A Study to Explore the Physiological Impact of AIR+ KN95 Masks on Children
Phase: NA
Conditions: Healthy Subjects
Sponsor: Innosparks Pte Ltd.

 
ST Engineering Innosparks Ptd. Ltd. 
10 Tampines North Drive 4, #05-07 
Singapore 528553 
T: (65) 6873 2074   F: (65) 6873 2048  
(Regn. No.: 198004216K)                                            
www.stengg.com 
 
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STUDY PROTOCOL 
 
PROTOCOL TITLE: 
A study to explore the physiological impact of AIR+ KN95 Masks on children 
 
PROTOCOL NUMBER: 1 
 
 
PROTOCOL 
VERSION:  
Version 8 
PROTOCOL DATE:  
26 April 2023 
 
PRINCIPAL INVESTIGATOR:  
 
Eugene Loy 
Business Development Manager 
Respiratory Protection 
Urban Environment Solutions 
ST Engineering Innosparks Pte. Ltd. 
10 Tampines North Drive 4, #05-07 
Singapore 528553 
T: (65) 6873 2074 
www.stengg.com 
 
 
 
 
STUDY SITE: 
School(s) designated by MOE 
 
 
 

 
 
 
 
 
 
 
 
 
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 TABLE OF CONTENTS 
 
1. BACKGROUND AND RATIONALE ............................................................................................. 4 
 
 
1.1.  
GENERAL INTRODUCTION.................................................................................... 4 
 
1.2.  
RATIONALE AND JUSTIFICATION FOR THE STUDY....................................... 5 
 
A.  
RATIONALE FOR THE STUDY PURPOSE............................................................ 5 
 
B.  
RATIONALE FOR DOSES SELECTED................................................................... 5 
 
C. 
RATIONALE FOR STUDY POPULATION..............................................................5 
 
D. 
RATIONALE FOR STUDY DESIGN ........................................................................5 
 
2. HYPOTHESIS AND OBJECTIVES .................................................................................................5 
 
 
2.1.  
HYPOTHESIS..............................................................................................................5 
 
2.2. 
PRIMARY OBJECTIVES............................................................................................6 
 
2.3. 
SECONDARY OBJECTIVES......................................................................................6 
 
2.4. 
POTENTIAL RISKS AND BENEFITS.......................................................................6 
 
A. 
END POINTS - EFFICACY.........................................................................................6 
 
B. 
END POINTS - SAFETY.............................................................................................6 
 
3. STUDY POPULATION.......................................................................................................................6 
 
 
3.1. 
LIST THE NUMBER OF SUBJECTS TO BE ENROLLED ......................................6 
 
3.2. 
CRITERIA FOR RECRUITMENT..............................................................................6 
 
3.3. 
INCLUSION CRITERIA..............................................................................................7 
 
3.4. 
EXCLUSION CRITERIA.............................................................................................7 
 
3.5. 
WITHDRAWAL CRITERIA.......................................................................................7 
 
3.6. 
SUBJECT REPLACEMENT........................................................................................8 
 
4. TRIAL SCHEDULE............................................................................................................................8 
 
5. STUDY DESIGN..................................................................................................................................9 
 
 
5.1 
SUMMARY OF STUDY DESIGN..............................................................................9 
 
6. METHODS AND ASSESSMENTS...................................................................................................10 
 
 
6.1. 
RANDOMISATION AND BLINDING.....................................................................10 
 
A. 
SCREENING VISITS AND PROCEDURES............................................................10 
 
B. 
STUDY VISITS AND PROCEDURES.....................................................................10 
 
C. 
FINAL STUDY VISIT...............................................................................................11 
 
D.  
POST STUDY FOLLOW UP AND PROCEDURES................................................11 
 
E. 
DISCONTINUATION VISIT AND PROCEDURES................................................12 
 
6.2 
STUDY VISITS AND PROCEDURES.....................................................................12 
 
7. TRIAL MATERIALS.........................................................................................................................12 
 
8. TREATMENT.....................................................................................................................................12 
 
9. SAFETY MEASUREMENTS............................................................................................................12 
 
 
 
9.1.  
DEFINITONS..............................................................................................................12 

