27 
13.3
14. 
Outcomes ........................................................................................................................... 27 
 Primary Outcome .............................................................................................................. 27 
14.1
 72-Hour Survival ......................................................................................................... 27 
14.1.1
 Secondary Outcomes ....................................................................................................... 28 
14.2
 Return of Spontaneous Circulation ............................................................................. 28 
14.2.1
 Airway Management Course ....................................................................................... 28 
14.2.2
 Survival to Hospital Discharge .................................................................................... 29 
14.2.3
 Neurologically-Intact Survival to Hospital Discharge ................................................... 29 
14.2.4
 Adverse Events ................................................................................................................ 29 
14.3
 Unexpected Adverse Events (UAE) ............................................................................. 30 
14.3.1
 Expected Adverse Events ........................................................................................... 30 
14.3.2
 Other Data ........................................................................................................................ 31 
14.4
 CPR Process Data ...................................................................................................... 31 
14.4.1
 Other Explanatory Mechanisms .................................................................................. 31 
14.4.2
15. 
Analysis Plan ..................................................................................................................... 32 
 CONSORT Diagram ......................................................................................................... 32 
15.1
 Intention-to-Treat vs As-Treated ....................................................................................... 32 
15.2
 Primary Analysis – 72-Hour Survival ................................................................................ 32 
15.3
 Secondary Analyses ......................................................................................................... 33 
15.4
 Subgroup Analyses .......................................................................................................... 33 
15.5
16. 
Sample Size ....................................................................................................................... 33 
 Sample Size Estimate ...................................................................................................... 33 
16.1
 Interim Monitoring Plan and Stopping Boundaries – Criteria for Terminating the Trial ...... 34 
16.2
17. 
Eligibility for Participating and Remaining in the Enrollment Phase of the Trial .......... 35 
18. 
Timeline ............................................................................................................................. 35 
 Milestones for the Planning Phase ................................................................................... 35 
18.1
 Milestones for Trial Execution and Subject Recruitment ................................................... 36 
18.2
19. 
Data Sources and Management ....................................................................................... 36 
 Data Sources .................................................................................................................... 36 
19.1
 Out-of-Hospital EMS Data .......................................................................................... 36 
19.1.1
 Hospital Data .............................................................................................................. 36 
19.1.2
 Post-Discharge Vital Status ........................................................................................ 37 
19.1.3
 Data Entry ........................................................................................................................ 37 
19.2
 Database Management ..................................................................................................... 37 
19.3
20. 
EMS Research Protocol Training ..................................................................................... 37 
 Overview of EMS Protocol Training Elements .................................................................. 37 
20.1
 Retraining and Feedback ................................................................................................. 38 
20.2
21. 
Guidance for Receiving Emergency Departments .......................................................... 38 
22. 
Study Monitoring ............................................................................................................... 39 
 Study Monitoring Committee ............................................................................................ 39 
22.1
 Data Safety and Monitoring Board .................................................................................... 39 
22.2
23. 
Regulatory Considerations ............................................................................................... 40 
 Human Subjects ............................................................................................................... 40 
23.1

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 Food and Drug Administration .......................................................................................... 40 
23.2
 Technical and Regulatory Information for the ET Tube ............................................... 40 
23.2.1
 Technical and Regulatory Information for the LT ........................................................ 41 
23.2.2
24. 
References ......................................................................................................................... 42 
25. 
Appendix 1 – Summary of Protocol Amendments .......................................................... 51 
 Version 4.2, December 10, 2014 ...................................................................................... 51 
25.1
 Version 5.0, February 19, 2015 ........................................................................................ 51 
25.2
 Version 5.1, April 1, 2015 ................................................................................................. 51 
25.3
 Version 6.0, June 27, 2016 ............................................................................................... 51 
25.4
26. 
Appendix 2 – List of Study Personnel ............................................................................. 52 
 Principal Investigator, Lead Facilitator .............................................................................. 52 
26.1
 Co-Investigators ............................................................................................................... 52 
26.2
 Liaisons with the Resuscitation Outcomes Consortium ..................................................... 52 
26.3
 Project Direction and Coordination ................................................................................... 53 
26.4
 Biostatisticians .................................................................................................................. 53 
26.5
 Liaisons with the National Heart, Lung and Blood Institute ............................................... 54 
26.6
27. 
Appendix 3 – Criteria to Enter and Remain in the Enrollment Phase of the Trial ......... 55 
 Criteria to Enter Enrollment Phase of Trial ........................................................................ 55 
27.1
 Criteria to Remain in Enrollment Phase of Trial ................................................................ 55 
27.2
28. 
Appendix 4 – Additional Information Justifying the Use of Exception from Informed 
Consent (EFIC) for Emergency Research ........................................................................ 56 
29. 
Appendix 5 – Example Patient Notification Forms for Use Under Exception from 
Informed Consent for Emergency Research ................................................................... 61 
 Notification Forms (for initially surviving Subjects) ............................................................ 61 
29.1
 Next of Kin Notification Letter (for family of subjects who did not survive) ......................... 64 
29.2
 Study Information Sheet (accompanies Next of Kin Notification Letter) ............................ 66 
29.3
 Script for EMS Notification of Next of Kin .......................................................................... 67 
29.4
 Sample Community Consultation Plan.............................................................................. 68 
29.5
 
 
 
 

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Key Study Information 
1.
 
Clinical Trial Registration 
1.1
This study is registered with www.clinicaltrials.gov as trial no. NCT02419573.  
 
Funding and Support 
1.2
The planning phase of this study is supported by grant award UH2-HL125163 from the National 
Heart, Lung and Blood Institute (NHLBI).  
Additionally, the ROC data coordinating center and sites are supported through a series of 
cooperative agreements through the NHLBI (5U01 HL077863-University of Washington Data 
Coordinating Center, HL077866-Medical College of Wisconsin, HL077867University of 
Washington, HL077871-University of Pittsburgh, HL077873-Oregon Health and Science 
University, HL077881-University of Alabama at Birmingham, HL077887-University of Texas SW 
Medical Center/Dallas, HL077908-University of California San Diego).  
The trial execution phase of this study is supported by grant award UH3-HL125163 from NHLBI. 
 
Study Leadership and Key Personnel 
1.3
This study is led by investigators and research personnel from the Department of Emergency 
Medicine, University of Alabama School of Medicine, Birmingham, Alabama and the Clinical Trials 
Center, University of Washington, Seattle, Washington. Execution of research activities will be 
facilitated by US regional coordinating centers of the Resuscitation Outcomes Consortium. 
 Principal Investigator, Lead Facilitator 
1.3.1
 
Henry E. Wang, MD, MS 
Professor and Vice Chair for Research 
Department of Emergency Medicine 
University of Alabama School of Medicine 
(205)-996-6526/(205)-410-1267 
hwang@uabmc.edu 
 Co-Investigators 
1.3.2
 
Susanne May, PhD 
Professor 
Principal Investigator 
ROC Clinical Trial Center 
University of Washington 
206-685-1302  
sjmay@uw.edu 
 
 
 

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Graham Nichol, MD 
Professor 
Medical Director, ROC Clinical Trial Center 
University of Washington 
206-685-1302  
nichol@uw.edu 
 
 
Acronyms and Abbreviations 
2.
 
ACLS 
Advanced Cardiac Life Support 
AED 
Automated External Defibrillator 
ALPS 
Amiodarone, Lidocaine or Placebo Study 
ALS 
Advanced Life Support 
BLS  
Basic Life Support 
CARES 
Cardiac Arrest Registry to Enhance Survival 
CC/PD 
Community Consultation/Public Disclosure 
CCC 
Continuous Chest Compression 
CI 
Confidence Interval 
CONSORT 
CONsolidated Standards Of Reporting Trials 
CPR 
Cardiopulmonary Resuscitation 
CTC 
Clinical Trial Center (University of Washington) 
DCC 
Data Coordinating Center 
DNAR 
Do Not Attempt Resuscitation 
DSMB 
Data Safety and Monitoring Board 
ECG 
Electrocardiogram 
ED 
Emergency Department 
EFIC 
Exception From Informed Consent 
EMS 
Emergency Medical Services 
EMT 
Emergency Medical Technician 
EOA 
Esophageal Obturator Airway 
ET 
Endotracheal 
ETC 
Esophageal Tracheal Combitube 
ETI 
Endotracheal Intubation 
FDA 
Food and Drug Administration 
ICU 
Intensive Care Unit 

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IDE 
Investigational Drug Exemption 
IRB 
Institutional Review Board 
KLT 
King Laryngeal Tube 
LT 
Laryngeal Tube 
LTAC 
Long Term Acute Care Facility 
LVAD  
Left Ventricular Assist Device  
MRS 
Modified Rankin Score 
NHLBI 
National Heart, Lung, and Blood Institute 
NIH 
National Institutes of Health 
NMB 
Neuromuscular Blocking/Blockade  
NRB 
Non-Rebreather Mask 
OHCA 
Out-of-Hospital Cardiac Arrest 
PART 
Pragmatic Airway Resuscitation Trial 
PCI 
Percutaneous Coronary Intervention 
PI 
Principal Investigator 
PRIMED 
Prehospital Resuscitation IMpedance valve and Early vs Delayed analysis 
ROC 
Resuscitation Outcomes Consortium 
ROSC 
Return of Spontaneous Circulation 
RSI 
Rapid Sequence Intubation 
SGA 
Supraglottic Airway 
SMC 
Study Monitoring Committee 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TAH 
Total Artificial Heart 
TH 
Therapeutic Hypothermia 
TTM 
Targeted Temperature Management 
UAB 
University of Alabama  
US 
United States 
UW 
University of Washington 
 
 
 
 
 
 

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SUMMARY - Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac Arrest 
3.
(Pragmatic Airway Resuscitation Trial) 
Aim: The objective of this pragmatic trial is to compare the effectiveness of primary (initial) 
endotracheal intubation (ETI) versus primary (initial) laryngeal tube (LT) airway management 
strategies upon 72-hour survival after out-of-hospital cardiac arrest (OHCA).  
Rationale: Cardiopulmonary arrest is the sudden cessation of heart function and circulatory blood 
flow resulting in whole-body ischemia. Sudden out-of-hospital cardiopulmonary arrest (OHCA) is a 
major public health problem affecting over 300,000 adults in the United States each year, with 
only 1 in 10 of treated patients surviving.1 Successful OHCA resuscitation requires circulation of 
oxygen to injured organs such as the heart and brain. Airway management is the process of 
opening the mouth and throat to deliver oxygen to the lungs for circulation to the vital organs.  
Endotracheal intubation (ETI), the insertion of a plastic breathing tube through the mouth and into 
the trachea, is the most common advanced airway management technique in OHCA resuscitation 
in North America. As the first to provide critical care in the out-of-hospital setting, paramedics in 
North America have performed ETI on OHCA victims for over 30 years. Despite its routine use, 
ETI involves many pitfalls. Adverse events associated with ETI include unrecognized tube 
misplacement or dislodgement, repeated intubation attempts, iatrogenic hyperventilation, hypoxia 
and bradycardia, and unintended interruptions in cardiopulmonary resuscitation (CPR) chest 
compression continuity.2-7 In the US, resources for paramedic ETI training are often inadequate.8 
Individual clinical experience is also sparse; in Pennsylvania, paramedics perform a median of 
one (1) ETI annually.9  
Supraglottic airways (SGA) such as the Laryngeal Tube (King Systems, Noblesville, IN), 
Combitube (Covidien, Ltd, Mansfield, MA), Laryngeal Mask Airway (LMA North American, San 
Diego, CA) and i-Gel (Intersurgical, Inc., Liverpool, NY) are simpler than ETI yet ventilate as well. 
Because of the fewer pitfalls and training requirements, many paramedics favor primary SGA over 
ETI. However, it is unclear if outcomes are improved with primary SGA- versus ETI-based airway 
management strategies. The LT is the most common SGA used by EMS personnel in the United 
States.10  
Hypotheses: The primary null hypothesis is that 72-hour survival is similar between primary 
Laryngeal Tube (LT) SGA and primary ETI airway management strategies. Evaluated secondary 
outcomes will include return of spontaneous circulation, survival to hospital discharge, 
neurologically intact survival at hospital discharge, airway management performance, and clinical 
adverse events.  
Study Design: This trial will use a cluster randomized design with periodic crossover. 
Responding EMS personnel will perform airway management using either a strategy of primary 
ETI (control) or primary LT insertion (intervention). The trial will be designed to detect the 
superiority of either primary ETI or primary LT airway management over the other intervention 
arm. 
Study Population:  
- 
Inclusion Criteria: Adult (age ≥18 years or per local interpretation), non-traumatic OHCA with 
EMS personnel on scene and requiring advanced airway insertion (ETI, LT) or ventilatory 
support such as by bag-valve-mask device or non-rebreather mask.  

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- 
Exclusion Criteria: Known pregnant women, known prisoners, patients with major facial 
trauma, major bleeding or exsanguination, patients receiving initial care by non-PART 
participating EMS agency capable of performing ETI, LT or other advanced airway insertion, 
patients with ET tube, LT or other advanced airway insertion prior to ROC EMS arrival, 
patients with a pre-existing tracheostomy, obvious asphyxial cardiac arrest (choking or 
hanging), patients with a left ventricular assist device (LVAD) or total artificial heart (TAH), 
patients with pre-existing “do-not-attempt-resuscitation” (DNAR) orders, inter-facility 
transports, and patients with a “do not enroll” bracelet.  
Study Therapies:  
- 
1) Primary Endotracheal Intubation (Control): Advanced-level EMS personnel will use ETI 
as the primary (initial) advanced airway management intervention. Basic-level EMS 
personnel will use bag-valve-mask (BVM) ventilation only.  
- 
2) Primary Laryngeal Tube Supraglottic Airway Insertion (Intervention): Advanced-level 
EMS personnel will use the Laryngeal Tube (LT) as the primary (initial) advanced airway 
management intervention, and basic-level EMS personnel will use bag-valve-mask 
ventilation. If trained to use LT, basic-level EMS personnel may perform LT insertion as the 
primary (initial) airway intervention.  
EMS agencies that do not utilize LT will be excluded from the trial. All other aspects of 
resuscitation will follow local EMS protocols, including chest compression methods, timing of 
rhythm analysis, and insertion of intravenous lines and administration of medications. If allowed 
by local protocol, advanced and basic-level EMS personnel may use a non-rebreather (NRB) 
mask instead of BVM ventilation. 
Outcomes:  
The primary outcome will be:  
1) 72-hour hospital survival, defined as patient status (alive/dead) at 72 hours after the initial 
onset of cardiac arrest. 
Secondary outcomes will include:  
1) Return of Spontaneous Circulation (ROSC), defined as the presence of palpable pulses 
upon ED arrival.  
2) Airway Management Clinical Course, including sequence of ETI/LT insertion, ETI/LT 
insertion success and time, number of ETI/LT insertion attempts, and airway conversion 
(change of LT-to-ETI, or ETI-to-LT) in the receiving Emergency Department. 
3) Adverse Events, including initially unrecognized airway misplacement (including 
endotracheal tube misplacement), inadequate ventilation requiring airway exchange, 
vomiting, oropharyngeal, hypopharyngeal or gastrointestinal trauma, and pneumothorax.4,11  
4) Hospital Survival, defined as patient status (alive/dead) at hospital discharge. 

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5) Hospital Survival with Good Neurologic Function, defined as Modified Rankin Score ≤3 
upon hospital discharge.  
Analysis: We will calculate the difference in outcomes divided by the estimated “robust” standard 
error based on the Huber-White sandwich estimator in order to account for within cluster 
correlation and variability, which might depart from the classical assumptions.12 To quantify the 
treatment effect, we will calculate the 95% CI for the difference in event rates. We will perform the 
analysis on an intention-to-treat (primary analysis) as well as treatment-received bases 
(secondary analysis). 
Sample Size: The trial will require 2,612 subjects (1,306 per group) to have 85% power to detect 
a 4.5% absolute difference in 72-hour survival, given baseline survival of 13.7% and an overall 
two-sided alpha of 0.05. To allow for subject withdrawal and lost-to-follow-up, the trial will enroll 
up to 3,000 subjects. 
Regulatory and Ethical Considerations: The trial will be carried out under federal rules for 
Exception from Informed Consent (EFIC) outlined by the guidance document “Waiver of Informed 
Consent Requirements in Certain Emergency Research” (Federal Register, Vol. 61, pp. 51531-
51533, November 1, 1996 - http://www.gpo.gov/fdsys/pkg/FR-1996-10-02/html/96-24968.htm), 
OHRP “Basic HHS Policy for Protection of Human Research Subjects” (45 CFR 46.101(i) - 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.101), and FDA regulations 21 
CFR 50.24. 
 
 

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Study Objective 
4.
The objective of this pragmatic trial is to compare the effectiveness of primary ETI versus primary 
LT airway management strategies upon 72-hour survival after OHCA. 
 
Background 
5.
 
Conceptual Framework 
5.1
Out-of-Hospital Cardiac Arrest is a Major Public Health Problem. Cardiopulmonary arrest is 
the critical illness of whole-body ischemia resulting from sudden cessation of heart function and 
circulatory blood flow. Sudden out-of-hospital cardiopulmonary arrest (OHCA) is a major public 
health problem affecting over 300,000 adults in the United States each year.1 Despite organized 
international efforts, only about 1 in 10 survive after OHCA. New strategies are needed to improve 
rates of neurologically intact survival from this devastating condition.  
Airway Management is Important in Cardiac Arrest Treatment. Successful resuscitation from 
OHCA requires delivery of life-saving oxygen to injured organs such as the heart and brain. 
Airway management is the process of opening the mouth and throat to deliver oxygen to the 
lungs. In the cardiac arrest victim, the oxygen delivered to the lungs is subsequently circulated to 
the vital organs through cardiopulmonary resuscitation (CPR) chest compressions.  
Endotracheal Intubation is the Most Common Airway 
Management Technique. Basic techniques for airway 
management include “head-tilt/chin lift” and the jaw 
thrust. However, to optimize airway patency, rescuers 
usually opt for more advanced airway management 
techniques. In North America, endotracheal intubation 
(ETI) is the most common advanced airway 
management technique in both in-hospital and out-of-
hospital settings. (Figure 1) ETI (or “intubation”) involves 
exposure of the vocal cords using a large lighted metal 
laryngoscope blade inserted in the mouth and insertion 
of a plastic breathing tube through the throat, between 
the vocal cords and into the trachea. ETI is the preferred 
method for airway management because it provides a 
direct conduit to the lungs, facilitates easier and more 
controlled delivery of oxygen, and protects the lungs 
from aspiration of vomitus. ETI is a complex technique 
involving over 100 psychomotor steps and is usually performed only by physicians or specially 
trained healthcare providers.13 
Intubation is Standard of Paramedic Cardiac Arrest Care But Has Many Pitfalls. As the initial 
provider of critical care in the field, US paramedics have performed ETI on OHCA victims for over 
30 years.14-17 However, numerous studies highlight the pitfalls associated with paramedic ETI. For 
example, unrecognized misplacement of the endotracheal tube (in the esophagus rather than the 
trachea) has been reported in up to one-fourth of paramedic ETI.18 While the endotracheal tube 
should ideally be placed on the first attempt, in a large series of 1,271 OHCA, we found that one-
fourth of ETI efforts required two or more attempts.6 While select studies report paramedic ETI 
Figure 1 - Endotracheal Intubation 

