Feasibility of Use of the PATH bCPAP Kit Including Oxygen Blenders in a Neonatal Population in Uganda
Phase: NA
Conditions: Respiratory Distress Syndrome, Infant, Premature
Sponsor: PATH

           
 
1 
 
 
 
 
 
 
 
 
FEASIBILITY OF USE OF THE PATH BCPAP 
KIT INCLUDING OXYGEN BLENDERS IN A 
NEONATAL POPULATION IN UGANDA 
 
 
 
 
 
 
 
Principal Investigators: 
James Nyonyintono, MBChB, M.Med. Surgery (Mak) 
Anna Hedstrom, MD 
 
 
Version Number:  1.6 
 
Date: 
16 July 2021 

 2 
Table of Contents 
 
Table of Contents ................................................................................................................................. 2 
Research Team .................................................................................................................................... 3 
Acronyms and Abbreviations ............................................................................................................ 65 
Operational definitions ....................................................................................................................... 65 
Abstract  ............................................................................................................................................... 76 
1.0  CHAPTER ONE: Introduction and Background..................................................................... 87 
2.0  CHAPTER TWO: Literature review ...................................................................................... 1110 
3.0  CHAPTER THREE: Statement of the problem, Justification and Conceptual framework
 .......................................................................................................................................................... 1312 
3.1 
Problem statement ......................................................................................................... 1312 
3.2 
Justification of the problem ........................................................................................... 1312 
3.3 
Study Product ................................................................................................................. 1514 
4.0  CHAPTER FOUR: Research questions, hypothesis and objectives .............................. 2019 
4.1 
Hypothesis ....................................................................................................................... 2019 
4.2 
General objective ........................................................................................................... 2019 
4.3 
Specific objectives .......................................................................................................... 2019 
5.0  CHAPTER FIVE: Methodology ............................................................................................. 2120 
5.1 
Study design ................................................................................................................... 2120 
5.2 
Study site ......................................................................................................................... 2120 
5.3 
Sample size ..................................................................................................................... 2221 
5.4 
Study population ............................................................................................................. 2423 
5.5 
Study procedure ............................................................................................................. 2524 
5.6 
Study variables 
5.7 
Data collection 
5.8 
Data management and analysis .................................................................................. 3332 
5.9 
Ethical considerations .................................................................................................... 3534 
References ...................................................................................................................................... 4342 
 
Appendices 
A. 
PATH bCPAP and Blenders Instructions for Use 
B. 
Verification test report and Substantial Equivalence Table 
C. 
bCPAP Therapy Guidelines of Care 
D. 
Data collection forms 
E. 
Consent form(s) and Standard Operating Procedure for Obtaining Consent 

 3 
Research Team  
 
Role 
Name, Title 
Responsibilities  
US Principal 
Investigator 
Anna Hedstrom, MD 
Assistant Professor/ 
Neonatologist, University 
of Washington 
• 
Training 
• 
Oversight - Overall study completion 
Country 
Principal 
Investigator 
James Nyonyintono, 
MBChB, M.Med. Surgery 
(Mak) 
Clinical Programs 
Manager, Kiwoko Hospital 
• 
Oversight - Day-to-day study 
oversight, ensuring that the study is 
conducted according to the protocol  
• 
Reporting - Adverse event 
confirmation and documentation 
• 
Protecting participants' rights 
• 
Communicating questions, concerns, 
and/or observations to the principal 
investigator and/or coordinating 
centre 
Sponsor - PATH 
Manjari Quintanar 
Solares, MD 
PATH Study 
Representative 
 
Patricia S. Coffey, PhD., 
MPH 
PATH Responsible Project 
Manager 
• 
Providing and managing funding and 
resources for study implementation 
 
Senior Advisor 
Maneesh Batra, MD, MPH 
University of Washington 
Professor/ Neonatologist 
• 
Training 
• 
Study Advisor 
Newborn Unit 
Oversight  
Josephine Nakakande, 
RN 
Newborn Unit nurse-in-
charge, Kiwoko Hospital 
• 
Oversight - Guideline adherence for 
bCPAP usage 
• 
Obtaining informed consent and 
enrolling participants  
• 
Training - Guidance of training 
• 
Oversight - Nurse oversight 
Data Collection 
Oversight and 
Consent  
Beatrice Niyonshaba, 
MPH  
Research, Monitoring and 
Evaluation Officer, Adara 
Development (Uganda) 
• 
Oversight of data recorders 
• 
Obtaining informed consent and 
enrolling participants 
• 
Reporting - Preparing and sending 
required reports to medical 
monitorsafety monitoring committee 
Data Recorders 
Nursing students - Kiwoko 
Hospital School of Nursing 
• 
Documentation - Via shift work, a data 
recorder will be in unit around the 
clock to record data on bCPAP 
patients 

 4 
• 
Documentation - Initial reports of 
adverse events 
Data Entry team 
Newborn unit data entry 
team (this team has 
experience with medical 
record data entry into 
online database) 
• 
Documentation - Record data from 
forms into REDCap 
Medical Monitor 
– Head of 
Safety 
Monitoring 
Committee 
Dr. Flavia Namiiro, 
MBChB, MMed 
(Pediatrics & Child 
Health) 
Ugandan paediatrician 
experienced in the care of 
neonates and use of 
bCPAP kits 
• 
Monitoring moderate and severe 
adverse events 
Safety 
Monitoring 
Committee 
Dr. Clare Nakubulwa, 
MBChB, MMed 
(Pediatrics) 
Ugandan paediatrician 
experienced in the care of 
neonates and use of 
bCPAP kits 
• 
Monitoring moderate and severe 
adverse events 
Safety 
Monitoring 
Committee 
Sheillah Bagayana, 
Bachelor Biomedical 
Engineering  
Sheillah is an experienced 
biomedical engineer with 
experience in oxygen and 
respiratory devices. 
• 
Monitoring moderate and severe 
adverse events 
Makerere 
University 
Senior Advisor 
Peter Waiswa, MBChB, 
MPH, PhD 
Associate Professor, 
Makerere University 
School of Public Health, 
• 
Oversight - Study Design Advisor 
Study support 
Heidi Nakamura, RN BSN 
Global Health Director, 
Adara Development (USA) 
• 
Oversight - Study logistic support 
• 
Ensuring that all study staff meet 
regulatory and fulfill training 
requirements 
• 
Training 
Study support 
Madeline Vaughan, MIPH 
Senior Programmes 
Director, Adara 
Development (Australia) 
• 
Oversight - Study logistic support 
Device support 
Sierra Jessup, BS  
Product Development 
• 
Oversight - Device support 

 5 
Technical Coordinator, 
PATH 
Biostatistician 
Paul Mubiri, M.Stat 
Research Officer under 
PERFORM2Scale Project, 
Makerere University 
• 
Reporting – Data analysis  
• 
Documentation - Creation and 
management of Redcap database 
Qualitative 
analysis Support 
Mohan Paudel, PhD, 
MPH 
Monitoring and Evaluation 
Manager, Adara 
Development (Australia) 
• 
Oversight - Qualitative Analysis 
• 
Reporting - Data analysis  
 

 6 
Acronyms and Abbreviations 
CPAP = Continuous Positive Airway Pressure 
bCPAP = Bubble Continuous Positive Airway Pressure 
EFS = Early feasibility study 
HCW= Healthcare worker 
RSS = Silverman Anderson Respiratory Severity Score[1] 
WHO = World Health Organization 
 
 
Operational definitions 
 
PATH bCPAP kit without blenders 
bCPAP (tubing/ cannula/ bubbler) without blenders 
PATH bCPAP kit with oxygen 
blenders 
bCPAP (tubing/ cannula/ bubbler) with blenders 
PATH blenders  
only the PATH blenders 
 
Kiwoko bCPAP refers to the pre-existing bCPAP that has been in place at Kiwoko hospital 
since 2012. It is assembled from spare parts and donated nasal cannulas.(12) 

 7 
Abstract  
Preterm birth is responsible for 1/3 of deaths under age five- the majority which occur in 
resource-constrained settings. Many of these deaths are due to respiratory failure which can 
be treated with bubble continuous positive airway pressure (bCPAP). Commercialized 
bCPAP devices are expensive, leading resource-constrained settings to make and use 
improvised devices. These improvised devices have not been tested for performance and 
run on 100% oxygen. WHO guidelines strongly advise against the use of 100% oxygen—
particularly with preterm newborns where it can cause blindness, lung and brain injury. 
To address this need, PATH has developed a low-cost bCPAP kit which includes oxygen 
blenders that do not require electricity nor a source of pressurized air to blend oxygen with 
air. We seek to conduct an early feasibility study to:  
1. assess the operational feasibility of using the PATH bCPAP kit including, when 
appropriate, in-line oxygen blending on neonatal patients and  
2. assess the usability and acceptability of the PATH bCPAP kit with oxygen blenders 
by healthcare workers. 
 
Newborns will be treated with the PATH bCPAP kit and a subset of these will also be treated 
with the PATH blender as needed to provide blended oxygen. Results from this study will be 
used to identify appropriate modification to the use procedures and/or the device as 
needed. Once testing is completed and product revision finalized, the PATH kit and 
blenders will allow resource-constrained settings to provide rigorously tested bCPAP 
therapy and blended oxygen to patients with reduced risk of morbidity from oxygen toxicity. 
 