 
 
 
 
 
 
 
 
 
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9.2.        COLLECTING, RECORDING AND REPORTING OF "UNANTICIPATED   
 
PROBLEMS INVOLVING RISK TO SUBJECTS OF OTHERS" - UPIRTSO   
 
EVENTS TO THE NHG DOMAIN SPECIFIC REVIEW BOARDS  
 
 
 
(DRSB)......................................................................................................................................12 
 
 
9.3.  
COLLECTING, RECORDING AND REPORTING OF SERIOUS ADVERSE   
 
EVENTS (SAEs) TO THE HEALTH SCIENCE AUTHORITY  
 
 
 
(HSA)........................................................................................................................................12 
 
 
9.4.  
SAFETY MONITORING PLAN...............................................................................12 
 
9.5.  
COMPLAINT HANDLING.......................................................................................12 
 
10. DATA ANALYSIS...........................................................................................................................13 
 
 
10.1 
DATA QUALITY ASSURANCE..............................................................................13 
 
10.2. 
DATA ENTRY AND STORAGE..............................................................................13 
 
11. SAMPLE SIZE AND STATISTICAL METHODS......................................................................13 
 
 
11.1 
DETERMINATION OF SAMPLE SIZE....................................................................13 
 
11.2.  
STATISTICAL AND ANALYTICAL PLANS..........................................................13 
 
A. 
GENERAL CONSIDERATIONS...............................................................................13 
 
B.  
SAFETY ANALYSES................................................................................................14 
 
C. 
INTERIM ANALYSES...............................................................................................14 
 D.          DESCRIBE THE TYPES OF STATICAL INTERIUM ANALYSES AND  
STOPPING GUIDELINES (IF ANY) THAT ARE PROPOSED, INCLUDING THEIR 
TIMING.......................................................................................................................14 
 
12. ETHICAL CONSIDERATIONS....................................................................................................14 
 
 
 
12.1.  
INFORMED CONSENT.............................................................................................14 
 
12.2. 
IRB REVIEW..............................................................................................................14 
 
12.3. 
CONFIDENTIALITYOF DATA AND PATIENT RECORDS..................................14 
 
13. PUBLICATIONS..............................................................................................................................14 
 
14. RETENTION OF TRIAL DOCUMENTS.....................................................................................15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
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1.1 General Introduction  
 
There is potential for severe haze episodes to occur in Singapore, and the main air pollutant in the event of 
haze is particulate matter (PM). Short-term exposure (continuous exposure to unhealthy daily average PSI 
levels over a period of a few days) to haze like the pattern seen in Singapore may cause irritation of the 
eyes, nose, and throat in healthy individuals. Haze particles can also affect the heart and lungs, especially 
in people who already have chronic heart or lung disease e.g., asthma, chronic obstructive pulmonary 
disease (COPD), or heart failure. 
 
Haze is a perennial problem in Singapore. Commercially available disposable particulate respirators are 
typically certified for surgical and occupational use. The test standards are specified according to adult 
breathing conditions and fit. As commercially available disposable masks designed for occupational use are 
mainly for adults, such masks do not fit well on children, they do not serve well as protection against 
Particulate Matter 2.5 (PM 2.5), an air pollutant found in transboundary smoke haze. 
 
Commercially available disposable particulate respirators are typically certified under the NIOSH and CE 
EN 149:2001+A1:2009 standards for surgical and occupational use. These respiratory masks are tested to 
filter particulate matter in the air with varying degrees of filtering efficiencies according to the respective 
categories, e.g. NIOSH KN95 certifies respirators to filter at least 95% of non-oil particulates. The test 
standards are specified according to adult breathing conditions and fit.  
 
Children’s respiratory minute volume and rate are different from adults. As commercially available 
disposable masks designed for occupational use are mainly for adults, such masks do not fit well on children, 
they do not serve well as protection against Particulate Matter 2.5 (PM 2.5). As haze is a perennial problem, 
and there is potential for severe haze episodes to occur again, there is a need to consider the development 
of disposable particulate respirator with enhanced safety and comfort specific for use in children.  
 
