Airway Clearance for Pediatric and Adult Cystic Fibrosis Patients Using a Portable Intra-Pulmonary Percussion Device (PIAPD)
Phase: NA
Conditions: Cystic Fibrosis
Sponsor: University of Florida

Protocol 3.9.2021 
NCT04743206 
Project Title: Airway Clearance for Pediatric and Adult Cystic Fibrosis Patients Using a Portable Intra-
Pulmonary Percussion Device 
Investigator(s): Joseph Russo, Silvia Delgado, Brittany Knight, Juliana Burt, Paul Davenport. 
Abstract: 
Airway clearance has a crucial role in the prevention of progression of lung disease in cystic fibrosis 
patients. Despite multiple options available for airway clearance, frequently cystic fibrosis patients have 
difficulties performing regular airway clearance in an at-home environment. We will compare 
pulmonary function testing and patient satisfaction with their current home device compared to the 
portable internal airway percussion device proposed (PIAPD). Our hypothesis is that there is no 
difference in pulmonary function testing after using PIAPD comparing to their home device. Our goal is 
to provide an equally effective, less expensive, alternative airway clearance technique for cystic fibrosis 
patients. 
Background:  
Cystic Fibrosis (CF) is an autosomal recessive disease that affects more than 30,000 people in the United 
States and more than 70,000 worldwide. The abnormal Cystic Fibrosis Transmembrane conductance 
regulator (CFTR) function leads to multiple organ manifestations. In the lungs, the dysfunctional CFTR 
mutation leads to abnormal thick, sticky mucus in the airways that traps microorganisms, leading to 
infections, inflammation and respiratory failure, which are the main causes of death in CF patients. Daily 
airway clearance plays a key role in preventing lung function deterioration in CF. Typically, a CF patient 
gets airway clearance therapy at least two times daily, each session lasting for about 30 minutes. There 
are different types of airway clearance therapies. Some of them are active, requiring patient 
cooperation and some coordination of breathing, while others are predominantly passive. In the United 
States, the most commonly utilized technique is high frequency chest wall oscillation, more commonly 
known as “the VEST”. This vibration loosens secretions in the bronchi that the patient will have to 
actively expel. The apparatus of vest therapy involves a wearable jacket, a hose pipe and an air 
compressor. This apparatus requires electric supply from the mains and is not portable.  
Vibrations can also be applied internally to airways through a mouthpiece. The existing devices that 
apply internal airway vibration include: Positive Expiratory Pressure Therapy (PEP), Flutter Valve therapy 
(Flutter) & Intrapulmonary Percussive Ventilation (IPV). PEP & flutter therapy involve portable, handheld 
devices without the need for electrical power. However, they both need patients’ active participation 
and they are only active during patients’ expiration phase of breathing. IPV is a modified ventilator that 
delivers pulses of air under pressure into airways. The equipment requires electricity and is not portable. 
IPV is only used within the hospital settings.  
Studies comparing different modes of airway clearance therapies have shown that they are all 
comparable to each other when used properly. A portable “Internal Airway Percussion” (PIAP) device 
that can deliver internal vibration to the airways both during inspiration and expiration and that requires 
patients’ minimal cooperation would in theory be superior to existing devices. High frequency oscillation 
(HFO) of bronchial airway surface liquid (ASL) is an experimental technique developed at UF for the 
transmission of high-frequency square form sound waves superimposed on normal breathing through a 
mouthpiece and into the airways. In this pilot study, we propose to test HFO as a means of airway 
clearance therapy in CF patients.  

