Bougie Use in Emergency Airway Management
Phase: NA
Conditions: Acute Respiratory Failure
Sponsor: Hennepin Healthcare Research Institute

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1 
Clinical Trial Protocol 
 
 
 
Study Title:    
Bougie use in Emergency Airway Management (BEAM) 
 
 
Investigators:  
Brian Driver, MD; Lauren Klein, MD; Jon Cole, MD; Matt 
Prekker, MD, Johanna Moore, MD; Robert Reardon, MD; James 
Miner, MD 
 
Phase: 
IV 
 
Contact:  
 
Hennepin County Medical Center 
 
 
 
Department of Emergency Medicine 
 
 
 
701 Park Ave, Mailstop R2 
 
 
 
Minneapolis, MN 55415 
 
 
 
612.293.8286 
 
Institutional  
Minneapolis Medical Research Foundation 
Review Board 
701 Park Ave, Suite PP7.700 
 
 
 
Minneapolis, MN 55415 
 
 
 
612.873.5300 
 
 
 
 
 
 
 
 
 
Date 
Protocol version 1.0:  
15 December 2015 
Protocol version 1.1:  
18 May 2016 
 
 
 
 

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2 
 
Table of Contents 
 
Table of Contents ....................................................................................................................................... 2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................................... 4 
1  
INTRODUCTION ................................................................................................................................ 5 
1.1 
Previous published literature ........................................................................................... 5 
1.2 
Rationale for further investigation ................................................................................. 7 
1.3 
Known risks of the interventions .................................................................................... 7 
1.3.1 Known risks of orotracheal intubation without a bougie ................................ 8 
1.3.2 Known risks of orotracheal intubation with a bougie ....................................... 8 
1.4 
Proposed Study Population ................................................................................................ 8 
2   STUDY OBJECTIVES ......................................................................................................................... 8 
2.1 
Primary outcome .................................................................................................................... 8 
2.2 
Secondary outcomes ............................................................................................................. 9 
3  
MEASUREMENT OF STUDY OUTCOMES ............................................................................. 10 
3.1 
Measurement of primary outcome .............................................................................. 10 
3.2 
Measurement of secondary outcomes ........................................................................ 10 
4 
INVESTIGATIONAL PLAN .......................................................................................................... 11 
4.1 
Overall Study Design and Plan ....................................................................................... 11 
4.1.1  Study Population and Randomization ................................................................... 11 
4.1.2  Study Treatment and Blinding ................................................................................. 11 
4.2 
Assessments ........................................................................................................................... 11 
4.2.1  Outcome Assessments .................................................................................................. 11 
4.2.2 Safety Assessments ........................................................................................................... 11 
4.3 
Study Duration ...................................................................................................................... 12 
5  
STUDY POPULATION SELECTION .......................................................................................... 13 
5.1 
Study Population .................................................................................................................. 13 
5.2 
Inclusion Criteria ................................................................................................................. 13 
5.3 
Exclusion Criteria ................................................................................................................ 13 
5.4 
Subject Withdrawal Criteria ........................................................................................... 13 
6 
STUDY CONSENT ........................................................................................................................... 14 
6.1 
Research involves no more than minimal risk to the subjects ........................ 14 
6.2 
The waiver or alteration will not adversely affect the rights and welfare of 
the subjects ........................................................................................................................................... 15 
6.3 
The research could not practicably be carried out without the waiver or 
alteration ............................................................................................................................................... 15 
6.3.1 Patient objection ............................................................................................................. 16 
6.3.2 LAR or Family member objection ........................................................................... 16 
6.4 
Notification after enrollment .......................................................................................... 16 
7 
STUDY PROCEDURES .................................................................................................................. 17 
7.1 
Study Entrance Criteria ..................................................................................................... 17 
7.2 
Enrollment .............................................................................................................................. 17 
7.3 
Baseline and ED Data Collection ................................................................................... 17 
7.4 
Adverse Event Assessments ........................................................................................... 17 