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success rates >90%, using US national data we observed ETI success rates of only 70%.19 
Paramedic ETI may lead to subsequent iatrogenic hyperventilation, which decreases coronary  
blood flow during CPR.20-22  
ETI may result in CPR Interruptions. 
Interruptions in CPR chest compressions – 
including even brief 20-second interruptions – 
may disrupt coronary blood flow, impairing 
OHCA survival.23,24 Using state-of-the-art 
cardiac monitor technology, we were able to 
identify chest compression interruptions 
associated with intubation efforts by City of 
Pittsburgh paramedics.7 In this series of 100 
OHCA, ETI efforts resulted in a median of two 
(2) CPR interruptions (IQR 1-3; range 1-6), 
totaling a median of 109.5 seconds (IQR: 54-
198; range 13-446). One-fourth of the CPR 
interruptions exceeded three (3) minutes. 
(Figure 2) 
Paramedic Intubation Training and Experience are Inadequate. While ETI is complex, 
opportunities for baseline training and continuing experience are inadequate.9,25 Compared with 
the 35-200 ETI required for emergency medicine residents, anesthesiology residents and nurse 
anesthetist trainees, US paramedic students must perform only five (5) ETI prior to graduation.26-
32 While the customary setting for learning ETI is in 
the operating room training under the tutelage of 
anesthesiologists, students at most nationally 
accredited paramedic training programs receive only 
2-4 days of this training experience.8 Some training 
programs are not able to provide any operating room 
training. Mannequins do not adequately recreate the 
“feel” of live human airways. 
Regular clinical experience is important for 
maintaining ETI skill. Throughout Pennsylvania in 
2003, practicing paramedics performed a median of 
one (1) ETI (interquartile range 0-3) annually; 39% 
performed no ETI, and 67% performed fewer than 
two (2) ETI.33 In Maine, Burton, et al. found that only 
40% of paramedics attempted ETI annually, and only 
1-2% of all paramedics performed five (5) or more 
ETI annually.34  
 
Supraglottic Airways (SGA) - Simpler 
Alternatives to Intubation. Supraglottic airways 
(SGA) offer simpler alternatives to ETI. SGA in 
current North American EMS use include the 
Laryngeal Mask Airway (LMA), Combitube and King 
Laryngeal Tube.35,36 SGA are inserted “blindly” 
 
King Laryngeal Tube 
(LT) 
 
 
Esophageal-Tracheal 
Combitube (ETC) 
 
Laryngeal Mask 
Airway (LMA) 
 
 
 
i-Gel 
Figure 3 – Supraglottic Airways (SGA) 
Only the King Laryngeal Tube (LT) will be tested in 
this study. 
Figure 2 – Duration of CPR chest compression 
interruptions from paramedic intubation efforts. 
0
30
60
90 120 150 180 210 240 270 300 330 360 390 420 450
Duration (sec)
Sum
Subsequent
First

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through the mouth and sit outside of the vocal cords.37 (Figure 3) Compared with ETI, SGAs offer 
simple and expeditious operation, lower skill acquisition and maintenance thresholds, and similar 
ventilatory characteristics. While previously reserved for contingency use in the event of 
unsuccessful ETI efforts, many EMS agencies now perform advanced airway management using 
a strategy of primary SGA insertion.38 While there are no relevant national data available, we are 
aware of this practice in select communities, including Kalamazoo, Michigan; Chesterfield County, 
Virginia; Collier County, Florida; and Dallas, Texas. 
Observational Data Offer Unclear 
Guidance. SGA are more pragmatic 
than ETI and would be expected to 
result in similar or better outcomes 
after OHCA However, OHCA 
outcomes after SGA insertion are 
unclear. In a secondary analysis of 
data from the Resuscitation Outcomes 
Consortium PRIMED study, we 
studied 10,455 adult OHCA, including 
8,487 (81.2%) who received ETI and 
1,968 (18.8%) who received SGA.10 
Compared with SGA, ETI was 
independently associated with higher 
adjusted odds of return of 
spontaneous circulation, survival to 
discharge, and survival to discharge 
with good neurologic function, even 
after multivariable adjustment for 
confounders. (Figure 4) 
We performed a similar analysis using 
8,701 adult OHCA from the national Cardiac Arrest Registry to Enhance Survival (CARES), 
including 5,591 (64.3%) ETI and 3,110 (35.7%) SGA.39 We found similar results associating ETI 
with better outcomes than SGA, even after multivariable and propensity score adjustment and 
matching. Other observational studies have reported similar associations.40-43 
Need for a Randomized Trial. Important analytic limitations of prior observational airway studies 
include a) the influence of confounding-by-indication, and b) the absence of information on 
practitioner skill, device preference, EMS agency protocols, and perception of patient severity.10,39-
42,44 These uncertain results from observational studies highlight that a randomized trial is the best 
way to differentiate outcomes between airway management strategies involving primary ETI and 
primary SGA insertion.  
To date, the only clinical trials of out-of-hospital airway management have not focused on adult 
OHCA or the LT. Gauche, et al. randomized children to different paramedic airway studies but 
included a heterogeneous disease population.45 Bernard, et al. randomized intubation techniques 
but focused on traumatic brain injury.46 Frascone, et al. randomized out-of-hospital patients to ETI 
or LT, but the study focused on airway placement success rates, not patient outcomes.47 A recent 
pilot trial compared ETI with SGA use in adult OHCA, but the study occurred in the United 
Kingdom, which has different EMS protocols, practices and airway device preferences than in the 
US.48 
Figure 4 - Preliminary Data – OHCA outcomes for ETI vs. SGA. 
Data from secondary retrospective analysis of 10,455 OHCA from 
the ROC PRIMED trial.10 
0
1
2
Adjusted Odds Ratio (95% CI)
1.40 (1.04, 1.89)
1.74 (1.49, 2.04)
0.84 (0.61, 1.16)
1.78 (1.54, 2.04)
Survival to Hospital 
Discharge
with Satisfactory 
Functional Status
24-Hour Survival
Complications 
ROSC 
Favor ETI
Favor SGA

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Pertinent Existing Evidence on Endotracheal and Laryngeal Tubes  
6.
 
Animal 
6.1
There have been only limited evaluations of LT outcomes in animal models of cardiac arrest. The 
feasibility of LT use has been demonstrated in porcine and rabbit models.49,50  
Segal, et al. compared the effect of the ET tube, LT, Combitube and laryngeal mask airway (LMA) 
upon carotid blood flow in a porcine model of cardiac arrest.51 In this study, carotid blood flow was 
determined by Doppler imaging, with post-mortem arteriograms in select animals. The authors 
found that carotid blood flow was lower for all supraglottic airway devices than ETT; [King (median 
10 ml/min; IQR 6-41), LMA (10; 4-39), and Combitube (5; -0.4-15)] versus ETT (21; 14-46) 
(p<0.05 for each SGA compared with ETT). The study was not powered to evaluate ROSC or 
survival endpoints. 
 
Human 
6.2
 Observational Studies 
6.2.1
Several analyses of adult OHCA cohorts have compared outcomes between patients receiving 
ETI and those receiving other airway management techniques, including SGA devices.  
Fouche, et al. performed a meta-analysis comparing differences in survival between advanced 
airway devices and basic airway interventions.52,53 Compared with basic airway interventions, ETI 
and SGA insertion were associated with poorer longer-term outcomes. However, the meta-
analysis did not directly compare outcomes between ETI and SGA.  
Select observational studies have directly compared outcomes between adults OHCA receiving 
ETI and those SGA (including the LT). (Table 1) Of note, there have been no direct comparisons 
between ETI and LT. Furthermore, these studies have important limitations, including 
retrospective designs, limited data on airway management devices used or the course of care, 
incomplete risk adjustment and confounding by indication. A prospective study with random 
allocation is necessary to overcome the limitations of these observational studies.  
 
 
 
 
 
 
 

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Study 
Population 
Comparison 
Primary Findings 
Limitations 
Wang, et al., 
Resuscitation  
201310 
ROC Network 
N=10,455  
 
(8,487 ETI, 1,968 
SGA) 
ETI vs. SGA  
(LT, LMA, 
Combitube) 
ETI associated with increased 
survival to hospital discharge 
(adjusted OR 1.40; 95% CI: 1.04, 
1.89), ROSC (1.78; 1.54, 2.04) and 
24-h survival (1.74; 1.49, 2.04) 
than SGA. 
 
Did not segregate 
SGA subtypes 
 
Did not evaluate 
BVM-only 
 
Confounding by 
indication 
 
McMullan, et al., 
Resuscitation,  
201454 
CARES Network 
n=10,691  
 
(5,591 ETI, 3,110 
SGA, 1,929 
none/BVM) 
ETI vs. SGA  
(LT, LMA, 
Combitube) 
 
ETI vs. BVM 
ETI associated with higher 
sustained ROSC (adjusted OR 
1.35; 95% CI 1.19-1.54), survival to 
hospital admission (1.36; 1.19-
1.55), hospital survival (1.41; 1.14-
1.76) and hospital discharge with 
good neurologic outcome (1.44; 
1.10-1.88) than SGA. 
 
BVM associated with higher 
survival to hospital admission 
(1.31; 1.16-1.49), hospital survival 
(2.96; 2.50-3.51) and hospital 
discharge with good neurologic 
outcome (4.24; 3.46-5.20) than 
[ETI or SGA]. 
 
Did not segregate 
SGA subtypes 
 
Confounding by 
indication 
 
Hasegawa, et al., 
JAMA 201341 
All-Japan Utstein  
N=649,359  
 
(41,972 ETI, 
239,550 SGA, 
367,837 BVM) 
 
ETI vs. SGA 
vs. BVM 
One-month neurologically 
favorable survival lower for ETI 
(adjusted OR 0.41; 95% CI, 0.37-
0.45) and SGA (0.38; 0.36-0.40) 
than BVM. 
LMA most common 
SGA 
 
Limited experience 
with ETI. 
 
No direct comparison 
of ETI vs. SGA 
 
Confounding by 
indication 
 
Tanabe, et al. 
J Emerg Med  
201343 
All-Japan Utstein 
N=138,248 
 
(16,054 ETI, 
34,125 LMA, 
88,069 
Esophageal-
Obturator Airway 
[EOA])  
 
ETI vs. LMA 
vs. EOA 
One-month neurologically 
favorable lower for LMA (aOR 0.77; 
95% CI: 0.64-0.94) and EOA (0.81; 
0.68-0.96) than ETI. 
 
Limited experience 
with ETI 
 
Many EOA 
 
Confounding by 
indication 
 
Shin, et al., 
Resuscitation  
201255 
Korean national 
OHCA database 
N=5,278  
 
(250 ETI, 391 
LMA, 4,637 
BVM) 
ETI vs LMA vs. 
BVM 
Survival to hospital discharge 
similar for ETI vs BVM (aOR 1.00; 
0.60-1.66) but lower for LMA vs. 
BVM (0.52; 0.32-0.85). 
Very few ETI or LMA 
 
Confounding by 
indication 
 
Table 1 – Observational studies comparing ETI with SGA in adult OHCA. 

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 Randomized Controlled Trials 
6.2.2
There have been few out-of-hospital randomized controlled studies of ETI or the LT. There have 
been no randomized trials comparing the effect of ETI and LT upon patient outcomes in adult 
OHCA. 
Gausche, et al. conducted one of the few randomized controlled trials of out-of-hospital ETI.45 In 
this study of 830 children requiring airway management, paramedics altered treatment between 
BVM (control) or BVM+ETI (intervention). Randomization occurred in odd/even day format. There 
was no significant difference in survival between the BVM group (123/404 [30%]) and the ETI 
group (110/416 [26%]) (OR 0.82; 95% CI: 0.61-1.11) or in the rate of achieving a good 
neurological outcome (BVM, 92/404 [23%] vs ETI, 85/416 [20%]) (OR 0.87; 95% CI: 0.62-1.22). 
Frascone, et al. compared ETI and LT performance in a randomized series of 213 adults requiring 
airway management.47 Randomization was performed at the patient level using blinded airway 
management pouches. The overall placement success rate was virtually equal across the two 
groups (ETI=80.2%, King LT=80.5%; p=0.97). The median time to placement between ETI and 
the King LT was also not significantly different (ETI=19.5 seconds vs. King LTS-D=20.0 seconds; 
p=0.80). The study was strictly focused on airway insertion performance and did not evaluate 
patient outcomes.  
Benger, et al. have completed the pilot phase of a trial in the United Kingdom comparing ETI 
versus i-Gel and LMA insertion in adult OHCA.48 Randomization occurred by participating 
paramedic. From a total of 1,375 OHCA undergoing active resuscitation, 615 patients were 
enrolled (232 i-Gel, 174 LMA, 209 usual practice [ETI]). The LMA arm was suspended after 10 
months due to staff safety concerns (forceful expulsion of blood and/or stomach contents from the 
gastric port of the LMA).56 The rates of transport to hospital, return of spontaneous circulation and 
hospital admission did not differ (p=0.28, p=0.91 and p=0.58 respectively). Survival to discharge 
was: i-Gel 10.3%, LMA 8.0%, usual practice 9.1% (p=0.73) and to 90 days was: i-Gel 9.5%, LMA 
6.9%, usual practice 8.6% (p=0.65). Neurocognitive function and quality of life at 90 days were 
not significantly different. The study group will soon start a larger scale trial of n=9,000 adult 
OHCA to more definitively ascertain outcome differences between ETI and i-Gel. 
 
Existing EMS Airway Practices 
7.
Historically, US paramedics have favored ETI over 
SGA for airway management of adult OHCA. 
However, a shift in practice occurred in the US 
approximately 5 years ago, with multiple US EMS 
agencies switching to SGA as the primary device in 
OHCA resuscitation. Several ROC EMS agencies 
(including those affiliated with the Dallas, Pittsburgh, 
and Portland centers) currently utilize SGA as the 
primary airway management device in patients with 
OHCA. (Table 2)  
We have verified in extensive discussions with the 
ROC EMS Operations committee that paramedics are 
willing to randomize OHCA patients to ETI or LT. 
 
Supraglottic Airway Used by EMS Agency 
 
King Laryngeal Tube 
28
 
Combitube 
2
 
Laryngeal Mask Airway 
0
 
i-Gel 
3
 
Supraglottic Airway Used by  
 
Primary Airway Used in Cardiac Arrest 
 
Endotracheal Intubation 
22
 
Supraglottic Airway (paramedic discretion) 
5
 
Supraglottic Airway (paramedic protocol) 
2
  
Other 
4
 
Table 2 - Airway management practices  
of 33 US EMS Agencies  
in the Resuscitation Outcomes Consortium 

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Overview of Trial Design 
8.
This trial will use a cluster randomized 
controlled design with periodic 
crossover. Responding EMS personnel 
will perform advanced airway 
management using either primary ETI 
(control) or primary LT insertion 
(intervention). The trial will be designed 
to detect the superiority of either primary 
ETI or primary LT airway management 
over the other intervention arm. 
 
Inclusion Criteria 
9.
This trial will include subjects meeting 
all of the following conditions:  
a) Out-of-hospital cardiac arrest 
(OHCA); 
b) Adult (age ≥18 years or per local interpretation); 
c) Non-traumatic etiology; 
d) Initiation of ventilator support (e.g. Bag-valve-mask device or non-rebreather mask. 
The trial will include EMS-witnessed arrests. The trial will include individuals experiencing 
recurrent OHCA during the same care episode. 
If a patient receives bag-valve-mask ventilation but not ETI or SGA, the patient will be included in 
the study per intention-to-treat principles, regardless of whether the patient regains consciousness 
or remains comatose. If allowed by local protocol, EMS personnel may use a non-rebreather 
(NRB) mask instead of BVM ventilation; these patients will similarly be included in the study per 
intention-to-treat principles. 
 
Exclusion Criteria 
10.
This study will exclude the following subjects: 
Protected Populations 
a) Known pregnant women; 
b) Known prisoners; 
 
Trauma 
 
Figure 5 - Overview of Trial Protocol 
ETI = Endotracheal Intubation; SGA = Supraglottic Airway 
BVM = Bag-Valve-Mask Ventilation 
Endotracheal Intubation
Advanced EMS: ETI 
Basic EMS: BVM
Laryngeal Tube
Advanced EMS: LT
Basic EMS: BVM (or LT)
CONTINUE RESUSCITATION
Adult Out-of-Hospital 
Cardiac Arrest

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c) Major facial trauma (visible major deformity, copious oral bleeding, etc); 
d) Major bleeding or exsanguination (e.g., major upper or lower GI bleed, visceral perforation, 
major uncontrolled bleeding from laceration or injury); 
Pre-Existing Conditions or Prior Treatment 
e) Patient receiving initial care by a non-PART participating EMS agency capable of 
performing ETI, LT or other advanced airway management.  
f) Patients with ET tube, LT or other advanced airway device inserted prior to participating 
EMS agency arrival (e.g., inserted by healthcare facility personnel); 
g) Patients with a pre-existing tracheostomy; 
h) Obvious asphyxial cardiac arrest (e.g., choking, foreign body aspiration, angioedema, 
epiglottitis, trauma to mouth and face, etc.); 
i) 
Patients with a left ventricular assist device (LVAD) or total artificial heart (TAH); 
j) 
Patients with pre-existing written “do-not-attempt-resuscitation” (DNAR) orders; 
k) Inter-facility transports; 
Other Exclusions 
l) 
Patients with a “do not enroll” bracelet. 
 
Trial Setting  
11.
EMS agencies associated with US Regional 
Coordinating Centers of the Resuscitation 
Outcomes Consortium will be selected for 
participation in this trial. (Figure 6) Conditions for 
selection include: 
a) US EMS agency; 
b) Affiliation with US ROC Regional 
Coordinating Centers; 
c) Use of the King LT as the primary SGA; 
EMS agencies that do not utilize King LT SGA will 
be excluded from the trial. 
Per the requirements of the NIH/NHLBI award 
supporting this clinical trial (RFA-HL-14-019, 
http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-
 
Figure 6 
The Resuscitation Outcomes Consortium 
Only select US sites (Alabama, Dallas, Milwaukee, 
Oregon, Pittsburgh and San Diego)  
will participate in the trial. 
 