ST Engineering Innosparks Pte. Ltd. developed a new type of disposable particulate respirator (hereon 
referred to as AIR+ KN95 Mask) that is suitable for use in both adults and children, from ages 7 and above. 
The masks come in S, M and L sizes, and have been tested according to the KN95 protocol for respirators.   
 
Studies have shown that prolonged wearing of disposable particulate respirators may lead to an increase in 
carbon dioxide (CO2) levels in the dead space of the respirator as well as in the re-breathing of the expired 
air when wearing it. The increased CO2 levels may result in headaches, increased irritability, and breathing 
difficulty. In addition, there is some discomfort due to the accumulation of heat and humid air in the dead 
space of between the respirator and face. However, the mask design is based on our previous AIR+ 
Smart Mask specifications, which was previously evaluated in a clinical trial performed in collaboration 
with NUH and the data published in a peer-reviewed journal1, showing no significant increase in CO2 
retention and the mask was found to be comfortable at rest and on mild exertion. The mask was 
commercially launched in 2015. 
STUDY PROTOCOL 
 
1. 
BACKGROUND AND RATIONALE 

 
 
 
 
 
 
 
 
 
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As the masks were developed specifically for school-going children, this study is designed to explore 
whether the new disposable particulate respirator is safe and effective for use in healthy children aged 7 to 
14 years of age. This is through measuring the variation of carbon dioxide levels in children whilst wearing 
the AIR+ KN95 Mask. End-tidal carbon dioxide pressure (ETCO2) is a good indicator of arterial carbon 
dioxide pressure (PaCO2) in healthy adults and children and has been used for continuous direct 
assessment of PaCO2 in clinical contexts. The normal range of PaCO2 is from 35 – 45 mmHg.  As there is 
a slight margin of difference between ETCO2 and PaCO2 values during measurement of about 1.6 +/- 
4.3mmHg, this study defines 30 to 50mmHg as the acceptable range for ETCO2 levels. 
 
1.2. Rationale and justification for the Study 
 
a.  
Rationale for the Study Purpose 
 
 
 
Haze is a perennial problem in Singapore. There is a need to consider the development of disposable 
particulate respirator with enhanced safety and comfort specific for use in children. 
 
ST Engineering Innosparks Pte. Ltd. developed a new type of disposable particulate respirator (AIR+ KN95 
Mask) that is suitable for use in both adults and children, from ages 7 and above.  
 
b. 
Rationale for Doses Selected (not applicable) 
 
No drugs are used in the study. 
 
c. 
Rationale for Study Population 
 
Commercially available disposable masks designed for occupational use are mainly for adults, such masks 
do not fit well on children.  As the masks under study were developed specifically for school-going children, 
this study is designed to explore whether the new disposable particulate respirator is safe and effective for 
use in healthy children aged 7 to 14 years of age.  
 
d.  
Rationale for Study Design 
 
This study entails the study of subjects doing various activities with and without donning on the mask. The 
baseline results of subjects without donning on the mask will serve as control. 
 
2. 
HYPOTHESIS AND OBJECTIVES 
 
2.1. 
Hypothesis 
 
We hypothesise that the subject’s measurements of end-tidal CO2 (ETCO2) levels of using AIR+ KN95 Mask 
will be within the acceptable range for ETCO2 levels of between 30 to 50mmHg. 
 
 
2.2 
Primary Objective 

 
 
 
 
 
 
 
 
 
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The primary objective is to evaluate the physiological impact of AIR+ KN95 Masks on end-tidal carbon dioxide 
(ETCO2) of children aged 7 to 14 years of age.   
 
 
2.3.  
Secondary Objectives 
 
The secondary outcomes include other physiological parameters such as oxygen saturation (SPO2), heart 
rate (HR) and respiratory rate (RR).  In addition, we will assess the general well-being and comfort level of 
the child when wearing the AIR+ KN95 Mask. 
 