 

 8 
1.0 CHAPTER ONE: Introduction and Background 
 
Preterm birth is responsible for 1/3 of paediatric deaths under age five.[2] Infants born very 
early suffer from respiratory distress syndrome due to under developed lungs and this is a 
leading cause of their deaths.[3] An additional 15% of children under age five die from 
trouble breathing due to respiratory tract infections such as pneumonia.[2] Continuous 
positive airway pressure (CPAP) provides constant distending pressure to the lungs and 
decreases the work of breathing for an infant. It is the recommended standard of care for 
respiratory failure caused by respiratory distress syndrome or pneumonia, and should be 
started as soon as the diagnosis is made.[4,5] The pressure provided by bubble CPAP 
(bCPAP) is regulated by the depth of the tube in the water bottle. The gas flow through the 
tube creates bubbling, and the resulting oscillations are helpful to a patient’s lungs. Because 
of this, bCPAP is considered superior to standard CPAP in treating neonatal respiratory 
failure. Commercialized devices are available (Figure 1)[6], but are rarely found in resource 
constrained settings due to the prohibitive cost. 
 
 
Figure 1. Commercialized bubble CPAP (bCPAP) circuit. These systems can cost up to 
10,000USD. Figure from: [7] 

 9 
 
Commercialized devices considered to be “low cost” do exist, however, at a price of 
US$900, resource-constrained sites still cannot afford them or cannot afford enough devices 
for the number of patients requiring treatment.[8] To address this care gap, the World Health 
Organization (WHO) recommends creating improvised bubble CPAP (bCPAP) devices using 
components available in the hospital, specifically tubing connected to bottles, with water to 
generate the necessary pressure.[7]  (Figure 2). These improvised kits, however, have 
variable performance in terms of pressure delivered due to the variation in the diameter and 
length of available tubing, lack of appropriate cannulae sizes, and incorrect assembly of 
parts.  
 
 
Figure 2. Improvised bCPAP created from a simple nasal cannula, as advised by the WHO. 
Although lifesaving, this system runs on 100% oxygen which can be toxic to patients. Figure 
from [7]. 
 
Additionally, most resource-constrained settings providing bCPAP therapy do not have a 
mechanism to provide blended gases (air and oxygen) to the baby. WHO guidelines strongly 
advise against the use of 100% oxygen with newborns—particularly preterm newborns—as 
it poses a risk for blindness, chronic lung disease and brain injury.[9,10] High resource 

 10
settings use a commercialized oxygen blender for this purpose. These blenders are not only 
expensive—about US$1,000 each—but require that both oxygen and air are supplied from a 
pressurized source such as a wall supply or cylinders. Further, the pressure of both gases 
must be roughly equal in magnitude and at a pressure beyond the capability of most oxygen 
concentrators. Pressurized air is rarely available in resource-constrained settings as it has 
very few uses beyond mechanical ventilation. Therefore, the provision of blended oxygen is 
not available in most resource limited settings providing bCPAP.  
 
 
 
 
 

 11
2.0 CHAPTER TWO: Literature review 
 
Neonatal mortality 
Over five million children under age five die annually worldwide - the majority in low resource 
settings.[11] The risk of death is highest in the first month of life, with 18 deaths per 1,000 
live births globally, accounting for 2.5 million deaths overall.[11] Over the last 30 years, 
paediatric mortality has improved more quickly than neonatal mortality due to more rapid 
improvements in post-neonatal mortality.[12] Neonatal deaths are now responsible for nearly 
half (47%) of all childhood mortality. [11] Sub-Saharan Africa has the highest burden of 
paediatric mortality- 16 times the average mortality rate in high income countries. [11] In 
Uganda, neonatal mortality remains 28/1000 live births, and the largest cause of death is 
prematurity.[13] Accelerating implementation of available, cost-effective interventions for sick 
newborns is a factor into reducing this mortality. 
 
Respiratory failure in neonates 
Respiratory failure is the final common pathway in the most frequent causes of neonatal 
death: preterm birth, infection, and birth asphyxia.[11] Preterm babies in particular have a 
deficiency in surfactant in their lungs and have difficulty keeping them open following birth. 
There is increasing attention on the care of the sick and small newborn including increased 
development of interventions for respiratory failure, such as bubble continuous positive 
airway pressure (CPAP).[14] 
 
Evidence for bubble CPAP 
Bubble Continuous Positive Airway Pressure (bCPAP) is a simple, form of respiratory 
support that has been shown to decrease mortality in neonates with respiratory distress in 
both high and low resource settings.[15-17] Pressure delivery in bubble CPAP is due to the 
flow of air through a tube placed under water. The pressure is dependent on the depth of this 
tube. Bubbles emerging from the tube create oscillations which are trasmittted to the 
patient’s lungs. Treatment with bCPAP has been associated with improved clinical outcomes 
compared with other forms of CPAP.[18,19] 
 
Bubble CPAP is increasingly used in low and middle income countries.[20-22] In Uganda it 
has been associated with improved mortality among preterm infants.[23,24] A 2020 
publication from Mbale reported, among patients <1500 grams birthweight, the mortality rate 
decreased from 39% to 27% after the initiation of bCPAP (44% reduction in mortality, OR 
0.56, 95%CI 0.36 – 0.86, p = 0.01).[23] The site of our study, Kiwoko Hospital, in Nakaseke 
district, was the site of bCPAP implementation in 2012 and one of the first published case 
series of such use in Uganda.[24]  
 
Bubble CPAP Devices 
Bubble CPAP is strongly recommended for treatment of premature lung disease.[25] 
However there are limitations to available devices- commercialized bCPAP can cost over 
10,000USD.[16]  Lower cost commercialized bCPAP devices exist, however they cost 900 
USD or more and low resource setings cannot afford enough units to serve the number of 
patients requiring bCPAP treatment.[26,27] The WHO recomends settings without access to 
commercialized devices create improvized bCPAP.[7] These improvised kits (Figure 2.)  and 

 12
described in section one), use spare parts that are commonly available in facilty settings and 
have allowed more settings to treat patients with bCPAP. Improvised kits have not been 
bench tested for reliability, and the design (using small bore oxygen tubing) varies 
considerably from those of commercialized designs. The need exists, therefore, for a low 
cost bCPAP design that has undergone testing to confirm it delivers accurate and 
appropriate pressure to a newborn. 
 
Oxygen Safety 
Oxygen is life saving for newborns and is included in the WHO model list of essential 
medicines.[28] Hower the use of 100% oxygen can be dangerous. Excessive oxygen use 
causes retinopathy of prematurity (ROP), blindness or visual impairment in preterm infants.  
This is one of the leading causes of blindness around the world, causing 32,200 cases in 
2010.[29] Currently ROP is most prevelent in middle income countries as neonatal care has 
scaled-up without safe oxygen management.[29] Oxygen-associated blindess is now being 
reported in Africa, likely associated both with increased oxygen use as well as ability to 
follow-up and detect this retinal damange in tertiary neonatal units.[30-32]  
Although 100% oxygen should never be used for bCPAP therapy, many resource limited 
sites implementing bCPAP have access only to 100% oxygen.[9] Blending oxygen with room 
air allows it to be titrated to the patient’s oxygen saturations and decreases the risk of 
hyperoxia. Low cost systems for delivering blended oxygen are required for safe bCPAP 
use.[9]  
 

 13
3.0 CHAPTER THREE: Statement of the problem, Justification 
and Conceptual framework 
 
3.1  Problem statement 
 
The use of bCPAP devices can reduce mortality related to respiratory failure in newborns. 
However, devices operated with 100% oxygen increase the risk of morbidity in survivors, 
due to oxygen toxicity. There is a critical need for a safe, rigorously tested, very low-cost 
bCPAP kit including oxygen blender to be made available to resource-constrained sites. 
 
3.2 Justification of the problem 
 
To address this need, PATH has developed a low-cost bCPAP kit which includes two fixed-
ratio oxygen blenders (Figures 3 and 4) that do not require a source of pressurized air. 
These simple and inexpensive devices sit in-line from the oxygen source and dilute the 
flowing stream of oxygen with room air, obviating the need for a pressurized source of air. 
The oxygen may be supplied from either high-pressure sources or low-pressure sources 
such as oxygen concentrators. Each of the two blenders are single plastic parts, injection 
moulded from a biocompatible, medical-grade polyethylene resin. No electricity is required 
for the blenders to provide a stable and constant mix of air and oxygen over the full range of 
clinically relevant pressure and flows for newborns.  
 
 
Figure 3. PATH BCPAP Kit with in-line blender (left) and close-up of oxygen blender 
(right)  
 

 14
 
Figure 4. Mechanism of oxygen blender 
 
Two fixed ratio blenders are available: a ‘low’ blend that provides 37% oxygen, and a ‘high’ 
blend that provides 60% oxygen. The actual ratio of oxygen and air necessarily depends on 
the concentration of oxygen supplied to the blender but remains constant and stable for any 
given input. 
 
Both the technological characteristics and intended use of PATH’s blenders are substantially 
equivalent to devices that are on the US market today. The mode of operation (air 
entrainment) has been employed by class 1 (low risk) oxygen diluter devices used for high-
flow oxygen masks that have been commercially available since the 1970’s. Oxygen 
blenders (class 2, moderate risk) have been commercially available for a similar period, and 
provide variable blends of air and oxygen for respiratory support requiring some pressure—
such as CPAP. The PATH fixed-ratio blenders combine the technological characteristics of 
the former (fixed-ratio air entrainment), with the intended use of the latter (CPAP therapy). 
 
