Effectiveness of the Aeroneb Compared to a Jet Nebulizer Fort the Delivery of Bronchodilator Therapy of Acute Severe Asthma
Phase: NA
Conditions: Asthma Exacerbation
Sponsor: Tufts Medical Center

Effect on Airflow of a Vibrating Mesh Nebulizer Compared to a Jet 
Nebulizer for Delivery of Bronchodilator Therapy to Acute Severe 
Asthma Patients in an Emergency Department 
NCT03029156 
Version Date: June 20, 2016

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TUFTS MEDICAL CENTER/TUFTS UNIVERSITY RESEARCH PROTOCOL  
 
Version date:    06/20/2016 
Principal Investigator: Nicholas S. Hill, MD 
Study Title: Effectiveness of the Aeroneb Compared to a Jet Nebulizer for the Delivery of Bronchodilator 
Therapy of Acute Severe Asthma  
 
I. 
Aim and Hypotheses 
Acute exacerbations of asthma remain a frequent cause of emergency department (ED) visits and 
hospital admissions.  About one-fifth to one-third of ED patients have poor short term responses to 
bronchodilator therapy and require admission to the hospital. The initial response to bronchodilator is 
an important indicator of favorable outcomes. The response to bronchodilator therapy is determined 
by patient-specific factors but it is also possible that the delivery method of bronchodilator therapy 
could be playing a role in the response to bronchodilator. Aeroneb system utilizes vibrating mesh 
technology to generate consistently sized particles with greater lung deposition. It may provide 
greater benefits in acute asthma exacerbations. 
 
Aim: To study whether Aeroneb nebulizer is more effective than small volume jet nebulizer in 
delivering bronchodilators in severe asthma exacerbation 
Hypothesis: Compared to small volume jet nebulizer, the Aeroneb nebulizer is more effective than a 
small volume jet nebulizer for delivering bronchodilator therapy in patients with acute severe 
asthma.   
We hypothesize that the mean of PEFR percentage of predicted at 30 minutes after the initial 
bronchodilator treatment in the Aeroneb group will be 10 points higher than the mean of PEFR 
percentage of predicted at 30 minutes after the initial bronchodilator treatment in the small volume 
jet nebulizer group. 
 
 
II. 
Background and Rationale 
 
A. Background:  
Acute exacerbations of asthma remain a frequent cause of emergency department (ED) visits and 
hospital admissions.  About one-fifth to one-third of ED patients have poor short term responses to 
bronchodilator therapy and require admission to the hospital1. The presence of peak expiratory flow 
rate (PEFR) < 40% is an indicator of severe asthma 2. In patients with peak flow <50% severe 
asthma, the improvement in PEFR at 30 minutes after the initial bronchodilator treatment is 
associated with favorable outcomes 3,. Initial response to bronchodilators may be affected by patient-
specific factors such as duration of symptoms and frequency of beta agonist use prior to ED 
admission.  It is also possible that the method of delivering bronchodilator therapy in the ED impacts 
outcome.  
 
The effectiveness of aerosol delivery systems in this clinical setting depends upon the capacity to 
generate particles that reach the small airways of the lower respiratory tract, which is the site of 
disease in acute asthma.  Jet nebulizers, which are often used in the ED treatment of asthma, are 
inexpensive systems that deliver aerosols of varying particle size and have been shown to be 
unreliable in delivering the bronchodilator drugs8. Vibrating mesh technology, which is employed in 
the Aeroneb system, produces consistently sized respirable particles of 3.4 µm mass mean 
aerodynamic diameter 6.  This improvement in aerosol delivery technology translates into greater 
lung particle deposition in both animal studies and in normal humans 7. Therefore, the Aeroneb 
nebulizer may be more effective that small volume jet nebulizer in the management of asthma 
exacerbations. 
 