2.4. 
Potential Risks and benefits: 
 
a.  
End Points - Efficacy 
 
There is no direct benefit in participating in this research. However, the knowledge gained would benefit other 
children and the public in the future. The results from this research will enable us to test the safety of the use 
of Air+ KN95 masks in children. This study will measure the carbon dioxide levels inside the mask and in the 
children as they wear it. 
 
b. 
End Points - Safety 
 
The study is designed to observe the impact of wearing the Air+ KN95 mask in children while at rest and on 
minimal exertion only. They may experience mild discomfort when wearing the mask whilst brisk walking on 
the treadmill. However, their vital signs will be monitored, and they will be encouraged to remove the mask if 
they feel uncomfortable.  
Studies have shown that prolonged wearing of disposable particulate respirators may lead to an increase in 
carbon dioxide (CO2) levels which may result in headaches, increased irritability, or breathing discomfort.  
Usually, this is resolved by simply removing the mask.  
 
3.  
STUDY POPULATION 
 
3.1. 
List the number of subjects to be enrolled. 
 
A total of 100 children will be recruited. Students aged 7 to 14 years old from two schools in Singapore [to be 
advised by MOE] will be invited to participate in this study.  The participants will be randomly selected from 
the pool of qualifying subjects. 
 
3.2. 
Criteria for Recruitment 
 
Students aged 7 to 14 years old from schools as selected by MOE will be invited to participate in this study. 
Since subjects are minors, one of the parent or legal guardians will sign the informed consent form. There 
will be no restrictions based on race or gender. The subject must satisfy the inclusion and exclusion criteria 
to be eligible for the study. A Parental Screening Form will be attached to the PARTICIPATION 
INFORMATION SHEET AND CONSENT FORM for the parent or legal guardian to declare any past medical 

 
 
 
 
 
 
 
 
 
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condition(s) of the subject. Should parents have doubts about any of the questions in the Parental Screening 
Form, they will be able to contact the PI directly. Similarly, should the study team wish to clarify their concerns 
regarding parents’ responses to the screening form prior to enrolling the subject, they will contact the parent 
directly. Any such communication between parent/legal guardian and PI will be documented in the study 
record. 
 
3.3. 
Inclusion Criteria 
 
The inclusion criteria are as follows: 
 
1. Aged between 7 and 14 years of age (inclusive) 
2. Subjects and their parents or legal guardian must provide their consent/ assent to take part in this study  
 
3.4. 
Exclusion Criteria 
 
The exclusion criteria are as follows: 
 
1. Subjects with any known cardiorespiratory conditions (including but not limited to the following: asthma, 
bronchitis, cystic fibrosis, congenital heart disease, emphysema) 
2. Subjects with any known medical conditions that may be exacerbated by strenuous activity, including but 
not limited to the following:  exercise-induced asthma, lower respiratory infection (including pneumonia, 
bronchitis) in the past 2 weeks, anxiety disorders, diabetes, hypertension, or epilepsy/ seizure disorder 
3. Subjects with any physical disability from medical, orthopaedic, or neuromuscular disorders 
4. Subjects who have an acute upper respiratory tract infection/ moderately severe rhinitis (i.e. blocked 
nasal passages) on the day of the study 
5. Subjects who may compromise the integrity of the mask fit (e.g. those with excessive facial hair) 
 
3.5. 
Withdrawal Criteria 
 
Subjects may withdraw voluntarily from participation in the study at any time.  
 
Also, subject will be withdrawn from the study if there is clinical suspicion of hypercarbia or the physiological 
parameters exceed their threshold: 
 
• 
ETCO2 > 50mmHg for at least 3 minutes sustained 
• 
SPO2 < 92% 
• 
HR and RR within 2.5 and 97.5 centiles by age as proposed by Wallis LA et al: 

 
 
 
 
 
 
 
 
 
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• 
Subject complains of symptoms such as dizziness & confusion, even if ETCO2 or SPO2 levels 
remain within the specified normal range i.e., ETCO2 <50mmHg and SPO2 >92% 
 
3.6. 
Subject Replacement 
 
Subjects who drop out will be replaced. 
 
4. 
TRIAL SCHEDULE 
 
Screening will be screened through forms given out to students for parents to fill up together with the letter of 
invitation and study information sheet. Only eligible subjects whose parents consented to join in the research 
study will be shortlisted. 
 