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7.4.1 Adverse Event Monitoring and Period of Observation .................................. 18 
7.4.2 Reporting Serious Adverse Events ......................................................................... 18 
7.5 
Safety-Related Stopping Rules ....................................................................................... 18 
8 
PLANNED STATISTICAL METHODS ...................................................................................... 19 
8.1 
General Considerations ..................................................................................................... 19 
8.2 
Sample size calculation ..................................................................................................... 19 
8.3 
Method of Assigning Study Patients to Treatment Groups ............................... 19 
8.4 
Population Description ..................................................................................................... 19 
8.4.1 Analysis Populations ..................................................................................................... 20 
8.4.2 Treatment Compliance ................................................................................................ 20 
8.5 
Outcome Analysis ................................................................................................................ 20 
8.6 
Statistical/Analytic Issues ............................................................................................... 20 
8.6.1 Handling of Missing Data ............................................................................................ 20 
8.6.2 Interim Analysis and Data Monitoring .................................................................. 21 
9 
ADMINISTRATIVE CONSIDERATIONS ................................................................................. 22 
9.1 
Institutional Review Board Approval ......................................................................... 22 
9.2 
Data monitoring committee ............................................................................................ 22 
9.3 
Protocol Violations/Deviations ..................................................................................... 22 
9.4 
Premature Closure of the Study .................................................................................... 22 
10 
LIST OF REFERENCES ............................................................................................................ 23 
 
 

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4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
 
Abbreviation 
Definition 
AE 
Adverse event 
DSMB 
Data safety and monitoring board 
ED 
Emergency Department 
ETT 
Endotracheal tube 
GEB 
Gum-elastic bougie 
HCMC 
Hennepin County Medical Center 
IRB 
Institutional review board 
ITT 
Intention-to-treat 
LAR 
Legally-authorized representative 
SAE 
Serious Adverse Event 
 
 

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5 
1  
INTRODUCTION 
 
Rapid and definitive airway management is an essential skill for all emergency 
physicians. Orotracheal intubation is the most common means to obtain a definitive 
airway, and is classically performed using an endotracheal tube with an intubating 
sylet inserted into the tube for rigidity.  The tube and stylet are passed under direct 
vision. Using these methods, the majority of patients in the emergency department 
can be successfully intubated, and therefore successfully oxygenated and ventilated. 
 
The concept of first-pass success, that is, passing the endotracheal tube successfully 
on the first intubation attempt, is paramount in emergency airway management.  It 
has been shown that for every attempt after the first, complications increase 
dramatically.1  While emergency medicine has been improving airway management 
and first pass success over the past several years, a large cross-sectional sample 
demonstrated that first pass success remains approximately 85%.2   First pass 
success is likely lower in the hands of less experienced operators, such as 
emergency medicine residents in training.  Therefore, there is substantial room for 
improvement.  A simple adjunct to endotracheal intubation, the gum elastic bougie 
(GEB), may increase first pass success and decrease rates of intubation-associated 
hypoxemia.  
 
The GEB is a 60 or 70-centimeter stylet with an approximately 30-degree angle at its 
tip.  When used during an intubation attempt, the GEB is passed between the vocal 
cords; then the endotracheal tube is passed over the GEB into the trachea.  The GEB 
essentially serves as a flexible guide into the trachea.   
 
It can enable successful intubation in difficult airways due to its flexible material, 
allowing the intubating provider to be able to direct its tip anteriorly through the 
vocal cords. Proper placement of the GEB can be performed by direct visualization, 
video assisted visualization, and also both the feeling of “clicks” as the GEB passes 
over tracheal rings and a “hard stop” when the GEB comes into contact with a 
mainstem bronchus at the level of the carina.3,4  
 
 
1.1 Previous published literature 
 
 
The first report of adjunctive GEB use in difficult endotracheal intubation was in 
1949, described by Macintosh.5 Although it did not receive much attention in the 
literature for many years thereafter, the late 1980’s and early 1990’s saw multiple 
case reports and case series describing the effectiveness of the GEB in these clinical 
scenarios. 3,6-8 As the GEB became more popular, several larger series were 
published supporting its use. One series of 2000 anesthesiology incident reports of 
difficult intubations concluded that the most successful airway adjunct was the 

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GEB.9  Another retrospective trial found a 99% success rate when using the GEB 
during 301 difficult intubations over an 8-year period.10    
 
Several prospective studies have also been published describing the use of the GEB 
in difficult airways. One prospective trial found that 199 out of 200 attempts at 
placing the GEB in the trachea were successful.11 In this study, the providers elected 
to use the GEB due to a poor laryngeal view or failed attempts at conventional sylet 
intubation. Another prospective observational cross-over study described the use of 
the GEB in cadaveric airways.12  The cadavers were manipulated to have either a 
Cormack-Lehane Grade 1 or Grade 3 view, and emergency medicine residents 
intubated them with either a stylet or a GEB. The authors found a trend toward 
increased success in the GEB group in the Grade 3 view cadavers but this result did 
not achieve statistical significance. 
 