The Aeroneb Nebulizer System is a portable medical device for single patient use that is intended to 
aerosolize physician-prescribed solutions for inhalation to patients on and off ventilation. 
The Aeroneb Adapter is an accessory specific to the Aeroneb Nebulizer. It facilitates intermittent and 

Page 2 of 13 
 
continuous nebulization and optional supply of supplemental oxygen to adult patients in hospital use 
environments via a mouthpiece or aerosol mask. The Aeroneb Nebulizer System and Adapter are 
FDA approved devices for nebulizing solutions including bronchodilators (albuterol and ipratropium). 
 
 
B. Rationale:  
Aeroneb system has advantages over the small volume nebulizer as mentioned above. These 
advantages may make it more efficient system to deliver the bronchodilator therapy and to treat the 
asthma exacerbations more effectively.  
This is the first study that we are aware of that will look at the use of Aeroneb system to deliver 
bronchodilator therapy in asthma exacerbations. 
The study will provide novel data to demonstrate whether the use of Aeroneb system to deliver 
bronchodilator therapy is advantageous to patients with severe asthma exacerbations.  
If the hypothesis is proven to be correct this will mean improved patient’s outcomes in severe 
asthma exacerbations and potentially shorter ER stay, reduction in the hospitalization rate and cost 
of care.  
  
 
 
III. 
Research Plan   
 
A. Experimental design:  
This is a prospective, single blinded, parallel, single center, randomized controlled clinical trial 
(n=68). Upon entry into the study, patients will be randomized to two groups: 
Treatment group: All the bronchodilator therapies during the ER visit (albuterol and 
ipratropium) will be delivered via Aeroneb nebulizer system. The asthma management will be 
as per the adult asthma protocol in the ER. 
Control group: All the bronchodilator therapies (Albuterol and ipratropium) will be delivered via 
small volume jet nebulizer system, which is currently the standard nebulizer device used in the 
emergency department at Tufts Medical Center. The asthma management will be as per the 
adult asthma protocol in the ER. 
 
B. Sample size and statistical analysis(es):  
Upon entry into the study patients will be randomized at a 1:1 ratio with permuted block design 
of 6 to one of the 2 groups. Randomization will be conducted using a computerized 
randomization scheme and secured in a sealed envelope for allocation.  
 
For a power calculation to determine the sample size, historical data was utilized from prior 
clinical study that examined the effect of bronchodilator (B2-agonist) treatment on the 
improvement of the peak flow measurement after 30 minutes of the initial bronchodilator 
treatment4. In this study, the mean PEFR improved from 27% to 39% at 30 minutes after the 
initial bronchodilator treatment. We hypothesize that mean PEFR of the intervention group at 
30 minutes of the bronchodilator therapy will be at least 10 points higher than the control 
group (i.e. mean PEFR ≥ 49% at 30 minutes of the initial bronchodilator therapy). Group 
sample sizes of 34 and 34 is required to achieve a power > 80% to reject the null hypothesis of 
equal means when the groups mean difference is 10.0 with a standard deviation for both 
groups of 14.4 and with a significance level (alpha) of 0.050 using a two-sided two-sample 
equal-variance t-test. 
 
Taking into consideration the screen failures the disqualification and drop-outs, we are 
anticipating enrolling around 110 patients in order to have 68 patients who will complete the 
study objectives. 
 
For the statistical analysis treatment evaluations will be performed on the principle of intention 
to treat (ITT) using the data collected from all randomized participants who completed the 
study procedures including the two parts of the informed consent form (ICF). Demographics 
and baseline characteristics of patients will be summarized for each group. Continuous variables 
will be reported as mean ± standard deviation, with minimum, median, and maximum values. 

