AirFLO2 Treatment for Hypoxia and/or Tachypnea in Patients With COVID-19
Phase: NA
Conditions: Corona Virus Infection, Respiratory Rate, Hypoxia, Covid19
Sponsor: Duke University

 
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AirFLO2 Treatment for Hypoxia and/or Tachypnea in Patients with COVID-19 
 
 
 
Research Protocol 
 
 
Version 3 – 21SEP2020 
 
NCT04649775 
 
 
 
 
 

 
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Study Summary 
 
Title 
AirFlO2 Treatment for Hypoxia and/or Tachypnea in 
Patients with COVID-19 
 
Short Title 
AirFLO2 with COVID-19 
IRB Protocol number 
Pro00105246 
Study Center 
Duke 
Study Aims 
Primary: 
Determine if use of the AirFLO2 device will reduce hypoxia in patients 
admitted to the hospital with COVID-19 infection. The aim of our 
study is to determine whether the use of the AirFLO2 device can 
improve hypoxia as measured by change between baseline P:F ratio 
and repeat P:F ratio between 1 to 6 hours after using the device.  
 
Secondary: 
Determine if use of the AirFLO2 device will  
a) Improve subjective symptoms related to dyspnea and comfort 
b) reduce risk of progression to high flow nasal cannula (HFNC), 
non-invasive ventilation (NIV), or invasive ventilation 
c) reduce intensive care unit (ICU) transfer risk 
d) reduce intubation risk 
e) reduce days of hospitalization 
f) increase survival to discharge 
 
Number of Subjects 
A targeted sample size of 46 subjects will be required, with an 
expected dropout rate of 10%, a total sample size of 50 subjects will 
be necessary to complete the study.  
 
Inclusion Criteria 
• Adults ≥18 years of age with confirmed COVID-19 infection 
• Patient must be able to complete  consent and hold mask 
• Baseline room air oxygen saturation </=94% or patient with new 
supplemental oxygen requirement at presentation or patient on 
supplemental oxygen at baseline and requiring up-titration of 
oxygen setting 
Patient must have access to an internet-connected device 
Exclusion Criteria 
• Tracheostomy 
• History of pneumothorax or known bullous lung disease 
• Recent cataract surgery 
• Patient receiving NIV (Noninvasive Ventilation) or HFNC (High 
Flow Nasal Cannula) 
• Patient receiving mechanical ventilation 
• Active TB 
• Seizures 

 
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• Delirium 
Study Schedule 
Following prescreening for eligibility, participants will provide 
consent.  It is expected the primary consent will be performed at 
the in-patient bedside with a study coordinator to facilitate and 
answer questions.  
 
After consent, baseline clinical data will be recorded and study 
related parameters post consent will be collected 
 
 
 
 
Parameter 
1 hr 
pre 
baseline 
1 hr 
2 hr 
4 hr 
6 hr 
8 hr 
12 hr 
Every 
24 hr 
disch
arge 
withd
raw 
death 
Sp02 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
ABG 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
P/F 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
NC L/m 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
HFNC  
 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
NIV 
 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Ventilat
or free 
 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Yes 
/No 
Roth 
scale 
 
X 
 
 
 
 
 
 
 
X 
 
 
CV 
 
X 
(betw een 
1 & 6hrs) 
 
 
 
X 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
LCQ 
 
X 
(betw een 
1 & 6hrs) 
 
 
 
X 
 
 
SOFA 
score 
 
X 
 
 
 
 
 
 
 
 
 
 
Platelet 
 
X 
 
 
 
 
 
 
 
 
 
 
Creatini
ne 
 
X 
 
 
 
 
 
 
 
 
 
 
MAP 
 
X 
 
 
 
 
 
 
 
 
 
 
Vasopre
ssor tx 
 
X 
 
 
 
 
 
 
 
 
 
 
Vasopre
ssor 
dose 
 
X 
 
 
 
 
 
 
 
 
 
 
Bilirubi
n 
 
X 
 
 
 
 
 
 
 
 
 
 
Glasgow 
coma 
scale 
 
X 
 
 
 
 
 
 
 
 
 
 
COVID-
19 
inflamm
 
X 
 
 
 
 
 
 
 
 
 
 

 
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atory 
markers 
D-
Dimer 
 
X 
 
 
 
 
 
 
 
 
 
 
Ferritin 
 
X 
 
 
 
 
 
 
 
 
 
 
CRP 
 
X 
 
 
 
 
 
 
 
 
 
 
Creatine 
kinase 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary objective:  
Determine if use of the AirFLO2 device will reduce hypoxia in patients admitted to the hospital with COVID-
19 infection. The aim of our study is to determine whether the use of the AirFLO2 device can improve 
hypoxia as measured by change between baseline PaO2:FiO2 ratio and repeat PaO2:FiO2 ratio between 
1 to 6 hours after using the device.  
 