The first randomized study to assess the efficacy of the GEB was conducted in 
1993.13 This study simulated cervical spine injuries to create a difficult airway.  The 
patients in this study had manual in-line stabilization maintained during intubation, 
which significantly decreased the view of the larynx. Patients were randomized to 
direct visualization versus intubation using a GEB. The authors found that all 
patients who had failed intubation in the direct visualization group were 
successfully intubated within 45 seconds using the GEB. Another randomized trial 
describing GEB use was published in 1996.14 The authors of this study randomized 
patients to a GEB versus a standard stylet during direct laryngoscopy. The authors 
created difficult intubation scenario by simulating a Cormack-Lehane Grade 3 view 
with laryngoscope placement. Each group had two attempts at intubation with their 
randomized equipment before they could cross over. They found that the GEB group 
was successful 96% of the time while the stylet group was successful 66% of the 
time after the first two attempts, demonstrating compelling evidence for the use of 
the GEB in difficult airways.   
 
 
Certain types of difficult airways may be more amenable to GEB-facilitated 
intubation.  One scenario that has been well described is the difficult trauma airway, 
particularly those with facial and neck trauma.13,15,16  The trauma airway provides a 
unique set of complications to airway control including active hemorrhage, 
distorted anatomy, and cervical immobility due to cervical collar use. Another 
scenario in which the use GEB is commonly described is in the setting of pre-
hospital difficult airways.17-20  Based on its observed success, one group reported 
that the GEB became part of a pre-hospital institutional algorithm for difficult 
airway management.17 
 
Most of the evidence describing the use of the GEB has stemmed from the 
anesthesiology literature, with relatively little reference to its use in the emergency 
departments. Few studies describe emergency providers utilizing the GEB on airway 
task-trainers,21 manikins,22,23 and cadavers,12 but all are limited by artificial airway 
simulations.  
 

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There are two observational trials in humans published in 2011 by the same group 
of authors.24,25 These trials report data on the use of the GEB as a rescue device after 
failed intubation. The success rates described in these trials were 20 out of 26 
(76.9%) and 70 out of 88 (79.6%) attempts, respectively. These success rates are 
lower that what is typically cited, but the authors identified limitations including the 
fact that the participants in their study were residents using the GEB for the first 
time, suggesting the need for education on its use prior to utilization in the 
emergency department. 
 
 
1.2 Rationale for further investigation 
 
Based on this review of the literature, there is evidence supporting GEB use as an 
adjunct for difficult airways.  However, because it is not always possible to 
anticipate a difficult airway, or even semi-difficult airway, before an intubation 
attempt begins, the bougie may improve the overall success of routine intubations 
as well, especially for patients with any difficult airway characteristics.    
 
However, while the GEB has significant face validity in its ability to improve 
intubation success, a large multi-center study demonstrated that only 3.5% of first 
attempts use the GEB.2  This speaks to the possibility that increasing the use of the 
GEB, a simple, low-cost intervention, may improve first pass success and decrease 
intubation-associated complications.   
 
The practice in the Emergency Department at Hennepin County Medical Center 
(HCMC), however, varies from nationwide practice in that the GEB is available for 
every first intubation attempt.  Based on the treating physicians preference, the GEB 
may or may not be used on the first attempt.  Thus, it is standard of care at HCMC to 
use and not use the GEB on the first attempt.  We have experienced faculty members, 
many of whom are airway experts, who feel strongly on both sides, with some 
stating that it should be used uniformly, and others saying that it should be reserved 
for intubations that are not successful on the first attempt.  Thus, there is a clinical 
equipoise on whether to use or not use a GEB on the first attempt.  
 
To our knowledge there are no randomized control trials studying first pass success 
and peri-intubation hypoxemia with and without the use of a GEB.  This proposed 
research study will attempt to answer the question of whether the use of the GEB is 
superior to non-use of the GEB in emergency department airway management. 
 
 
1.3 Known risks of the interventions 
 
While the procedure of endotracheal intubation has many inherent risks, there are 
no significant differences in risk between orotracheal intubation with  and without a 
bougie. 

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8 
 
1.3.1 Known risks of orotracheal intubation without a bougie 
 
Risks of orotracheal intubation without a bougie include: inability to pass the ETT 
and stylet past the hypopharnx through the vocal cords, and inability to slide the 
endotracheal tube over the stylet.  There are rare case reports of breakage of the 
metal tip of the stylet.  Patients intubated with an endotracheal tube without a 
bougie are at risk for airway perforation, oropharyngeal trauma, laryngeal trauma, 
tracheobronchial trauma, and esophageal intubation.  
 