In the USA, the PATH blenders would be considered a class 2 device and would follow the 
substantial equivalence regulatory pathway, otherwise known as a 510(k) or premarket 
notification. Typically, class 2 devices are not required to demonstrate clinical safety or 
efficacy as their technological characteristics are well understood and their intended uses 
are identical to those of devices already cleared. Characterization of the device’s safety and 
performance can be demonstrated through performance testing of the flow, pressure and 
oxygen fraction. The verification test report for the bCPAP kit and blenders can be found in 
Appendix B. 
 
We seek to conduct an early feasibility study (EFS), which is a limited clinical investigation of 
a device in development, typically before the device design has been finalized, for a specific 
indication (e.g., innovative device for an established intended use). The purpose of this study 
is to assess the operational feasibility, usability and acceptability of the device in a resource-
constrained setting.  Although there have been no prior studies in human populations with 
this device, oxygen blenders are a critical safety component of bCPAP therapy; providing 
unblended (100%) oxygen to premature infants can cause blindness, chronic lung disease, 
and brain damage. The World Health Organization recommends that blended oxygen or 
compressed air—not pure oxygen—be used for these patients.[7] 

 15
 
Once this study is completed, the device labelling and design may be revised if needed and 
prepared for manufacture by Sinapi biomedical (Stellenbosch, South Africa). This low-cost 
bCPAP kit with oxygen blenders will allow resource-constrained sites to provide rigorously 
tested bCPAP therapy and blended oxygen to patients with reduced risk of morbidity from 
oxygen toxicity. This study is aligned with WHO priorities. In 2018, the WHO called for more 
research to be done to explore simpler, cheaper technology to improve supportive care of 
newborns who require oxygen, including safe bCPAP therapy—estimating that the 
introduction of a low cost bCPAP kit with blenders in central and district hospitals would 
prevent 178,000 neonatal deaths in Africa each year.[27,33]  
 
3.3 Study Product 
Overview 
The PATH bCPAP kit with oxygen blenders is intended to provide respiratory support to a 
neonate in respiratory distress where higher level means of respiratory support are not 
available. (See Appendix A for product label and instructions for use). This product is a 
single-use device for the purposes of this study. No changes to device design will be made 
during the study. 
 
PATH’s fixed-ratio, in-line oxygen blenders are small, single-use, injection moulded devices 
intended to provide a stable blend of air and oxygen to a neonate on bCPAP therapy. 
(Instructions for use in Appendix A). A blender is inserted (in-line) into the inspiratory limb of 
a bCPAP respiratory circuit and works by entraining room air into a stream of pressurized 
oxygen (based on the Bernoulli principle), producing a gently pressurized and blended gas 
that is delivered to the neonate (see Figures 4 and 5). The device provides a fixed ratio of air 
and oxygen that is consistent over the entire range of clinically relevant pressures (3 to 10 
cmH2O) and remains consistent despite changes in flow (1 to 10 LPM). The blend is stable 
within ± 5% of the blender’s nominal blend-ratio when used with 100% oxygen source, 
irrespective of the flow and pressure from the oxygen source, or the flow and pressure of the 
blended gas delivered to the neonate. 
 

 16
 
Figure 5. Diagram showing the components of the PATH bCPAP circuit (tubing, 
cannula and bubbler) as well as placement of PATH oxygen blenders 
 
Flow and pressure of the blended gas are adjusted in the same manner as respiratory 
circuits containing no blender (i.e., by adjustment of the flow of gas entering the system and 
depth of the bubbler straw within the bCPAP bottle, respectively). To change the blend ratio, 
the blender is simply replaced with another to achieve a higher or lower percentage of 
oxygen delivered. Currently two fixed-ratio blenders have been developed; a “low blender” 
with a blend-ratio of 37% and a “high” blender with a blend-ratio of 60% (see Figure 6). The 
rationale for having two blends for this study is two-fold: (1) more blend ratios would 
complicate the decision-making process by the healthcare worker and (2) more blend ratios 
could increase the amount of time spent swapping out blenders. However, additional blend 
ratios between 37% and 60% can be produced if this study suggests that more blending 
options would be of benefit.  
 
 
Figure 6. 37% and 60% oxygen blenders  
 
Fixed-ratio oxygen blenders 
(to dilute oxygen) 
Short, binasal cannula 
(attaches to baby) 
Bubbler 
Oxygen 
source 
Cannula 
adapter 
Circuit tubing 
(expiratory) 
Bubbler straw 
Bubbler stand 
Circuit tubing 
(inspiratory) 
Bubbler lid 
Bubbler straw holder 

 17
In facilities with access to both pressurized air and oxygen, commercially available, fully 
adjustable oxygen blenders can be used to adjust the blend ratio between 21% (room air) 
and 100% oxygen. Both air and oxygen must be provided at equal pressures of 50 psi in 
order for the blender to perform accurately. For this reason, commercially available, 
adjustable blenders cannot be used with oxygen concentrators because the pressure 
generated by these devices is too low. 
 
In contrast, the PATH fixed-ratio oxygen blenders do not depend on a source of pressurized 
air, as air is drawn from the room itself. Furthermore—and unlike a commercially available, 
adjustable oxygen blender—the oxygen can be provided by an oxygen concentrator. Choice 
of blend ratio is limited, however, to the discrete fixed-ratio blenders at hand. As noted 
earlier, changes in blend ratio are accomplished by replacing one fixed-ratio blender for 
another of the desired percentage of oxygen. 
  
Design & Manufacture 
Sinapi biomedical is an ISO 13485:2016-certified medical device manufacturer based in 
Stellenbosch, South Africa. They were responsible for production, labelling, and packaging 
of the fixed-ratio oxygen blenders intended for use in the study. Sinapi has 18 years of 
experience in production of medical devices that are distributed in both South Africa and 
across Europe. bCPAP kits and blenders were produced in Sinapi’s production clean room 
environment and each kit and blender were visually inspected and tested for performance 
(oxygen fractionation) to ensure proper performance. Results of this testing can be found in 
the verification test report (Appendix B) 
 
PATH’s bCPAP kit and blenders are an investigational device, produced in South Africa. It 
does not fall under the jurisdiction of the US Food and Drug Administration (FDA), but given 
the lack of regulation for investigational devices in Uganda (the location of the study), FDA 
guidelines have been used as a best practice. In the US, the pathway for marketing 
authorization is based on the potential risk a device poses to human safety. In the US, 
variable-blend oxygen blenders are classified as class II devices and would be cleared 
based on the 510(k) (substantial equivalence) pathway. If a 510(k) pathway were followed, 
the predicates for the oxygen blender would be as follows: 
 
• 
§868.5330 (Product code: BZR; Class 2): A breathing gas mixer is a device intended 
for use in conjunction with a respiratory support apparatus to control the mixing of 
gases that are to be breathed by a patient. Predicates: Precision Blender; Bird 
Air/Oxygen Blender. 
• 
§868.5600 (Product code: BYF*; Class 1): A venturi mask is a device containing an 
air-oxygen mixing mechanism that dilutes 100 percent oxygen to a predetermined 
concentration and delivers the mixed gases to a patient. Predicates: Salter air 
entrainment oxygen mask.  
 
Class II devices generally do not require clinical data to be generated in order to obtain 
marketing authorization, as their safety and effectiveness is well documented in the literature 
and the mechanism of action well understood.[34] Fixed-ratio oxygen blenders (entrainment 
devices) are classified as class I (low risk) devices, but are indicated for use with adult, high 
flow masks. Because our fixed-ratio oxygen blender is intended for use with neonates, we 

 18
have taken the most conservative approach and assumed the 510(k) [i.e. class II] pathway 
for marketing authorization would be required if the device were to be marketed in the United 
States. See Appendix B for Substantial Equivalence Table. 
 
The fixed-ratio oxygen blender is in the final stages of development. The design has been 
rigorously tested at the bench to ensure its safety and performance. Table 1 lists the testing 
that has been conducted on the 37% and 60% blenders. Table 2 lists the composition and 
manufacturer of the bCPAP kit components. 
 
Table 1. Status of Fixed-Ratio Oxygen Blender Verification Tests 
Verification test 
Criteria 
Status 
Blend stability* 
Stable blend (±5% of nominal FiO2) 
Passed 
Temperature & humidity Stable blend at 30 °C and 70% relative 
humidity 
Passed 
Noise 
< 80 dBA 
Passed 
Shelf life† 
Stable blend at 1 year 
Pending 
Biocompatibility 
Per ISO 18562-2:2017 
Passed 
 
*Blend stability testing has been conducted under worst case conditions of flow, pressure, 
temperature and humidity. 
† Shelf life testing is based on accelerated aging test results at the time of writing and is intended to 
ensure performance of the device for the duration of the study. However, real-time shelf life testing is 
ongoing, and it is expected that the actual shelf life of the device will be confirmed to be much longer. 
 
Table 2. Components of the bCPAP kit 
Component 
Material 
Manufacturer 
Bubbler stand 
Acrylonitrile Butadiene Styrene (ABS) 
3D printed 
(custom) 
Cannula adapter* 
Polypropylene (PP) 
Protolabs (custom) 
Blenders (37% & 
60%)* 
Polypropylene (PP) 
Protolabs (custom) 
Short, binasal 
cannula** 
Polyvinylchloride (PVC), silicone 
Neotech 
Bubbler straw holder 
Nitrile rubber 
McMaster 
Bubbler straw 
High density polyethylene (HDPE) 
McMaster 
Bubbler & bubbler lid 
Polyethylene terephthalate (PET), high 
density polyethylene (HDPE) 
McMaster 
Circuit tubing* 
Polyvinylchloride (PVC), thermoplastic 
elastomer (TPE) 
McMaster 
*  These components are not in direct contact with the patient but are in contact with the respiratory 
gases that flow to the patient. 
** This component is in contact with the patient’s nares. There are multiple sizes provided to fit the 
range in neonatal nares sizes. 
 