Protocol 3.9.2021 
 
NCT04743206 
If the PIAP device is non-inferior to the SOC device, it would provide CF patients several advantages. The 
current VEST therapy, which is SOC for airway clearance, can cost anywhere from $5,000 to $20,000 for 
some of the newer models. The device under study could be made and provided to patients at a fraction 
of this cost. Furthermore, patients with CF are extremely vulnerable to respiratory infections and 
complications arising from such. In the time of COVID-19, this portable system can be used in the 
patient’s home and carried with them wherever they go. This provides a highly portable as well as cost-
effective option for airway clearance which will allow them to have greater flexibility where airway 
clearance is performed and allow them greater freedom to pursue activities that they enjoy.  
The PIAP device,(as pictured in Figure 4) that we have developed has been previously tested in several 
IRB-02 approved pilot studies here at the University of Florida by Dr. Paul Davenport in a population of 
healthy volunteers. Published results of these studies report this device’s waves produce vibrations 
within the airways, loosening Airway Surface Liquid (ASL), enhancing airway clearance and decreasing 
the sense of breathing effort. Furthermore, the IAP device was found to painlessly increase exhalation of 
intra airway molecules and droplets in healthy individuals.  
For this study, we would like to test this unique, custom designed, inexpensive, portable IAP device 
(PIAPD) as a comfortable alternative for airway clearance in CF patients.  
Specific Aims:  
1. To determine if Portable Internal Airway Percussion Device (PIAPD) is a non-inferior at-home 
method of airway clearance in patients with CF, we will compare changes in pulse oximetry and 
forced expiratory volume in one second (FEV1) prior to and 2 hours after airway clearance 
performed with standard airway clearance devices vs. the PIAPD. The primary endpoint will be a 
comparison of results of the aforementioned pulmonary function testing between the two 
devices. 
2. Secondary endpoints include will include comparison of patient satisfaction (tolerability and 
acceptability) with standard airway clearance devices and PIAPD.  
3. We will measure CF patient perception of breathing effort and device use for both methods.  
 
Study Design: This is a pilot study where we aim to compare initial use of the standard airway clearance 
device (SACD) (as pictured in Figure 2) with subsequent use of a PIAPD in patients ages 6-21 years with 
stable CF. Our primary hypothesis, stated as Null, is that there is no effect of on FEV1 2 hours after use 
and there is no effect on perception of effort and efficacy for the PIAPD device.  
General Inclusion Criteria: 
• 
Ages 6-21 years 
• 
Stable CF as determined by pulmonary physician assessment 
• 
Assents to forego additional experimental treatments during the study 
• 
Currently using and familiar with airway clearance therapy for treatment of CF 
• 
Participant (or parent or legal guardian if the participant is a minor) is willing to provide 
Informed Consent 
 
General Exclusion Criteria: 
• 
FEV1 < 40% predictive 
• 
Pneumothorax 
• 
Hemoptysis 

Protocol 3.9.2021 
 
NCT04743206 
• 
COVID-19 diagnosis within last 14 days  
• 
Non-compliance 
• 
Inability to obtain informed consent 
• 
Any condition that, in the opinion of the investigator, would interfere with the study conduct or 
the safety of the participant 
 
Additional Exclusion Criteria: Outpatient Arm (in addition to general exclusion criteria above)  
• 
Decrease in FEV1 > 10% from baseline over last 12 months 
• 
Antibiotic Initiation for acute CF exacerbation 
• 
Hospitalization for CF Exacerbation 
 
Additional Exclusion Criteria: Inpatient Arm (in addition to general exclusion criteria above)  
• 
Failure to increase FEV1 > 10 % from initial PFTs on admission by day 9 of hospitalization.  
 
Our patients will be recruited from our CF outpatient Clinic and from our CF inpatient population. 
Participants will be randomly assigned to perform airway clearance with the Standard Airway Clearance 
device (SACD) or Portable Internal Airway Percussion device (PIAPD). A large majority of our patients will 
be using VEST therapy as their standard of care airway clearance. A few might be using an 
Intrapulmonary Percussion Device that uses a mechanism different from the device we will be testing. 
Based on past experience, it is unlikely that this will present a significant source of variability.  
After discussing the study with a prospective participant and obtaining informed consent, participants 
will be randomized to either the standard of care or experimental group:  
Outpatient arm:  
On day 1, baseline FEV1 as measured on Smart One® portable home spirometer (Figure 1) and 
pulse oximetry will be obtained before and 2 hours after airway clearance, either performed 
with SACD method, PIAPD at 15hz. The frequency of the device will stay at 15 hz for the 
duration of the study as it has been previously shown to be the most effective frequency for 
better airway clearance (i.e., getting deeper into the airways). Participants will also be asked to 
give a rating of breathing effort using a Modified Borg Dyspnea Scale.  
For the next two weeks, airway clearance therapy, either performed 
with SACD method or PIAPD, will be performed by the patient daily 
(CF patients perform airway clearance daily as part of standard of 
care for their disease). Spirometry/pulmonary function testing will 
be collected twice per week over the two-week period with a pre 
and post FEV1, pulse oximetry, and rating of breathing effort. This testing will be done via telemedicine 
so that the PI or co-investigator can assist the patient with the PIAPD if necessary and conduct the 
testing in a safe and efficacious manner. At the end of the two weeks, the participant will be asked to 
complete a short survey regarding the ease of use and acceptability of the airway clearance device they 
had been using for the first part of the study.   
At the end of the initial 2-week period, the patient will be crossed-over to the other arm of the study 
and the same procedures will be repeated as per the above procedures. At the end of the study, 
patients will return the PIAPD device to the study team. 
FIGURE 1 
Figure 1: Smart One® portable home 
spirometer is the standard of care for at-
home measurement of FEV-1. 