 
1.3.2 Known risks of orotracheal intubation with a bougie 
 
Risks of orotracheal intubation with a bougie includes: inability to pass the GEB past 
the hypopharynx through the vocal cords, and inability to pass the endotracheal 
tube over the bougie 25.  There are rare mechanical complications that have been 
reported with the GEB, including breakage of the GEB tip,26 and fracture of the 
material.27 Major medical complications of GEB use are rare.. The reported 
complications of GEB use include hemopneumothorax 28, pharyngeal wall 
perforation,29 traumatic bleeding within the airway,30,31 and tracheal injury.32  
Several of these case reports describe patients with post-surgical and complex 
airway anatomy, and GEB use as the sole inciting mechanism for the trauma is 
debatable..  
 
 
 
 
1.4 Proposed Study Population 
 
Adult patients undergoing orotracheal intubation in the ED with a Macintosh blade 
(using either video or direct laryngoscopy) for any indication will be randomized to 
use of the GEB during the first intubation attempt. All other care will be at the 
discretion of the treating emergency physician. 
 
 
 
 
2   STUDY OBJECTIVES 
 
2.1 Primary outcome 
 
The primary outcome of this study will be first pass success.   
 

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First pass success is defined as placement of the endotracheal tube (ETT) into the 
trachea on the first attempt.  An attempt begins when the laryngoscope enters the 
mouth, and ends if either of the following occur: 
1. the laryngoscope leaves the mouth, regardless of whether an attempt was 
made to pass the endotracheal tube or bougie.   
2. if the operator cannot intubate the trachea with the first tube device (ETT or 
bougie), and switches to any other tube device, even if the laryngoscope 
blade remains in the mouth.     
 
 
A patient will be considered to achieve the primary outcome if they are intubated 
successfully on the first attempt. 
 
Tracheal position of the ETT is confirmed immediately using a standard protocol 
involving multiple modalities (physical exam, capnography, and chest x-ray, among 
others).  
 
 
2.2 Secondary outcomes 
 
1) 
First pass success without hypoxemia.    Hypoxemia is defined as a pulse 
oximetry value (SpO2) less than 90% at any point during intubation, or a 
drop of more than 10% from baseline if starting below 90%.  The outcome of 
hypoxemia will be recorded beginning when the first attempt begins and 
ending one minute after inflation of the ETT cuff.     
 
A patient will be considered to achieve this outcome if 1) they are intubated 
successfully on the first attempt, and 2) do not experience hypoxemia on the 
first attempt. 
 
 
2) 
Time to intubation (first attempt only). Time to intubation will be defined as 
the time elapsed between the beginning of the intubation attempt to inflation 
of the ETT cuff when the tube is in the trachea.   
 
3) 
Esophageal intubation: defined as passage of the ETT into the esophagus, 
with subsequent ventilation, and then removal.  Clinically, esophageal 
intubation is identified by the absence of end-tidal carbon dioxide, abnormal 
physical exam, and hypoxia.  This does not count passage of the ETT into the 
esophagus during the attempt if the ETT is removed during the attempt.   
 
4) 
Hypoxemia, as defined above. 
 

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3  
MEASUREMENT OF STUDY OUTCOMES 
 
3.1 Measurement of primary outcome 
 
A trained research assistant will be present in the room for all study subjects.  This 
trained assistant will observe the intubation and record the number of attempts.  
The intubating physician will also be asked the number of attempts at the end of the 
case.  In cases where there is a discrepancy between the research assistant and the 
intubating physician, the video for the stabilization case will be reviewed to 
determine the actual number of attempts.   
 
 
3.2 Measurement of secondary outcomes 
 
For secondary outcome 1): First pass success will be measured as described above.  
For hypoxemia, a research assistant will record the SpO2 at the beginning of the 
attempt and every 20 seconds thereafter, until 1 minute after inflation of the ETT 
cuff.  The lowest SpO2 will also be recorded, even if this does not fall at a 20-second 
interval.   
 
For secondary outcome 2): The research assistant will have a stopwatch and record 
the time to intubation, as defined in 2.2. 
 
For secondary outcome 3): The intubating physician will fill out a data collection 
sheet after the intubation.  This form will include whether there was an esophageal 
intubation, as defined in 2.2. 
 
For secondary outcome 4):.  Hypoxemia will be measured, as described above in 
secondary outcome 1). 
 
 
 
 

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4 
INVESTIGATIONAL PLAN 
 
4.1 Overall Study Design and Plan 
 
This Phase IV study is designed as a randomized, unblinded, two-arm study that will 
be conducted at a single center. The primary aim is to determine if first pass success 
differs by more than 9% (absolute difference) in patients who use a GEB during the 
first intubation attempt compared to those that do not.   
 