The nasal cannula is the only component of this device that will be in direct contact with the 
patient.  The Neotech RAM Cannula used in the PATH bCPAP kit (see: 
https://www.neotechproducts.com/product/neotech-ram-cannula/# ) is CE marked and FDA 
registered so it meets the ISO 10993 standard for biocompatibility.  The Neotech RAM 

 19
Cannula is not manufactured with DEHP, which is the most common phthalate plasticizer in 
medical devices.   
The purpose of this study is not to confirm the safety or efficacy of PATH’s bCPAP kit 
and blenders, as this has already been established by bench testing against the 
predicate. Rather it is to evaluate the feasibility of using fixed-ratio blenders to reduce 
the amount of oxygen delivered to neonates to meet oxygen saturation targets as 
indicated by pulse oximetry in instances where the only existing choice is to provide 
100% oxygen. Exceeding oxygen saturation targets by use of 100% oxygen is 
extremely harmful and can lead to permanent eye, lung and brain damage, especially 
for those neonates born prematurely.  
 
 

 20
4.0 CHAPTER FOUR: Research questions, hypothesis and 
objectives 
 
4.1  Hypothesis  
We hypothesize that the PATH bCPAP kit with oxygen blenders will be easy to use by 
healthcare workers treating neonates in respiratory failure and allow the patient to receive 
less than 100% oxygen when no other standard blending mechanism is available. 
 
4.2  General objective 
The purpose of this research is to conduct an early feasibility study (EFS) of PATH’s bCPAP 
kit including use of PATH oxygen blenders when no other standard blending mechanism is 
available. 
 
4.3  Specific objectives 
Primary Objectives: 
1. To assess the operational feasibility of using the PATH bCPAP kit including, 
when appropriate, in-line oxygen blending on neonatal patients. 
2. To assess the usability and acceptability of the PATH bCPAP kit with oxygen 
blenders by healthcare workers. 
 
Secondary Objective: 
1. To report clinical characteristics, demographics and outcomes of patients treated 
with the PATH bCPAP kit and blenders in a newborn care unit in rural Uganda. 
 
 
 

 21
5.0 CHAPTER FIVE: Methodology 
5.1 Study design 
This is an early feasibility study to evaluate the device’s human interface and its impact on 
operator technique. As such, it is a limited clinical investigation. The study will help to obtain 
insights into: successful use of PATH’s bCPAP kit with oxygen blenders, operator technique 
challenges, human factors (such as use errors and difficulties comprehending procedural 
steps) and patient characteristics that may impact device performance (anatomical 
limitations). The experience obtained from the study will be used to identify appropriate 
modification to the use procedures and/or the device as needed. 
 
The study will take place in a newborn care unit at Kiwoko hospital, Uganda with experience 
using bCPAP and blended oxygen. It will use mixed methods, employing both quantitative 
and qualitative approaches. We will conduct prospective data collection of the usability and 
acceptability of the PATH bCPAP kit with oxygen blenders through observation of and in-
depth interviews with healthcare workers, as well as prospective data collection of the 
clinical characteristics and outcomes of patients treated with the kit and blenders. 
 
5.2  Study site  
The study site is the newborn care unit of Kiwoko Hospital, a rural, private, not-for-profit, 
secondary level care hospital that acts as a referral centre for three districts in central 
Uganda. Neonates below 44 weeks corrected gestational age are admitted to the newborn 
unit. Half of the admissions are born at the hospital and the remaining half are born at home 
or transferred from another facility. This unit is accredited for 38 beds, and during 2018 it 
provided care for 1,223 newborns.(11) There are around 36 nurses on staff in the newborn 
unit with four to six of them on duty each eight hour shift, as well as one to two assigned 
general practice or paediatric physicians. Electricity is constantly available with the back-up 
of a generator. The unit provides thermoregulation, intravenous hydration, continuous or 
intermittent nasogastric feeding, phototherapy, antibiotics, oxygen therapy via concentrator 
and intermittent or continuous pulse oximetry. Neither mechanical ventilation nor surfactant 
is available in the unit. In Kampala, where mechanical ventilation and surfactant are 
available, the cost is prohibitively expensive for the population served by Kiwoko Hospital.  
 
Providing bCPAP therapy with improvised bCPAP kits is the standard of care for respiratory 
failure in the unit since 2012. The existing Kiwoko bCPAP is assembled from spare parts 
and donated nasal cannulas.(12) This improvised kit will be referred to as the Kiwoko 
bCPAP kit for purposes of this protocol. 
 
Patients at Kiwoko have intermittent access to blended oxygen while on bCPAP therapy. 
This is provided by the combination of flow from an oxygen concentrator and an air 
compressor. A connector, shaped like the letter Y, combines the flow from the two sources 
to provide blended oxygen and air to the patient. (Figure 7.). Adjusting the ratio of flows from 
each determines the amount of oxygen delivered. Unfortunately, these air compressors 
cannot be sourced in-country and have been brought in from the United States. High 
demand for clinical use of the compressors dictates the devices run continuously. Despite 
regular maintenance, these devices often breakdown and repair parts are difficult to source. 

 22
The system is not sustainable nor scalable. The number of patients who can receive blended 
oxygen is limited by the availability of these compressors—typically 0-2 are functioning at 
one time. This can result in some babies receiving bCPAP therapy with up to 100% oxygen. 
 
 
Figure 7. Oxygen blending system in place at Kiwoko Hospital. This system can provide a 
more precise blend of oxygen than the PATH blender but, due to reliance on a functioning 
air compressor, is very limited in its availability to serve patients. 
 
5.3 Sample size 
As this is an early feasibility study with no control or comparator arm, the sample size will be 
purposeful and not hypothesis driven.  
 
Patients: 
The sample size for patients will allow for reasonable frequency of use of the device by 
healthcare workers and at the same time for risk mitigation in line with an early feasibility 
study.  
 
During the period of study, up to 40 patients will be treated with the PATH bCPAP. This 
maximum of 40 patients in this study is selected to ensure that we will achieve our 
required sample size of 15 infants who are treated with the PATH bCPAP kit and 
blender. All enrolled patients will receive treatment with the PATH bCPAP kit (cannula, 
tubing, bubbler bottle), although not all may require the use the PATH blender. Patients may 
have two methods of blending available during the study according to the following decision 
logic (Figures 8 and 9):  
 
• 
An air compressor will be used as first choice if available. The number of 
patients in this scenario is dependent on the availability of functional air compressors; 
see Study Site section 5.2 for further details. 

 23
• 
When a functional air compressor is not available, the patient will receive treatment 
with the PATH blenders. Our aim is to treat 15 patients using the PATH blenders. No 
additional patients will be enrolled in the study after this target has been achieved.   
 
 
Figure 8. Methods of oxygen blending during study. The study may enrol up to 40 patients 
on the PATH bCPAP kit to ensure a subset of 15 patients will also use the PATH oxygen 
blender (B). 
 
 
 
Figure 9. Flowchart of expected patient recruitment (percentages and n’s estimated). A total 
of 30+ enrolled patients treated with PATH bCPAP may be required to ensure the target of 
15 patients are also treated with the PATH blenders. 
 
 

 24
Sample size for patients is being estimated knowing that at Kiwoko Hospital, an average of 
12 patients are treated with bCPAP therapy per month[35], per the Table 3 below. 
 
Table 3. Expected recruitment and PATH blender use based on study length and 
functional compressors. 
 
Study 
length (in 
months) 
Expected number 
of patients on 
CPAP 
Enrolled patients 
with 80% consent 
Patients with use of 
PATH blender (air 
compressor not 
available ~50% of 
time) 
1 
12 
9 
4 
2 
24 
19 
10 
3 
37 
29 
15 
4 
49 
39 
20 
5 
61 
48 
24 
 
Healthcare workers: 
Bedside observations: We will observe the care of bCPAP patients with or without PATH 
blender use provided by healthcare workers in the newborn care unit. This will include all or 
most of the 40 permanent healthcare workers in the newborn care unit who care for patients 
on bCPAP therapy and have consented to participate in the study.  
 
Qualitative interviews: Up to 15 of those same healthcare workers who were observed 
using the PATH bCPAP kit with blenders will be interviewed within the first five days of their 
first use of the PATH bCPAP kit with blenders. Additionally, five of those healthcare workers 
that used the PATH bCPAP and blenders kit three or more times during study period will be 
interviewed again towards the end of the study to probe if their experience changed with 
familiarity of use. 
 
5.4 Study population 
Patients: 
Inclusion criteria for use of PATH bCPAP and oxygen blenders: Newborns <44 weeks 
post menstrual age with respiratory failure requiring treatment with bCPAP therapy during 
the period of study and whose parent or legal guardian consented to participation in the 
study, within 24 hours of bCPAP initiation. 
 
Exclusion criteria: No parental nor legal guardian consent to participation in the study. 
 
Patients will be withdrawn from the study if their parent or legal guardian withdraws consent. 
If this occurs, they will no longer be treated with PATH bCPAP nor blenders. 
 