Dallas
Portland
Alabama
Seattle-King Co
San Diego
Toronto
Pittsburgh
Vancouver
Milwaukee
Data Coordinating
Center, Seattle
Ottawa
Memphis
Orange County

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14-019.html), which do not allow foreign components, only US EMS agencies will participate in 
the trial.  
Candidate EMS agencies will need to meet prequalification criteria to enter the enrollment phase of 
the trial. (Appendix 3) 
 
Interventions 
12.
 EMS Personnel Training Levels 
12.1
The interventions in this trial may involve coordination between advanced- and basic-level EMS 
personnel.57 
- 
Advanced-level EMS personnel (Advanced Life Support, ALS, paramedic, advanced care 
paramedic) perform advanced-level interventions, including intravenous drug administration, 
manual defibrillation, and advanced airway management interventions (ETI and SGA).  
- 
Basic-level EMS personnel (Basic Life Support, BLS, Emergency Medical Technician, EMT) 
perform basic measures such as CPR and automated defibrillation. Bag-valve-mask 
ventilation is their primary airway management intervention, although select EMS agencies 
may perform SGA (LT) insertion.58,59 In general, basic-level EMS personnel in the US do not 
perform ETI.  
EMS organization and response to OHCA vary across ROC. In some EMS agencies, all 
responding personnel are trained at the advanced level. In other agencies, OHCA care is tiered, 
with both basic-level and advanced-level 
EMS personnel responding to OHCA. 
Select BLS EMS personnel among ROC 
EMS agencies perform SGA insertion 
(Table 2). The trial design will try to 
accommodate all configurations of EMS 
response. 
 Primary Endotracheal Intubation 
12.2
(Control Arm) 
In this traditional model of OHCA airway 
management, advanced-level EMS 
personnel will use ETI as the primary 
(initial) airway management intervention. 
If the EMS agency is assigned to this 
arm, basic-level EMS personnel will use 
bag-valve-mask ventilation only even if 
they would normally use an LT.  
 ETI Device and Technique 
12.2.1
ETI involves placement of a flexible plastic breathing tube between the vocal cords and into the 
trachea. The customary approach to ETI is through the patient’s mouth (orotracheal intubation). 
The operator inserts a metal lighted blade (laryngoscope) into the patient’s mouth to displace the 
Figure 7 – Example of Endotracheal Tube 
(from http://commons.wikimedia.org/wiki/Image: 
Endotracheal_tube_inserted.png) 

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tongue and expose the vocal cords. The operator the places the ET tube directly through the 
vocal cords. (Figure 7) 
 ETI Techniques Permitted in the Trial 
12.2.2
Conventional orotracheal intubation is the preferred approach for the primary/initial intubation 
attempt. Orotracheal ETI is the most common approach in OHCA. EMS personnel may use video 
laryngoscopy for the primary/initial intubation attempt.  
Alternate approaches to ETI (for example, nasotracheal intubation, digital intubation) are less 
common in OHCA and will not be allowed for the initial intubation effort.  
If the EMS agency is assigned to the primary ETI arm, and an alternate ETI technique is used for 
the primary/initial intubation attempt, the case will be excluded from the study.  
If the EMS agency is assigned to the primary ETI arm, and if initial orotracheal ETI attempts are 
unsuccessful, the EMS agency may use alternate ETI techniques in a “rescue” capacity. 
  Primary Laryngeal Tube Insertion (Intervention Arm) 
12.3
In this test model of OHCA airway management, 
advanced-level EMS personnel will use LT as the 
primary (initial) airway management intervention. 
Basic-level EMS personnel will use bag-valve-mask 
ventilation. If trained to use LT, basic-level EMS 
personnel may perform LT insertion. 
 LT Device and Technique 
12.3.1
The LT is a novel airway device that is inserted 
blindly through the mouth. The device is designed 
so that the distal end sits in the proximal 
esophagus. A single port results in inflation of 
proximal (hypopharyngeal) and distal (esophageal) 
cuffs. Fenestrations between the cuffs allow 
insufflated air and oxygen to indirectly enter the 
tracheal. (Figure 8) 
King Systems is the manufacturer and distributor of 
LT airways in the United States. There are several 
such models, including reusable (autoclavable) 
models as well as models with an esophageal port. 
We expect that EMS agencies will use only the 
disposable models of the King LT (LT-D and LTS-
D). 
Use of the LT in adults with OHCA has been 
described in a range of studies.60-62  
 
 
Figure 8 – Examples of Laryngeal Tube  
http://www.ambuusa.com/usa/products/clinical_studi
es/king_lt%E2%84%A2.aspx 
 
http://theopsdeck.com/MEDKIT%20CONTENTS/PR
OD%20-%20AWY.King%20LTD.PMI.htm 
 

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 Limitation of the Trial Intervention Arm to the Laryngeal Tube 
12.3.2
Only LT use will be permitted in the intervention arm of this trial. Combitubes, LMAs, i-Gels or 
other supraglottic airway devices use will not be permitted in this study.  
In North America, the most common SGA in EMS use are the King Laryngeal Tube (King LT – 
King Systems, Noblesville, IN), Combitube (Covidien, Inc, Mansfield, MA), Laryngeal Mask Airway 
(LMA – LMA North America, San Diego, CA) and the i-Gel (Intersurgical, Inc., Wokingham, United 
Kingdom). In preparation for this trial, we have collected information on the airway management 
practices of 33 US EMS agencies that have actively participated in prior ROC OHCA trials and 
that indicated interested in participating in the trial. (Table 2) The vast majority utilize the King 
Laryngeal Tube. A small number of EMS agencies use the Combitube or i-Gel.  
The resource limitations of this trial do not allow for subset analysis of multiple SGA devices. 
Therefore, only the LT will be permitted in this study.  
EMS personnel may utilize other SGA devices 
on non-trial patients.  
 Research Procedures 
12.4
The airway interventions specified in this trial 
will be implemented by EMS personnel within 
the context of local Basic Life Support (BLS) 
and Advanced Cardiac Life Support (ACLS) 
protocols and practices. Customary BLS 
interventions include assessment of pulse, 
initiation of chest compressions, operation of 
automated external defibrillator, and opening 
and management of the airway. Customary 
ACLS interventions include assessment of 
pulse, initiation of chest compressions, 
assessment of cardiac rhythm, delivery of 
rescue defibrillation shocks, insertion of 
intravenous lines, administration of drugs, and 
opening and management of the airway. 
(Figure 9) While there is general unified 
approach to BLS and ACLS, some EMS 
agencies have implemented minor 
modifications. For example, while some 
agencies perform an immediate ECG rhythm 
check before initiating chest compressions, 
others first perform 1-2 minutes of chest 
compressions before ECG rhythm check. 
Some agencies delay insertion of airway 
device until after initiation of intravenous line 
and medications. 
This protocol does not dictate the timing or 
sequence of ETI or LT insertion. Basic- and 
 
Figure 9 - American Heart Association  
Algorithm for Adult Cardiac Life Support  
ETI or LT insertion may typically occur at boxes 6 and 10, 
“Consider advanced airway.”63 EMS agencies will follow 
local ACLS protocols. 

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advanced-level EMS personnel will perform airway management (ETI, LT or BVM) during 
resuscitation as guided by local protocol or practice. 
Upon arriving upon the scene of a potentially eligible subject, treating EMS personnel will initiate 
resuscitation measures per local BLS and ACLS protocol. Patient assessment, initiation and style 
of chest compressions, rhythm assessment, shock delivery, intravenous line insertion, and drug 
administration will be performed according to local protocol and practices. 
Simultaneously, EMS personnel will verify eligibility for the trial (i.e., satisfaction of inclusion 
criteria and absence of any exclusion criteria).  
At the point where they are ready to perform advanced airway insertion, EMS personnel will select 
the airway management technique to which they have been randomized (ETI or LT). EMS 
personnel will perform ETI or LT insertion using techniques consistent with local protocol.  
EMS personnel will verify successful and correct placement of the ET tube or LT according to 
local protocols. Customary methods for confirming tube placement including physical examination 
(chest rise), auscultation of chest for presence of breath sounds, auscultation of epigastrium for 
absence of gastric sounds, use of a bulb syringe detection, use of a colorimetric end-tidal carbon 
dioxide detector, and use of a waveform digital end-tidal carbon dioxide detector. 
EMS personnel will secure airway device in place per local protocol. Standard methods for 
securing the ET tube and LT airway include adhesive tape, umbilical “twill” tape and commercial 
tube holders.64,65  Of note, the LT cannot be secured using an ET tube commercial tube holder; 
rescuers should use adhesive tube or a tube holder designed for the larger diameter of the LT.  
After securing the airway device, EMS personnel will continue with standard resuscitation 
measures. Decisions for termination of resuscitation in the field or transporting to receiving 
Emergency Department are not dictated by this trial. 
Upon arrival at the receiving ED, resuscitation – including management of the airway – may 
continue according to local practices and protocol. Resuscitation efforts will continue until 
terminated by ED staff. If there is restoration of spontaneous circulation, post-arrest care will 
proceed according to local protocols and practice. 
 Protocol Considerations 
12.5
 Number of Airway Insertion Attempts 
12.5.1
Successful ETI or LT insertion may require multiple attempts. With “attempt” defined as passage 
of the laryngoscope blade into the mouth, Wang, et al. observed that first-attempt success for 
paramedic ETI of OHCA was 70%, with up to four attempts needed to reach the 90% success 
threshold.6 EMS practitioners generally try to minimize the number of ETI attempts because of the 
propensity of oral injury and because multiple attempts may signal ETI futility and the need to 
proceed to alternate airway management techniques. In clinical practice, some EMS protocols 
limit practitioners to 3, 2 or even 1 unsuccessful ETI attempt before proceeding to alternate 
“rescue” airway measures.  
This trial will not dictate or limit the number of ET tube or LT insertion attempts. However, we will 
monitor the number of insertion attempts for each device. Training for the trial will emphasize a) 

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definition of “ETI attempt” as insertion of laryngoscope between the teeth (not insertion of ET 
tube), b) definition of “LT attempt” as insertion of LT airway between the teeth, c) methods for 
reporting the number of attempts for each airway device, and d) strategies for minimizing ETI or 
LT insertion attempts. 
 Unsuccessful Airway Insertion and Rescue Interventions 
12.5.2
An important metric in this study is the rate of unsuccessful ETI or LT insertion and the need for 
rescue airway interventions. While success rates for OHCA ETI and SGA insertion in OHCA are 
relatively high (approximately 90%), the time-critical nature of OHCA requires that rescue airway 
interventions be initiated promptly.66,67 Clinical signs of airway insertion or ventilation failure 
include the inability to place the airway, inability to confirm proper airway device placement, 
detectable air leak on insufflation resulting in suboptimal chest rise.  
In the event that EMS personnel are not able to insert or ventilate through the assigned airway, 
they may revert to any alternate airway management strategy. For example, if the patient is 
assigned to ETI but intubation efforts are unsuccessful, EMS personnel may revert to bag-valve-
mask ventilation or LT insertion. Conversely, if the patient is assigned to LT but insertion efforts 
are unsuccessful, EMS personnel may revert to bag-valve-mask ventilation or ETI. In all cases, 
subjects will be analyzed by their assigned treatment, per intention-to-treat principles.  
While select EMS agencies may carry additional SGA other than the LT, during training we will 
encourage the use of LT as the preferred rescue device in the event of unsuccessful ETI. 
Alternate intubation techniques (nasotracheal intubation, digital intubation, etc.) may be used in a 
rescue capacity in the event of failed initial orotracheal intubation or LT insertion. 
Some EMS agencies perform needle jet ventilation or open cricothyroidotomy. This trial does not 
preclude the use of these techniques in the event of unsuccessful initial airway insertion.  
 Confirmation of Airway Placement 
12.5.3
An important adverse event of ETI is initially unrecognized misplacement of the ET tube, including 
unrecognized placement in the esophagus or hypopharynx. Unrecognized misplacement of the 
ET tube may result in suboptimal delivery of oxygen to the lungs. National consensus guidelines 
recommend the use of multiple techniques for conforming proper ET tube placement, including 
auscultation of lungs (for presence of breath sounds) and epigastrium (for absence of gastric 
sounds), use of an esophageal detector device (bulb detector device), use of a colorimetric end 
tidal carbon dioxide detector, or use of a digital or waveform end-tidal carbon dioxide detector.68 
ET tube misplacement may impact the apparent effectiveness of the ETI arm. Therefore, this trial 
will monitor the techniques used for verifying ET tube placement.  
While this trial will not dictate ET tube placement confirmation techniques, best practices for 
verifying tube placement will be emphasized during training. We will similarly encourage receiving 
EDs to use best practices when verifying the proper placement of an EMS placed ET tube. 
Airway misplacement is less of a concern for the LT because the device is intended to be placed 
in the esophagus. Because of the design of the LT, it is highly unusual for the device to be placed 
intratracheally. There are no national guidelines for verifying proper LT placement.  

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 Use of Neuromuscular Blocking Agents 
12.5.4
The use of neuromuscular blocking (NMB) agents to facilitate ETI is termed “Rapid Sequence 
Intubation” (RSI). Most OHCA patients are flaccid and do not require RSI. On rare occasion, an 
OHCA patient may develop trismus, requiring the use of RSI. RSI is technique reserved for a very 
small subset of specially trained paramedics. Of the ground EMS agencies in ROC that will 
participate in the trial, few use RSI. Also, an air medical crew capable of performing RSI may be 
present on scene of an OHCA.  
Subjects receiving NMB (RSI) prior to (or during) ETI or LT insertion efforts will be examined in 
separate subgroup analyses.  
Subjects receiving NMB agents after successful airway insertion will not be examined separately. 
 Absence of a Bag-Valve-Mask-Only Arm 
12.5.5
This trial will not have a BVM-only arm. Some prior observational studies suggested higher 
survival with BVM-only vs ETI or SGA techniques.41 However, many practitioners and community 
individuals perceive a need to provide some form of ventilatory support in OHCA. In our 
preparation for this trial, ROC EMS personnel indicated discomfort with a BVM-only arm. 
Furthermore the resource constraints of this pragmatic trial preclude the recruitment of an 
adequate number of subjects to have sufficient power to detect clinically important differences in a 
three arm trial. 
 Emergency Department Management of the EMS Airway Device 
12.5.6
Most trial patients will be transported to a receiving ED for continued resuscitation care. There are 
currently no clinical practice guidelines for the ED management of an EMS-placed ET tube or 
SGA. In general, ED practitioners will verify placement of the EMS ET tube, although practices 
vary widely. If the ET tube is determined to be misplaced or insufficiently ventilating, ED 
physicians may opt to remove and replace the tube.  
With SGA such as the LT, ED practices similarly vary, with some practitioners leaving the airway 
in place for the duration of resuscitation and others opting for immediate replacement with ETI. 
There are no national practice guidelines for the ED management of an EMS-placed SGA, 
although select textbook chapters offer practical guidance.69 
In practical terms, if the EMS-placed LT is functioning well, ED practitioners may continue using 
the device, deferring ETI until there is restoration of pulses. In contrast, if there is evidence that 
the LT is malfunctioning, immediate replacement with ETI or another SGA may be indicated. 
Replacement of the LT with ETI may occur with a variety of approaches including exchange over 
a gum elastic bougie (Eschman tube), bronchoscopic replacement over an Aintree catheter, or 
removal and ETI using direct laryngoscopy. 
The pragmatic scope of this trial will focus on out-of-hospital EMS management of the airway. 
This trial will not dictate practices for ED management of EMS-placed airways. However, in 
preparation for the trial we will provide receiving ED with guidelines on best practices for the 
management of EMS-placed airways. The guidelines will outline strategies for: 

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- 
ED verification of EMS-placed ET tubes, including the use of at least two confirmatory 
techniques as well as the use of end-tidal carbon dioxide detection.  
- 
Decision points for immediate replacement of an EMS ET tube.  
- 
Management of EMS-placed LT airways, including methods and decision points for 
continued use or replacement with an ET tube.  
 EMS Personnel Airway Management Experience 
12.5.7
Studies highlight that EMS personnel experience may influence the course and outcomes of 
airway management efforts. For example, using Pennsylvania statewide EMS data we have found 
that paramedic ETI experience is associated with increased patient survival.70 As described 
previously, opportunities for EMS airway training are limited, and paramedics in some practice 
settings perform few clinical ETI.33,34 
The evaluation of paramedic airway management experience and its influence on OHCA 
outcomes is beyond the scope of this study. This study will not track the number of airway 
procedures performed by individual EMS personnel.  
 Post-Arrest Care 
12.5.8
This study will not dictate elements of post-arrest care. Receiving hospitals will provide post-arrest 
care according to local protocols and practices.  
Case-control studies have evaluated the effectiveness of combinations of hospital-based 
treatments in patients resuscitated from cardiac arrest in a variety of settings.61,71-75 All have 
reported improved outcomes when compared with historical controls. Collectively, these studies 
demonstrate that hospital-based care of those resuscitated from OHCA impacts patient outcomes 
and potentially modifies the effect of prehospital interventions for cardiac arrest. Thus experts have 
recommended a standardized approach to try to achieve optimal outcomes after resuscitation from 
cardiac arrest.76  
This pragmatic trial is not focused upon elements of post-arrest care. Given the random treatment 
assignment, we expect to see an equal distribution of post-arrest care practices in each study 
arm.  
The trial will monitor the provision of key post-arrest care elements: 
- 
Therapeutic Hypothermia (TH) and Targeted Temperature Management (TTM) – TH 
and TTM refer to the active reduction and/or control of body temperature. In the context of 
OHCA, TH/TTM is intended to improve outcomes through the prevention of cellular level 
organ damage, especially of the brain. Two randomized trials have demonstrated the safety 
and effectiveness of mild TH/TTM) via external cooling methods in comatose survivors of 
adult VF OHCA.77,78 Another recent trial demonstrated no difference in survival or favorable 
neurologic status between TTM strategies using 33°C and 36°C as targeted body temperatures.79 
We will monitor the use of TH/TTM among enrolled subjects. We will define TH/TTM as a) any 
active attempt to lower and/or control body temperature ≤36˚C, b) continuation of temperature 
control efforts for at least 12 hours, and c) whether a minimum temperature <34°C is 

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achieved. Each of these three factors was associated with survival in a post hoc analysis of 
patients enrolled in the ROC PRIMED trials. 
- 
Percutaneous Coronary Intervention (PCI) – Up to 71% of patients with cardiac arrest 
have coronary artery disease, and nearly half have an acute coronary occlusion.80-82 There is 
a high incidence (97%) of coronary artery disease in patients resuscitated from OHCA who 
undergo immediate angiography and a 50% incidence of acute coronary occlusion.81 We will 
monitor early use of PCI within 6 hours of the initial 
OHCA resuscitation. We will monitor the use of both 
coronary angiography as well as interventions (e.g., 
coronary artery stenting). 
- 
Withdrawal of Care – Reliable prognostic factors 
are established after post-arrest day three, but an 
analysis of observational data from an in-hospital 
cardiac arrest registry demonstrated that the 
majority of declarations of do not attempt 
resuscitation (DNAR) status or withdrawal of life-
supporting therapies occur prematurely.83 In the 
ROC PRIMED Trial, the timing of withdrawal-of-
care varied. (Figure 10) We will monitor the 
assignment and timing of physician order for ‘do not 
resuscitate’ status or withdrawal of care.  
 
Random Allocation and Blinding 
13.
 Random Allocation Method 
13.1
The airway intervention will be cluster randomized at the EMS agency level with periodic 
crossover. Each site will be subdivided into multiple clusters by EMS agency, station, or other unit 
as appropriate to the site’s EMS structure. Each cluster will be scheduled to crossover to the 
opposite treatment – typically once or twice per year during the trial. The use of crossovers is 
efficient and minimizes unbalanced treatment assignment.  
If more than one participating EMS agency is present on scene, the first arriving unit will 
determine the study treatment assignment. If a non-ROC EMS agency arrives first on scene, the 
subsequent first arriving ROC EMS agency will perform airway management as randomized.  
The randomization of clusters will be stratified by site. Within each site, clusters will be organized 
into relatively homogeneous groups with respect to the number of patients expected to be treated 
over the course of the study in that cluster. All clusters will crossover between intervention 
assignments at least once (i.e., have at least two distinct treatment periods). If necessary, some 
clusters with high episode rates will crossover more than once.  
Random assignment of treatment sequence will be performed by the coordinating center prior to 
the start of the study.  
 
Figure 10 - Timing of  
Withdrawal-of-Care  
in the ROC PRIMED Study 

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 Rationale for Cluster Randomization 
13.2
The clustered design with crossover is the most feasible, efficient and practical design in this 
study. In our protocol development efforts, ROC EMS personnel clearly indicated a preference for 
the cluster-crossover approach. ROC EMS agencies have had extensive experience with this 
approach in the prior PRIMED and CPR Feedback trials, and the ongoing CCC OHCA trial.84-86  
Randomization by event would add unacceptable complexity for EMS providers who already must 
deal with the need for immediate therapy in OHCA. Event level randomization requires the 
preparation of treatment envelopes (potentially biased) or blinded airway equipment pouches, 
which is neither feasible nor practical given the range of different airway equipment used by EMS. 
Randomization by telemetry is not feasible due to the time-critical nature of OHCA and airway 
management and the varying systems of on-line EMS medical command throughout ROC. While 
the Gausche, et al. trial utilized alternate day randomization (odd day=BVM, even day=BVM±ETI), 
ROC EMS personnel believed that this approach would be difficult and prone to protocol 
violation.45 The ongoing UK airway trial led by Benger, et al. is randomizing subjects by 
paramedic.48 This strategy may result in selection bias and can be problematic if multiple study 
paramedics (each assigned to different arms) are delivering care. 
 Blinding of Treatment Assignment  
13.3
This trial will use cluster randomization techniques. Furthermore, the type of airway device used 
by EMS personnel cannot be concealed. Therefore, blinding of the random assignment is not 
possible.  
 