There is only one study visit. Subjects will be de-identified and coded at source. Data on subject’s gender, 
age, race, height, and weight will be obtained. An on-site screening questionnaire will also be administered 
by the study team to check on the participant’s current condition. Each will then undergo a mask fit test to 
determine the right mask size for the face, and test for leakage by performing the following exercises in 
sequence, which would take 12 minutes each: normal breathing, deep breathing, turning their heads sideways, 
up and down, speaking, and bending exercise as described in Section 6.1. Subject will be excluded if he/she 
is unable to be fitted with any of the mask sizes.   
 
If the subject passes the fit test, he/she will don the monitoring equipment and athletic wear.  The equipment 
will monitor breathing rate and heart rate. Oxygen and carbon dioxide concentrations will also be monitored. 
 
The subjects will then be assessed while at rest and on mild exertion.  Parameters obtained will be 
recorded in de-identified case report form. Please refer to figure 1 in section 5.1. 
 
The test will be carried out in a closed and controlled environment, with temperature range of 26-32 
degrees Celsius, relative humidity between 50-80%, and wind speed of <1.5m/s (light breeze). 
 
The general well-being and comfort level of the children whilst wearing the mask will be self-rated using a 
visual analogue scale at the end of the study procedure. 
 

 
 
 
 
 
 
 
 
 
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5.  
STUDY DESIGN 
 
5.1. 
Summary of Study Design 
 
This study is designed to explore and determine whether the new disposable particulate respirator is safe 
and effective for use in healthy children aged 7 to 14 years of age.  
 
Figure 1 shows the algorithm of the summary design. 
 
 
 
Figure 1. Study Design 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
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6. 
METHODS AND ASSESSMENTS 
 
 
6.1. 
Selection of Test Subjects 
 
a. Screening Visit and Procedures 
 
Pre-test actions 
An invitation letter with study information sheet which contains the study’s objectives, procedures, risk and 
benefits will be sent to all subjects aged 7 to 14 years old from the selected schools. Their parents will 
complete a questionnaire to ascertain the students’ general well-being, and to ensure that the appropriate 
criteria for selection / exclusion are applied. Contact of the designated study team member will be provided 
for any queries.  
 
Subjects who fulfil the eligibility criteria, whose parents return the Reply form expressing their willingness to 
participate, will proceed on to the study enrolment.  
  
The total number of eligible students may exceed the stated sample size, in which case the participants will 
be randomly selected from the pool of qualifying subjects. 
 
b. Study Visit and Procedures 
 
On-site pre-screening 
An on-site screening questionnaire will be administered by the study team to check on the participant’s current 
well-being. Informed consent and/or assent if applicable will be obtained. 
 
Mask fit test 
 
Biometric data (gender, age, race, height, and weight) of the subjects will be recorded.  De-identified case 
report form will be used to record data. Each will then undergo a mask fit test to determine the right mask size 
for the face, and test for leakage by performing the following exercises in sequence, which would take 12 
minutes each: normal breathing, deep breathing, turning their heads sideways, up and down, speaking and 
bending exercise. The fit test will be performed using the Portacount Respirator Fit Tester which indicates the 
fit factor (ratio of ambient air particle concentration vs. in-mask particle concentrations). A high fit factor will 
indicate a good seal, and the passing fit factor is 12.5 (8% leakage) based on respirator certification EN 
149:2001+A1:2009 FFP2 standards. Should a subject keep failing the fit test despite trying on all the sizes, 
they will be excluded from the study.   
 
The study 
 
Subjects who pass the fit test will don the monitoring equipment and athletic wear. The physiological 
monitoring equipment will comprise a pulse oximeter and an ETCO2 monitor. The pulse oximeter will measure 
through the use of a finger sensor the percent SPO2% as well as the HR (beats per minute/bpm). The ETCO2 
measurement (in mmHg) will be made through the use of a nasal cannula and will be used to determine the 
level of carbon dioxide within the test participant as well as the RR (breaths per minute) 1. 

 
 
 
 
 
 
 
 
 
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Impact on subject’s physiological measurements for different interventions will then be assessed while at rest 
and on mild exertion.   
 