Patients admitted to the Kiwoko Hospital newborn unit are <44 weeks post menstrual age, 
primarily neonates (<28 days of age) in the first 3 days of life. Approximately 50% of the 
population admitted to the newborn unit is preterm (born before 37 weeks gestation). Half of 
admissions were born outside Kiwoko [35,36]. The decision to initiate bCPAP therapy is 

 25
made according to unit guidelines and physician/nurse discretion based on assessment of 
the degree of respiratory failure (See Appendix C). Fifteen percent of patients admitted to 
the Kiwoko newborn unit are treated with bCPAP therapy, with a birthweight distribution as 
shown in Table 4.[35] Unit guidelines specify criteria for adjustment of bCPAP pressures, 
oxygen blends and weaning off bCPAP support. Median length of bCPAP therapy is 3 days. 
The baseline mortality for patients treated with bCPAP in the Kiwoko unit is 34%.[35] 
 
Table 4. Anticipated PATH bCPAP kit use by birthweight category based on average 
Kiwoko bCPAP kit use in the Kiwoko newborn unit 
 
Birthweight Category 
Percent of overall bCPAP use 
expected of this category[37] 
<1kg 
8% 
1-1.4kgs 
22% 
1.5-2.4 kgs 
33% 
2.5-4kgs 
35% 
>4kgs 
2% 
 
Patients will be withdrawn from the study if their parent or legal guardian withdraws consent. 
If this occurs, they will be changed to the previous Kiwoko bCPAP kit and blending will be 
provided via air compressor when available. If there are no functioning air compressors at 
that time, blending will not be available, and bCPAP therapy will be provided by oxygen 
concentrator only. 
 
 
Healthcare workers: 
Inclusion criteria:  
• 
Healthcare workers (nurses and midwives) who care for patients on bCPAP 
therapy with or without blenders at Kiwoko’s newborn unit during the period of 
study, and who provided informed consent to be observed and interviewed 
 
Exclusion criteria: Healthcare workers that did not provide informed consent to be 
observed or interviewed. 
 
5.5  Study procedure 
Patients: 
During the study, all patients admitted to the newborn care unit with respiratory failure will be 
evaluated for treatment with bCPAP per unit standards. All patients that meet treatment 
criteria will receive bCPAP. Patients for whom consent is available will be enrolled and start 
bCPAP therapy with the PATH kit. Patients for whom consent is not given or not available 
will start Kiwoko bCPAP. Patients who began bCPAP therapy with the Kiwoko kit and obtain 
consent within 24 hours of starting their bCPAP therapy may switch from Kiwoko to PATH 
bCPAP (see description of this process below). Patients with >24 hours of Kiwoko bCPAP 
therapy are no longer eligible for enrolment.  
 

 26
The PATH bCPAP kit is comprised of the same components as the Kiwoko bCPAP kit 
currently in use (nasal cannula, connectors, tubing, bottle - see section 8.0 “products”). Set-
up time is expected to be comparable to the Kiwoko bCPAP kit. There is no significant 
difference in performance between the PATH and the Kiwoko bCPAP kits in the absence of 
the blenders. The only new feature of the PATH bCPAP kit is the option of using the fixed 
ratio oxygen blenders. The PATH blenders enable the bCPAP system to provide less than 
100% oxygen without the use of an air compressor. The PATH bCPAP kit with blenders is 
single use and will be discarded after use on one patient. Standard of care will not change 
with the use of the PATH bCPAP kit with or without blender—the unit will continue to 
administer bCPAP therapy in accordance with unit guidelines (see Appendix C) and 
physician/nurse discretion. If parents decline consent, the patient will be treated using the 
Kiwoko bCPAP kit that was previously in use. Patients may also be photographed, video or 
audio recorded if parents/ legal guardians specifically consent to this. 
 
Patients who start bCPAP therapy using the Kiwoko bCPAP kit, and then have consent 
obtained in the first 24 hours of treatment, will switch to the PATH bCPAP kit. The PATH 
bCPAP kit will be assembled prior to the switch over, allowing the circuits to be easily 
exchanged by disconnecting the tubing to the cannula and connecting the new PATH kit 
tubing. The cannula (and tape affixing it to the patient’s face) will not be changed as both 
Kiwoko bCPAP and PATH bCPAP use the same cannula. This switchover will occur very 
quickly- the brief interruption of pressure to the patient is similar to what occurs with other 
procedures on bCPAP, such as suctioning or cannula adjustments.  
 
During the study, oxygen blending for patients treated with PATH bCPAP will occur by the 
following two methods- and will be used in this order of preference (see Figure 8 “Methods of 
oxygen blending during study” in section 5.3):  
1.) blending via air compressor (standard of care in unit and used when available) 
2.) blending via PATH blender (when no compressor available) 
 
Some patients will receive blending via both systems during their bCPAP treatment course 
due to changing availability of the air compressor (i.e. if it stops working or one becomes 
available as another patient has stopped using it).  
 
Patients not enrolled in the study will continue to have blending available by standard of care 
(use of air compressor when available). When the air compressors are not available the 
patients are treated with the oxygen concentrator which emits the closest oxygen 
requirement to meet their needs (see explanation below under “oxygen use”). Patients may 
receive 100% oxygen if there are no concentrators emitting lower percentages. As identified 
earlier, the use of 100% oxygen is not recommended as it increases the risk of morbidities 
such as blindness, chronic lung disease and brain injury.  
 
 
bCPAP Use 
The unit will continue to use bCPAP therapy in accordance with unit guidelines (see 
Appendix C) and physician/nurse discretion. Kiwoko’s newborn unit currently provides a high 
standard of care which will not change during the period of study.  
 

 27
Current bCPAP therapy standard of care in Kiwoko’s newborn care unit: 
• 
Nurse to patient ratio is usually 1:4. 
• 
Continuous oxygen saturation monitoring when initially placed on bCPAP therapy. 
• 
Patient assessment every 15 to 30 minutes in the first hour after being placed on a 
bCPAP kit.  
• 
Patient assessment including vital signs every 3 hours after condition stabilizes. 
• 
Patient who remains unstable is monitored more regularly as needed until stable. 
• 
In the case where there is an inadequate number of oxygen saturation monitors, a 
baby with stable vital signs who is close to coming off bCPAP therapy may receive 
intermittent spot checks for oxygen saturations. 
 
Additional care offered during the study: 
• 
Additional oxygen saturation monitors will be provided to the unit for this study. This 
will allow all bCPAP therapy patients to receive continuous monitoring throughout 
their entire course of treatment with bCPAP. 
• 
Research assistants will notify staff if the bCPAP with or without blenders is set-up 
incorrectly or they have other concerns about patient safety. 
 
Oxygen Use 
In the Kiwoko newborn care unit, oxygen concentrators are used for the delivery of oxygen. 
They are tested regularly for the amount of oxygen they provide, as older concentrators 
often provide a lower concentration of oxygen. During the study, oxygen concentrators will 
be tested weekly and labelled with the percentage of oxygen they produce.  
 
Patients will receive continuous pulse oximetry monitoring while on bCPAP therapy in order 
to titrate oxygen according to the patient’s needs. However, oxygen saturations of sick 
infants can fluctuate frequently, making oxygen adjustments a challenge. There is a delicate 
balance between too little and too much supplemental oxygen exposure, as both can lead to 
harmful conditions, especially in premature infants. Consistent with WHO recommendations 
for oxygen use in neonates, the saturation goals are defined in the Table 5 below.(15) It is 
standard to set the alarm limits to 2% below and 2% above the target range. 
 
Table 5. Target oxygen saturation ranges based on gestational age 
 
SpO2 target 
range (%) 
Monitor Alarm Setting (%) 
LOW 
HIGH 
Less than 32 weeks gestation or <1250 
grams 
88 – 95* 
86 
97* 
Equal or greater than 32 weeks gestation 
and >1250grams 
90 – 95* 
88 
97* 
* For any infant in room air (no supplemental oxygen), the high monitor alarm can be set at 
100%. 
 

 28
Nurses will titrate oxygen based on saturations as is current standard of care per Table 6 
below: 
 
Table 6. Bedside actions based on patient oxygen saturations 
Patient Oxygen Saturation 
Action 
Any time oxygen saturation falls below 
SpO2 target range 
 
• 
Assess infant for problems and 
reposition as needed 
• 
Troubleshoot bCPAP system (check 
connections, nasal interface, assess for 
presence of secretions) 
• 
Check pulse oximeter sensor and 
reposition or replace as needed 
Oxygen saturation is still below SpO2 target 
range (but still at or above 80%) for 5 
minutes 
or 
Oxygen saturation falls below 80% for 1 
minute 
• 
Increase percentage of oxygen 
delivered 
• 
Monitor saturations closely for 10-15 
minutes after making the change 
Oxygen saturation drops severely and the 
baby needs emergency attention  
• 
Increase oxygen percent immediately 
Oxygen saturation above SpO2 target range 
for 5 minutes  
• 
Decrease percentage of oxygen 
delivered 
• 
Monitor saturations closely for 10-15 
minutes after making the change 
 
There are times when the air compressors on the unit may not be functioning or are 
unavailable due to high demand. This creates two possible scenarios for oxygen blending 
during the study (Figure 6, Tables 7 and 8). 
 
 
 
Figure 10. Scenarios of oxygen blending for enrolled patients during study. Patient’s 
blending scenario may change throughout course due to changing availability/functioning of 
air compressors. 
 

 29
Table 7. Scenario 1- Adjusting oxygen delivery in current standard of care (when air 
compressor is available): 
 
Percent Oxygen 
Required 
How to Deliver 
Lowest possible  
All flow from air compressor 
No flow from the oxygen concentrator 
Low  
Minimal flow from oxygen concentrator, most 
from air compressor 
Middle 
Flow split between air compressor and oxygen 
concentrator 
High  
Most flow from oxygen concentrator, minimal 
from air compressor 
Highest possible  
All flow from oxygen concentrator 
No flow from the air compressor 
 
Table 8. Scenario 2- Adjusting oxygen delivery with PATH blender (when no air 
compressor is available): 
 
Percent Oxygen 
Required 
How to Deliver 
Low  
Place 37% blender^ in line 
Higher  
Place 60% blender^ in line 
Highest possible  
All flow from oxygen concentrator 
No blender use 
^ The actual percentage of oxygen delivered to patient will be dependent 
on the concentration of oxygen provided by concentrator. 
 