Protocol 3.9.2021 
 
NCT04743206 
Inpatient arm:  
Patients who are admitted to the hospital for a normal seasonal disturbance of their CF are admitted, as 
SOC, for a 14-day in-patient stay. When patients are admitted, they bring their VEST system, as this is 
the standard of care device used by over 95% of CF patients for airway clearance therapy. Following 
admission, patients  will be informed of the study by the PI or one of the designated co-investigators. All 
study procedures will be explained and ample time to ask questions will be allotted. If the patient agrees 
to participate written informed consent will be obtained and the following procedures performed:  
Hospital Stay Days 1-3: Patients will only use their SOC airway clearance therapy. This will allow for a 
“wash-out period” providing all the patients with good airway clearance prior to collecting data (some 
patients may have had poor compliance prior to hospitalization). The participant will also be asked to 
complete a short survey regarding the ease of use and acceptability of their SOC airway clearance 
device, at the end of this 3-day wash-out period. Furthermore, during this period, we will get daily 
spirometry with a portable spirometer once per day after first airway clearance of the day, along with 
pulse oximetry.  
Hospital Stay Day 4: If, in the judgement of the PI, the participant has stabilized, we will randomize them 
to use either their SOC device or the study device. On Day 4, patients will be randomized to SOC or the 
new airway clearance device. We will collect the patient’s ratings of breathlessness with the Modified 
Borg Dyspnea Scale and perform spirometry again with the Smart One® portable spirometry device 
before and two hours after airway clearance procedures for the first airway clearance of the day. We 
will also obtain pulse oximetry.  
Hospital Stay Day 5: we will alternate the modality for the first airway 
clearance session of the day (using whichever device they were not 
randomized to use on Day 4), repeating the Modified Borg Dyspnea 
Scale and performing spirometry again before and two hours after 
airway clearance along with pulse oximetry. At this point, they will have 
used both the airway clearance devices, and they will be asked to 
complete a short survey regarding the ease of use and acceptability of 
the study airway clearance device.   
Hospital Stay Days 6-9: we will continue with daily spirometry, dyspnea 
measurements and pulse oximetry once per day after the first airway 
clearance of the day using the study device.  
Hospital Stay Days 10-14: patients who have increased their FEV1 by 
at least 10% from admission by day 9 of hospitalization and whose 
symptoms have clinically improved, will be given the choice of 
whether to use their SOC device or the experimental study device. Whichever device they choose, they 
will use for two airway clearance sessions, along with dyspnea measurements, and pulse oximetry on 
days 10-14 of hospitalization.  
At the end of the two weeks, the participant will be asked to complete a short survey regarding the ease 
of use and acceptability of each airway clearance device they had been using for the study.  At the end 
of the study, we will ask that the patient return the experimental device to the study team. 
Figure 2: The Vest® Airway Clearance 
System is the standard of care for airway 
clearance in both adult and pediatric 
l
i
FIGURE 2 

Protocol 3.9.2021 
 
NCT04743206 
Safety Endpoints:  
Outpatient: For the outpatient population, we will cease use of the experimental device if, during any 
airway clearance session with the aforementioned device, the patient experiences severe shortness of 
breath (as measured by the Borg Scale), chest pain or any type of discomfort beyond that which would 
be expected from performing this type of therapy. We will also cease use of the experimental device if, 
for any reason, the patient decides they don’t want to keep using it. Other stopping criteria would 
include: if there is a significant drop (>10 %) of the patient baseline FEV1 or if the patient or family 
changes their mind about participating in the study. 
Inpatient: For the inpatient population, we will cease use of the experimental device If there is a 
significant drop ( >10 %) of the patient baseline FEV1, if the attending physician and/or PI consider it is 
not safe for the patient to continue participating in the study, if the patient develops a secondary 
infection during their hospitalization. As per the above criteria, we will also cease use of the 
experimental device if, during any airway clearance session with the aforementioned device, the patient 
experiences severe shortness of breath (as measured by the Borg Scale), chest pain or any type of 
discomfort beyond that which would be expected from performing this type of therapy or if the patient 
or family changes their mind about participating in the study. 
A schematic of the experimental set-up and procedure is presented in Figure 5. The IAP apparatus was 
constructed from an acoustic wave controller (HPG1, Velleman_ Inc., Fort Worth, TX) connected to an 
amplifier (MG10, Marshall Amplification PLC, Bletchley, Milton Keynes, UK). The IAP delivered acoustic 
waves to the airways with adjustable waveforms, frequencies, and pressure amplitudes (Figure 4). A 
pressure transducer (Stoelting 50110, Stoelting Co., Wood Dale, IL) was used to measure the pressure 
amplitude of the IAP and to convert the measured values to the equivalent wave amplitudes. 
 