4.1.1  Study Population and Randomization 
 
Adult patients undergoing orotracheal intubation in the ED with a Macintosh blade 
(using either video or direct laryngoscopy) for any indication will be enrolled into 
the study.   
 
If the patient meets all of the eligibility criteria, he/she will be enrolled and 
randomized at a 1:1 ratio to undergo intubation with or without a GEB for the first 
attempt. The randomization will be permuted-block with random block sizes of 2, 4, 
6, 8, and 10.  The randomization will be stratified into two groups: 1) those with any 
of the following: cervical collar, obesity (gestalt), and apparent facial or neck 
trauma; and 2) those with none of those characteristics.  A trained research 
coordinator who will not be performing any data collection or chart review during 
the study will generate the treatment assignments. 
 
The study allocations will be sealed in sequentially numbered opaque envelopes and 
stored in the critical care area.  When an eligible patient is enrolled, the next 
sequential envelope will be opened to reveal the treatment assignment.  Skipping a 
study number is not allowed. 
 
4.1.2  Study Treatment and Blinding 
 
The study will be unblinded because it is not possible to blind physicians to this 
study, and no sham intervention is possible. 
 
4.2 Assessments 
 
4.2.1  Outcome Assessments 
 
Described in section 3 
 
4.2.2 Safety Assessments 
 
Any adverse events related to the use or non-use of the GEB should be observed 
immediately in the ED during the intubation process.  If either device fails to 

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12 
intubate the patient, a second attempt will be performed.  The second attempt can 
proceed with any device or strategy that the intubating physician feels is best for the 
patient.  Direct trauma to the mouth, upper airway, and airway are possible in both 
groups. Full assessment of the mouth, upper airway, and airway is not possible 
without exposing the patient to further harm from repeated laryngoscopy and 
bronchoscopy.  Therefore, to assess any direct trauma, the intubating physician will 
be asked if there was any direct trauma to the mouth, upper airway, or airway, and 
if there was any excessive bleeding during or after intubation while in the ED.   
 
 
4.3 Study Duration 
 
A patient’s participation in this trial will begin at enrollment, and end 1-minute after 
successful intubation.  No further data will be collected from the patient or 
electronic medical record.  

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5  
STUDY POPULATION SELECTION 
 
5.1 Study Population 
 
Adult patients undergoing orotracheal intubation in the ED with a Macintosh blade 
(using either video or direct laryngoscopy) for any indication will be enrolled into 
the study.  To be eligible for enrollment, the patient must meet all of the inclusion 
criteria and none of the exclusion criteria. 
 
The subgroup of patients with any of the following difficult airway characteristics 
will be the primary analysis population, though all enrolled patients will be included 
in a secondary analysis.  Difficult airway characteristics include: cervical immobility, 
obesity, large tongue, short neck, small mandible, facial or neck trauma, airway 
edema, blood in the airway, or vomit in the airway. 
 
 
5.2 Inclusion Criteria 
 
Patients must meet all of the following criteria to be eligible to participate in the 
study: 
 
1.   
The patient must be undergoing orotracheal intubation in the ED with 
a Macintosh blade (using either video or direct laryngoscopy)  
2.  
The patient must be presumed to be 18 years of age or older at the 
time of enrollment. 
 
5.3 Exclusion Criteria 
 
Patients who meet any of the following criteria are not eligible to participate in this 
study: 
 
1. 
Known anatomic distortion of the upper airway or perilaryngeal 
structures. 
2. 
Prisoner or under arrest 
3. 
Known or suspected to be pregnant, based on the opinion of the 
treating physician. 
 
 
5.4 Subject Withdrawal Criteria 
 
As the study duration is very short, there will not be time for subject withdrawal. 
 
 

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6 
STUDY CONSENT 
 
This investigation will be conducted under 45 CFR 46.116 Waiver of Informed 
Consent, as both devices are standard of care.  
 
45 CFR 46.116 (d) is copied below:  
 
(d) An IRB may approve a consent procedure which does not include, or 
which alters, some or all of the elements of informed consent set forth in this 
section, or waive the requirements to obtain informed consent provided the 
IRB finds and documents that: 
 
 (1) The research involves no more than minimal risk to the subjects; 
 (2) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects; 
 (3) The research could not practicably be carried out without the 
waiver or alteration; and 
 (4) Whenever appropriate, the subjects will be provided with 
additional pertinent information after participation. 
 (e) The informed consent requirements in this policy are not 
intended to preempt any applicable federal, state, or local laws which 
require additional information to be disclosed in order for informed 
consent to be legally effective. 
 (f) Nothing in this policy is intended to limit the authority of a 
physician to provide emergency medical care, to the extent the 
physician is permitted to do so under applicable federal, state, or local 
law. 
 