All patients, whether enrolled in the study or not, will receive standard care after bCPAP 
treatment. There will not be any study-related treatment or follow up provided at the end of 
this study. Patients discharged from the newborn care unit are offered follow-up visits free of 
cost at Kiwoko Hospital as is the standard of care. 
 
Study Costs 
All neonates who are admitted to the NICU and require bCPAP therapy can access it 
regardless of the parent’s financial means.  The hospital charges a base rate for admission, 
which is not affected by length of stay, nor basic treatments provided - bCPAP therapy is 
considered a part of basic treatment and is not an extra charge. At the time of discharge, 
patients are required to pay their bill. Families without financial means to pay their bill at 
discharge are considered for financial aid from the hospital.  
 
 
5.6  Study variables  
See Table 10 in Section 5.8.2 

 30
5.7 Data collection 
 
Healthcare workers: 
From the onset of the study, consented healthcare workers will be observed as they set up 
and use the PATH bCPAP kit with or without the oxygen blenders. If they have consented, 
healthcare workers may also be photographed, video or audio recorded. Observations 
conducted across the study period will ensure that different levels of familiarity with use of 
the blenders are observed.  
• 
Right after the observation (or the next day if not enough time available), the 
healthcare workers will be asked to complete a usability scale related to their 
experience with the PATH bCPAP kit with or without oxygen blenders. We will collect 
data from healthcare workers in all 15 cases of use of the PATH bCPAP kit with the 
blenders.  
• 
Up to 15 of those same healthcare workers who were observed using the PATH 
bCPAP kit with the blenders will also be interviewed within the first five days of 
having used the PATH bCPAP kit and blenders for the first time.  
• 
Additionally, five of those healthcare workers that used the PATH bCPAP kit with 
blenders three or more times during study period will be interviewed again toward the 
end of the study, to probe if their experience changed with familiarity of use. 
 
Data Collection: 
A quality assurance activity will take place the week prior to the study to ensure HCW are 
following protocols re: oxygen blending with the existing Kiwoko bCPAP kit. No study data 
will be collected at this time. 
 
Table 9. Study Timeline 
Timeline 
Activity 
2 weeks before study start 
Train In-Unit Research Assistants 
2 weeks before study start 
Train Data Team on REDCap Data Entry 
2 weeks before study start 
bCPAP and blending training for healthcare 
workers (education on PATH bCPAP kit and 
blender) 
1 week before study start 
Quality Assurance with Kiwoko bCPAP kit  
Study start  
Change to PATH bCPAP/blender and start data 
collection 
Throughout data collection 
Initial interviews with HCW after their initial use of 
PATH bCPAP kit/blender 
3-4 months into data collection 
Repeat interviews for selected healthcare workers 
with more familiarity of use of PATH bCPAP 
kit/blender 
4 months total of data collection 
Study end (3.5 months of PATH kit use) 
 
5.7.1 Training  
In order to standardize care, nurses and physicians working in the newborn care unit will 
receive mandatory refresher training two weeks prior to start of data collection. Refresher 
training will include clinical presentation of respiratory failure and providing treatment with 

 31
bCPAP. They will also receive training in the use of the PATH bCPAP kit, including the 
blenders. Healthcare workers who complete training will be recorded in a list and these are 
the only providers who will care for PATH bCPAP patients during the period of study. It is 
assumed the PATH bCPAP kit with oxygen blenders will be no more time intensive than the 
current system to set up or use, and there will be no additional charting requirements for the 
nurses. 
 
To avoid disrupting clinical care of patients and to increase data quality, research assistants 
will be present 24 hours a day, all days of the week, at the bedside of patients receiving 
bCPAP therapy with or without PATH blenders during the study period. Research assistants 
will be nursing students trained to record clinical data points of patients on bCPAP therapy. 
They will serve in a purely observational role and will not provide patient care, nor make any 
modifications to treatment. 
 
5.7.2 Tools 
See “Data Collection Forms” in Appendix D, these include: 
• 
Patient Data Form 1 (Demographics and Admission Clinical Data) 
• 
Patient Data Form 2 (Clinical Course and bCPAP Settings) 
• 
Concentrator FIO2 Output Form 
• 
Newborn Unit Shift Form 
• 
Adverse Event Record 
• 
Unanticipated Adverse Device Effects (UADE) Event Record 
• 
Healthcare Worker (HCW) Usability Form 
• 
Healthcare Worker (HCW) Observation of bCPAP With or Without Blenders Set-up 
Form 
• 
Healthcare Worker (HCW) Initial Interview Guide 
• 
Healthcare Worker (HCW) Follow-Up Interview Guide 
 
Data will be collected on the forms at the following timepoints: 
 
Table 10. Patient Specific Data Collection Timing: 
Form 
Event 
 
bCPAP 
initiation 
Blender 
start or 
change 
bCPAP 
pressure 
change 
bCPAP 
stopped 
Patient 
discharged/ 
deceased 
Unanticipated 
Adverse 
Device Effect 
or Adverse 
Event 
Healthcare 
Worker (HCW) 
Observation of 
bCPAP With or 
Without Blender 
Set-Up 
X 
 
 
 
 
 
Patient Data 
Form 1 
(Demographics 
X 
 
 
X 
X 
 

 32
and Admission 
Clinical Data) 
Patient Data 
Form 2 (Clinical 
course and 
bCPAP settings) 
X 
X 
X 
X 
 
 
Adverse Event 
Record 
 
 
 
 
 
X 
Unanticipated 
Adverse Device 
Effects (UADE) 
Event Record 
 
 
 
 
 
 
X 
 
Table 11. Unit/Equipment Specific Data Collection Timing: 
 
Each Shift 
Each Week 
Newborn Unit Shift Form 
X 
 
Concentrator FIO2 Output Form 
 
X 
 
Table 12. Nursing Specific Data Collection Timing: 
 
With Each PATH 
bCPAP initiation 
Initial Interview 
Final Interview 
HCW Initial Interview Guide 
 
 
X 
 
HCW Follow-up Interview Guide 
 
 
X 
HCW Usability Form 
X 
 
 
 
 
 

 33
5.8  Data management and analysis 
5.8.1 Data management 
All quantitative data will be collected using case report forms and entered in REDCap 
software. The software will be programmed with internal checks to ensure completeness and 
logical entries. Data will be later transferred to Stata V.15 for analysis.  
Qualitative data analysis: paper transcripts, files of data and audio recordings from in-depth 
interviews will be kept securely under key and lock. Audio recordings will be downloaded 
and stored in a password protected computer and transcribed. A codebook with code 
definitions and a data analysis plan will be developed before the coding exercise starts. As a 
quality control measure, about 10 primary documents will be double coded (manually and 
electronically). Transcripts will then be exported into NVivo software for electronic coding 
and analysis using content thematic approach guided.  
 
5.8.2 Data analysis 
 
Table 13 presents a summary of variables, data sources and analysis plan.  We will evaluate 
operational feasibility by analysing the domains below; each domain uses information from 
mixed data sources.  We will create an index measure for each domain, all of which will be 
weighted equally.  We will sum these index measures to determine overall operational 
feasibility.   
• 
Ease of correct use:  Median set-up time, frequency of correct set up, time to change 
blender, types and frequencies of user errors, frequency of changes to blend 
provided per day, frequency of bCPAP level adjustment per day 
• 
Integration into service delivery: Count of patients treated with PATH bCPAP, 
Frequency of blending via air compressor and PATH blenders, Frequency of known 
bCPAP complications 
• 
Confirmation of device functionality: Median and IQR of: FIO2 administered by PATH 
blenders (determined by blender used and FIO2 provided by concentrator), level of 
bCPAP (and min/max), total air/oxygen flow to bCPAP device (subset) 
• 
Concentrator output:  Ability to determine FIO2 delivered to patient 
• 
Device malfunction: Frequency of device malfunctions with and without adverse 
events 
  
Table 13. Summary of Relevant Data Analysis for Study Objectives 
Objective 
Variables 
Source of Data 
Statistical analysis 
Objective 1: To 
assess the 
operational 
feasibility of 
using the PATH 
bCPAP kit 
including, when 
appropriate, in-
line oxygen 
Observed use of kit by HCWs 
including completion of set-up 
steps, time to set-up, description 
of difficulties 
• Healthcare 
Worker 
(HCW) 
Observation 
of bCPAP 
With or 
Without 
Blender Set-
Up 
We will determine 
frequency of various 
parameters/variables 
collected on the use and 
set-up of the kit 
Mean, standard deviations, 
medians and interquartile 
ranges will be used for 

 34
blending on 
neonatal 
patients 
• Patient data 
form 2 
(clinical 
course and 
bCPAP 
settings) 
 
• Concentrator 
FIO2 output 
form 
continuous variables based 
on their distribution 
Objective 2: To 
assess the 
usability of the 
PATH bCPAP 
kit with oxygen 
blenders by 
healthcare 
workers. 
Scores of usability by healthcare 
workers about ease of device 
set-up, learning the device, 
difficulty of use satisfaction with 
device and desire for continued 
use. 
• HCW usability 
form 
We will use frequency table 
to summarize the 
responses on the Likert 
scale.  
 