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Categorical variables will be reported as n and %. All statistical testing will be two-sided with 
alpha=0.05. 
For the primary outcome, mean PEFR at 30 minutes post-bronchodilator treatment, analysis of 
covariance (ANCOVA) with adjustment for baseline PEFR will be utilized.  
ANCOVAs with adjustment for baseline values, and incorporating repeated measures where 
appropriate, will be utilized for the following secondary outcomes: absolute value of PEFR 
(L/Min) at 30 minutes, PEFR percentage of predicted at 60 minutes and 180 minutes, FEV1 
percentage of predicted as well as absolute FEV1 (L/Sec) at 30 minutes, 60 minutes and 180 
minutes, Borg dyspnea score at 30 minutes, 60 minutes and 180 minutes, accessory muscle 
use score at 30 minutes, 60 minutes and 180 minutes, and heart rate at 30 minutes, 60 
minutes and 180 minutes.  
 
The outcomes which are measured at different time points will be averaged for each group and 
plotted to visualize the trajectory of those outcomes.  
 
Differences in length of stay (hours) in the ER and the total doses of albuterol and ipratropium 
will be compared using T-tests or non-parametric methods (e.g., Mann-Whitney test) as 
depending on the distribution of the data. The proportion of patients in each group who require 
hospitalization will be compared using a Chi-square test. 
 
 
 
C. Subject Characteristics 
1. Subject criteria:  
The study will be conducted at the emergency department at Tufts Medical Center. 
  
a) Inclusion criteria:  
-Acute asthma exacerbations presenting to the emergency room 
-Peak expiratory flow rate at presentation <50%40% of predicted  
-Enrolment within 90 minutes of the arrival to the ER  
-Age 18-55 years old 
 
b) Exclusion criteria:  
 
 
-History of chronic obstructive pulmonary disease 
-Clinical evidence to suggest a non-asthmatic cause of bronchospasm as determined by 
the treating physician 
-Clinical evidence of acute coronary syndrome 
-Respiratory failure requiring mechanical ventilation either invasive or non-invasive 
-Tachyarrhythmia other than sinus 
-Agitated or uncooperative 
-Inability to provide informed consent 
 
 
c) Withdrawal/Termination criteria:  
The subject will be withdrawn from the study if any of the following: 
-The subject develops respiratory failure requiring mechanical ventilation (invasive or 
non-invasive) 
-The subject becomes unable to perform peak flow measurement at the pre-specified 
time points 
-The treating physician determines that it is not clinically advisable to continue with the 
study. 
-The subject opts to decline to sign the second part of the informed consent form. In 
this case, the data collected may not be used for the study. 
 
 

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A study participant will have the right to withdraw from the study at any point of the 
study. 
 
A study participant may not participate in another research study while participating in 
this study. 
 
 
D. Risk/benefit assessment:  
 
1. Physical risk:  
Patients in both the intervention and control arms are at risk for developing respiratory 
failure as a result of severe asthma exacerbation and it is unknown if the risk of such 
complications is higher in any arm. It is possible that the Aeroneb group patient my 
experience more frequent side effects related to potentially more albuterol and 
ipratropium delivery and those side effects may include tremor and arrhythmias. 
 
2. Psychological risk: 
There is no increased psychological risk to the study participants from the study for 
either arm 
 
3. Social risk:  
There is no increased social risk to the study participants from the study for either arm 
 
4. Economic risk 
There is no increased economic risk to the study participants from the study for either 
arm. 
 
5. Benefit of participating in the study:  
a) Patients randomized to the intervention group may benefit from the increased 
bronchodilator delivery by Aeroneb system  
 
b) Future asthma patients may benefit from this study if Aeroneb system is proven to be 
more effective in treating severe asthma exacerbation 
 
 
E. Specific methods and techniques used throughout the study:  
 
1. Laboratory tests:  
      No additional laboratory test is required in the study. 
 
2. Study Procedures:  
-The patient presenting with acute severe asthma exacerbations to the emergency room will 
be screened by the PI, co-investigator or research coordinator to determine their eligibility 
based on the inclusion and exclusion criteria. 
 