Outcomes 
14.
 Primary Outcome 
14.1
 72-Hour Survival 
14.1.1
The primary outcome of the trial is 72-hour hospital survival, defined as patient status 
(alive/dead) at 72 hours after the initial onset of cardiac arrest.  
While studies of OHCA are traditionally designed to evaluate neurologically-intact survival to 
hospital discharge, the use of 72-hour survival as the primary outcome is consistent with the 
pragmatic focus of this trial:88 
- 
Pragmatic Focus and Interpretation – A pragmatic trial focuses on real-world clinical 
endpoints, with less attention paid to secondary, explanatory or mechanistic endpoints. 
Some EMS and hospital practitioners believe that out-of-hospital interventions have more 
plausible connections with proximal outcomes (such as 72-hour survival) rather than later 
outcomes (such as neurologically intact survival to hospital discharge).  
- 
Sample Size – The use of 72-hour survival requires far fewer subjects than more distal 
outcomes such as neurologically-intact survival to hospital discharge (<3,000 vs. >18,000  

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- 
subjects). A larger targeted enrollment is 
not feasible given the resource limitations 
for this trial. 
- 
Associations at 72 hours are expected 
to be similar to those observed at later 
time points – In a prior study of 1,496 
adult OHCA in Pittsburgh, we observed 
that the vast majority of OHCA deaths 
(90.6%) occurred within three days.87 
(Figure 11) In our post hoc analysis of 
airway management practices in the 
ROC PRIMED trials, associations 
between 24-hour survival and airway type 
(ETI or SGA) persisted for neurologically 
intact survival to hospital discharge. 
(Figure 4) 
- 
Accommodates therapeutic 
hypothermia and care withdrawal window – A commonly assessed outcome in OHCA is 
24-hour survival. In this trial we have extended this window to 72 hours because many 
OHCA patients receive therapeutic hypothermia, a process that requires 48-72 hours.89 
Also, national guidelines for cardiac arrest care suggest that withdraw of care should not be 
considered until at least 72 hours after the initial cardiac arrest event.90  
 Secondary Outcomes 
14.2
Secondary trial outcomes will include: 
 Return of Spontaneous Circulation  
14.2.1
ROSC will be defined as the presence of palpable pulses upon ED arrival.  
 Airway Management Course  
14.2.2
To characterize the course of airway 
management, this study will collect a limited 
number of airway management variables. 
- 
Sequence and success of ETI/LT 
insertion attempts. EMS personnel 
will report the sequence and success of 
airway devices insertion efforts. 
Potential airway intervention 
combinations are summarized in Table 
2.  
- 
Number of airway insertion 
attempts. For each subject, EMS 
personnel will separately report the 
Figure 11 - Survival curve of 1,496 adult OHCA 
(Pittsburgh, PA).  
Most (90.6%) deaths occurred within  
3 days (72 hours) of the cardiac arrest event.87 
First  
(Randomly 
Assigned)  
Airway 
Intervention 
Second 
“Rescue”  
Airway 
Intervention 
(if first 
unsuccessful) 
Third “Rescue”  
Airway 
Intervention 
(if second 
unsuccessful) 
 
ETI 
LT 
 
ETI 
LT 
BVM 
Other Airway 
(including 
alternate ETI 
techniques) 
 
 
BVM 
Other Airway 
(including 
alternate ETI 
techniques) 
 
Table 2 – Potential EMS Airway Intervention 
Combinations 
 

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number of ETI attempts (successful or unsuccessful) and number of LT attempts (successful 
or unsuccessful). 
- 
Successful airway insertion time. EMS personnel will report the time of successful ETI or 
LT insertion. 
- 
Airway course in receiving Emergency Department. The purpose of these data is to 
ascertain how the receiving ED utilizes airway devices placed by EMS personnel. Research 
coordinators will review ED records to determine the course of airway management during 
initial ED resuscitation. For cases arriving at the ED with ongoing CPR, this time period 
encompasses the time elapsed until the 
achievement of ED ROSC. For cases 
arriving at the ED with ROSC, this time 
period encompasses the first 20 
minutes in the ED.  
These data do not pertain to airway 
interventions performed after the 
achievement of ROSC (for those 
arriving with ongoing CPR) or after the 
first 20 minutes in the ED (for those 
arriving at the ED with ROSC). 
Potential EMS/ED airway interventions 
are summarized in Table 3. 
 Survival to Hospital Discharge  
14.2.3
While this study is not designed to evaluate associations with survival to hospital discharge, we 
will nonetheless monitor and assess this outcome. 
 Neurologically-Intact Survival to Hospital Discharge 
14.2.4
While this study is not intended to have adequate power to detect associations with 
neurologically-intact survival to hospital discharge, we will nonetheless monitor and assess this 
outcome. MRS has concurrent validity with other measures of neurological recovery after stroke 
and brain injury.91,92 MRS has been previously used in a cohort of neurosurgical patients with in-
hospital cardiac arrest,93 a cohort of survivors of OHCA,94 and a cohort of survivors of arrest in 
either setting.95 
Neurologic status at discharge will be assessed using the modified Rankin Score (MRS), which 
can be determined through medical record review.96,97 The MRS uses a seven-point ordinal scale; 
0 (no symptoms at all) to 6 (death). Patients who die before discharge will be assigned an MRS of 
6. For analytic purposes, MRS at discharge is often dichotomized to MRS ≤3 (“good”) vs. 4-6 
(“poor”).98,99  
 Adverse Events 
14.3
The trial will identify a range of out-of-hospital and in-hospital adverse events information to help 
assess the safety of the interventions.  
EMS Airway 
Intervention  
on ED Arrival 
ED Airway Intervention 
ETI 
LT 
BVM 
Other Airway 
Continue use of EMS airway 
Replace with ED ETI 
Replace with other ED airway 
 
Table 3 – Potential Emergency Department  
Airway Interventions 

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 Unexpected Adverse Events (UAE) 
14.3.1
These will be defined as any serious unexpected adverse effect on health or safety or any 
unexpected life-threatening problem caused by, or associated with the interventions if that effect or 
problem was not previously identified in nature, severity, or degree of incidence in the investigation 
plan or application (including a supplementary plan or application), or any other unexpected 
serious problem that relates to the rights, safety or welfare of subjects. The death or neurological 
impairment of an individual patient is not considered an unexpected adverse event in this study. 
 Expected Adverse Events 
14.3.2
The following are events commonly observed in patients who experience cardiac arrest or 
resuscitative efforts after its onset, or who receive airway management efforts, and may or may not 
be attributable to specific resuscitation therapies.4,11,100-108 These events will be monitored and 
reported but not considered as adverse events of the study intervention.  
- 
Unsuccessful EMS airway insertion. This event includes unsuccessful EMS ETI or LT 
insertion efforts. This event does not include ED airway insertion efforts. This event will be 
determined from EMS records. 
- 
Multiple EMS airway insertion attempts. This event includes 3 or more EMS attempts to 
perform ETI, or 3 or more EMS attempts to insert the LT. This event does not include ED 
airway management efforts. This event will be determined from EMS records. 
- 
Unrecognized EMS airway misplacement or dislodgement. This event includes 
unrecognized EMS endotracheal tube placement in the esophagus or hypopharynx, or 
displacement of a correctly placed ET tube. Airway misplacement and dislodgements are 
difficult to differentiate; this trial will not differentiate these events. Airway 
misplacement/dislodgement events will be determined from EMS and ED records. 
This event does not include right mainstem intubations. This event does not include 
instances where EMS personnel immediately recognize and correct ET tube misplacement. 
This event does not include ED airway misplacements.  
Misplacement and dislodgement events are unique to ETI and do not apply to the LT. 
- 
Inadequate EMS ventilation. This event includes instances where EMS personnel a) 
perceive that a successfully inserted airway device is resulting in inadequate ventilation and 
b) therefore opt to change to another airway management device or technique. Inadequate 
ventilation connotes a) inability to insufflate any oxygen (airway obstruction) or b) 
inadequate chest rise on insufflation. Potential reasons for inadequate ventilation may 
include device obstruction, misplacement, malfunction or cuff leak, among others.  
Inadequate ventilation will be based upon EMS personnel assessment, and will be 
determined from EMS patient care records.  
- 
Airway swelling or edema. A described complication of the LT is the development of major 
tongue, pharyngeal or hypopharyngeal swelling, which may interfere with ventilation.109 
While usually associated with instances of prolonged LT ventilation (several hours), some 
clinicians have reported the occurrence of this event during resuscitative efforts. This event 

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will be based upon EMS and ED personnel assessment and will be determined from EMS 
and ED patient care records. The timeframe for surveillance for this event will be limited to 
the earlier of a) replacement of the LT with an ET tube, or b) the first 24 hours of 
hospitalization. While generally associated with LT insertion, we will monitor the occurrence 
of airway swelling or edema regardless of inserted airway device.  
- 
Oropharyngeal or hypopharyngeal injury. Advanced airway insertion may result in injury 
to the oropharynx and hypopharynx, including soft tissue lacerations, injury to teeth, and 
perforation of pharyngeal, hypopharyngeal or other anatomic structures, among others. This 
event will be determined by review of the discharge summary and ED physician records and 
will be limited to injuries identified during the first 24 hours of hospitalization. 
- 
Pneumothorax. Airway insertion and ventilatory efforts may cause pulmonary barotrauma, 
resulting in pneumothorax. This event will be determined from radiology or ED physician 
interpretation of the first chest x-ray or computed tomography (CT) performed in the ED.  
- 
Pneumonia and aspiration pneumonitis. Pneumonia and aspiration pneumonitis are 
known sequelae of cardiac arrest and airway management. This event will be defined as the 
presence of an infiltrate or consolidation as reported by radiology interpretation of chest x-
rays or computed tomography (CT) performed during the first 72 hours of hospitalization.  
 Other Data 
14.4
Additional data will be collected from the out-of-hospital, Emergency Department and hospital 
care phases.  
 CPR Process Data 
14.4.1
All participating ROC EMS units have automated external defibrillators (AED) and/or manual 
monitor/defibrillators capable of monitoring individual components of CPR process; for example, 
the delivery of individual chest compressions, chest compression rate, interruptions, and fraction, 
and (in select cases) chest compression depth. Currently, all CPR process data files are uploaded 
to the UW CTC. While this archiving process will continue during the study (in order to allow for 
rhythm audits), CPR process data analysis will not be part of this trial. However, additional grants 
may provide funding for the review of the electronic ECG, entry of data into the database, analysis 
of CPR process data and selected audits.  
 Other Explanatory Mechanisms 
14.4.2
Physiologic mechanisms hypothesized to influence OHCA outcomes after paramedic airway 
management include CPR interruptions, hyperventilation, and carotid artery impingement.7,20,21,51 
This trial focuses on pragmatic outcomes and will not examine these mechanisms.  

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Analysis Plan 
15.
 CONSORT Diagram 
15.1
Figure 12 provides the anticipated 
CONSORT Diagram for the trial. The 
trial will exclude OHCA that do not meet 
inclusion criteria, as well as those who 
do not require ventilatory support. The 
remaining subjects will be enrolled and 
randomized in the trial. 
 Intention-to-Treat vs As-Treated 
15.2
The intention-to-treat comparison will 
include the two treatment arms: 
primary-ETI and primary-LT. Where 
allowed by local protocol, the primary-
LT arm will allow for BLS LT insertion.  
The as-treated comparison will 
encompass the initial advanced airway 
technique received by the subject, 
whether the airway insertion is 
successful or unsuccessful. Practically, 
this will account for situations where 
randomization is violated; for example, 
use of the ETI when the patient is randomized to primary-LT, or BLS rescuer use of LT when the 
patient is assigned to primary-ETI (and hence BLS BVM). In cases where rescuers use only BVM 
(without resorting to ETI or LT insertion), this will not be considered a protocol violation, and the 
subject will be retained in the assigned randomization. In cases where rescuers use a different 
technique as the initial airway intervention (other than ETI or LT), the subject will be excluded 
from the as-treated analysis.  
While this trial focuses on two airway management strategies (primary-ETI and primary-LT), in 
execution the course of airway management may encompass other airway management 
endpoints, including BVM ventilation, use of ETI other than orotracheal technique, use of a SG 
other than LT, or use of an another airway management technique (for example, 
cricothyroidotomy). Also, airway insertion efforts may prove unsuccessful, necessitating the use of 
alternate airway techniques. Therefore, a second as-treated comparison will consider the final 
result of EMS airway management efforts: a) ETI, b) LT, c) BVM, and d) other airway technique.  
 Primary Analysis – 72-Hour Survival 
15.3
The primary hypothesis is that there is no difference in OHCA 72-hour survival between primary 
LT- and primary-ETI airway management strategies. The primary outcome of interest is 72-hour 
survival. We will calculate the difference in outcomes divided by the estimated “robust” standard 
error based on the Huber-White sandwich estimator in order to account for within cluster 
correlation and variability, which might depart from the classical assumptions.12 To quantify the 
treatment effect, we will calculate the 95% CI for the difference in event rates. Since 
 
 
Figure 12 - Anticipated CONSORT Diagram 
Randomized to Primary-ETI 
(n=___)
ALS ETI (n=___)
BLS BVM + ALS ETI (n=___)
Randomized to Primary-LT 
(n=___)
ALS LT (n=___)
BLS LT (n=___)
BLS BVM + ALS LT (n=___)
Adult Out-of-Hospital 
Cardiac Arrest (n=___)
Requires Ventilatory
Support (n=___)
As-Treated:
ALS ETI (n=____)
ALS LT (n=____)
BLS LT (n=___)
BLS BVM + ALS ETI (n=___)
BLS BVM + ALS LT (n=___)
BLS LT + ALS ETI (n=___)
BVM only (n=____)
Other airway (n=____)
Exclusions (N=___):
Pregnant, prisoner, 
traumatic, asphyxia, inter-facility 
transport, pre-existing ETI or LT, 
pre-existing tracheostomy, etc.
As-Treated Analysis
(Initial Attempted ETI)
(n=___):
ALS ETI (n=___)
BLS BVM + ALS ETI (n=___)
As-Treated Analysis 
(Initial Attempted LT)
(n=___):
ALS LT (n=___)
BLS LT (n=___)
BLS BVM + ALS LT (n=___)
As-Treated:
ALS ETI (n=____)
ALS LT (n=____)
BLS LT (n=___)
BLS BVM + ALS ETI (n=___)
BLS BVM + ALS LT (n=___)
BLS LT + ALS ETI (n=___)
BVM only (n=____)
Other airway (n=____)

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randomization includes all eligible OHCA patients, we will not stratify the primary analysis by initial 
cardiac rhythm. We will perform the analysis on intention-to-treat (primary) as well as as-treated 
(secondary) bases.  
 Secondary Analyses 
15.4
In a similar manner, we will also study associations between the trial interventions and the 
secondary outcomes detailed in Section 14.2, including return of spontaneous circulation, airway 
management course, adverse events, hospital survival, and hospital survival with good neurologic 
function. 
 Subgroup Analyses 
15.5
OHCA outcomes are known to vary for different patient subsets. For example, OHCA survival is 
approximately 28.4% for patients with an initial “shockable” cardiac rhythms (ventricular fibrillation 
or tachycardia) and 6.2% for non-shockable rhythms (pulseless electrical activity and asystole). 
We will explore multiplicative associations between airway management strategy (ETI vs. LT) and 
the pertinent subgroups, including:  
- 
Initial cardiac rhythm (shockable vs. non-shockable); 
- 
Bystander witnessed arrest (yes vs. no); 
- 
EMS response time (911 call to arrival on-scene: <10 vs. ≥10 mins);  
- 
BLS unit capability of performing LT insertion (yes vs. no); 
- 
Time of airway placement after rescuer arrival on-scene (early [<10 minutes] vs. later [≥10 
minutes]);  
- 
Use of NMB (RSI) before or during airway insertion efforts (yes vs no); 
- 
Age (<65 vs. ≥65 years). 
- 
Placement of advanced airway after ROSC. 
- 
Initial airway management with non-rebreather mask only (passive ventilation). 
Initial airway management with video laryngoscopy. If 
an [airway x subgroup] interaction is statistically 
significant, we will stratify the analysis by the 
subgroup.  
 
Sample Size 
16.
 Sample Size Estimate 
16.1
The sample size estimate is based upon the primary 
outcome of 72-hour survival. Table 4 provides total 
sample size requirements to detect effect differences 
 
Statistical Power (1-β) 
Effect Size 
(Absolute 
Difference) 
80% 
85% 
90% 
4.0% 
2,856 
3,266 
3,892 
4.5% 
2,284 
2,612 
3,112 
5.0% 
1,872 
2,142 
2,550 
Table 4 - Sample Size Estimates  
Effect sizes based upon 13.7% baseline 72-hour 
survival. 

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in 72-hour survival after OHCA, with an overall significance level (adjusted for interim analyses) of 
0.05 and accommodating up to a 5% loss of precision due to cluster randomization (with 
crossover).  
The estimated effect sizes are based upon observations from the ROC PRIMED Trial. In ROC 
PRIMED, baseline 72-hour survival was 13.7%. There was a 5.0% absolute difference in 72-hour 
survival between ETI (13.7%) and SGA (8.7%). To account for potential confounders, for this trial 
we will use a more conservative figure of 4.5% to represent a minimal clinically significant 
difference. We designed the trial to have 85% power to detect this difference. Therefore, the 
required minimum sample size is 2,612 subjects (1,306 per group). To allow for subject 
withdrawal and loss to follow-up, we have budgeted to enroll up to a total of 3,000 subjects.  
The participating US ROC sites (Alabama, Dallas, Milwaukee, Pittsburgh, Portland and San 
Diego) historically treated over 3,000 OHCA requiring advanced airway management in 2013. 
Therefore, we expect to have adequate capacity to enroll the requisite number of subjects over 
the anticipated three-year study period. 
 Interim Monitoring Plan and Stopping Boundaries – Criteria for Terminating the Trial 
16.2
With input from the Data Safety and Monitoring Board (DSMB), prior to initiation of the trial, we will 
develop a monitoring plan to guide early termination of the trial. Factors influencing stopping 
decision may include (a) formal stopping rules based upon the primary analysis, (b) information on 
safety outcomes by treatment group, (c) consistency between results for primary and secondary 
outcomes, and (d) consistency of treatment effects across subgroups. 
 
 
 
Lower Stopping Boundary (SGA Better) 
Analysis 
Cum. 
Sample  
Size 
Prop. Max 
Stat Info 
Absolute 
Difference 
Adjusted 
Difference 
95% 
Confidence 
Interval 
P-value 
1 
654 
0.25 
-0.108 
-0.098 
(-0.154, -0.041) 
0.001 
2 
1,306 
0.50 
-0.102 
-0.092 
(-0.135, -0.053) 
<0.001 
3 
1,958 
0.75 
-0.092 
-0.084 
(-0.120, -0.052) 
<0.001 
4 
2,612 
1.00 
-0.029 
-0.029 
(-0.059, 0.000) 
0.050 
 
 
 
 
 
 
 
 
 
 
Upper Stopping Boundary (ETI Better) 
Analysis 
Cum. 
Sample  
Size 
Prop. Max 
Stat Info 
Absolute  
Difference 
Adjusted 
Difference 
95%  
Confidence  
Interval 
P-value 
1 
654 
0.25 
0.125 
0.116 
(0.058, 0.172) 
<0.001 
2 
1,306 
0.50 
0.118 
0.109 
(0.069, 0.151) 
<0.001 
3 
1,958 
0.75 
0.106 
0.099 
(0.066, 0.135) 
<0.001 
4 
2,612 
1.00 
0.029 
0.029 
(0.000, 0.059) 
0.050 
Table 5 - Interim Stopping Boundaries for 72-Hour Survival 
The formal stopping boundaries are asymmetric, two-sided designs which are included in the 
unified family of group sequential stopping rules.110,111 (Table 5) The boundaries are asymmetric, 
because the utility/ease of use/training for a SGA is judged to be preferable to ETI. The tests for 

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superiority of either intervention will be based upon boundaries with parameters P=(0,0), 
R=(0.2,0.2), A=(0.355,0.29), and epsilon=c(1,1), with a two-sided overall alpha level of 0.05.79  
We envision conducting 4 total analyses (3 interim + 1 final). The study does not include any 
futility boundaries because obtaining estimates in either direction will be informative; even an 
estimate that both treatments yield similar 72-hour survival is informative.  
At the conclusion of the clinical trial, reported point estimates, 95% confidence intervals, and p-
values for the primary outcome will be adjusted for the true sampling distribution accounting for 
the stopping rule. Point estimates from interim analyses will be based on the bias adjusted point 
estimate.112 Confidence intervals and p-values will be calculated from the ordering of the outcome 
space based upon the maximum likelihood estimate.113 The stopping rules described above can 
be implemented using S+SeqTrial (S+SEQTRIAL User’s Manual, Insightful, Inc., Seattle WA, 
2000). 
 