A snorkel-like tube connected to the amplifier was adopted for transmitting the 
generated waves through a mouthpiece commonly used for pulmonary function 
tests (Figure 3). To ensure the produced air pressure waves are transmitted down 
the respiratory system, the opposite end of the mouthpiece 
was connected to a 5 cm H2O/L/sec respiratory resistor 
(Model #7100R, Hans Rudolph, Inc., Shawnee, KS) throughout 
both the inspiration and expiration portions of the breathing 
cycle. Sampling bags used for aerosol sampling were 1-liter 
Tedlarbags (SKC Inc., Pittsburgh, PA) which had internal 
dimensions of 241 · 254mm2 as a deflated bag, with a wall 
thickness of *50 lm and single polypropylene (hose/valve and septum) fittings. 
 
FIGURE 3 
Figure 3: a snorkel-like tube connected to 
the amplifier was adopted for transmitting 
the generated waves through a mouthpiece 
commonly used for pulmonary function 

Protocol 3.9.2021 
 
NCT04743206 
Study Device: 
High Frequency Oscillator (HFO): The device involves 1) A mouthpiece commonly 
used in performing pulmonary function tests, or delivering nebulized medications 
and 2) A High-Frequency Oscillator (HFO) that will be connected via a side port to 
the mouth piece. This device transmits high frequency square form audio waves 
through a mouthpiece or mask interface to airways. HFO device vibrates the 
airways thereby lifting micro molecules of airway linings in to aerosols. During 
quiet tidal breathing, these aerosols escape the lungs through exhaled breath. 
Exhaled breath passes through a special filter that traps these aerosols and micro 
molecules of airway linings.  
Study Procedures and the Device Interaction:  
 
 
The study involves subjects breathing through a 
mouthpiece. The mouthpiece may be connected to 
HFO, or R tube exhaled breath condensate (EBC) 
device, other forms of commercially available EBC 
devices that collects exhaled breath or to an 
Aerosol Particle Counter (APC). The study 
procedure causes no discomfort and requires 
minimal patient cooperation. 
The exhalation port of the mouthpiece of HFO will 
have a special filter that traps aerosolized airway 
surface liquid (ASL) as well as microparticles 
present in exhaled breath.  
 
 
 
 
Statistical Analysis 
We shall cross-tabulate the pre- and post-treatment spirometry measures for study condition and 
group. Significance for association will be obtained by repeated measures ANOVA. The false positive and 
false negative rates will be estimated by exact binomial confidence limits. This is a pilot study that is 
seeking a promising outcome as opposed to a definitive one. We shall consider the result as promising if 
(a) no false positives occur and (b) the false negative rate is below 50%. 
 Power/Sample Size: The study will have a goal to recruit 50 CF (10 inpatient and 40 outpatient) patients. 
Initial data analysis to be completed after the first 25 patients have completed each test condition.  
FIGURE 5 
FIGURE 4 
Figure 4: The PIAPD experimental device 
utilizes high frequency audio waves to 
oscillate aerosols in airway linings and allow 
the to escape through exhaled breath  
Figure 5: this High Frequency Oscillator 
(HFO) has been designed to filter ASL as 
well as microparticles present in exhaled 
breath. 

Protocol 3.9.2021 
 
NCT04743206 
Measurable outcomes and expected timeline: We expect the PIAPD is equal to standard airway 
clearance in CF patients. We expect PIAPD will decrease the sense of breathing effort and increase 
patient sense of efficacy. 
Compliance/Accountability/Regulatory 
 
Statement of Compliance 
 
This study will be conducted in compliance with the protocol and will be generally consistent with 
current Good Clinical Practices (GCP), adopting the principles of the Declaration of Helsinki and all 
applicable regulatory requirements (ICH E6, 45CFR46, and FDA 21CFR sections 11, 50, 56, 312). 
 