A total score generated by 
summing 10 items.  
Means, standard 
deviations and ranges will 
be reported. 
 
Objective 2: To 
assess 
acceptability of 
the 
PATH 
bCPAP kit with 
oxygen blenders 
by 
healthcare 
worker. 
Themes from HCW interview 
questions about what is liked 
best, least about the PATH 
bCPAP and blenders, ease-of-
use initially and over time, 
difficulty of use, adequacy of 
blends available, adequacy of 
training, what could be 
changed, would HCW continue 
to use the PATH kit with or 
without blenders if they were 
available after the study end? 
• HCW Initial 
Interview 
Guide 
• HCW Follow-
up Interview 
Guide 
 
Notes from in-depth 
interviews will transcribed 
and imported in NVivo 
software, analysed using 
content and thematic 
techniques (mainly 
inductive approach) 
Secondary 
objective: To 
report clinical 
characteristics, 
demographics 
and outcomes 
of patients 
treated with the 
PATH bCPAP 
kit and blenders 
in a newborn 
care unit in rural 
Uganda 
Demographics and clinical 
characteristics  
• Patient Data 
Form 1 
(Demographics 
and Admission 
Clinical Data) 
Frequencies, proportions 
and totals will be used to 
summarize categorical 
data with median and 
interquartile ranges for 
continuous variables. 
 
 
 

 35
5.9 Ethical considerations 
5.9.1 Informed consent  
Written, informed consent will be sought from the parents or legal guardian of every newborn 
started on bCPAP therapy, and who are available within 24 hours of initiation. When the 
legal guardians are available within 24 hours of bCPAP initiation, study personnel (nurses 
with experience in bCPAP therapy and blending, and fluent in Luganda) not caring for the 
infant will approach the legal guardians of eligible patients and inform them of the objectives 
of the research. Informed consent forms will be available in both English and Luganda and 
only IRB approved versions will be used. Study personnel obtaining consent will be fully 
trained on the recruitment and informed consent process and have human subjects research 
certification. The consent process is detailed in the Standard Operating Procedure for 
Obtaining Consent (Appendix E). 
 
Patients: 
Any patient who may benefit from care beyond that available at Kiwoko hospital are offered 
transfer (at their expense) to another facility. Meanwhile care for a newborn begins as soon 
as the patient is admitted. Using parental assent for admission and treatment is standard of 
care in the unit. Patients may require emergent initiation of bCPAP therapy due to 
respiratory failure. Patients often do not have a parent or legal guardian present at the time 
of bCPAP initiation, as the mother may still be in the operation theatre after a caesarean 
section, recovering from delivery, or away from the unit and unreachable by phone. In such 
instances, it is not appropriate to wait to obtain consent before the initiation of bCPAP 
therapy, as delaying the initiation of therapy could be life-threatening and would be contrary 
to WHO guidelines. (4)  
 
If the patient does not have a parent of legal guardian available at the time of 
admission, standard of care will remain the same, and the patient will have bCPAP therapy 
initiated using the Kiwoko device as soon as it is clinically indicated. As soon as they are 
available to meet with study personnel, the parent or legal guardian will be approached for 
consent to the study and to the use of the PATH bCPAP kit and blender. Consent must be 
gained within 24 hours of bCPAP initiation to be eligible to participate in the study. If parents 
choose to consent, the Kiwoko bCPAP kit will be replaced with the PATH bCPAP kit and 
blender and the baby will be enrolled in the study. (Process described in section 5, study 
procedures). 
 
If a parent or legal guardian is available at the time of admission, admitting staff will 
obtain an initial verbal consent from the parent to initiate them on the PATH bCPAP kit and 
blender. It may be inappropriate to pull the parents away for full consent at the time of 
admission due to: the time involved with obtaining the full consent process, the emergent 
nature of bCPAP therapy and the stress and pressure of having a sick newborn. In this 
instance, verbal consent will be gained. We will seek to obtain full written consent within 12 
hours of receiving verbal permission. Please see the stand-alone verbal consent script, 
which is also included in the Consent Standard Operating Procedure (Appendix E). If after 
the full consent process, the parents no longer want to be a part of the study, the patient will 
be changed back to standard of care for the unit. The parents will receive a clear explanation 
of the alternative, including whether an air compressor is available for blending. If an air 

 36
compressor is not available at that time, we will state clearly that their baby may receive 
100% oxygen and the potential consequences of such. Study information that has been 
gathered up to this point will not be retained by study personnel. 
 
 
Formal consent process 
Study personnel (nurses with experience in bCPAP therapy and blending, and fluent in 
Luganda) not caring for the infant will inform parent or legal guardian of the objectives of the 
research and obtain consent. This consent will be obtained in a private location within the 
newborn unit as available. If the parent or legal guardian is unable to read, an impartial 
witness will be present to ensure they understand the study and their rights. Risks as well as 
benefits and alternatives to study participation will be discussed. The parent or legal 
guardian will be informed that if they decline study participation, the patient will be treated 
with Kiwoko bCPAP kit, and oxygen will be blended if an air compressor is available. Study 
personnel will ask for parents to explain back to them the study intervention. Consent forms 
will include a contact of the Makerere IRB chairperson. Consent will be documented with 
parental signature or thumbprint.  
 
Parents will have access to in-unit study personnel 24x7 to ask further questions (in 
Luganda or English). The parent or legal guardian can withdraw from the study at any time 
during the study.   
 
Determination of continued device use will be at the discretion of the attending medical 
provider. 
 
Healthcare worker consent: 
Healthcare workers (nurses and midwives) who care for patients receiving bCPAP therapy 
with or without blending in the Kiwoko unit will be approached to participate in the study by 
research personnel who are not in a supervisory position to the worker.  
 
Risks as well as benefits and alternatives to study participation will be discussed. Consent 
forms will include a contact of the Makerere IRB chairperson. Consent will be documented 
with signature. Consent will be obtained for obtaining photographs, video or audio recording 
of the healthcare worker or they may decline this. 
 
Healthcare personnel will have access to the country principal investigator (PI) to ask further 
questions. The health care worker can withdraw from the study at any time during or after 
the study is complete. 
 
5.9.2 Confidentiality 
All subjects’ confidentiality will be protected by not including names in data forms nor any 
personal identifiers in study report. Each participant will be assigned a study number and this 
linkage list/key will be kept separately from study forms, stored in a locked cabinet in a 
hospital office.  The study code that links the study number to each participant will be 
destroyed immediately upon determination that the data set is final and locked. 
 

 37
• 
Study subjects (nor their parents/guardians) will not be contacted after the study for any 
reason.  
• 
Paper data collection forms will be accessible only to the data collectors, data entry 
team, medical monitorsafety monitoring committee and principal investigators. They will 
be stored in a locked cabinet in a hospital office. They will be maintained indefinitely after 
the completion of the study by Adara Development as long as secure storage is 
available. 
• 
Video or audio recording of patients and/or healthcare worker observations and 
interviews will be maintained on the recording device which will be stored in a locked 
cabinet in a hospital office. The files will be uploaded to a password protected Adara 
server. 
• 
Database software (REDCap [38]) will be maintained on the Adara server and password 
protected—only accessible by the data entry personnel, PIs, database designer, and 
biostatisticians/ data analysis team. These de-identified electronic databases may be 
maintained after the study time period per usual practices in password-protected 
database based at Adara. 
• 
Funding recipients of Grand Challenges Canada (the sponsor of this study) must deposit 
data arising from Grand Challenges Canada-funded research into open access 
repository. All data in the repository will not include any personal identifiable information. 
 
5.9.3 Risks, risk mitigation and adverse event reporting 
Participation in this study does not raise the underlying risk associated with neonatal 
respiratory failure necessitating bCPAP therapy (i.e., death, disability, lung disease) in a 
resource-constrained setting. The rate of complications of the PATH bCPAP kit with blender 
should not differ from other improvised bCPAP kits as recommended by WHO. The baseline 
mortality for patients treated with bCPAP therapy in the Kiwoko Unit is 34%[35]. Most 
complications of bCPAP therapy are mild and can be addressed through careful bedside 
nursing management.[39] 
 
 
 
Mild Physical Risks: 
• 
Nasal irritation: A bCPAP system uses a nasal cannula as the patient interface. It is 
important that the cannula have a close fit in the nasal openings to prevent any loss 
of pressure. Multiple sizes of cannula are provided in the PATH kit to allow proper 
sizing for each patient. There is a risk of skin irritation from the nasal cannula due to 
rubbing or pressure from the cannula on surrounding areas. Standard of care for a 
patient on bCPAP therapy includes skin assessments every 3 hours. Proper sizing 
and positioning of the cannula, along with diligent skin care can prevent this 
complication. 
• 
Abdominal distention: The bCPAP system works by administering a gentle flow of 
pressure into the infant’s lungs to help them breath. An unavoidable but mild 
complication results from the flow of pressure that also enters the oesophagus and 
into the stomach. Accumulation of air in the stomach can lead to mild distention of 
the abdomen. An orogastric tube inserted into the patient’s stomach and attached to 
an empty syringe (no plunger) will help eliminate any accumulated air. Positioning the 
patient to rest in a prone position can also help with abdominal distention. 