Secondary Objectives: 
Determine if use of the AirFLO2 device will  
g) Improve subjective symptoms related to dyspnea and comfort 
h) reduce risk of progression to high flow nasal cannula (HFNC), non-invasive ventilation (NIV), or 
invasive ventilation 
i) reduce intensive care unit (ICU) transfer risk 
j) reduce intubation risk 
k) reduce days of hospitalization 
l) increase survival to discharge 
 
Background and Significance: 
The coronavirus disease 2019 (COVID-19) outbreak that started in Wuhan, China in December 2019 
has now extended across the globe with > 1 million cases world-wide and 52,863 deaths as of April 1, 
2020 (Johns Hopkins data). In North Carolina, 2016 cases have thus far been identified with 24 deaths 
and 184 admitted to hospitals in the state. These numbers are rapidly rising. In patients admitted with 
acute viral infection due to COVID-19, traditional methods to treat respiratory failure with non-invasive 
positive pressure ventilation are often being bypassed for fear of aerosolization of virus resulting in 
presumptive intubation for COVID-19 and a shortage of ventilators (PMID: 32212516). There is an 
urgent need to identify interventions which can retard or block progression to ARDS and reduce the 
need for invasive ventilation.  
 
In adults with COVID-19 at risk for respiratory failure, the addition of conventional oxygen is 
recommended for O2 saturations </=94%.  If hypoxemia progresses, the Surviving Sepsis Campaign 
recommends using high flow nasal cannula over conventional oxygen therapy and a  high PEEP strategy 
in the management of ARDS (PMID:32222812). 
 
Methods:  
We propose an innovative device that can provide a low-cost, non-invasive, portable method to provide 
positive end expiratory pressure to improve oxygenation by decreasing respiratory muscle work of 
breathing, decreasing atelectasis, and increasing functional residual capacity (PMID: 23115688). Our 
novel device (Figure 1) features a mask, an adjustable pressure (5-20cm H2O) outflow valve to meet 
individual patients’ needs and an inflow valve to allow for free-flowing inhalation. If short of breath, the 
patient will apply the AirFlO2TM mask over their nose and mouth, forming an air-tight seal. The patient can 
breathe through the outflow valve; the valve will create positive pressure within the mask according to the 

 
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adjustable pressure setting. The pressure provided by the mask helps to reduce atelectasis and recruit 
alveoli to reduce ventilation-perfusion mismatch. By leveraging well established technologies, we have 
created an accessible device with a low barrier for training and adoption. In addition, it can easily be 
decontaminated by removing the valve, wiping down and performing a simple at-home washing protocol 
with soap and water. 
 
Design & Procedures:  
 
We propose an unblinded, randomized, controlled trial for use of the AirFlO2 device for patients admitted 
to Duke Hospital with COVID-19 and tachypnea (RR >20 breaths/min) and/or hypoxia (Oxygen 
saturation </=94% on room air or requiring supplemental oxygen at baseline). 
  
Inclusion criteria: 
• 
Adults ≥18 years of age with confirmed COVID-19 infection 
• 
Patient must be able to complete  consent and hold mask 
• 
Room air oxygen saturation </=94%, patient with new supplemental oxygen requirement, or 
patient on supplemental oxygen at baseline and requiring up-titration of oxygen setting 
• 
Patient must have access to an internet-connected device 
 
Exclusion criteria: 
• 
Tracheostomy (current) 
• 
History of pneumothorax or known bullous lung disease 
• 
Recent cataract surgery 
• 
Patient receiving NIV (Noninvasive Ventilation) or HFNC (High Flow Nasal Cannula) 
• 
Patient receiving mechanical ventilation 
• 
Active TB 
• 
Seizures 
• 
Delirium preventing patient from providing informed consent or self-applying mask 
 
Study groups: 
We will enroll n=50 patients with hypoxia (O2 saturation 90% or less on RA) and use clinical data 
including:  
• 
Room air oxygen saturation 
• 
PaO2/FiO2 ratio 1 hour prior to and then 1, 2, 4, 8, 12 and every 24hours after using AirFLO2. 
o If arterial blood gas result is not available for any time point then the P:F ratio will be 
imputed using the SpO2.  
o If the patient is on nasal cannula, the estimated FiO2 delivery will be calculated based on 
the oxygen flow rate in liters per minute (LPM). 
• 
Transition to HFNC or NIV 
• 
ICU transfer  
• 
Ventilator free days 
• 
Survival to discharge 
• 
Cardiovascular (CV) Questionnaire, Cough questionnaire, and Roth score will be completed at 
baseline, and before discharge by all consented participants and  the two questionniares 
repeated 1-6 hours after using the device for subjects randomized to receive the AirFLO2. 
 