Eligibility for Participating and Remaining in the Enrollment Phase of the Trial 
17.
Prior to entering the enrollment phase of the trial, each EMS agency must demonstrate readiness 
to participate in the study. EMS agencies must also meet select compliance benchmarks to 
remain the enrollment phase of the trial. Specific criteria for participating and remaining in the 
enrollment phase are listed in Appendix 3. 
The trial will not have a formal run-in phase.  
The study leadership will appoint a Study Monitoring Committee (SMC - Section 22) to oversee 
and review EMS agency study compliance. The SMC will meet on a bi-monthly basis to review 
enrollment and protocol adherence. The SMC will have the authority to recommend removal of an 
EMS agency from trial participation for protocol or data collection noncompliance.  
 
Timeline  
18.
 Milestones for the Planning Phase 
18.1
The Year 1 planning phase of this trial is scheduled for September 15, 2014 - July 30, 2015. The 
parameters of the grant award for this trial specify that the certain milestones must be met during 
the Year 1 planning phase prior to proceeding to the Year 2-5 trial execution/subject enrollment 
phase. 
Tasks that will be completed during the Year 1 planning phase include: 
- 
Develop and finalize trial protocol; 
- 
Register trial at www.clinicaltrials.gov; 
- 
Obtain Food and Drug Administration (FDA) review for Investigational Device Exemption 
(IDE); 
- 
Finalize selection and definition of data elements; 
- 
Program and test data base; 

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- 
Obtain initial Institutional Review Board (IRB) approval; 
- 
Initiate Exception from Informed Consent (EFIC) community consultation and public 
disclosure (CC/PD); 
- 
Develop and test EMS training materials; 
- 
Establish site subawards. 
A program evaluation will be performed by an independent agency appointed by NHLBI. 
 Milestones for Trial Execution and Subject Recruitment 
18.2
Trial execution and subject recruitment will occur over the 4-year period August 1, 2015 – July 30, 
2019.  
We expect 6 ROC regional coordinating centers encompassing over 33 EMS agencies to 
participate in the trial. We expect participating EMS agencies to complete a brief period (2-4 
months) of data collection to demonstrate readiness for the enrollment phase of the trial. We 
expect recruitment of subjects to occur through July 30, 2018 (3 years). Trial close-out and 
analysis will occur during August 1, 2018 – July 30, 2019.  
 
Data Sources and Management 
19.
 Data Sources 
19.1
Data will be collected prospectively as patient care progresses. This will include a review of all 
EMS and hospital records.  
 Out-of-Hospital EMS Data 
19.1.1
Out-of-hospital data will be determined from EMS clinical care documentation, including EMS 
dispatch records and patient care records.  
CPR process files will be collected and archived but will not be analyzed as part of the primary 
trial effort (although additional grant funding may support this effort in the future). 
 Hospital Data 
19.1.2
Hospital records that will be reviewed for this trial may include: 
- 
Emergency Department and inpatient physician clinical documentation 
- 
Emergency Department and inpatient nurse clinical documentation 
- 
Radiology reports 
- 
Operative reports 
- 
Procedural notes 
- 
Discharge summary 
- 
Death note and certificate 

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 Post-Discharge Vital Status 
19.1.3
This trial will not require the determination of post-discharge vital status. 
 Data Entry 
19.2
The DCC will provide web-based HTML forms to collect necessary information from the 
participating sites. Web entry forms will have dynamic features such as immediate checks on data 
and relationships within a form and between forms. Details and clarification about data items will 
be provided using pop-up windows and links to appropriate sections of the on-line version of the 
Manual of Operations. Data encryption and authentication methods will be used. The DCC will 
build additional features into the web entry forms including: forms transmission history, access to 
past forms, tracking of data corrections, and the capability to save and re-load incomplete forms. 
 Database Management 
19.3
The DCC will use a two-tiered database structure. A front-end database will serve the web entry 
needs, using a database management system well-suited to handling updates from multiple 
interactive users. The data from this database will be transferred periodically (e.g., weekly) to a 
data repository that can be used by statistical software packages. These data sets will be the basis 
for data queries, analyses and monitoring reports. Various versions of this database will be kept as 
needed, e.g., for quarterly performance reports. Backup of data and programs will be performed at 
frequent intervals. Access to data will be limited to those who need access to perform their tasks. 
The database management system is able to manage large quantities of data, to merge data from 
multiple databases as required, to handle complex and possibly changing relationships, and to 
produce analysis datasets that can be imported into a variety of statistical analysis packages. 
 
EMS Research Protocol Training 
20.
 Overview of EMS Protocol Training Elements 
20.1
Training of EMS personnel for this trial will encompass didactic and practical modalities. The 
salient components of EMS personnel training are described below. While we will develop a 
master set of training materials, individual regional coordinating centers will be permitted to 
customize the format to suit local needs.  
Prior to entering the trial, participating EMS agencies will summarize their experience with and 
standard training practices (format, frequency) for both airway devices.  
All participating EMS agencies will receive initial training in the trial protocol. Key elements of 
training will include: 
- 
Scientific Basis for the Trial – This section include level-appropriate presentation of the 
scientific principles of airway management, a summary of prior studies of OHCA airway 
management, and the rationale for the current randomized trial. All EMS personnel that may 
potentially carry out study procedures will be required to undergo training.  
- 
Review of Study Protocol – This section will include the following: overall study design, 
inclusion and exclusion criteria, the process of exception to informed consent under 

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emergency circumstances, the study protocol and procedures, data reporting, and 
contingency measures.  
- 
Protocol Practicum – EMS personnel will have the opportunity to simulate execution of the 
trial protocol in “hands-on” fashion. This practical experience will encompass the use of 
mannequins that can accommodate ETI and LT insertion. EMS personnel will be given the 
opportunity to practice to proficiency each component of the protocol. EMS personnel will 
have the opportunity to integrate the trial procedures in the context of other ACLS 
interventions. Various permutations of the study protocol will be presented, including each of 
the study arms and scenarios with unsuccessful initial airway attempts. 
- 
Data Reporting – Select data elements specific to airway management are required for this 
trial; for example, the sequence of airway interventions, the number of attempts, the timing 
of successful airway insertion, and adverse events. The training will review definitions and 
reporting practices for each of these data elements.  
- 
Cognitive Post-Test – A cognitive post-test will cover key trial procedures and may be 
completed online or as a written or verbal component of the training sessions. A record of 
training completion will be maintained by each site or EMS agency. 
 Retraining and Feedback 
20.2
All EMS agencies will receiving periodic training in trial procedures. Retraining will focus on proper 
execution of research procedures and reporting of data. Where possible, retraining will occur before 
each crossover period and as required by the ROC Study Monitoring Committee. 
In keeping with the pragmatic design of the trial, the trial will not prescribe the frequency, methods or 
modalities for training in airway management techniques. EMS agencies will provide airway management 
skills training using their existing practices. 
EMS personnel will receive study performance feedback throughout the trial.  
 
Guidance for Receiving Emergency Departments 
21.
The practices and procedures employed by receiving Emergency Departments will not be dictated 
by this trial. However, to each potential receiving ED we will provide information on best ED 
practices for managing EMS-placed airways. This information will include: 
- 
Overview of the Trial – We will provide an overview of the rationale for the trial and the trial 
interventions. We will provide an overview of the LT airway and its function. 
- 
Best Practices for Confirming EMS ET Tube Placement – Best practices for confirming 
EMS ET tube placement will be reviewed. Emphasis will be placed on a) the need for using 
multiple modalities for confirming ET tube placement, b) the use of waveform capnography 
as a preferred modality for confirming tube placement, c) the use of direct laryngoscopic 
revisualization when placement is uncertain. Emphasis will be placed on the preference of 
maintaining EMS ET tube use over emergent ED re-intubation.  
- 
Best Practices and Strategies for Managing EMS-Inserted LT Airways – Best practices 
for confirming EMS LT airway placement will be reviewed. The guidelines will encourage 

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using of the EMS LT for ongoing resuscitation, with conversion to ETI deferred until ROSC. 
Strategies for LT conversion to ETI will be reviewed, including direct laryngoscopy and 
intubation, exchange of LT to ET tube over a bougie, exchange of LT to ET tube over an 
Aintree catheter, and cricothyroidotomy or tracheotomy.  
 
Study Monitoring 
22.
 Study Monitoring Committee 
22.1
The study leadership will appoint a Study Monitoring Committee (SMC) to oversee EMS 
participation and performance in the trial. The SMC will include, at minimum, the PI, the lead co-
investigators, select members of the DCC, select members of the trial workgroup, select PIs from 
participating sites, and select representatives of NIH. The SMC will work with the study leadership 
to develop criteria for EMS agencies to enter and remain in the enrollment phase of the trial. 
Based upon reports provided by the DCC, the SMC will monitor EMS agency enrollment 
performance on a bi-monthly basis.  
The SMC will have the final authority to authorize EMS agency participation in and/or suspension 
from participation in the trial.  
 Data Safety and Monitoring Board  
22.2
ROC has an existing independent Data Safety and Monitoring Board (DSMB) that will monitor 
adverse events throughout the trial and review outcomes data for possible harm. The DSMB was 
appointed by NHLBI. The committee will review and approve the protocol before the study 
commences. In addition, the committee will approve an interim monitoring plan before study 
initiation and review the results of the interim analyses. Although the DSMB will make the final 
decision about the interim monitoring plan, we anticipate that the DSMB will evaluate treatment 
compliance and the rate of adverse events between the treatment and control arms at intervals to 
be determined by the DSMB, expected to be approximately semi-annually. The DSMB will also 
monitor primary, secondary and mechanistic study outcomes between the treatment and control 
groups including main effects and a priori subgroups as specified elsewhere in the protocol. The 
DSMB will advise the investigators if a change in the protocol is warranted based on this interim 
monitoring.  
The DCC will forward DSMB reports to study investigators, the Institutional Review Board, and the 
sponsor in accordance with the 1996 guidance from OHRP regulations 46.101 (i), as is our current 
practice. 
Clinical staff will report all potential adverse events to the coordinating center as soon as possible. 
These will be collected in both a structured (standard form) and open (describing any difficulties 
encountered) form. All potential adverse events will be reviewed as to treatment arm and further 
classified by: a) Severity (life-threatening, serious, non-serious); and b) Expected vs. Unexpected. 
Expected adverse events will be recorded as noted in the hospital discharge summary by each 
enrolling site, reported to overseeing agencies as required by federal regulations and local 
requirements, and reviewed periodically by our independent data safety monitoring board.  
For suspected unexpected serious adverse reactions (SUSAR), the coordinating center will promptly 
notify the DSMB as well as appropriate regulatory agencies, site and sponsor. The coordinating 

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center will tabulate and report compliance, data quality, and non-serious adverse events on a 
regular basis. 
The SMC will carry out recommendations provided by the DSMB. 
 
Regulatory Considerations 
23.
 Human Subjects 
23.1
Because of the unconscious nature of cardiac arrest victims and the time-critical nature of OHCA 
care, the trial will be carried out under “Exception from informed consent required for emergency 
research” (EFIC) rules outlined in by the guidance document “Waiver of Informed Consent 
Requirements in Certain Emergency Research” (Federal Register, Vol. 61, pp. 51531-51533, 
November 1, 1996 - http://www.gpo.gov/fdsys/pkg/FR-1996-10-02/html/96-24968.htm), OHRP 
“Basic HHS Policy for Protection of Human Research Subjects” (45 CFR 46.101(i) - 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.101), and FDA regulations 21 
CFR 50.24.84,85,114  
The use of EFIC is justified because the victims of OHCA are in a life-threatening situation, 
available OHCA treatments are unproven or unsatisfactory, and obtaining informed consent prior 
to enrollment is not feasible because of their unconscious and critically-ill state, and trial 
interventions must be administered before consent from the subjects' legally authorized 
representatives is feasible. Cardiac arrest is a short-lived illness, for which immediate 
interventions cannot be delayed without irreparable harm to the patient.  
In conformance with EFIC rules, measures to protect the rights and welfare of subjects will 
include, at least; a) community consultation, b) public disclosure, c) independent data monitoring, 
and d) notification of a legally authorized representative or family members of a subject’s 
enrollment in the trial, with opportunity to discontinue trial participation.  
Additional details are provided in Appendix 4. Suggested notification documents are provided in 
Appendix 5. 
 Food and Drug Administration 
23.2
Based upon review of a formal application submitted by the study team, the FDA confirmed that 
the trial is exempt from FDA Investigational Device Exemption (IDE) regulations. (Communication 
from FDA to Henry Wang, MD, January 8, 2015.) 
 Technical and Regulatory Information for the ET Tube 
23.2.1
The ET tube is listed in the FDA Medical Devices Database under the device name “Tube, 
Tracheal (w/wo connector)” and is classified as Device Class 2.  
 
 

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 Technical and Regulatory Information for the LT 
23.2.2
Models of the King LT airway are listed in the FDA Medical Devices Database. (Table 6) The 
predicate device is “Airway, Oropharyngeal, Anesthesiology.” There is no 510(K) number for the 
King LTS-D model, as it is considered a minimal modification of the LT-D and LTS models. We 
expect that only disposable versions of the King LT will be used in this study. 
 
Manufacturer 
FDA 
510(K) # 
Models 
KING SYSTEMS, CORP 
NOBLESVILLE, IN 
K021634 
KING LT, MODELS # KLT 100, KLT 101, KLT 102, KLT 103, 
KLT 104, KLT 105 
 
K033186 
KING LT-D DISPOSABLE OROPHARYNGEAL AIRWAY, 
MODELS KLT 203, KLT 204 AND KLT 205 
 
 
K033189 
KING LTS REUSABLE OROPHARYNGEAL AIRWAY WITH 
DRAIN/ /SUCTION CHANNEL, MODELS KLT 303, KLT 304 
AND KLT 305 
 
  
Table 6 – King LT Models and Corresponding FDA 510(K) Numbers 
 
 
 
 

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References 
24.
1. 
Go AS, Mozaffarian D, Roger VL, et al. Heart Disease and Stroke Statistics--2014 
Update: A Report From the American Heart Association. Circulation 2013. 
2. 
Kette F, Reffo I, Giordani G, et al. The use of laryngeal tube by nurses in out-of-
hospital emergencies: preliminary experience. Resuscitation 2005;66:21-5. 
3. 
Khan SA, Siddiqui MM, Khan RM. Laryngoceles and the laryngeal tube. Anaesthesia 
2003;58:391. 
4. 
Bein B, Carstensen S, Gleim M, et al. A comparison of the proseal laryngeal mask 
airway, the laryngeal tube S and the oesophageal-tracheal combitube during routine 
surgical procedures. European journal of anaesthesiology 2005;22:341-6. 
5. 
Dunford JV, Davis DP, Ochs M, Doney M, Hoyt DB. Incidence of transient hypoxia and 
pulse rate reactivity during paramedic rapid sequence intubation. Annals of emergency 
medicine 2003;42:721-8. 
6. 
Lee JS, Nam SB, Chang CH, Han DW, Lee YW, Shin CS. Relationship between 
arterial and end-tidal carbon dioxide pressures during anesthesia using a laryngeal 
tube. Acta anaesthesiologica Scandinavica 2005;49:759-62. 
7. 
Kurola J, Pere P, Niemi-Murola L, et al. Comparison of airway management with the 
intubating laryngeal mask, laryngeal tube and CobraPLA by paramedical students in 
anaesthetized patients. Acta anaesthesiologica Scandinavica 2006;50:40-4. 
8. 
Richebe P, Verdonck O, Biais M, Breton Y, Cros AM, Maurette P. [Clinical evaluation 
of the single use Laryngeal Tube in adults: the LTD]. Annales francaises d'anesthesie 
et de reanimation 2005;24:1250-4. 
9. 
Asai T, Moriyama S, Nishita Y, Kawachi S. Use of the laryngeal tube during 
cardiopulmonary resuscitation by paramedical staff. Anaesthesia 2003;58:393-4. 
10. Wang HE, Szydlo D, Stouffer JA, et al. Endotracheal intubation versus supraglottic 
airway insertion in out-of-hospital cardiac arrest. Resuscitation 2012;83:1061-6. 
11. Turan A, Kaya G, Koyuncu O, Karamanlioglu B, Pamukcu Z. Comparison of the 
laryngeal mask (LMA) and laryngeal tube (LT) with the new perilaryngeal airway 
(CobraPLA) in short surgical procedures. European journal of anaesthesiology 
2006;23:234-8. 
12. White H. Maximum likelihood estimation of misspecified models. Econometrica 
1982;50:1-25. 
13. Wang HE, Kupas DF, Greenwood MJ, et al. An algorithmic approach to prehospital 
airway management. Prehospital emergency care : official journal of the National 
Association of EMS Physicians and the National Association of State EMS Directors 
2005;9:145-55. 

DO NOT REPRODUCE WITHOUT PERMISSION 
43
 
 
Pragmatic Airway Resuscitation Trial  
Version 7.0 – November 29, 2016 
Clinical Trial Protocol  
 
 
 
  
14. DeLeo BC. Endotracheal intubation by rescue squad personnel. Heart Lung 
1977;6:851-4. 
15. Guss DA, Posluszny M. Paramedic orotracheal intubation: a feasibility study. Am J 
Emerg Med 1984;2:399-401. 
16. Jacobs LM, Berrizbeitia LD, Bennett B, Madigan C. Endotracheal intubation in the 
prehospital phase of emergency medical care. Jama 1983;250:2175-7. 
17. Stewart RD, Paris PM, Winter PM, Pelton GH, Cannon GM. Field endotracheal 
intubation by paramedical personnel. Success rates and complications. Chest 
1984;85:341-5. 
18. Katz SH, Falk JL. Misplaced endotracheal tubes by paramedics in an urban 
emergency medical services system. Annals of emergency medicine 2001;37:32-7. 
19. Wang HE, Mann NC, Mears G, Jacobson K, Yealy DM. Out-of-hospital airway 
management in the United States. Resuscitation 2011;82:378-85. 
20. Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-threatening 
problem during cardiopulmonary resuscitation. Critical care medicine 2004;32:S345-
51. 
21. Aufderheide TP, Sigurdsson G, Pirrallo RG, et al. Hyperventilation-induced 
hypotension during cardiopulmonary resuscitation. Circulation 2004;109:1960-5. 
22. Paradis NA, Martin GB, Rivers EP, et al. Coronary perfusion pressure and the return of 
spontaneous circulation in human cardiopulmonary resuscitation. Jama 
1990;263:1106-13. 
23. Cheskes S, Schmicker RH, Christenson J, et al. Perishock pause: an independent 
predictor of survival from out-of-hospital shockable cardiac arrest. Circulation 
2011;124:58-66. 
24. Christenson J, Andrusiek D, Everson-Stewart S, et al. Chest compression fraction 
determines survival in patients with out-of-hospital ventricular fibrillation. Circulation 
2009;120:1241-7. 
25. Roth H, Genzwuerker HV, Rothhaas A, Finteis T, Schmeck J. The ProSeal laryngeal 
mask airway and the laryngeal tube Suction for ventilation in gynaecological patients 
undergoing laparoscopic surgery. European journal of anaesthesiology 2005;22:117-
22. 
26. National Highway Traffic Safety Administration. Emergency Medical Technician 
Paramedic:National Standard Curriculum (EMT-P). 1998. (Accessed Oct 8, 2004, at 
http://www.nhtsa.dot.gov/people/injury/ems/EMT-P/.) 
27. de Oliveira Filho GR. The construction of learning curves for basic skills in anesthetic 
procedures: an application for the cumulative sum method. Anesth Analg 2002;95:411-
6, table of contents. 