-The required treatment must not be delayed for a research related reason and patients will 
still be eligible for enrollment after receiving the treatment as long as their PEFR<50%40% 
of predicted and the enrollment occur within 90 minutes of the ER arrival time. 
 
- The initial part of the consenting process will cover the essential elements of the informed 
consent in a concise manner to ensure timely process 
 
-Eligible patient will be randomized using the method mentioned above to either the 
intervention arm or the control arm. The randomization should take place within 90 minutes 
of the ER arrival, however, every effort will be made to enroll the patient as soon as 
possible; patients will be enrolled as long as their PEFR is less than 50% 40% of predicted 
regardless of the number of bronchodilator treatment they received prior to the 
randomization. 
 

Page 5 of 13 
 
-The assignment will be blinded to the recording investigator and the treating physician but 
not to the patient or the nurse or respiratory therapist who is administering the 
nebulization. In order to avoid any delay in administering the treatments, the sets of 
Aeroneb nebulizer and small volume jet nebulizer will be stored in identical boxes and will 
be readily available in the ER.  
In order to blind the treating physician and the recording investigator, a sign “treatment in 
progress” will be displayed at the outdoor of the ER room when the patient is getting the 
bronchodilator treatment. The nebulizer devices will be placed in the box between the 
bronchodilator treatment sessions. The physician and the recording investigator will be 
asked if possible to see the patients only when the sign is taken off the outdoor. 
 
-Once assigned, all the bronchodilator treatments in the ER will be administered using the 
nebulizer device assigned to that patient. 
 
-The Peak flow and FEV1 will be measured using Spirometer (micro I). Both values will be 
obtained through the same exhalation maneuver. 
 
-Patient will be treated and managed according to the asthma ER adult protocol or as 
directed by the ER physician who is in charge of patient’s care 
 
-After the study procedures have been performed and the subject is determined to be in 
stable condition and have the capacity to make medical decisions, the investigator will 
approach the subject again and review all the elements of the ICF again with the subject. 
The collected data will be used only if the subject signs both parts of the informed consent.  
 
-Within two weeks of the subject participation, the research team will attempt to conduct a 
phone interview with the subject to obtain their feedback on the study procedures and 
mainly on the informed consent process. The phone interview questionnaire is included in 
the supplement 
 
-The research team will report to the IRB the progress of the study including the consent 
process after enrolling the first 10 patients. 
 
 
 
 
 
3. Subject Timeline:  
During the study several data will be recorded, most of them are standard hospital 
recording, which are conducted frequently. These data will be collected at baseline and at 
multiple points after the initial bronchodilator therapy (at 30±10 minutes, 60±10 minutes, 
at 180 ± 10 minutes and upon disposition from the ER). All recorded data are obtained 
through noninvasive measurements. No samples of any body component will be taken that 
it not part of the normal standard hospital protocols. 
The results that will be collected are summarized in table 1.  
 
3.1 Baseline readings 
Once patient is enrolled in the study, baseline characteristics such as gender, age, height, 
weight, BMI and race will be collected, as well as smoking history and past medical history 
including prior ER visits for asthma exacerbations, prior intubation for asthma exacerbation 
and the use of any respiratory therapy at home will be investigated and data will be 
collected. Clinical data such as respiratory and heart rate, blood pressure, O2 sat and FIO2 
will be recorded. Peak flow and FEV1 will be measured by spirometer micro I during the 
same exhalation maneuver and they will be recorded. 
 