Prior to study initiation, the protocol and the informed consent documents will be reviewed and 
approved by UF’s Institutional Review Board (IRB). Any amendments to the protocol or consent 
materials will be approved before they are implemented. 
 
Adverse Event Reporting and Safety Monitoring 
 
In the event of an adverse event the following definitions and processes will be used/followed: 
  
Adverse Event Definitions 
 
In this clinical research study, an adverse event (AE) is any occurrence or worsening of an undesirable or 
unintended sign, symptom or disease that is associated with study procedures. As an observational 
study, AEs occurring between study visits will not be reported unless deemed associated with study 
procedures. Throughout the study, the investigator must record AEs related to study procedures on 
source documents regardless of severity. 
 
Unexpected Adverse Event 
 
An AE is considered unexpected when the nature (specificity) or severity of the event is not consistent 
with the risks described in the protocol or informed consent document for specific protocol-required 
interventions. 
 
Grading Adverse Event Severity 
 
This study will utilize the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events 
(CTCAE Version 3.0) to classify AE severity. 
 
All AEs Grade 2 or greater pertaining to study procedures will be recorded on the UF IRB adverse event 
log, which will be review by the IRB annually at continuing review. The investigator will make a 
determination as to the relation to participation in the study. Events will be assessed and reported in 
accordance with the ICH Guidelines for Good Clinical Practice and per the guidance of the DHHS Office 
for Human Research Protections (OHRP). Should there be an adverse event or unanticipated problem 
that is both serious and unexpected it will be evaluated by the PI and reported to the IRB as appropriate 
per current regulatory guidelines. 
 
Informed Consent 

Protocol 3.9.2021 
 
NCT04743206 
 
Participants will sign their own informed consent form (or in the case of parents, they will consent for 
their child). This study will require written assent from minors. This study does not allow for use of 
legally authorized representatives or LARs. Each participant will receive a signed copy of their informed 
consent for their records. Participants will have the opportunity to ask questions before they sign the 
consent form and when a study coordinator calls them to confirm their information. 
 
Risks and Benefits 
 
Aside from the normal shortness of breath, which is expected as part of doing standard of care airway 
clearance and pulmonary function testing, there are no discomforts or risks associated with study that 
we know of. This research study may also include risks that are unknown at this time.  
If the portable airway device works as well as the standard airway clearance device, it will potentially 
provide a less expensive, portable alternative for patients with CF that they can use in their homes 
without coming to clinic and during telemedicine visits with their physician.  
 
It is also possible, that patients may not see an improvement and may even see a worsening of their 
airway clearance as measured by FEV-1 while using the experimental device.  
 
Confidentiality 
 
Investigators and staff will maintain the highest degree of confidentiality permitted for the clinical and 
research information obtained from subjects participating in this study. When a participant signs a 
consent they will be assigned a study ID which will be attached to their surveys and data. All study 
records will be locked in secure filing cabinets in locked offices in UF research space.   
 
Conflicts of Interest 
 
The investigators have no financial interests in any entity which could potentially benefit from the 
outcomes of this research. This study is internally funded by the Department of Medicine and the 
investigational device being used was created by Dr. Paul Davenport who has previously used the device 
in several UF IRB approved research protocols. This device has been reviewed by the UF Office of 
Technology and Licensing, who determined that the invention was not eligible for a patent or other 
licensing as it was too “similar” to currently approved/marketed products. The justification for the use of 
this device in the clinical space, is that it is much cheaper than the current airway clearance devices 
currently on the market making it ideal for patients with no insurance or lower incomes. Additionally, 
with the advent of COVID-19 patients with CF are at increased risk when leaving their house and coming 
to the clinic in order to perform pulmonary function testing and airway clearance. The device under 
investigation is portable and can be utilized in the home environment and monitored by the provider 
with telemedicine.   
 
Protocol deviations 
 
Any deviations from the protocol will be filed, as appropriate, on our deviation log and reported at the 
annual continuing review. Any deviations which have the potential to impact participant safety will be 
reported per UF guidelines. 
 
Data handling and record keeping 

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Data collection will comply with all applicable guidelines regarding patient confidentiality and data 
integrity. REDCap data security protocols provide private, secure, and encrypted transmission of data 
between server and client computers over the public Internet network. All data systems are HIPAA 
compliant.