DO NOT REPRODUCE WITHOUT PERMISSION 
44
 
 
Pragmatic Airway Resuscitation Trial  
Version 7.0 – November 29, 2016 
Clinical Trial Protocol  
 
 
 
  
28. Accreditation Council for Graduate Medical Education: Emergency Medicine - 
Guidelines for Procedures and Resuscitations. 2004. (Accessed November 12, 2004, 
at http://www.acgme.org/acWebsite/RRC_110/110_guidelines.asp#res.) 
29. Council on Accreditation of Nurse Anesthesia Educational Programs: Standards for 
Accreditation of Nurse Anesthesia Educational Programs. Park Ridge, Illinois; 2004. 
30. Konrad C, Schupfer G, Wietlisbach M, Gerber H. Learning manual skills in 
anesthesiology: Is there a recommended number of cases for anesthetic procedures? 
Anesth Analg 1998;86:635-9. 
31. Kopacz DJ, Neal JM, Pollock JE. The regional anesthesia "learning curve". What is the 
minimum number of epidural and spinal blocks to reach consistency? Reg Anesth 
1996;21:182-90. 
32. Charuluxananan S, Kyokong O, Somboonviboon W, Pothimamaka S. Learning manual 
skills in spinal anesthesia and orotracheal intubation: is there any recommended 
number of cases for anesthesia residency training program? J Med Assoc Thai 
2001;84 Suppl 1:S251-5. 
33. Wang HE, Kupas DF, Hostler D, Cooney R, Yealy DM, Lave JR. Procedural 
experience with out-of-hospital endotracheal intubation. Crit Care Med 2005;33:1718-
21. 
34. Burton JH, Baumann MR, Maoz T, Bradshaw JR, Lebrun JE. Endotracheal intubation 
in a rural EMS state: procedure utilization and impact of skills maintenance guidelines. 
Prehosp Emerg Care 2003;7:352-6. 
35. Gabrielli A, Layon AJ, Wenzel V, Dorges V, Idris AH. Alternative ventilation strategies 
in cardiopulmonary resuscitation. Curr Opin Crit Care 2002;8:199-211. 
36. Hagberg C, Bogomolny Y, Gilmore C, Gibson V, Kaitner M, Khurana S. An evaluation 
of the insertion and function of a new supraglottic airway device, the King LT, during 
spontaneous ventilation. Anesth Analg 2006;102:621-5. 
37. Guyette FX, Greenwood MJ, Neubecker D, Roth R, Wang HE. Alternate airways in the 
prehospital setting (resource document to NAEMSP position statement). Prehosp 
Emerg Care 2007;11:56-61. 
38. Fales W, Farrell R. Impact of New Resuscitation Guidelines on Out-of-Hospital Cardiac 
Arrest Survival (abstract). Academic Emergency Medicine 2007;14:S157-S8. 
39. McMullan JT, McNally B, Gerecht R, Bonomo J, Robb R, Wang HE. Airway 
Management and Outcomes After Out of Hospital Cardiac Arrest in the CARES 
Network (abstract). Circulation 2013;128:A9545. 
40. Hanif MA, Kaji AH, Niemann JT. Advanced airway management does not improve 
outcome of out-of-hospital cardiac arrest. Academic emergency medicine : official 
journal of the Society for Academic Emergency Medicine 2010;17:926-31. 

DO NOT REPRODUCE WITHOUT PERMISSION 
45
 
 
Pragmatic Airway Resuscitation Trial  
Version 7.0 – November 29, 2016 
Clinical Trial Protocol  
 
 
 
  
41. Hasegawa K, Hiraide A, Chang Y, Brown DF. Association of prehospital advanced 
airway management with neurologic outcome and survival in patients with out-of-
hospital cardiac arrest. JAMA : the journal of the American Medical Association 
2013;309:257-66. 
42. Studnek JR, Thestrup L, Vandeventer S, et al. The association between prehospital 
endotracheal intubation attempts and survival to hospital discharge among out-of-
hospital cardiac arrest patients. Academic emergency medicine : official journal of the 
Society for Academic Emergency Medicine 2010;17:918-25. 
43. Tanabe S, Ogawa T, Akahane M, et al. Comparison of neurological outcome between 
tracheal intubation and supraglottic airway device insertion of out-of-hospital cardiac 
arrest patients: a nationwide, population-based, observational study. The Journal of 
emergency medicine 2013;44:389-97. 
44. Kajino K, Iwami T, Kitamura T, et al. Comparison of supraglottic airway versus 
endotracheal intubation for the pre-hospital treatment of out-of-hospital cardiac arrest. 
Critical care 2011;15:R236. 
45. Gausche M, Lewis RJ, Stratton SJ, et al. Effect of out-of-hospital pediatric 
endotracheal intubation on survival and neurological outcome: a controlled clinical trial. 
JAMA : the journal of the American Medical Association 2000;283:783-90. 
46. Bernard SA, Nguyen V, Cameron P, et al. Prehospital rapid sequence intubation 
improves functional outcome for patients with severe traumatic brain injury: a 
randomized controlled trial. Annals of surgery 2010;252:959-65. 
47. Frascone RJ, Russi C, Lick C, et al. Comparison of prehospital insertion success rates 
and time to insertion between standard endotracheal intubation and a supraglottic 
airway. Resuscitation 2011;82:1529-36. 
48. Benger JR, Voss S, Coates D, et al. Randomised comparison of the effectiveness of 
the laryngeal mask airway supreme, i-gel and current practice in the initial airway 
management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study 
research protocol. BMJ open 2013;3. 
49. Birkholz T, Irouschek A, Kessler P, Blunk JA, Labahn D, Schmidt J. Feasibility of the 
laryngeal tube airway for artificial ventilation in pigs and comparison with the laryngeal 
mask airway. Lab animal 2008;37:371-9. 
50. Yamamoto Y, Inoue S, Abe R, Kawaguchi M, Furuya H. Airway management with the 
laryngeal tube in rabbits. Lab animal 2007;36:33-5. 
51. Segal N, Yannopoulos D, Mahoney BD, et al. Impairment of carotid artery blood flow 
by supraglottic airway use in a swine model of cardiac arrest. Resuscitation 
2012;83:1025-30. 
52. Carlson JN, Reynolds JC. Does advanced airway management improve outcomes in 
adult out-of-hospital cardiac arrest? Annals of emergency medicine 2014;64:163-4. 

DO NOT REPRODUCE WITHOUT PERMISSION 
46
 
 
Pragmatic Airway Resuscitation Trial  
Version 7.0 – November 29, 2016 
Clinical Trial Protocol  
 
 
 
  
53. Fouche PF, Simpson PM, Bendall J, Thomas RE, Cone DC, Doi SA. Airways in out-of-
hospital cardiac arrest: systematic review and meta-analysis. Prehospital emergency 
care : official journal of the National Association of EMS Physicians and the National 
Association of State EMS Directors 2014;18:244-56. 
54. McMullan J, Gerecht R, Bonomo J, et al. Airway management and out-of-hospital 
cardiac arrest outcome in the CARES registry. Resuscitation 2014;85:617-22. 
55. Shin SD, Ahn KO, Song KJ, Park CB, Lee EJ. Out-of-hospital airway management and 
cardiac arrest outcomes: a propensity score matched analysis. Resuscitation 
2012;83:313-9. 
56. Ocker H, Wenzel V, Schmucker P, Steinfath M, Dorges V. A comparison of the 
laryngeal tube with the laryngeal mask airway during routine surgical procedures. 
Anesthesia and analgesia 2002;95:1094-7, table of contents. 
57. Davis DP, Garberson LA, Andrusiek DL, et al. A descriptive analysis of Emergency 
Medical Service Systems participating in the Resuscitation Outcomes Consortium 
(ROC) network. Prehospital emergency care : official journal of the National 
Association of EMS Physicians and the National Association of State EMS Directors 
2007;11:369-82. 
58. Ochs M, Vilke GM, Chan TC, Moats T, Buchanan J. Successful prehospital airway 
management by EMT-Ds using the combitube. Prehosp Emerg Care 2000;4:333-7. 
59. Cady CE, Pirrallo RG. The effect of Combitube use on paramedic experience in 
endotracheal intubation. Am J Emerg Med 2005;23:868-71. 
60. Bernhard M, Beres W, Timmermann A, et al. Prehospital airway management using 
the laryngeal tube. An emergency department point of view. Der Anaesthesist 
2014;63:589-96. 
61. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment 
protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 
2007;73:29-39. 
62. Gruber E, Oberhammer R, Balkenhol K, et al. Basic life support trained nurses 
ventilate more efficiently with laryngeal mask supreme than with facemask or laryngeal 
tube suction-disposable--a prospective, randomized clinical trial. Resuscitation 
2014;85:499-502. 
63. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life 
Support: 2010 American Heart Association Guidelines for Cardiopulmonary 
Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S729-S67. 
64. Cook TM, McCormick B, Asai T. Randomized comparison of laryngeal tube with 
classic laryngeal mask airway for anaesthesia with controlled ventilation. British journal 
of anaesthesia 2003;91:373-8. 
65. Khan SA, Siddiqi MM, Khan RM. Diffusion of nitrous oxide into the cuff of the laryngeal 

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tube. Anaesthesia 2003;58:291. 
66. Hubble MW, Brown L, Wilfong DA, Hertelendy A, Benner RW, Richards ME. A meta-
analysis of prehospital airway control techniques part I: orotracheal and nasotracheal 
intubation success rates. Prehospital emergency care : official journal of the National 
Association of EMS Physicians and the National Association of State EMS Directors 
2010;14:377-401. 
67. Hubble MW, Wilfong DA, Brown LH, Hertelendy A, Benner RW. A meta-analysis of 
prehospital airway control techniques part II: alternative airway devices and 
cricothyrotomy success rates. Prehospital emergency care : official journal of the 
National Association of EMS Physicians and the National Association of State EMS 
Directors 2010;14:515-30. 
68. Cook TM, McKinstry C, Hardy R, Twigg S. Randomized crossover comparison of the 
ProSeal laryngeal mask airway with the Laryngeal Tube during anaesthesia with 
controlled ventilation. British journal of anaesthesia 2003;91:678-83. 
69. Wang HE, Thomsen DP. Airway Management. In: Cone DC, Brice JH, Delbridge TR, 
Myers JB, eds. Emergency medical services : clinical practice and systems oversight. 
Second edition. ed: Kendall/Hunt; 2009:p.383-403. 
70. Chiu CL, Murugasu J, Chan L. The use of modified VBM laryngeal tube compared to 
Laryngeal Mask Airway during spontaneous ventilation. Anaesthesia and intensive 
care 2003;31:187-92. 
71. Wolcke BB, Mauer DK, Schoefmann MF, et al. Comparison of standard 
cardiopulmonary resuscitation versus the combination of active compression-
decompression cardiopulmonary resuscitation and an inspiratory impedance threshold 
device for out-of-hospital cardiac arrest. Circulation 2003;108:2201-5. 
72. Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: 
effective implementation of therapeutic hypothermia to improve patient outcome after 
cardiac arrest. Critical care medicine 2006;34:1865-73. 
73. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary intervention and 
mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-
elevation acute myocardial infarction. Resuscitation 2007;74:227-34. 
74. Wolfrum S, Pierau C, Radke PW, Schunkert H, Kurowski V. Mild therapeutic 
hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment 
elevation myocardial infarction undergoing immediate percutaneous coronary 
intervention. Critical care medicine 2008;36:1780-6. 
75. Rittenberger JC, Guyette FX, Tisherman SA, DeVita MA, Alvarez RJ, Callaway CW. 
Outcomes of a hospital-wide plan to improve care of comatose survivors of cardiac 
arrest. Resuscitation 2008;79:198-204. 
76. Gaieski DF, Band RA, Abella BS, et al. Early goal-directed hemodynamic optimization 
combined with therapeutic hypothermia in comatose survivors of out-of-hospital 

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cardiac arrest. Resuscitation 2009;80:418-24. 
77. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-
hospital cardiac arrest with induced hypothermia. The New England journal of 
medicine 2002;346:557-63. 
78. Group HaCAS. Mild therapeutic hypothermia to improve the neurologic outcome after 
cardiac arrest. The New England journal of medicine 2002;346:549-56. 
79. Asai T, Kawashima A, Hidaka I, Kawachi S. The laryngeal tube compared with the 
laryngeal mask: insertion, gas leak pressure and gastric insufflation. British journal of 
anaesthesia 2002;89:729-32. 
80. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive 
care unit following cardiac arrest. Intensive care medicine 2004;30:2126-8. 
81. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in 
survivors of out-of-hospital cardiac arrest. The New England journal of medicine 
1997;336:1629-33. 
82. Pell JP, Sirel JM, Marsden AK, Ford I, Walker NL, Cobbe SM. Presentation, 
management, and outcome of out of hospital cardiopulmonary arrest: comparison by 
underlying aetiology. Heart 2003;89:839-42. 
83. Vollmer T, Genzwuerker HV, Ellinger K. Fibreoptic control of the laryngeal tube 
position. European journal of anaesthesiology 2002;19:306-7. 
84. Aufderheide TP, Nichol G, Rea TD, et al. A trial of an impedance threshold device in 
out-of-hospital cardiac arrest. The New England journal of medicine 2011;365:798-
806. 
85. Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with 
out-of-hospital cardiac arrest. The New England journal of medicine 2011;365:787-97. 
86. Hostler D, Everson-Stewart S, Rea TD, et al. Effect of real-time feedback during 
cardiopulmonary resuscitation outside hospital: prospective, cluster-randomised trial. 
Bmj 2011;342:d512. 
87. Wang HE, Min A, Hostler D, Chang CC, Callaway CW. Differential effects of out-of-
hospital interventions on short- and long-term survival after cardiopulmonary arrest. 
Resuscitation 2005;67:69-74. 
88. Chamberlain D, Cummins RO. Recommended guidelines for uniform reporting of data 
from out-of-hospital cardiac arrest: the 'Utstein style'. European Resuscitation Council, 
American Heart Association, Heart and Stroke Foundation of Canada and Australian 
Resuscitation Council. European journal of anaesthesiology 1992;9:245-56. 
89. Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. 
The New England journal of medicine 2010;363:1256-64. 

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90. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S, Quality Standards 
Subcommittee of the American Academy of N. Practice parameter: prediction of 
outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-
based review): report of the Quality Standards Subcommittee of the American 
Academy of Neurology. Neurology 2006;67:203-10. 
91. Hop JW, Rinkel GJ, Algra A, van Gijn J. Changes in functional outcome and quality of 
life in patients and caregivers after aneurysmal subarachnoid hemorrhage. Journal of 
neurosurgery 2001;95:957-63. 
92. Weimar C, Kurth T, Kraywinkel K, et al. Assessment of functioning and disability after 
ischemic stroke. Stroke; a journal of cerebral circulation 2002;33:2053-9. 
93. Rabinstein AA, McClelland RL, Wijdicks EF, Manno EM, Atkinson JL. 
Cardiopulmonary resuscitation in critically ill neurologic-neurosurgical patients. Mayo 
Clinic proceedings 2004;79:1391-5. 
94. van Alem AP, de Vos R, Schmand B, Koster RW. Cognitive impairment in survivors of 
out-of-hospital cardiac arrest. American heart journal 2004;148:416-21. 
95. Raina KD, Callaway C, Rittenberger JC, Holm MB. Neurological and functional status 
following cardiac arrest: method and tool utility. Resuscitation 2008;79:249-56. 
96. Newcommon NJ, Green TL, Haley E, Cooke T, Hill MD. Improving the assessment of 
outcomes in stroke: use of a structured interview to assign grades on the modified 
Rankin Scale. Stroke; a journal of cerebral circulation 2003;34:377-8; author reply -8. 
97. Merino JG, Lattimore SU, Warach S. Telephone assessment of stroke outcome is 
reliable. Stroke; a journal of cerebral circulation 2005;36:232-3. 
98. Aufderheide TP, Kudenchuk PJ, Hedges JR, et al. Resuscitation Outcomes 
Consortium (ROC) PRIMED cardiac arrest trial methods part 1: rationale and 
methodology for the impedance threshold device (ITD) protocol. Resuscitation 
2008;78:179-85. 
99. Stiell IG, Callaway C, Davis D, et al. Resuscitation Outcomes Consortium (ROC) 
PRIMED cardiac arrest trial methods part 2: rationale and methodology for "Analyze 
Later vs. Analyze Early" protocol. Resuscitation 2008;78:186-95. 
100. Baubin M, Rabl W, Pfeiffer KP, Benzer A, Gilly H. Chest injuries after active 
compression-decompression cardiopulmonary resuscitation (ACD-CPR) in cadavers. 
Resuscitation 1999;43:9-15. 
101. Baubin M, Sumann G, Rabl W, Eibl G, Wenzel V, Mair P. Increased frequency of 
thorax injuries with ACD-CPR. Resuscitation 1999;41:33-8. 
102. Huang YT, Ravi Kumar AS. Classical skeletal injuries shown on 18F-FDG PET/CT 
following successful cardiopulmonary resuscitation. Clinical nuclear medicine 
2013;38:395-6. 

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103. Cho SH, Kim EY, Choi SJ, et al. Multidetector CT and radiographic findings of lung 
injuries secondary to cardiopulmonary resuscitation. Injury 2013;44:1204-7. 
104. Smekal D, Hansen T, Sandler H, Rubertsson S. Comparison of computed tomography 
and autopsy in detection of injuries after unsuccessful cardiopulmonary resuscitation. 
Resuscitation 2013;84:357-60. 
105. Kim EY, Yang HJ, Sung YM, et al. Multidetector CT findings of skeletal chest injuries 
secondary to cardiopulmonary resuscitation. Resuscitation 2011;82:1285-8. 
106. Hoke RS, Chamberlain D. Skeletal chest injuries secondary to cardiopulmonary 
resuscitation. Resuscitation 2004;63:327-38. 
107. Bush CM, Jones JS, Cohle SD, Johnson H. Pediatric injuries from cardiopulmonary 
resuscitation. Annals of emergency medicine 1996;28:40-4. 
108. Powner DJ, Holcombe PA, Mello LA. Cardiopulmonary resuscitation-related injuries. 
Critical care medicine 1984;12:54-5. 
109. Gaither JB, Matheson J, Eberhardt A, Colwell CB. Tongue engorgement associated 
with prolonged use of the King-LT laryngeal tube device. Annals of emergency 
medicine 2010;55:367-9. 
110. Kittelson JM, Emerson SS. A unifying family of group sequential test designs. 
Biometrics 1999;55:874-82. 
111. Pampallona S, Tsiatis AA. Group sequential designs for one-sided and two-sided 
hypothesis testing with provision for early stopping in favor of the null hypothesis. J 
Stat Planning and Inference 1994;42:19-35. 
112. Whitehead J. On the bias of maximum likelihood estimation following a sequential test. 
Biometrika 1986;73:573-81. 
113. Emerson S, Fleming T. Parameter estimation following group sequetial hypothesis 
testing. Biometrika 1990;77:875-92. 
114. Tisherman SA, Powell JL, Schmidt TA, et al. Regulatory challenges for the 
resuscitation outcomes consortium. Circulation 2008;118:1585-92. 
 