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The dyspnea will be graded with Borg score9 as outlined in figure 1 and the accessory 
respiratory muscle10 use will be graded as outlined in figure 2. Cough will be recorded as 
present or absent. 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
No difficulty 
 
 
Moderately hard 
 
Hard 
 
Very hard 
 
 
Very, very hard 
 
 
Score 0 – 6: 
Moderate 
respiratory 
distress 
 
 
 
Score 7 – 10: 
Severe  
respiratory 
distress 
 
 
 
  Fig. 1 Borg Scale to assess Dyspnea 
 
 
0 
No visible tonic or phasic use of neck muscles 
1 
Neck muscles taut but with no respiratory modulation  
(i.e., tonic activity) 
2 
Mild respiratory modulation in neck muscle contraction 
3 
Moderate phasic activity  
(no supraclavicular or intercostal indrawing) 
4 
Vigorous phasic activity with indrawing 
5 
Vigorous phasic activity with abdominal paradox 
 
 
  Fig. 2 Accessory muscle use  
 
 
Baseline readings upon enrolment  
Routine 
test 
Study 
test 
Gender 
• 
 
Age 
• 
 
Height 
 
• 
Weight 
 
• 
BMI 
 
• 
Race 
 
• 
Smoking history (Number of pack years) 
• 
 
Respiratory medications (home medication list) 
• 
 
History of prior intubation for asthma exacerbation 
 
• 
Number of hospitalization for asthma exacerbations in the last 
year 
 
• 
Bronchodilator treatment in the EMT  
 
• 
Respiratory rate 
• 
 
Heart rate 
• 
 
Systolic/diastolic blood pressure 
• 
 
O2 sat 
• 
 
FIO2 
• 
 
Dyspnea score 
 
• 
Cough 
 
• 
Respiratory accessory muscle use 
 
• 

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Peak flow (percentage from predicted) 
• 
 
Peak flow (L/Min) 
• 
 
FEV1 (percent of predicted) 
 
• 
FEV1 (Liter) 
 
• 
At (30±10) minutes after nebulizer treatment 
 
 
Respiratory rate 
• 
 
Heart rate 
• 
 
Systolic/diastolic blood pressure 
• 
 
O2 sat 
• 
 
FIO2 
• 
 
Dyspnea score 
 
• 
Cough 
 
• 
Respiratory accessory muscle use 
 
• 
Peak flow (percentage from predicted) 
• 
 
Peak flow (L/Min) 
• 
 
FEV1 (percent of predicted) 
 
• 
FEV1 (Liter) 
 
• 
At (60±10) minutes after nebulizer treatment 
 
 
Respiratory rate 
• 
 
Heart rate 
• 
 
Systolic/diastolic blood pressure 
• 
 
O2 sat 
• 
 
FIO2 
• 
 
Dyspnea score 
 
• 
Cough 
 
• 
Respiratory accessory muscle use 
 
• 
Peak flow (percentage from predicted) 
• 
 
Peak flow (L/Min) 
• 
 
FEV1 (percent of predicted) 
 
• 
FEV1 (Liter) 
 
• 
At (180±10) minutes after nebulizer treatment 
 
 
Respiratory rate 
• 
 
Heart rate 
• 
 
Systolic/diastolic blood pressure 
• 
 
O2 sat 
• 
 
FIO2 
• 
 
Dyspnea score 
 
• 
Cough 
 
• 
Respiratory accessory muscle use 
 
• 
Peak flow (percentage from predicted) 
• 
 
Peak flow (L/Min) 
• 
 
FEV1 (percent of predicted) 
 
• 
FEV1 (Liter) 
 
• 
Upon disposition from the ER 
 
 
Disposition (Home, floor or ICU) 
 
• 
Length of stay in the ER (from ER arrival time to disposition 
order placement time) 
 
• 
Intubation in the ER  (Yes or No) 
 
• 
Need for NIV ventilation 
 
• 
Number of total albuterol treatment during the ER stay 
 
• 
Total accumulative dose of albuterol during the ER stay 
 
• 
Number of total ipratropium treatment during the ER stay 
 
• 
Total accumulative dose of ipratropium during the ER stay 
 
• 
Total dose of steroid (prednisone equivalent in mg) 
 
• 

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Table 1 
 
3.2 
During the study 
The following variables (respiratory rate, heart rate, BP, O2 sat, FIO2, Dyspnea Borg 
score, cough, respiratory accessory muscle, peak flow and FEV1) will be recorded at 
the following time points after initial bronchodilator therapy (30±10 minutes, 60±10 
minutes, 180±10 minutes and at the disposition from the ER). If the patient is 
discharged from the ER within 3 hours from the initial bronchodilator therapy then 
the data collection at 3 hours mark will be waived. 
 