Determining the parameters for mild exertion 
 
Mild exertion will be achieved using treadmills at speeds that represent realistic children activity levels during 
play. As the subjects are of varying ages and heights, with correspondingly different levels of physiological 
reserves, it may not be feasible to assign a specific treadmill speed that would indicate a uniform level of mild 
exertion.  
Based on the known normal resting heart rate of healthy children ages 7-14 years of 70 to 100 beats per 
minute, this study proposes to keep the actual speed of the treadmill flexible and primarily depend on the 
subject achieving a target heart rate zone of 50- 60% of maximum heart rate. The rationale for choosing this 
target is based on studies in adults were achieving a target heart rate zone of 50- 60% of maximum heart 
rate would yield an exercise intensity of about 40% of maximal oxygen consumption (VO2max), which is a 
good indicator of aerobic endurance. For adults, the anaerobic threshold is about 50-60% of VO2max. There 
is no literature on VO2max for children, hence, to be conservative, we have referenced adult threshold and 
taken 40% of VO2max as children’s normal anaerobic threshold. As such, to attain a stable ETCO2 during 
aerobic exercise and before the subject crosses the anaerobic threshold, we aim to keep to 50-60% of 
predicted maximal heart rate.   
The most common method to estimate maximum heart rate within the exercise community is to use the 220 
– age formula. This study proposes a more conservative assumption of a maximum heart rate of 194bpm, 
and a target heart rate zone to be achieved on the treadmill of between 100 – 120bpm. As an additional safety 
measure, subjects should be encouraged to talk comfortably while on the treadmill. This would indicate that 
the activity level is appropriate. The child will be led to a target heart rate before 3 minutes of steady state 
data would be taken. Given the physiological differences between different children, as well as their varying 
levels of fitness, different times may be required to attain the requisite heart rate for the test. 
 
The test will be carried out in a closed and controlled environment, with temperature range of 26-32 degrees 
Celsius, relative humidity between 50-80%, and wind speed of <1.5m/s (light breeze). 
 
The general well-being and comfort level of the children whilst wearing the mask will be self-rated using a 
visual analogue scale at the end of the study period. 
 
The study should take about 50 minutes and will be completed within the same day. 
 
 
c. Final study Visit: 
 
After the completion of the study procedure, there will be no follow-up or repeat visits required.  
 
d. Post Study Follow up and Procedures  
 
Not applicable  
 

 
 
 
 
 
 
 
 
 
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e. Discontinuation Visit and Procedures  
 
Subjects may withdraw voluntarily from participation in the study at any time.  
 
6.2 
Study Visits and Procedures 
 
There is only one study visit. 
 
7. 
TRIAL MATERIALS 
 
AIR+ KN95 Mask tested according to the KN95 protocol for respirators 
 
• 
AE220L 
• 
AE220M 
• 
AE220S 
 
8. 
TREATMENT 
 
Not applicable 
 
9. 
SAFETY MEASUREMENTS 
 
9.1. 
Definitions 
 
No adverse events are anticipated.  
 
9.2. 
Collecting, Recording and Reporting of "Unanticipated Problems Involving Risk to Subjects 
or Others" - UPIRTSO events to the NHG Domain Specific Review Boards (DSRB) 
 
NAD 
 
9.3. 
Collecting, Recording and Reporting of Serious Adverse Events (SAEs) to the Health Science 
Authority (HSA) 
 
No drugs are used. 
 
9.4. 
Safety Monitoring Plan 
 
Data will be coded at source and identifiers will also be removed 
 
9.5. 
Complaint Handling -  
 
The PI is responsible for handling complaints and ensuring the safe conduct of the procedures listed above.  
 
 

 
 
 
 
 
 
 
 
 
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10.  
DATA ANALYSIS 
 
10.1. 
Data Quality Assurance 
 
Data collection will be performed by the study team members. Training on proper data collection and data 
entry methods will be provided to all staff involved in the study.  A data quality assurance system which will 
include appointing designated supervisors to oversee the quality of the fieldwork, logic checks on data, etc. 
will be setup. 
 