 
 
 

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Appendix 1 – Summary of Protocol Amendments 
25.
 Version 4.2, December 10, 2014 
25.1
- 
Results of initial protocol development.  
- 
Protocol version sent to FDA. 
 Version 5.0, February 19, 2015 
25.2
- 
Revisions made in response to DSMB comments 
- 
Removal of duplicate inclusion/exclusion criteria 
- 
Modification of EFIC references from FDA to OHRP rules. 
- 
Approved by DSMB on March 4, 2015 
 Version 5.1, April 1, 2015 
25.3
- 
Minor revision of exclusion criteria to exclude patients receiving initial care by non-PART 
participating EMS agency capable of performing ETI, LT or other advanced airway insertion.  
Minor revision to inclusion criteria simplifying inclusion criteria for use of bag-valve-mask. 
 Version 6.0, July 13, 2016 
25.4
- 
Modifications to permit NRB in lieu of BVM as part of inclusion criteria, if allowed by local 
protocol. 
- 
Clarification of chest CT as an alternative to chest x-ray. 
- 
Clarification of hospital survival and hospital survival with good neurologic function as 
defined secondary outcomes. 
- 
Updates to list of planned subgroup analyses. 
- 
Updates to list of key study personnel. 
 
 
 
 
 
 
 

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Appendix 2 – List of Study Personnel 
26.
 Principal Investigator, Lead Facilitator 
26.1
 
Henry E. Wang, MD, MS 
Professor and Vice Chair for Research 
Department of Emergency Medicine 
University of Alabama School of Medicine 
(205)-996-6526/(205)-410-1267 
hwang@uabmc.edu 
 Co-Investigators 
26.2
 
Graham Nichol, MD 
Professor, Division of General Internal Medicine 
Medical Director, ROC Clinical Trial Center 
University of Washington 
206-685-1302  
nichol@uw.edu 
 
Susanne May, PhD 
Professor 
Principal Investigator 
ROC Clinical Trial Center 
University of Washington 
206-685-1302  
sjmay@uw.edu 
 Liaisons with the Resuscitation Outcomes Consortium  
26.3
 
Myron Weisfeldt, MD (ROC Study Chair) 
Professor 
Department of Medicine 
Johns Hopkins University  
mlw5@jhmi.edu 
 
Joseph P. Ornato, MD (ROC Cardiac Chair) 
Professor and Chair 
Department of Emergency Medicine 
Virginia Commonwealth University 
ornato@aol.com 
 
Mo Daya, MD (ROC Principal Investigators) 
Professor  
Department of Emergency Medicine 
Oregon Health Sciences University  
mdaya@ohsu.edu 
 

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Ken Sternig, NREMT-P (ROC EMS Operations) 
Milwaukee County EMS 
Kenneth.Sternig@milwcnty.com 
 
Dana Zive (ROC Research Coordinators) 
Research Sr. Instructor  
Center for Policy and Research in Emergency Medicine 
Department of Emergency Medicine 
Oregon Health Sciences University  
zived@ohsu.edu 
 
Pam Owens (ROC EMS Operations) 
Department of Emergency Medicine 
University of Texas Southwestern 
pamela.owens@utsouthwestern.edu 
 
Donna Kelly (ROC Research Coordinators) 
University of California San Diego 
dlkelly@ucsd.edu 
 Project Direction and Coordination 
26.4
 
Shannon Stephens, NREMT-P 
Project Director  
Department of Emergency Medicine 
University of Alabama at Birmingham 
205-934-5890 
swstephens@uabmc.edu 
 
Michelle Doyle, RN, MHA 
Deputy Director 
ROC Clinical Trial Center 
University of Washington 
206-616-0417 
mdoyle4@uw.edu 
 
Heather Herren, RN, MPH 
Cardiac Project Manager 
ROC Clinical Trial Center 
University of Washington 
206-685-1302  
hherren@uw.edu 
 
 Biostatisticians 
26.5
 
Robert Schmicker, MS 
ROC Clinical Trial Center 

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University of Washington 
206-616-0434  
rschmick@uw.edu 
 
 
David Prince, MS 
ROC Clinical Trial Center 
University of Washington 
206-685-1302  
dprince3@uw.edu 
 
 Liaisons with the National Heart, Lung and Blood Institute 
26.6
 
George Sopko, MD, MPH 
Project Officer 
Division of Cardiovascular Sciences 
Heart Failure and Arrhythmias Branch 
National Heart, Lung and Blood Institute  
National Institutes of Health 
301-435-0504 
sopkog@nhlbi.nih.gov 
 
Debra Egan, M.Sc., M.P.H.  
Clinical Trial Specialist/Contractor 
Division of Cardiovascular Sciences 
Heart Failure and Arrhythmias Branch 
National Heart, Lung and Blood Institute  
National Institutes of Health 
301-435-6333 
debrae@nhlbi.nih.gov 
 
 
 

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Appendix 3 – Criteria to Enter and Remain in the Enrollment Phase of the Trial 
27.
 Criteria to Enter Enrollment Phase of Trial 
27.1
The following are preliminary criteria only. Final criteria will be developed and approved by the 
SMC and DSMB. 
- 
Completion of written agreement to enter the trial. 
- 
Completion of Federal Wide Assurance with sponsoring institution and Institutional Review 
Board. 
- 
Verification of measures for collecting airway data elements required for the trial. 
- 
Verification of LT as the primary SGA for use in the trial. Verification of LT availability on all 
EMS units. Description of supply and re-supply plan for LT used in the trial. 
- 
Verification of protocol training for all EMS personnel. 
- 
Provision of trial information and ED airway best practices guidelines to all receiving 
Emergency Departments. 
- 
Case notification and data entry within 72 hours of the event. 
- 
Correct reporting of all required EMS data elements, with <10% missing entries. 
- 
Correct reporting of all required hospital data elements, with <10% missing entries.  
 Criteria to Remain in Enrollment Phase of Trial 
27.2
This section will be finalized by the DSMB and SMC. 
To remain in the trial “evaluable” phase, EMS agencies must complete all of the following 
requirements on either [ 1) 70% of eligible cases (determined by cumulative or 60-day running 
window), or 2) 3 consecutive cases.] 
- 
Case notification and data entry within 72 hours. 
- 
Correct execution of protocol, with attention to conformance with assigned airway 
intervention. 
- 
Correct reporting of all required EMS data elements, with <10% missing entries. 
- 
Correct reporting of all required hospital data elements, with <10% missing entries.  
EMS agencies that are suspended from the trial may re-enter the trial by achieving the “Criteria to 
Enter the Active Evaluable Phase” requirements. 
 

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Appendix 4 – Additional Information Justifying the Use of Exception from Informed 
28.
Consent (EFIC) for Emergency Research 
We have outlined below how the study design applies to federal criteria for EFIC 
(http://www.hhs.gov/ohrp/policy/hsdc97-01.html). 
  
(1) The human subjects are in a life-threatening situation, available treatments are 
unproven or unsatisfactory, and the collection of valid scientific evidence, which may 
include evidence obtained through randomized placebo-controlled investigations, is 
necessary to determine the safety and effectiveness of particular interventions. 
The proposed trial is a multicenter pragmatic randomized clinical trial comparing ETI- versus 
SGA-airway management in patients with non-traumatic out-of-hospital cardiac arrest. These 
patients are in an immediate life-threatening situation with a mortality approaching 90%. The 
standard of care for prehospital management of these patients includes the timely provision of 
CPR and advanced life support including airway management. 
Endotracheal intubation (ETI) is the insertion of a plastic breathing tube through the mouth and 
into the trachea. As the initial provider of critical care in the field, US paramedics have performed 
ETI on OHCA victims for over 30 years.14-17 However, numerous studies highlight the pitfalls 
associated with paramedic ETI.  
For example, unrecognized misplacement of the endotracheal tube (in the esophagus rather than 
trachea) has been reported in up to one-fourth of paramedic ETI.18 While the endotracheal tube 
should ideally be placed on the first attempt, in a large series of 1,271 OHCA, we found that one-
fourth of ETI efforts required two or more attempts.6 While select studies report paramedic ETI 
success rates >90%, using US national data we observed ETI success rates of only 70%.19 
Paramedic ETI often leads to subsequent iatrogenic hyperventilation, which decreases coronary 
blood flow during CPR.20-22  
Interruptions in CPR chest compressions – including even brief 20-second interruptions – may 
disrupt coronary blood flow, impairing OHCA survival.23,24 Using state-of-the-art cardiac monitor 
technology, we were able to identify chest compression interruptions associated with intubation 
efforts by City of Pittsburgh paramedics. In this series of 100 OHCA, ETI efforts resulted in a 
median of 2 CPR interruptions (IQR 1-3; range 1-6) totaling a median of 109.5 seconds (IQR: 54-
198; range 13-446).7 One-fourth of the CPR interruptions exceeded three minutes.  
While ETI is complex, opportunities for baseline training and continuing experience are 
inadequate.9,25 Compared with the 35-200 ETI required for emergency medicine residents, 
anesthesiology residents and nurse anesthetist trainees, US paramedic student must perform 
only five (5) ETI prior to graduation.26-32 While the customary setting for learning ETI is in the 
operating room training under the tutelage of anesthesiologists, students at nationally accredited 
paramedic training programs receive only 2-4 days of this training experience.8 Some training 
programs are not able to provide any operating room training. Mannequins do not adequate 
recreate the “feel” of live human airways. 
Regular clinical experience is important for maintaining ETI skill. Using 2003 statewide data from 
Pennsylvania, we found that paramedics performed a median of 1 ETI (interquartile range 0-3) 

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annually; 39% performed no ETI, and 67% performed fewer than two ETI.33 In Maine, Burton, et 
al. found that only 40% of paramedics attempted ETI annually, and only 1-2% of all paramedics 
performed five or more ETI annually.34  
Supraglottic airways (SGA) offer simpler alternatives to ETI. SGA in current North American EMS 
use include the Laryngeal Mask Airway (LMA), Combitube and King Laryngeal Tube.35,36 SGA are 
inserted “blindly” through the mouth and sit outside of the vocal cords.37 (Figure 3) Compared with 
ETI, SGAs offer simple and expeditious operation, lower skill acquisition and maintenance 
thresholds, and similar ventilatory characteristics. While typically reserved for contingency use in 
the event of unsuccessful ETI efforts, many EMS agencies perform primary SGA insertion.38 
While there are no national data descriptions, we are aware of this practice in Kalamazoo, 
Michigan, Chesterfield County, Virginia, Collier County, Florida, and Dallas, Texas. 
We propose a large randomized trial focused on evaluation of these two interventions in the out-
of-hospital cardiac arrest population, with sufficient statistical power to detect changes in 
outcome.  
 
(2) Obtaining informed consent is not feasible because: 
i. 
The subjects will not be able to give their informed consent as a result of 
their medical condition; 
ii. 
The intervention under investigation must be administered before consent 
from the subjects' legally authorized representatives is feasible; and 
iii. There is no reasonable way to identify prospectively the individuals likely 
to become eligible for participation in the clinical investigation. 
The study interventions need to be administered as an early intervention after the onset of cardiac 
arrest. In this uncontrolled setting the patient is unconscious and unable to provide consent for 
study enrollment. Legal next-of-kin are often not immediately available at the scene, nor is it 
practical for the prehospital provider to explain the study and receive consent while caring for the 
cardiac arrest patient. Since we are studying out-of-hospital cardiac arrest, which is frequently the 
first manifestation of cardiovascular disease, there is no way to prospectively identify individuals 
who are likely to become eligible for this trial. 
 
(3) Participation in the research holds out the prospect of direct benefit to the subjects 
because: 
i. 
Subjects are facing a life-threatening situation that necessitates 
intervention; 
ii. 
Appropriate animal and other preclinical studies have been conducted, and 
the information derived from those studies and related evidence support 
the potential for the intervention to provide a direct benefit to the individual 
subjects; and 
iii. Risks associated with the investigation are reasonable in relation to what 
is known about the medical condition of the potential class of subjects, the 

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risks and benefits of standard therapy, if any, and what is known about the 
risks and benefits of the proposed intervention or activity. 
As defined, these patients with cardiac arrest are facing a life-threatening situation that requires 
immediate intervention. 
Previous animal and human studies have been conducted, and suggest the potential for a direct 
benefit to individual subjects in cardiac arrest via improved hemodynamics and short-term survival 
advantage. 
The risks associated with the investigation are reasonable in relation to what is known about the 
medical condition of the candidate subjects, the risks and benefits of standard therapy. While 
airway management is an important priority in OHCA resuscitation, the best airway strategy is 
unknown. Compared with SGA, ETI has enormous system-level costs, including increased 
training and skills maintenance burden, and the heightened risk of serious adverse events (for 
example, tube misplacement or dislodgement). If SGAs achieves superior outcomes than ETI, this 
would indicate that EMS systems should switch to SGAs for OHCA resuscitation. If ETI proves 
superior to SGA, this would prompt efforts to optimize current ETI practices. If there is no 
difference in OHCA outcomes, this would affirm that EMS practitioners can select airway devices 
that best suit their preferences or practice setting. 
(4) The clinical investigation could not practicably be carried out without the waiver. 
This study could not be conducted without the waiver of consent due to the need to administer the 
interventions as early as possible after the onset of cardiac arrest. Cardiac arrest patients are 
unable to provide consent. 
(5) The proposed investigational plan defines the length of the potential therapeutic 
window based on scientific evidence, and the investigator has committed to attempting 
to contact a legally authorized representative for each subject within that window of 
time and, if feasible, to asking the legally authorized representative contacted for 
consent within that window rather than proceeding without consent. The investigator 
will summarize efforts made to contact legally authorized representatives and make this 
information available to the IRB at the time of continuing review. 
Cardiac arrest is a time-critical condition. Victims of cardiac arrest collapse unpredictably in a 
range of public and private areas. Paramedics must mobilize to the patient side, bringing all 
portable monitoring equipment, medications, airway and ventilation equipment. In addition, 
paramedics must coordinate all resuscitation tasks, including delivery of chest compressions, 
insertion of intravenous line, and administration of medications. Documentation of clinical care 
and execution of trial procedures are difficult under these conditions.  
Since this is an immediately life-threatening situation, it will not be possible to obtain consent prior 
to or at the actual time of treatment. A script describing the study will be provided to a recognized 
LAR on scene, when feasible, but it is acknowledged that the acute circumstances may only 
rarely if ever afford such an opportunity. We will make every effort to contact legal representatives 
after admission to the hospital to notify them that the patient was enrolled in a randomized trial 
and provide an opportunity to withdraw from further participation. Although OHRP regulations do 
not require that written informed consent be obtained once the patient is enrolled for continued 

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participation, the local IRB will determine whether a signed document is desirable for continued 
participation. 
If legal representatives are not immediately available, research personnel will attempt to contact 
the subject’s legal representative as soon as feasible and a summary of these efforts will be 
documented in the patient’s chart. If the subject becomes competent during the study period then 
he/she will be approached by research personnel for notification of enrollment. 
(6) The IRB has reviewed and approved informed consent procedures and an informed 
consent document consistent with Department of Health and Human Services (HHS)- 
Office for Human Research Protections (OHRP) Sec. 46.116 and 46.117 of 45 CFR Part 
46. 
All procedures and notification/consent forms will be approved by the Institutional Review Board 
(IRB) of each study site prior to the onset of the trial. 
(7) Additional protections of the rights and welfare of the subjects will be provided, 
including, at least: 
i. 
Consultation (including, where appropriate, consultation carried out by the 
IRB) with representatives of the communities in which the clinical 
investigation will be conducted and from which the subjects will be drawn; 
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; 
iv. Establishment of an independent data monitoring committee to exercise 
oversight of the clinical investigation; and 
v. 
If obtaining informed consent is not feasible and a legally authorized 
representative is not reasonably available, the investigator has committed, 
if 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. 
(i) In U.S, centers, community consultation as outlined by the local IRB will be undertaken prior to 
IRB approval. Since the population eligible for enrollment includes all citizens in the study regions 
it will not be possible to target any particular small group. The community consultation plan for 
each study site will have to be individualized to fit the IRB requirements. Appendix 5 contains an 
example of a community consultation plan that has been used in another study of this nature. 
Feedback from the community will be obtained by research personnel regarding any concerns 
they may have about potential enrollment. If requested, bracelets will be made available that 
could be worn by members of the community who do not want to participate. 

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(ii) & (iii) Public disclosures will be performed both prior to study enrollment and at the completion 
of the study in the form of multimedia press releases organized by the Resuscitation Outcomes 
Consortium. These will include plans for the study including potential risks and benefits and a 
summary of the results of the study upon completion. In the event that the press releases are not 
widely circulated, advertisements will also be placed in local papers describing the study. 
(iv) An independent data monitoring committee will exercise oversight of the study as described 
below.  
(v) We expect that all patients who meet the enrollment criteria will be unconscious. Any delay in 
medical care that would be required for the paramedic to attempt to obtain consent from the 
patient’s legal guardian would be life threatening. Thus it will not be feasible to attempt to obtain 
informed consent during the initial therapeutic window. However, a brief written script describing 
the study (Appendix 5, Section 29.4) will be developed for presentation to a LAR on-scene by the 
prehospital provider, when feasible, giving an opportunity to object to study enrollment. Because 
the acute circumstances of cardiac arrest rarely if ever afford even such a limited opportunity 
without compromising patient care in process, determine if or when presenting this script is 
feasible, in light of these safety considerations, will be left to the clinical discretion of the provider..  
The local ROC investigator will provide information about the emergency research study to the 
patient or their representative at the earliest feasible opportunity after administration of the 
intervention and given an opportunity to withdraw from further participation. Once the patient 
reaches the hospital no further research interventions will occur except for data collection. The 
local IRB will determine whether a signed document is desirable for continued participation. In the 
event that a patient or their family withdraws from ongoing participation survival from hospital 
discharge will be ascertained from publically available sources.  
 
 
 

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Appendix 5 – Example Patient Notification Forms for Use Under Exception from 
29.
Informed Consent for Emergency Research 
 Notification Forms (for initially surviving Subjects) 
29.1
 
Title of Research: 
 
Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac Arrest 
IRB Protocol #: 
[XXXXXXX] 
Investigator:   
[XXXXXXX] 
Sponsor:  
The National Institutes of Health 
 
 
The University of Alabama at Birmingham 
 
 
University of Washington 
Please note that the term “you” used in this document refers to either you or your family member 
You had a cardiac arrest and survived. The Emergency Medical System (EMS) providers quickly 
started cardiopulmonary resuscitation (CPR). This includes breathing for you by inserting a tube 
(an airway tube) into your windpipe and pumping on your chest. They may have applied electricity 
to your heart, often referred to as defibrillation, to try and restore a normal heart beat. You were 
enrolled in a research study conducted by [institution] through the Resuscitation Outcomes 
Consortium (ROC). ROC is the largest prehospital clinical research consortium in the world, 
focusing on research in the areas of prehospital cardiopulmonary arrest and severe traumatic 
injury. The purpose of this notification form is to give you information about this study. You may 
ask questions about the purpose of the research, why you were enrolled, the possible risks and 
benefits, your rights as a research participant, and anything else about the research or this form 
that is not clear. We will give you a copy of this form for your records.  
Cardiac arrest is an extreme emergency during which the patient will die within a few minutes if 
treatment is not begun immediately. Patients in cardiac arrest are unconscious and unable to 
discuss their treatment, and any time taken to discuss their treatment with family robs the patient 
of immediately starting life-saving measures. Because of this and because an airway tube must 
be inserted quickly after a cardiac arrest, you were entered into the study at the scene of the 
event. In this situation, oversight groups who are responsible for supervising and regulating such 
studies, including the United States Office for Human Research Protections (OHRP), have 
allowed us to enter people into the study without first obtaining written consent. This permission 
was granted only after informing and seeking input from the local community as required by an 
oversight group. These requirements may have included household surveys, press releases, and 
lectures to the medical and lay public. 
There are also other safeguards in place for this research. First, the National Heart, Lung, and 
Blood Institute of the National Institutes of Health (NIH) which is supporting this research, had an 
independent Data and Safety Monitoring Board to review the research to make sure it was 
scientifically sound. The DSMB also monitors the results of the research during the course of the 
study to be sure of patient safety. Finally, a local group associated with the University of [ ] is also 
monitoring the research.  