3.3 
Upon disposition from the ER 
The following data will be collected: the disposition location (home, floor or ICU), 
length of stay in the ER (from ER arrival time to the disposition order placement 
time), intubation in the ER, need for NIV ventilation, number and total doses of 
albuterol treatments in the ER and number and total doses of ipratropium in the ER. 
 
 
 
F. Assessment of Subject Safety and Development of a Data and Safety Monitoring Plan 
 
1. Definition of Serious Adverse Event (SAE) and Adverse Event (AE) for this study:  
For the purposes of this study a SAE is a serious adverse event that is life-threatening or 
results in death, hospitalization or prolonged hospitalization, significant 
disability/incapacitation, congenital anomaly or birth defects, or may jeopardize the 
subject’s health and may require medical or surgical intervention to prevent one of the 
other listed outcomes. A SAE does not necessarily have to have a causal relationship with 
the study treatment. SAE may not be uncommon in the study due to the acute nature of 
patients presenting with severe asthma exacerbations that may be enrolled into the study. 
The study will be conducted in the emergency room, which provides a high level of 
monitoring and is capable of managing SAE in this acute patient group. It is possible that 
the Aeroneb group patients may experience more frequent side effects related to potentially 
more albuterol and ipratropium delivery and those side effects may include arrhythmia and 
tremor. Those side effects will be monitored closely and patients will be placed on 
continuous cardiac monitoring during the ER visit to capture any arrhythmia. 
 
2. Reporting timeframe for SAEs and AEs:  
SAEs will be reported to the IRB within five business days of the event occurring. The 
investigators will record and track any SAE or AE that might occur during the study. If a 
disproportionate number of events occur in either of the groups, then the study will be 
stopped. A “disproportionate number” is defined as one showing a statistically significant 
difference in SAEs and AEs occurrence after the recruitment of half the sample size (34 
patients).  
 
3. Accountability procedures as they relate to drugs, devices, and data:  
The Principal Investigator Dr. Nicholas Hill and the research team member Haval Chweich, 
MD will be accountable for the study and interface with Aerogen, the study sponsor.  
 
4. Data and Safety Monitoring Plan:   
We do not anticipate serious complications attributable to the device, but will monitor 
patients for potential adverse effects such as discomfort or cough. Any serious adverse 
events that occur during use are more likely due to the underlying disease than the device 
itself, but will be reported promptly to the IRB by the investigators per the reporting 
timeframes described above. 
 
The Research team will report to the IRB the process of the informed consent after enrolling 
10 patients (if this occurs before the study continuing review). 
 

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G. Subject Participation 
 
1. Recruitment:  
Patients presenting with severe asthma exacerbation to Tufts Emergency Room will be 
recruited on to the study. Patients who meet any exclusion criteria will not be screened for 
possible enrollment. Patients will be approached at their bedside by the PI, co-investigator 
or research coordinator.  No advertisements will be used.   
 
 
2. Registration:  
Patients, that can potentially take part in the study, will be assessed by the PI or the co-
investigator for their ability to fulfill the eligibility criteria and meet the exclusion criteria, as 
listed above. 
 
3. Screening Interview/questionnaire: Not applicable 
 
4. Transportation: Not applicable 
 
5. Informed consent process and timing of obtaining of consent:  
 
The participant must have the full mental capacity to provide the consent. The consenting 
process will be two steps process, each step will involve face-to-face meeting with one of 
the study investigators at bedside in the ER room 
 
1-The first part of the consent will cover all the essential elements of the informed consent. 
Given the acuity of the medical condition, it is anticipated that the total amount of time 
given to this step of the informed consent will be no longer than10 minutes. No study 
related procedures will be conducted until this step of the informed consent is signed off by 
the subject. Permission will also be obtained from the primary provider for the participation 
of the patient in the study before a discussion with the patient regarding consent occurs.  
 