10.2. 
Data Entry and Storage 
 
Data will be collected first in hard copies that will be stored in a locked drawer in the Pi's locked office. The 
data will subsequently be entered into password-protected stand-alone desk top computer in the PI's office 
as well as a password-protected laptop. All documents will be password protected. Access to the data will be 
controlled by passwords only known to the investigators and the passwords will be changed periodically.  
 
 
11. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
11.1. 
Determination of Sample Size  
 
It is anticipated that a child at rest will have a mean ETCO2 of 40 mmHg with standard deviation of 
approximately 8 mmHg.  Based on the proposed safety threshold of 50mmHg and below for the ETCO2, an 
increase of 10 mmHg after the subject wears a mask would indicate non-inferiority.  A more stringent tolerance 
level of 5mmHg in ETCO2 will be assumed given the variability of the ETCO2 measurements among the 
children. 
 
Assuming a one-sided test size of 5% and one-sided power of 80%, at least 80 subjects will be required.  To 
account for the children who may withdraw during the study, a total of 100 children will be recruited, distributed 
across the age groups.   
 
11.2. 
Statistical and Analytical Plans 
 
a. General Considerations 
 
The primary outcome of the study is ETCO2.  The 95% upper confidence limit of the increase in ETCO2 after 
wearing a mask will be computed.  The proportion and its associated 95% confidence intervals of children 
whose ETCO2 are > 50mmHg for at least 3 minutes sustained will also be presented.  Similar analysis will 
be carried out for other physiological parameters such as SPO2, HR and RR.  In addition, the change in mean 
of visual analogue scale after the child wears the mask will be compared using the paired-t test and adjusted 
for baseline imbalance using regression analysis.   
 
These analyses will be repeated for physiological parameters collected while at rest and on mild exertion. 
 
 

 
 
 
 
 
 
 
 
 
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b. Safety Analyses 
 
NAD 
 
c. Interim Analyses 
 
This will not be done. 
 
d. Describe the types of statistical interim analyses and stopping guidelines (if any) that are proposed, 
including their timing. 
 
NAD 
 
 
12. 
ETHICAL CONSIDERATIONS 
 
12.1. 
Informed Consent 
 
A written, informed consent, and assent if necessary, will be taken from eligible subjects and parents or legal 
gardian prior to administering the study proper. The consent acquisition process will  be conversed in the 
language preferred by the subject’s parents/legal gardian. 
 
12.2. 
IRB review 
 
This study has been reviewed by the Parkway Independent Ethics Committee (PIEC) and the Ministry of 
Education (MOE), Singapore. 
 
12.3. 
Confidentiality of Data and Patient Records 
 
Only members of the study team e.g PI, con-investigator, and study coordinator, will have access to the data. 
Data collected will be de-identified and coded at source. The patient identifier and assigned code will be kept 
in hard copy under lock and key in the PI’s office. A back up soft copy will be maintained in a password-
protected document in a stand-alone desk top computer in the PI’s office. Confidentiality of the data will be 
maintained at all times. 
 
13.  
PUBLICATIONS 
 
The study findings can be published as manuscripts or in databases with the individual patient's identity and 
particulars kept anonymously. All manuscripts must acknowledge that the data are collected from the 
proposed study. The investigators are responsible for reviewing and agreeing to all the publications, ensuring 
that the samples and data are used in the manner outlined in the protocol, and disseminating results to the 
respective collaborators/co-authors in a timely manner.  
 
 
 

 
 
 
 
 
 
 
 
 
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14. 
RETENTION OF TRIAL DOCUMENTS  
 
Data and identifiers that is collected in hard copies including assigned code will be kept in hard copy under 
lock and key will be stored in a secured storage room. The data will be stored in a stand-alone computer 
that will be password protected and stored in a secure location within their office premises. All documents 
will be password protected. Data that is entered into software will not contain any identifiers. It will be stored 
for 10 years following the end of the study and then deleted/destroyed. 
 
 
References 
 
1 Daniel Yam Thiam Goh, Meng Wai Mun, Wei Liang Jerome Lee, Oon Hoe Teoh, Dimple D. Rajgor. A randomised clinical trial 
to evaluate the safety, fit, comfort of a novel KN95 mask in children. Scientific Reports (2019)