 
6.1 Research involves no more than minimal risk to the 
subjects 
 
The use or non-use of the GEB both are the current standard of care in the 
Emergency Department.  The decision whether to use a GEB depends on the 
intubating physician’s preferences and biases.  The resident physicians (who 
perform approximately 98% of the endotracheal intubations) receive extensive 
training in intubating with and without a GEB, and routinely perform endotracheal 
intubation with and without a GEB. 
 
Though patients requiring intubation are critically ill by definition, and have 
significant risk of morbidity and mortality throughout the hospital stay, this risk is 
imparted by the underlying illness or injury, and should not be altered more than 

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15 
minimally by the use or non-use of a GEB for intubation.  Because both methods are 
acceptable as standard of care for the first intubation attempt, there is currently no 
reason to think that one has any higher risk than the other; that is, there is minimal 
added risk to the patient beyond the risk caused by their severe illness or injury. 
 
 
 
6.2 The waiver or alteration will not adversely affect the 
rights and welfare of the subjects 
 
There is no reason this waiver of consent could adversely affect the rights nor 
welfare of the subjects.  All subjects will receive the highest level of care provided by 
the HCMC Emergency Physicians.  All other care is at the discretion of the treating 
physicians. 
 
6.3 The research could not practicably be carried out 
without the waiver or alteration 
 
Patients who require emergent endotracheal intubation in the ED are critically ill by 
definition.  Many are obtunded or comatose; others are dyspneic and unable to talk; 
still others have myriad severe illnesses that preclude an involved discussion 
regarding the study along with its risks and benefits.  For these reasons, it is not 
practical to obtain informed consent for this investigation for the vast majority of 
critically ill patients. 
 
A patient who requires emergent endotracheal intubation has a pressing need for 
medical intervention that cannot be delayed for any reason.  Orotracheal intubation 
must be completed on an emergent basis, and cannot wait for the consent of a 
legally authorized representative (LAR), unless the LAR is at the bedside of the 
patient. 
 
Patients who are critically ill often become critically ill unexpectedly.  There are a 
multitude of acute illnesses that occur without warning: major trauma, head trauma, 
stroke, spontaneous intracranial hemorrhage, sepsis, drug overdose, acute coronary 
syndrome, and many others.  There is no reasonable method to prospectively 
identify individual patients likely to become eligible for participation in this clinical 
trial. 
 
If only critically ill patients who were able to provide informed consent were 
included in this study, the results would not be generalizable to critically ill who 
could not provide informed consent, as this is a more ill cohort. 
 
Previous randomized trials examining emergency intubation have been completed 
under a waiver of informed consent.33,34 
 

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16 
 
6.3.1 Patient objection 
 
Because this trial involves no more than minimal risk to the patient, and because 
endotracheal intubation must be completed emergently, the patient will not be 
approached for consent.  In the unlikely event the patient is able to have a reasoned 
conversation prior to intubation, the patient will be asked if he/she would like to 
decline being in a research study.  If the patient declines, he/she will not be enrolled.  
 
6.3.2 LAR or Family member objection 
 
If a LAR or family member is at the bedside prior to endotracheal intubation, they 
will be asked if they object to the patient being enrolled in an emergency airway 
investigation.  If they object, the patient will not be enrolled 
 
6.4 Notification after enrollment 
 
As the soonest feasible opportunity after study enrollment, the patient or the 
patient’s LAR will be notified of the study enrollment.  Details of the investigation 
will be provided on an information sheet with the contact information of the 
investigators and research office.   
 
Because the study will have been completed 1 minute after successful intubation, it 
will not be possible to withdraw from the study.   
 
 
 

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17 
7 
STUDY PROCEDURES 
 
Detailed descriptions of patient evaluations required for this protocol are described 
in this section.  These evaluations will be performed during the indicated times of 
the study as detailed. 
 
7.1 Study Entrance Criteria 
 
At baseline, each patient will be reviewed for eligibility against the study entrance 
criteria.  Patients who do not meet the study entrance criteria will not be allowed to 
participate in the study.   Patient eligibility according to the study inclusion and 
exclusion criteria will be confirmed at baseline.   
 
7.2 Enrollment 
 
If the patient is eligible for enrollment and neither the patient nor a LAR or family 
member object to enrollment, the patient will be enrolled into the study.  Upon 
enrollment, the study allocation will be revealed and disclosed to the treating 
physicians.  
 