The patient will be provided with a copy of the consent form to read and all questions will be 
answered prior to their signing the first part of the consent. In order to determine the 
subject’s understanding of the study, the subject will be asked to describe his understanding 
of the study back to the investigator obtaining the consent. The subject will be encouraged 
to call the investigator with any questions.  No study procedures will be performed other 
than chart review to determine eligibility prior to obtaining informed consent. The 
investigators recognize the potential vulnerability of the patient in this setting (i.e., being 
acutely ill) and thus will terminate the consent discussion in any situation where the patient 
appears to be uncomfortable or apprehensive about providing consent for participation in 
the study.  
 
2-The second part of the informed consent will take place after the study procedures have 
been performed and the patient condition has been stabilized. The investigator will meet 
face-to-face with the subject and review the ICF again with the subject in more detailed 
manner. The subject will be asked to sign a separate section of the ICF re-consenting that 
they agreed to participate in the study.  
 
Subjects who do not sign the second part of the ICF will be withdrawn from the study and 
data collected on those subjects may not be used for the study. 
  
 
 
It will be explained that if they refuse to be in the study it will not affect their care or 
medical treatment outside of the study.    
 

Page 10 of 13 
 
 
 
If non-English speaking persons will be enrolled, state the informed consent 
process for enrolling the subjects, including who will conduct the consent 
interview, use of interpreters, translated documents, etc.: Only English speaking 
persons will be enrolled as it will be difficult to communicate with non-English speaking 
patients about the PEFR maneuvers and the dyspnea scoring. Timely assistance from the 
interpreter service personnel may not be feasible given the acuity of the cases. Interpreter 
phone will not be sufficient as it would be hard to demonstrate the maneuver though phone 
interpretation.   
 
 
 
6. Location where study will be performed:  
The study will be performed at the Emergency Room at Tufts Medical Centre. Study records 
will be kept in a locked filing room.  
 
 
7. Personnel who will conduct the study, including: 
a. Present during study procedure(s) and their proximity during the study:  
The PI, co-investigator or the research coordinator will oversee the study procedure. 
Normal clinical care of patients will be performed by the patient’s assigned nurse, 
respiratory therapist and doctor in the emergency room. 
 
 
b. Primary responsibility for the following activities:  
 
i. Obtaining informed consent:  
The principal investigator and the co-investigators will be responsible for obtaining 
the informed consent from the patients. 
 
ii. Providing on-going information to the study sponsor and the IRB:  
 
Dr. Nicholas Hill and Dr. Haval Chweich will be responsible for providing on-going 
information to the study sponsor and the IRB. 
 
 
iii. Maintaining participant's research records:  
 
Dr. Chweich will be responsible for maintaining the participant’s research records. 
The records will be maintained up to 7 years as per the IRB policy. 
 
8. Subject fees:  
There will be no fees paid to subjects for the study. It is part of their emergency visit care 
treatment 
 
9. Study results:  
 
Study results will not be given to patients. 
 
 
10. Procedures to protect subject confidentiality:  
 
Patient confidentiality will be maintained under normal emergency room procedures which 
are in compliance with the HIPPA rules. 
 

Page 11 of 13 
 
 
11. Confidentiality: 
 
a. Certificate of Confidentiality:  
 
Certificate of confidentiality is not relevant for this research study 
 
 
b. How data will be coded, recorded, and stored to protect confidentiality:  
 
Study participants will be allocated a study number, which will be used as a study 
identifier on all study forms. The study data and records will be kept locked. 
 
 
c. Parties who will have access to the date, including the key to the identity 
code:  
 
The study PI, Dr. Nicholas Hill and research team member Dr. Haval Chweich will 
have access to the study data and the identity codes. 
 
 
d. Parties who will have access to research records:  
 
The study PI, Dr. Nicholas Hill and research team member Dr. Haval Chweich will 
have access to the study data. 
 