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Purpose of the Research 
The purpose of this study is to determine whether one of two airway tubes that are currently being 
used in the prehospital setting is better than the other. The two tubes being compared are 1) the 
“endotracheal tube,” which is a plastic breathing tube inserted into the airway (windpipe), and 2) a 
“supraglottic airway”, which is a tube inserted into the esophagus (the opening to the throat and 
stomach, where you swallow), to block off the esophagus so that air only goes into the lungs. Both 
types of tubes are used by EMS providers, but prior studies have not shown whether one works 
better than the other.  
EMS providers treat cardiac arrest by performing cardiopulmonary resuscitation (CPR). This 
includes pushing on the chest with the heel of their hands to help the blood move, and if needed, 
helping a person to breathe by inserting a tube through the mouth into the throat so that air is able 
to reach the lungs. When a person cannot breathe on his or her own, an airway tube allows 
oxygen to reach the lungs and be circulated throughout the body during CPR. 
The EMS providers who cared for you when you had your cardiac arrest are participating in a 
research study to see if we can determine whether one airway tube is better than another. 
Because of the seriousness of your illness and the immediate need for treatment, the providers 
were unable to ask for your permission to participate in the study. However, we told the public 
about this study before it started. Also, the [name of institutional] Institutional Review Board 
reviewed this study before it started and gave us permission to enroll subjects without their 
consent. The study is being supervised locally by Dr. [full name] of [institution]. This study is being 
conducted in six regional community centers within the US, and will enroll over 3,000 persons. 
Explanation of Procedures 
In this study, all participating EMS providers are using the same airway tube for a period of time, 
and then will switch to the other tube for the same amount of time. You had one of these two 
airway tubes inserted as part of this study. When EMS personnel cared for you, they performed all 
the procedures they would have normally performed. In the event that the EMS personnel were 
not able to use the airway tube being studied, they would have used an alternate method, such as 
a different type of airway tube.  
After you were admitted to the hospital, all of the treatments for your cardiac condition were 
determined by your physicians, and this study did not interfere with such treatment in any way. 
Airway tubes inserted by EMS personnel may be removed or replaced at the doctor’s discretion.  
As part of this study, we will record some information about you. We will collect information from 
the EMS agency about your medical condition when they arrived, and what care they 
administered to you. We will also collect information from your hospital stay about the care you 
received here, any reports from operations or other procedures you had (such as X-rays or other 
imaging), what medications you were given, and how long you stayed in the hospital.  
Risks and Benefits of the Research 
If there is any benefit to you from being in the study, it has already occurred. You will receive no 
further benefit from being in this study. However, your participation in this study will benefit society 
if we are able to show whether one of the two airway tubes being studied has better results. 

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Patient safety is carefully monitored and recorded for any complications from study treatments. As 
is possible with any medical intervention, there are risks involved with having an airway tube 
inserted; however, since this study uses two airway tubes that are currently being used by EMS 
providers, being enrolled in this study does not add additional medical risks.  
The risks of insertion of an airway tube include unsuccessful airway insertion, multiple insertion 
attempts, airway tube misplacement (tube is inserted incorrectly), inadequate ventilation (tube 
does not allow enough air passing into the lungs), vomiting after airway insertion, cuts, scrapes, or 
perforations to the soft tissues inside the mouth of throat, injury to teeth, and a collapsed lung.  
Alternatives 
The best known emergency care for cardiac arrest was given to you by the EMS personnel. 
Cardiac arrest is normally treated, in part, with the use of airway tubes, including the types used in 
this study. 
Confidentiality 
Your confidentiality will be respected; information that discloses your identity will not be released 
without your consent unless required by law or regulation. Research records and medical records 
identifying you may be inspected in the presence of the investigator or his designate by 
representatives of the Research Outcomes Consortium (ROC), the National Institutes of Health 
(NIH), Office for Human Research Protections (OHRP), and the Institutional Review Boards (IRB 
– the committee that protects the rights of research subjects) of [institution]. Records that identify 
you by name or initials will not be allowed to leave the research offices of the investigators. 
Information about your condition will be sent to the ROC study Coordinating Center at the 
University of Washington in Seattle, WA. All information sent to the Coordinating Center is coded 
and no personal identifiers such as name, phone number, or address are included. 
You have been assigned a specific code number. A key linking you to the code number is kept in 
a secure location and will be available only to the investigators and research staff at this 
institution. The study enrollment log is password protected and stored on the [explain site-specific 
data storage]. This study is expected to be completed by 2019. The data will be stored as per the 
[institution]’s IRB requirements for a period of [x] years and only then will the paper documents be 
shredded and data destroyed on-site. 
Results from this study, without personal identity information, may be reported in scientific 
meetings, articles or other appropriate communication. If during the course of the study, new 
information becomes available, we will provide it to you. A description of this clinical trial will be 
available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include 
information that can identify you. At most, the website will include a summary of the results. You 
can search this website at any time. 
[Include site-specific billing information]  
Voluntary Participation and Withdrawal 
You may withdraw from further participation in this study at any time after receiving this 
notification without penalty or loss of benefits to which you are otherwise entitled by telling us or 
by contacting the investigators at [phone number of local investigator]. We will, however, keep the 

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data collected up to the date that you withdraw yourself so that we are able to report on the safety 
of the study.  
Cost of Participation 
There will be no cost to you for participation in the research. The costs of your standard medical 
care will be billed to your insurance company in the usual manner.  
Payment for Research-Related Injuries 
[local institution], The University of Alabama at Birmingham, and the National Institutes of Health 
have not provided for any payment if you are harmed as a result of taking part in this study. If 
such harm occurs, treatment will be provided; however, this treatment will not be provided free of 
charge. 
Significant New Findings 
[Local PI] and [his/her] staff will provide any significant new findings that develop during the 
course of the study that may affect your willingness to continue in the research study. 
Questions 
[Include local institution’s required language for contacting the local PI with questions about the 
study, and information to contact the local IRB about “rights as a research participant,” or with 
concerns or complaints about the research] 
Legal Rights [Need for this section will vary by institution.] 
[You are not waiving any of your legal rights by signing this document.] 
Signatures [Need for this section will vary by institution.] 
[Your signature below indicates that you agree to continue to participate in this study. You will 
receive a copy of this signed consent form.]  
 
 
 
 
 
 
 
 
 
 
 
 Next of Kin Notification Letter (for family of subjects who did not survive) 
29.2
 
Date 
To the Family of (insert patient’s name) 
Address 
Address 
Dear Family Member: 
We understand that this letter may come at a time that is difficult for your family, and we offer our 
condolences for your loss. We are aware a death is often an unexpected event and may have 
devastating personal consequences. 
 

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Your family member experienced a cardiac arrest and was transported to [institution]. We want to 
assure you that your family member received the best medical care currently practiced for 
treatment of cardiac arrest. In addition to the standard treatments for cardiac arrest, your family 
member was entered into a research study called “[Pragmatic Trial of Airway Management in Out-
of-Hospital Cardiac Arrest]”. We are writing you now to inform you that this occurred. This was 
done without their consent because they required emergency care that could not be delayed to 
allow adequate consideration of informed consent. No further action on your part is required. We 
are including with this letter, a description of the study. In addition to receiving the study 
intervention, research data and routine clinical information was collected as part of the study. Your 
family member’s personal information will remain confidential. You may request that we not collect 
any further information on your family member by calling the number listed below; however, we 
cannot discard any information we collected prior to your request.  
Your loved one’s participation in this study will contribute a great deal to better understanding how 
we can improve the treatment of patients who have a cardiac arrest. Apart from our sharing this 
information with you, you will receive no further contact from study personnel. 
This research is overseen by the Institutional Review Board (IRB) of [institution]. They oversee the 
safety of subjects in medical research. This study was described to the general population 
through the media in newspapers, radio and television. Community opinion was sought, and 
community leaders and citizens agreed that this study was needed. The ROC (Research 
Outcomes Consortium), located at [institution], is part of the largest Prehospital clinical research 
consortium in the world, focusing on research in the areas of Prehospital cardiopulmonary arrest 
and severe traumatic injury. If you have any questions about the research study, please feel free 
to contact me or my staff at the number listed below. If you have any questions about your family 
member’s rights as a research participant, or concerns or complaints about the research, you may 
contact the [institution’s name, name of IRB, phone number, and hours of operations]. You may 
also call this number in the event the research staff cannot be reached or you wish to talk to 
someone else. 
We apologize for this intrusion. Please accept our sincere condolences to you and your family. 
Kindest regards, 
[PI] 
 
 

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 Study Information Sheet (accompanies Next of Kin Notification Letter) 
29.3
 
Title: Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac Arrest 
Your family member was treated for a cardiac arrest by Emergency Medical Services (EMS) 
personnel, and at [institution]. When he/she was being treated at the scene and in the emergency 
department, he/she was unconscious and/or unable to reliably talk with us about his/her wishes. 
During this time your family member was enrolled in a study called “Pragmatic Trial of Airway 
Management in Out-of-Hospital Cardiac Arrest”. 
An Institutional Review Board (IRB) at [local site] has given us permission to do this study in 
which subjects are enrolled without their consent. This process is called exception from informed 
consent for emergency research.  
During a cardiac arrest, cardiopulmonary resuscitation (CPR) is performed by EMS personnel. 
This includes breathing for the patient by inserting an airway tube into the windpipe, and pumping 
on the patient’s chest. The purpose of this study is to determine whether one of two airway tubes 
that are currently being used is better than the other. The two tubes being compared are 1) the 
“endotracheal tube,” which is a plastic breathing tube inserted into the airway (windpipe), and 2) a 
“supraglottic airway”, which is a tube inserted into the esophagus (the opening to the throat and 
stomach, where you swallow), to block off the esophagus so that air only goes into the lungs. Both 
types of tubes are used by EMS providers, but prior studies have not shown whether one works 
better than the other.  
The study is being done throughout the United States and Canada by an emergency medicine 
network called the Resuscitation Outcomes Consortium (ROC), of which Dr. [local PI] is a 
member. The ROC is the largest prehospital clinical research consortium in the world, focusing on 
research in the areas of prehospital cardiopulmonary arrest and severe traumatic injury. This 
study is funded by a grant received from the U.S. National Institutes of Health. 
Your family member’s participation in this study will help us to better understand treatment of 
cardiac arrest and how we can improve the care of future cardiac arrest patients. Our study 
evaluates the usual care and procedures routinely performed by Emergency Medical Service 
(EMS) Agencies throughout the United States and Canada. If you have any questions, concerns, 
or complaints about the research or a research related injury including available treatments, you 
may contact Dr. [PI] or [his/her] staff and they will be glad to answer any of your questions. Their 
number is [ local site PI’s number ] .  
[Insert instructions for after-hours calls, as well as for questions about your rights as a research 
participant, and also for concerns or complaints about the research. Include office hours]  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Website will 
include a summary of the results. You can search this Website at any time. 
 
 

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 Script for EMS Notification of Next of Kin 
29.4
 
Emergency Provider Script for Verbal Notification of Exception from Informed Consent  
 
 
TITLE OF RESEARCH: 
Pragmatic Trial of Airway Management in Out-of-Hospital Cardiac 
Arrest 
 
IRB PROTOCOL: 
[Local information] 
 
INVESTIGATOR: 
[Local information] 
 
SPONSOR: 
National Institutes of Health (NIH) 
 
University of Alabama at Birmingham 
 
University of Washington 
 
Instructions:  
While at the scene, when the participating emergency medical system (EMS) provider determines 
the patient has met the study inclusion and exclusion criteria, the following information may be 
provided as feasible to the conscious and alert patient, legally authorized representative, and/or 
family member of the patient who has experienced a cardiac arrest. 
The purpose of the study information script is to attempt to provide an opportunity for verbal 
objection to study enrollment or to offer the opportunity to decline further participation, if already 
enrolled, only if the situation is both safe and does not adversely affect patient care and/or 
transport. The acute circumstances should only rarely, if ever, afford such opportunities.  
EMS providers will be trained to attempt notification only in situations when feasible to conscious 
or alert patient, legal representative or family member. 
 
Script: 
1. You (or your loved one) appear to have suffered a cardiac arrest and needs treatment to 
open the airway to introduce oxygen to the body to protect the brain and body from oxygen 
deprivation.  
  
2. I want to let you know that we (EMS Agency Name) are conducting a research study that 
tests two different types of breathing tubes that are commonly used by EMS personnel for 
cardiac arrest patients. 
 
3. Treatment needs to be done quickly, but we want to give you the option of not being 
enrolled in the study. 
 
4. If you say no we will treat you (or your loved one) according to our standard protocols. 
Someone will give you more information when we reach the hospital.  
 
 
 
 

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 Sample Community Consultation Plan 
29.5
The following is an example community consultation plan from a prior interventional trauma study 
that we implemented with the Resuscitation Outcome Consortium IRB protocol, F120425003 – 
Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR). Participating sites will 
develop individualized community consultation plans for the trial. 
 
A. Goal 
The community consultation process is designed to allow the public to provide input before the 
study begins. Community consultation also provides an opportunity to learn more about 
community members’ understanding of the research and how they weigh the potential benefits 
and risks associated with the proposed study. This requires a clear presentation of the purpose of 
the study, the treatment, the potential risks and benefits of the study, along with the best available 
estimates of the results. 
B. Objectives 
- 
1. Communicate with a variety of audiences and special interest groups with the target 
population being 15-45 years of age for traumatic injury. 
- 
2. Remind the community of the overall goal to improve emergency care (i.e., improve the 
public’s health). 
- 
3. Educate the community that clinical research is vital to improving health care and saving 
lives and help them understand why emergency exception from informed consent is needed. 
- 
4. Describe the proposed study and its relationship to current gaps in our knowledge about 
treating critically injured patients. 
- 
5. Assess the community’s understanding of the proposed research, associated risks and 
benefits, and emergency trauma care research. 
- 
6. Solicit input from community members regarding the acceptability of the study and their 
concerns about the study. 
C. Message 
We need the community’s help to begin this important medical research. Members of our 
community need to provide their opinions on the study and the unique nature of the emergency 
exception from informed consent before the studies can begin. We encourage dissemination of 
information to the community and feedback from the community. A task force of ROC staff, IRB 
representatives and members of the public should initiate and encourage this important two-way 
communication through websites, newsletters and press releases. 
This vital research depends on the combined efforts of the research staff and the trauma care 
providers at UAB. They have joined forces to improve emergency trauma care in our community. 

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By working with a consortium, we can obtain scientifically valid results that help identify more 
effective trauma treatments in less time.  
Patient safety is our highest concern. Before implementation, the study must be approved by 
three different panels of scientists not directly affiliated with the study. The study will also have 
independent and ongoing safety monitoring.  
Eligible patients either receive current standard of care treatments, many of which are unproven in 
terms of benefit, or alternatives that have shown potential promise. The assignment of treatment 
will occur by chance (i.e., assignment will be random; by chance). No eligible patient will receive 
preferential treatment. 
Drawing on earlier studies, the researchers hope the therapy being studied will be better than 
current standard of care treatment. But, this promising treatment has not been proven to be better 
in a large clinical trial. This is the final step before a treatment becomes standard of care. 
There is no additional charge to the eligible patient for participation in these studies. 
The investigators recommend that people who don’t want to participate in the study wear a clearly 
identifiable “Opt Out Of ROC Research” bracelet. It is not practical to pre-enroll study participants 
given the magnitude and duration of the study.  
Our primary goal is community education and informing the public about exception from informed 
consent. The UAB trauma center is the only trauma center in Central Alabama. As such, patients 
from across central Alabama, who are transport by a participating EMS agency, will be eligible for 
enrollment if they meet the inclusion criteria and are transported to the UAB trauma center. 
Participating EMS agencies are: Air Methods (LifeSaver helicopters), Bessemer Fire Department, 
Birmingham Fire and Rescue, Center Point Fire District, Hoover Fire Department, NorthStar EMS, 
and Regional Paramedical Services in Walker and St. Clair county will be trained and participate 
in this study. Most eligible participants will comes from Jefferson, Shelby, Walker, St. Clair, 
Talladega, Chilton, Blount, Calhoun, Cullman, Etowah, Winston, Tuscaloosa, Greene, Pickens, 
Fayette, Bibb, Perry, Hale, Clay and Coosa and counties. 
In conducting community consultation activities, the UAB ROC staff ensures that representatives 
from the communities involved in the research have an opportunity to participate in the 
consultation process. The UAB ROC staff proposes this multi-facetted approach for effective and 
broad-based community consultation and public disclosure activities so that members of as many 
different groups within the local ROC communities will have an opportunity for input. 
1. Prior to start up: Mass Media 
- 
Exposure in a large circulating newspaper. 
- 
Exposure in networks affiliated with local television stations in conjunction with the University 
Media Relations department. 
- 
Be available to answer questions raised by the public. 

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2. Prior to start up: Local infrastructure 
- 
Provide designated information telephone for questions/comments.  
- 
Provide an accessible website (www.uab.edu/arc) with additional information on the study 
(FAQ), opt-out methods, and contact information for the investigators and IRB. 
- 
Keep a log of the questions and comments for subsequent IRB review. 
3. Prior to start up: Local Media/Geographic Region/Site 
- 
Announcement in the Birmingham News (at 1 month prior and start of data collection) 
- 
A Random Digit Dialing survey of the eligible counties listed above will be solicited about 
this research study. The UAB Survey Research Unit will conduct the Random Digit Dialing 
survey and these results will be shared with the UAB IRB. Each county will be weighted 
based on the percent of population (see attached distribution).  
- 
Attached is a manuscript described our previous experience using social media We propose 
utilize the same method and will develop a 90 character ad that will be an external link from 
Facebook, to the UAB ROC website (www.uab.edu/arc). This ad will be on the side bar and 
will appear only on Facebook users 15 years of age and older, and whom live within a 50 
mile radius of Birmingham. According to Facebook, there are 592,240 Facebook users that 
meet that criteria. Our proposed ad (Listed below) would be displayed on the side-bar of this 
at-risk population of Facebook user accounts. If a user clicks on the ad, they are redirected 
to the UAB ROC website, where they can find information about this specific protocol (see 
FAQ, how to Opt-Out of the ROC studies, and contact information for the UAB ROC office). 
Using Google Analytics software, we can provide quantifiable information to the IRB about 
the number of visitors to each webpage, including the number of visitors to the study 
description page, and opt-out page.  
- 
Be available to answer questions raised by the public. 
4. During the study period: Mass and Local Media/Geographic Region 
- 
Periodic (≈6 months) updates of study progression to media. 
- 
Be available to answer questions raised by the public. 
5. Completion of the study period: Mass and Local Media/Geographic Region 
- 
Coordinated media press release with the NIH, and UAB media relations. 
- 
Posting the study summary on the Alabama ROC website. 
- 
Be available to answer questions raised by the public. 
 
 

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Opt-Out of the ROC studies  
We respect the wishes of members of our community that do 
not wish to be enrolled in the ROC research clinical trials. If 
community members do not want to participate in these 
research trials, they can request to Opt-Out. We offer a 
silicone bracelet with the words “Opt-out of ROC Research” engraved on it. Community members 
will have to wear this bracelet during the time this study is being conducted beginning now – 
through the year 2015.  
Even if someone opts out, there is no guarantee that under emergency circumstances the 
bracelet will be attached to the person. The individual might still be enrolled in the study. In the 
unlikely event they are enrolled after they have requested not to be enrolled; we will not use any 
of the information collected, and all information pertaining to the enrollment will be destroyed. 
Two Ways to get your Opt-Out of the ROC Research material.  
- 
Contact or visit the ARC office at (205) 934-9532 or via email: alabamaroc@uabmc.edu 
- 
Stop by the ROC research office and pick up an Opt-Out wrist band. Our office is located in 
the Kracke Building on the Campus of UAB, room 531. The address is 1922 7th Avenue 
South Birmingham, Alabama. 
 
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