 38
 
 
Moderate Physical Risks: 
• 
Nasal skin breakdown: With extended use, irritated skin surrounding the nasal 
openings may breakdown. Care includes diligent skin care and close observation. As 
tolerated, short breaks may be used to allow the skin time to heal. Discontinuation of 
bCPAP therapy may be an option if the infant’s condition allows. This complication 
can be avoided with frequent assessment, proper sizing and positioning of the 
cannula, along with diligent skin care. 
• 
Feeding intolerance: Accumulation of air in the stomach and intestines can lead to 
feeding intolerance (decreased digestion of milk, vomiting). Ensuring proper 
placement of the orogastric tube will help decrease this complication. The patient 
should receive a thorough examination to rule out other abdominal pathology that 
might be causing the distention. Smaller, more frequent feedings and placing the 
prone can also help to improve tolerance of feedings. 
 
 
Severe Physical Risks: 
• 
Hypoxia/hyperoxia: All use of oxygen poses a risk of hyperoxia when the amount 
delivered is higher than required. Blending oxygen with air provides the ability to 
administer levels of oxygen less than 100%. This poses a risk of hypoxia, when the 
percentage of oxygen administered is less than the patient requires. However 
blended oxygen is the only safe way to administer oxygen per WHO guidelines.[7] 
Risk of both hyperoxia and hypoxia is reduced by closely monitoring the patient’s 
oxygen saturations via pulse oximetry. All patients enrolled in the study will receive 
continuous monitoring by pulse oximetry. 
• 
Pneumothorax: Pneumothorax (reported rate of pneumothorax with bCPAP therapy 
in high resource settings in the literatures is 1.9%).[39] This can be life-threatening, 
but often can be treated with needle decompression, as is the standard of care at 
Kiwoko.[39] Early identification and prompt intervention are important to decrease 
risks of this complication. Refresher training will include assessment, identification 
and treatment for pneumothorax. 
 
There is no psychological, social nor economic risk to the patient nor family with study 
participation when compared to standard of care in the unit. 
 
There is no psychological, social nor economic risk to healthcare workers that participate in 
this study. 
 
Risk Mitigation 
The Kiwoko Hospital newborn care unit has been providing bCPAP therapy since 2012. The 
nursing staff are knowledgeable and experienced in the care of the patient receiving bCPAP 
therapy. Additional refresher training will take place before the study to ensure 
standardization of care. Patients will be closely monitored around the clock for complications 
of bCPAP use. Given need to titrate oxygen to saturations, patients will be monitored via 
continuous pulse oximetry.  
 

 39
Table 14: Adverse Events and Mitigation of Risk 
 
Event 
Mitigation 
Mild adverse events:  
Nasal irritation 
• 
Provide diligent skin care 
• 
Ensure proper fit, size, and position of cannula, 
add padding when indicated 
Abdominal distention 
• 
Ensure orogastric tube is allowing accumulated 
air in the stomach to be vented between feeds 
• 
Position infant prone 
• 
Moderate adverse events: 
Nasal breakdown 
• 
Provide diligent skin care 
• 
Ensure proper fit, size, and position of cannula, 
add padding when indicated 
• 
Consider short time periods off bCPAP if 
tolerated or discontinue bCPAP therapy if 
appropriate 
Feeding intolerance 
• 
Exam/review to screen for abdominal 
pathology 
• 
Ensure orogastric tube is allowing accumulated 
air in the stomach to be vented between feeds 
• 
Consider adjusting feeding volume or timing 
• 
Position infant prone 
• 
Serious adverse events: 
Hypoxia/Hyperoxia 
• 
Continuous monitoring with pulse oximetry 
• 
Adjustment of oxygen concentration according 
to patient need 
Pneumothorax 
• 
Early identification (diagnosed by sudden 
deterioration, unilateral loss of breath sounds, 
bedside X-ray or ultrasound as available) 
• 
Needle thoracentesis 
Death (34% expected 
mortality rate on bCPAP at 
Kiwoko) 
 
 
Care for injury  
If a baby has an injury or illness from the study device or the procedures required for this 
study, the reasonable medical expenses required to treat such injury or illness will be paid 
for by Adara, Kiwoko, PATH or another relevant party who is involved in conducting the 
investigation (collectively referred to as the Study Collaborator/s). Free medical treatment 
will be provided at Kiwoko Hospital for any trial-related injuries, as determined by the 
Primary Investigator and Study Collaborators of the Study. If necessary, the costs of referral 
and management of an illness will be also be paid for. 
 
The coverage for such injury or illness is only available if the principal investigator and the 
Study Collaborators, where relevant, have decided that the injury/illness is directly related to 

 40
the device or procedures and is not the result of a pre-existing condition or the normal 
progression of the baby’s medical condition.  In particular, the independent medical 
monitorsafety monitoring committee will be involved in the determination of whether an injury 
in a study participant is related to study procedures or device (and not the underlying infant’s 
health condition). 
  
Adverse Event Reporting 
The standard of care will be followed as with any complications that results from/are 
associated with bCPAP use. Complications can be reported on the “HCW Observation of 
bCPAP Set-Up With or Without Blenders” form or the “Patient Data Form 2—Clinical Course 
and bCPAP Settings” and then will be reported on the adverse event record as described 
below. 
 
Adverse events will be recorded on Adverse Event Record (Appendix D) and be treated as 
follows: 
 
• 
Mild Adverse Events: assessed and followed by study personnel, treated by nurses 
and closely monitored until resolved.  
 
• 
Moderate adverse events: assessed and addressed by country PI, monitored 
closely until resolution, recorded and reported to the IRB (as required) as well as 
notifying medical monitorthe safety monitoring committee within 72 hours. 
 
• 
Serious adverse events: assessed and addressed by country PI, monitored closely 
until resolution, recorded and reported to the IRB (as required) as well as notifying 
medical monitorthe safety monitoring committee within 24 hours.  
 
In addition, Unanticipated Adverse Device Effects (UADE) will be monitored and reported 
using the UADE Event Record (Appendix D).  The USFDA defines a UADE as: “any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects”. 
 
Managing and reporting unanticipated problems or protocol deviations 
Unanticipated problems: 
• 
Any breaches in confidentiality will be remedied immediately by the study team 
and reported to the country PI. 
• 
Protocol deviations will be addressed by the country PI (to ensure the best care 
of the patient) and protocol deviations will be noted in the records for that patient. 
• 
Changes at the site that affect the conduct of the research will be addressed by 
the study PI and, as necessary, reported to the Makerere IRB and PATH’s 
Research Ethics Committee. 
  

 41
5.9.4 Study and safety monitoring 
Safety of the participants is of utmost importance. Patients will have continuous pulse 
oximetry monitoring and frequent physical and vital sign assessment. The average nurse to 
patient ratio in the newborn care unit is 1:4. Patients are reviewed daily by a doctor and a 
doctor is on call 24x7 for the newborn care unit. The country PI will be available for 
consultation and a safety monitoring committee n independent medical monitor will review 
moderate and severe adverse events (as described below). Patients requiring higher level of 
care (need for mechanical ventilation) will be offered transfer to a referral centre at their own 
expense, as is standard of care in unit. 
 
This study will have a safety monitoring committee n independent medical monitor to 
evaluate adverse events and make recommendations for continuing or stopping a trial 
instead of a Data Safety Monitoring Board (DSMB) for the following reasons:  
 
1. the local investigators will have access to all data and  
2. patients will be accrued too quickly to allow for a DSMB to complete safety 
monitoring.  
 
The medical monitorsafety monitoring committee includes two  is a Ugandan physicians 
experienced in the care of neonates and use of bCPAP, and a biomedical engineer with 
experience in oxygen and respiratory devices. They will be available via mobile phone or 
computer to review moderate and severe adverse events within 48 hours and discus findings 
with the principal investigator. 
Study Stop Criteria: If the following criteria are met the medical monitorsafety monitoring 
committee will report to the IRBs, study sponsor and may stop the study: 
 
1. Mortality rises to 50% of patients treated with bCPAP therapy, assessed over 10 
patients.  Baseline mortality of patients on bCPAP therapy at Kiwoko (recorded from 
2013- 2018) is 34% (standard deviation 8%)).[35] This threshold would be triggered 
by the death of 5 patients out of 10 which is 2 standard deviations above the baseline 
(34% + 16%). 
2. Pneumothoraces are detected in 15% or more of patients treated with bCPAP 
therapy, assessed over 10 patients (1.9% occurrence reported in literature).[39] 
 
In addition, the study will be stopped if a UADE results in patient injury that is unresolved or 
requiring medical intervention to resolve. 
 
5.9.5 Benefits 
Individuals treated with bCPAP therapy (whether in the study or not) will have the benefit of 
closer monitoring as they will be on continuous pulse oximetry. (The current standard of care 
for the unit allows for intermittent pulse oximetry once the patient is stable).  
 
The research assistants will also check the set-up of the bCPAP circuit and can alert nurse if 
set-up incorrectly or if they have any concerns about patient safety. 
 
All study patients also will all have access to blended oxygen to decrease their risk of 
oxygen toxicity. (The current standard of care for the unit is blending oxygen only when air 

 42
compressors are functioning. There are times where there are not enough functioning air 
compressors, which leaves patients without blended oxygen.) 
 
Once testing is completed and product revision finalized, the PATH kit and blenders have 
the potential to improve quality of care for newborns in Uganda and beyond. It will allow 
resource-constrained settings to provide bCPAP therapy while reducing the risk of morbidity 
from oxygen toxicity. This low-cost device has the potential to prevent and estimated 
178,000 neonatal deaths in Africa each year, and many more across the globe.[27] 
 
Healthcare workers who participate in this study will benefit from receiving refresher training 
on diagnosis and management of respiratory distress syndrome in newborns. 
 
Participants and their families will not receive compensation for participation in this study. 
Healthcare workers will not receive compensation for participation in this study. 
 

 43
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