 
12. Collaboration:  
 
This is not a collaborative study. 
 
 
13. Alternatives:  
 
Patients not participating in this study will receive usual ER care as determined by the ER. 
 
 
14. How new information will be conveyed to the study subject and how it will be 
documented:  
 
In the event new information is discovered about the study, a letter describing the new 
information will be mailed to the contact address for each subject who participated in the 
study. 
 
 
15. Payment, including a prorated plan for payment:  
 
There will be no payment for participants. The study is part of Emergency Room care that a 
patient is receiving as part of their visit.  
 
 
16. Payment for a research-related injury:  
 

Page 12 of 13 
 
Aerogen (the study sponsor) agrees to reimburse the site for the costs of the care and 
treatment of any illness or injury to a subject directly resulting from his or her participation in 
the Study; provided, however, that such illness or injury is not a result of the negligence or 
misconduct of Site, Principal Investigator or any of Site’s employees. 
 
 
I. Outcomes:  
 
The expected outcome of the study is that the Aeroneb system arm will have higher PEFR after 
treatment with bronchodilator as compared with the small volume jet nebulizer arm. It is also 
expected that the improvement in the PEFR in the Aeroneb arm will translate in improvement in 
the respiratory outcomes like dyspnea, accessory muscle use, length of ER stay and need for 
hospitalization. 
Primary outcome: the mean of PEFR percentage of predicted at 30 minutes after the initial 
bronchodilator treatment in the Aeroneb group will be 10 points higher than the mean of PEFR 
percentage of predicted at 30 minutes after the initial bronchodilator treatment in the small 
volume jet nebulizer group. 
Secondary outcomes: 
- Change in the absolute value of PEFR (L/minute) at 30 minutes after the initial bronchodilator 
treatment in the Aeroneb group compared to the small volume jet nebulizer group 
-Change in the PEFR percentage of predicted at 60 minutes and 180 minutes after the initial 
bronchodilator treatment in the Aeroneb group compared to the small volume jet nebulizer 
group 
-Change in the FEV1 percentage of predicted at 30 minutes, 60 minutes and 180 minutes after 
the initial bronchodilator treatment in the Aeroneb group compared to the small volume jet 
nebulizer group 
-Change in the absolute FEV1 (L/Second) at 30 minutes, 60 minutes and 180 minutes after the 
initial bronchodilator treatment in the Aeroneb group compared to the small volume jet 
nebulizer group 
-The Borg dyspnea score at 30 minutes, 60 minutes and 180 minutes after the initial 
bronchodilator treatment in the Aeroneb group compared to the small volume jet nebulizer 
group 
-The accessory muscle use score at 30 minutes, 60 minutes and 180 minutes after the initial 
bronchodilator treatment in the Aeroneb group compared to the small volume jet nebulizer 
group 
-The heart rate at 30 minutes, 60 minutes and 180 minutes after the initial bronchodilator 
treatment in the Aeroneb group compared to the small volume jet nebulizer group 
-Length of stay in the ER 
-Percentage of patients requiring hospitalization  
-The total dose of albuterol used in each group 
-The total dose of ipratropium used in each group  
 
  
J. Tissue banking considerations: Not applicable 
 
VULNERABLE POPULATIONS:  
 
The study will recruit patients with severe acute asthma exacerbations. These patients are vulnerable due 
to the severity of their illness. The risk of providing this alternative method of bronchodilator delivery is 
not greater than minimal to the patient as this device has been FDA approved for the delivery of 
bronchodilator.  
 
 
 
 
 
 

Page 13 of 13 
 
 
 
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