7.3 Baseline and ED Data Collection 
 
Baseline vital signs will be collected immediately after randomization.  If time 
permits, the intubating physician will be asked to determine which, if any, difficult 
airway characteristics the patient has.  This data will be recorded on a structured 
data collection form.  Attempts at endotracheal intubation will be collected in real 
time.  Further baseline information, and information regarding difficult airway 
characteristics (if not already gathered), will be obtained after the patient has left 
the critical care area.  All data gathered is listed in Appendix 1.   
 
 
7.4 Adverse Event Assessments 
 
Any adverse events (AE) related to the use or non-use of the GEB should be 
observed immediately in the ED during the intubation process.  If either device fails 
to intubate the patient, a second attempt will be performed.  The second attempt can 
proceed with any device or strategy that the intubating physician feels is best for the 
patient.  Direct trauma to the mouth, upper airway, and airway are possible in both 
groups. Full assessment of the mouth, upper airway, and airway is not possible 
without exposing the patient to further harm from repeated laryngoscopy and 
bronchoscopy.  Therefore, to assess any direct trauma, the intubating physician will 
be asked if there was any direct trauma to the mouth, upper airway, or airway, and 
if there was any excessive bleeding during or after intubation while in the ED.   
 

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18 
7.4.1 Adverse Event Monitoring and Period of Observation 
 
AEs will be monitored continuously while the patient is in the ED, during which any 
AE related to the study would be evident..  
 
 
7.4.2 Reporting Serious Adverse Events 
 
The local IRB will be notified of any related severe and unexpected, life-threatening, 
or fatal SAE as soon as possible, generally within 24 hours depending on the day of 
week.  The data safety and monitoring board will also be notified as soon as possible.   
 
 
7.5 Safety-Related Stopping Rules 
 
An independent data safety and monitoring board (DSMB) will be established to 
provide an ongoing, independent review and assessment of the safety data, and to 
safeguard the interests and safety of the participating patients in the study. 
 
On an ongoing basis, the DSMB will review SAEs that are judge to be at least possibly 
related to the study.  The DSMB will be notified immediately of the SAE and 
requested to make an assessment within five working days.  Based on the DSMB’s 
assessment of the event, as well as evaluation of the overall accumulating safety 
data from the trial, the DSMB will make a recommendation as to whether the study 
should be halted if there is a safety concern or should continue as planned. 
 
See section 8.7.2 for possible stopping after the planned interim analysis. 
 
 
 
 

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19 
8 
PLANNED STATISTICAL METHODS 
 
8.1 General Considerations 
 
All statistical analyses will be performed with STATA Version 12.1 (StataCorp. 2011. 
College Station, TX).   
Unless otherwise specified, summary tabulations will be presented by treatment 
group. For categorical variables, the number and percentage of patients within each 
category (with a category for missing data as needed) of the parameter will be 
presented. For continuous variables, the number of patients, mean, median, 
standard deviation, minimum, and maximum values will be presented. Time-to-
event data will be summarized using Kaplan-Meier estimates of the 25th, 50th, and 
75th percentiles with associated two-sided 95% CI, as well as percentage of 
censored observations.  
Formal statistical hypothesis testing will be performed on the primary and key 
secondary outcomes, with all tests conducted at the 2-sided, 0.05 level of 
significance.  
8.2 Sample size calculation 
Assuming a first pass success rate in the GEB group of 95%, to detect an absolute 
difference of 9% (86% without use of GEB) with 80% power between groups, 374 
patients (187 per group) with a difficult airway characteristic will need to be 
enrolled.  Approximately 1,500 patients are intubated annually in our Emergency 
Department.  Because of logistic considerations, we predict that only 1,000 patients 
will be able to be enrolled, 30-40% of whom will have a difficult airway 
characteristic.  Therefore, we plan to enroll for 1 calendar year, or until we enroll 
1,000 patients, whichever occurs first.  If we have not enrolled 374 patients with a 
difficult airway characteristic at that time, we will discuss with the IRB about 
extending the timeframe of the investigation. 
This sample size calculation was performed in STATA version 12.1 with the 
following command: sampsi 0.95 0.86, p(0.8). 
 