Additional clinical data pertaining to overall disease severity as measured by the Sequential Organ 
Function Assessment (SOFA) score and inflammatory markers related to COVID-19 infection will be 
collected: 
• 
SOFA score 
o Platelet count 

 
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o Creatinine 
o Mean arterial pressure 
o Vasopressor treatment and dose 
o Bilirubin 
o Glasgow Coma Score (extracted from clinical documentation) 
• 
COVID-19 inflammatory markers 
o D-dimer 
o Ferritin 
o C reactive protein (CRP) 
o Creatine kinase 
o Lymphocyte percentage 
 
These clinical data will be obtained via chart review. For each lab value, the collection time point nearest 
to study enrollment will be recorded. 
 
Subject Recruitment and Compensation  
Study participants will be recruited from the COVID-19 positive in-patient population at Duke Hospital.  
Subjects will not be compensated for their participation in the trial.  
Patients will receive the AirFLO2 which will be collected and destroyed upon discharge from the hospital.  
 
Consent Process  
Consent will be obtained by a COVID Core CRC with the participant. No additional consent is required 
for analysis of clinical data. 
 
Randomization 
After consent, subjects will be randomized to the intervention or the control group via randomization 
software. 
 
Intervention 
Intervention subjects will receive the AirFLO2 device and training via video with reinforcement from the 
coordinator how to use and to self-apply it. Bedside nurses will also be given instructions, access to the 
study video and verbal training as well, so that they can answer simple questions for the patients. 
Initially the CRC will hand device to the patient.  Oxygen saturation at baseline will be recorded. The patient 
will set the PEEP at 5 on the mask, then hold the mask firmly against the face, take a full slow deep breath in, 
then exhale steadily out until out of breath. Record oxygen saturation. Wait 3-5 minutes then repeat maneuver 
with PEEP at 10. Record oxygen saturation. Repeat again with PEEP at a setting of 15, then again at 20. The 
highest O2 saturation achieved with the lowest PEEP is the PEEP setting to use. If oxygen saturation does 
not change or decreases, leave at PEEP of 5. 
 
All other elements of patient care will be managed by the treating physician(s).  
 
Control 
Control subjects will receive usual care, managed by the treating physician(s).  
 
Data Analysis & Statistical Considerations  
 
Sample size calculation was performed, assuming a hypothesized increase in P:F ratio of +25 in the 
intervention group, no change in P:F ratio in the control group, and standard deviation of 30 in both 
groups. With these assumptions, for statistical power of 80%, a sample size of 46 subjects will be 
required. With an expected dropout rate of 10%, a sample size of 50 subjects will be necessary to 
complete the study.  
 

 
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Groups will be analyzed by intention to treat. Per-protocol analyses will also be performed. 
 
Descriptive statistics will be reported for the overall subject population, and for the two groups.  
 
The primary outcome of intra-subject change in P:F ratio before and after using the device will be 
analyzed with a paired student’s t-test. The absolute change and percent change in P:F ratio will be 
compared between the control and intervention groups with student’s t-tests. A multivariate analysis will 
be performed comparing the change in P:F ratio using linear regression, controlling for baseline P:F ratio, 
baseline overall disease severity (SOFA), and baseline COVID-19 related disease activity markers. 
 
Secondary outcomes of risk for high flow nasal cannula, noninvasive ventilation, invasive ventilation will 
be compared between the intervention and control groups with the χ-squared test. Survival to discharge 
will be compared with the χ-squared test. Logistic regression analysis will be performed for each of these 
outcomes, controlling for baseline P:F ratio, baseline overall disease severity (SOFA), and baseline 
COVID-19 related disease activity markers. 
 
Ventilator-free days will be compared using the student’s t-test for bivariate analysis, and linear 
regression for multivariate analysis, controlling for baseline P:F ratio, baseline overall disease severity 
(SOFA), and baseline COVID-19 related disease activity markers. 
 
Secondary outcomes of questionnaires related to subject symptoms before and after using the device 
will be analyzed for intra-subject change in questionnaire scores using paired student’s t-tests. A 
multivariate analysis will be performed comparing the change in questionnaire scores using linear 
regression, controlling for baseline questionnaire score, baseline P:F ratio, baseline overall disease 
severity (SOFA), and baseline COVID-19 related disease activity markers. 
 
Privacy, Data Storage & Confidentiality  
Storage of clinical data is outlined in Pro00105246; subjects will be de-identified per Pro00105246.  
 
Figure 1