8.3 Method of Assigning Study Patients to Treatment Groups 
See section 4.1.1. 
8.4 Population Description 
 

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20 
8.4.1 Analysis Populations 
The intent-to-treat (ITT) population will be the primary outcome analysis 
population.  This group will include all patients who are endotracheally intubated 
after randomization, excluding those intubated with a device other than a Macintosh 
Blade, because this group could not possibly use a bougie or endotracheal tube.  
Patients who have no intubation attempt performed will not be a part of the ITT 
population and will be considered screening failures.  This will sometimes occur 
because emergent endotracheal intubation is planned, but the patient’s condition 
sometimes rapidly improves, obviating the need for intubation.  Because this is a 
patient group that is vastly different than patients who are intubated, and because 
they received no airway procedure, they will not be included in the ITT analysis. 
The primary outcome will be analyzed for the subset of patients in the ITT 
population who have any difficult airway characteristic.  This will be the main 
outcome of the investigation.  The data from all enrolled patients will also be 
presented in the final analysis, as it is plausible that the GEB improves first pass 
success significantly in even routine intubations.   
8.4.2 Treatment Compliance 
It is anticipated there will no patient compliance issues.  The actual device used for 
the first intubation attempt will be recorded, and the number of times this deviates 
from protocol will be recorded.  The IRB will be notified of all protocol deviations. 
8.5 Outcome Analysis 
 
The chi square test will be used to compare the primary outcome between the two 
treatment groups, with the primary analysis including only those with any difficult 
airway characteristic, and a secondary analysis of all enrolled patients. 
 
Secondary outcomes with categorical and continuous variables will be analyzed as 
the appropriate confidence interval of the difference between the two groups, again 
stratified by the presence of any difficult airway characteristic. 
 
Other data will be presented descriptively. 
 
 
8.6 Statistical/Analytic Issues 
 
8.6.1 Handling of Missing Data 
 
For the primary outcome, if both the research assistant data collection form and the 
treating physician post-intubation collection form are missing, the stabilization case 

` 
 
21 
video will be reviewed to determine if first pass success without hypoxemia was 
achieved.  If the video is not available, the patient will be excluded from the analysis.   
 
Secondary outcomes: if data for these outcomes is missing, the stabilization case 
video will be reviewed to ascertain the true value(s). If the video is missing, the 
patient will be excluded from analysis of the relevant outcomes.  
 
8.6.2 Interim Analysis and Data Monitoring 
 
An interim analysis will be performed after 500 patients are enrolled.  The data will 
be analyzed for the primary outcome only.   
The trial will be stopped early only for futility.  After the data from the first 500 
patients is analyzed, a sensitivity analysis will be performed.   An analysis will be 
performed with a sample size of 1000 patients  (equal allocation in both arms) with 
the following assumptions: 
• First pass success rate with non-use the GEB remains the same in the second 
half of the trial 
• First pass success rate with use of the GEB is 15% higher (absolute difference, 
up to a success rate of 100%) than observed in the first half of the study 
 
If no difference is found in first pass success with this analysis, then the trial will be 
stopped early for futility.  
As detailed in section 9.2, an independent DSMB will be established to provide an 
ongoing, independent review and assessment of the safety data, and to safeguard 
the interests and safety of the participating patients in the study.  Any additional 
analyses for DSMB review may be scheduled at the discretion of the DSMB.  
 
 

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22 
9 
ADMINISTRATIVE CONSIDERATIONS 
 
9.1 Institutional Review Board Approval 
 
The study will not be initiated until written IRB approval has been obtained for this 
investigation. 
9.2 Data monitoring committee 
 
An independent DSMB will be established to provide an ongoing, independent 
review and assessment of the safety data, and to safeguard the interests and safety 
of the participating patients in the study. The DSMB will include Michelle Biros, MD. 
*** 
On an ongoing basis, the DSMB will review SAEs that are judged to be at least 
possibly related to study drug. The DSMB may also be asked to review on an 
ongoing basis other SAEs of concern. The DSMB will be notified immediately of the 
SAE and requested to make an assessment within five working days.  Based on the 
DSMB’s assessment of the event, as well as evaluation of the overall accumulating 
safety data from the trial, the DSMB will make a recommendation as to whether the 
study should be halted if there is a safety concern or should continue as planned. 
 
9.3 Protocol Violations/Deviations 
 
The investigator will conduct the study in compliance with the protocol. The 
protocol will not be initiated until the IRB and the appropriate regulatory 
authorities have given approval. Changes to the protocol will require written IRB 
approval opinion prior to implementation, except when the modification is needed 
to eliminate an immediate hazard(s) to patients. The IRB may provide expedited 
review and approval for minor change(s) in ongoing studies that have the approval 
of the IRB.  
Any departures from the protocol will be fully documented as a protocol deviation. 
Protocol deviations will be required to be submitted to the IRB. 
9.4 Premature Closure of the Study 
 
If the investigator, DSMB, or regulatory authorities discover conditions arising 
during the study that indicate that the clinical investigation should be halted due to 
an unacceptable patient risk, the study may be terminated.   
 
 

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23 
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