Evaluating the Non-Inferiority of Airmod to Capnostream™35 on Respiratory Rate Monitoring and User Experience Clinical Evaluation
Phase: NA
Conditions: Respiratory Rate
Sponsor: Heroic Faith Medical Science Co., Ltd.

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Version date:2021/10/1 
Evaluation the Non-Inferiority of Airmod to 
Capnostream™35 on Respiratory Rate Monitoring and 
User Experience Clinical Evaluation  
Protocol Number: HF-AM-01-2021 
Principal Investigator: <Principal investigator> 
Sponsor: Heroic Faith Medical Science Co., Ltd. 
Version Number:  3.0 
1 October 2021 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
1/2/3/4/5/6/
8/9/10 
Minor fixed of description (no effect with 
study design) and added supplementary 
section (10.2). 
Found some description errors (no effect 
with study design). Meanwhile, give further 
information to complement the protocol. 
Identifiers: NCT05263791

  
 
 
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Table of Contents 
STATEMENT OF COMPLIANCE ...................................................................................................................... 1 
1 
PROTOCOL SUMMARY ........................................................................................................................ 2 
1.1 
Synopsis ......................................................................................................................................... 2 
1.2 
Schema .......................................................................................................................................... 4 
1.3 
Schedule of Activities (SoA) ........................................................................................................ 6 
2 
INTRODUCTION ..................................................................................................................................... 7 
2.1 
Study Rationale ............................................................................................................................. 7 
2.2 
Background.................................................................................................................................... 8 
3 
OBJECTIVES AND ENDPOINTS ......................................................................................................... 9 
4 
STUDY DESIGN .................................................................................................................................... 11 
4.1 
Overall Design ............................................................................................................................. 12 
4.2 
Scientific Rationale for Study Design....................................................................................... 12 
4.3 
Justification for Dose .................................................................................................................. 12 
4.4 
End of Study Definition .............................................................................................................. 12 
5 
STUDY POPULATION ......................................................................................................................... 12 
5.1 
Inclusion Criteria ......................................................................................................................... 12 
5.2 
Exclusion Criteria ........................................................................................................................ 13 
5.3 
Lifestyle Considerations ............................................................................................................. 13 
5.4 
Screen Failures ........................................................................................................................... 13 
5.5 
Strategies for Recruitment and Retention ............................................................................... 13 
6 
STUDY INTERVENTION ..................................................................................................................... 14 
6.1 
Study Intervention(s) Administration ........................................................................................ 14 
6.1.1 
Study Intervention Description .............................................................................. 14 
6.1.2 
Dosing and Administration ..................................................................................... 15 
6.2 
Preparation/Handling/Storage/Accountability ......................................................................... 16 
6.2.1 
Acquisition and accountability ............................................................................... 16 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ......................................... 16 
6.2.3 
Product Storage and Stability ................................................................................ 16 
6.2.4 
Preparation ............................................................................................................... 17 
6.3 
Measures to Minimize Bias: Randomization and Blinding .................................................... 17 
6.4 
Study Intervention Compliance ................................................................................................. 17 
6.5 
Concomitant Therapy ................................................................................................................. 17 
6.5.1 
Rescue Medicine ..................................................................................................... 17 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................................. 17 
7.1 
Discontinuation of Study Intervention ...................................................................................... 17 
7.2 
Participant Discontinuation/Withdrawal from the Study ........................................................ 17 
7.3 
Lost to Follow-Up ........................................................................................................................ 18 
8 
STUDY ASSESSMENTS AND PROCEDURES .............................................................................. 18 
8.1 
Efficacy Assessments ................................................................................................................ 18 
8.2 
Safety and Other Assessments ................................................................................................ 19 
9 
STATISTICAL CONSIDERATIONS ................................................................................................... 20 
9.1 
Statistical Hypotheses ................................................................................................................ 20 
9.2 
Sample Size Determination ....................................................................................................... 20 
9.3 
Populations for Analyses ........................................................................................................... 21 
9.4 
Statistical Analyses..................................................................................................................... 21 
9.4.1 
General Approach ................................................................................................... 21 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ...................................................... 21 
9.4.3 
Analysis of the Secondary Endpoint(s) ................................................................ 22 

  
 
 
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9.4.4 
Safety Analyses ....................................................................................................... 24 
9.4.5 
Baseline Descriptive Statistics .............................................................................. 24 
9.4.6 
Planned Interim Analyses ...................................................................................... 24 
9.4.7 
Sub-Group Analyses .............................................................................................. 24 
9.4.8 
Tabulation of Individual participant Data ............................................................. 24 
10 
SUPPORTING DOCUMENTATION ................................................................................................... 25 
10.1 
Abbreviations ............................................................................................................................... 25 
10.2 
supplementAry ............................................................................................................................ 26 
10.2.1 
Patient Monitoring Period (Time frame) ............................................................... 26 
10.2.2 
study population ...................................................................................................... 26 
10.2.3 
Inclusion criteria ...................................................................................................... 26 
10.2.4 
Exclusion criteria ..................................................................................................... 27 
10.2.5 
Intended for use ...................................................................................................... 27 
10.2.6 
SAP ABstract ........................................................................................................... 27 
10.2.7 
Examples of Excluded measurement .................................................................. 28 
10.3 
Protocol Amendment History .................................................................................................... 28 
11 
REFERENCES ...................................................................................................................................... 30 
 

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Evaluation the Non-Inferiority of Airmod to Capnostream™35 on Respiratory Rate Monitoring and User Experience Clinical 
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Protocol No.: HF-AM-01-2021 
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1 
STATEMENT OF COMPLIANCE 
 
This study will be conducted in accordance with standard operating procedures of the Sponsor (or 
designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as 
required by the following: 
 
● Principles of the World Medical Association (WMA) Declaration of Helsinki - Ethical 
Principles for Medical Research Involving Human Subjects (October 2013) 
● ICH E6 (R2) Good Clinical Practice: Integrated Addendum to ICH E6 (R1): Guidance for 
Industry - E6(R2) Good Clinical Practice: Consolidated Guidance, United States (US) 
Department of Health and Human Services, Food and Drug Administration (FDA) (March 
2018) 
● ISO 14155: Clinical investigation of medical devices for human subjects - Good clinical 
practice (July 2020) 
● Law of Taiwan Ministry of Health and Welfare regarding clinical studies, including Medical 
Care Act, Pharmaceutical Affairs Act, Medical Devices Act, Human Subjects Research Act, 
Regulations on Human Trials and Regulations for Good Clinical Practice 
● Title 21 of the US Code of Federal Regulations (US 21 CFR) regarding clinical studies, 
including Part 50 and Part 56 concerning informed subject consent and Institutional Review 
Boards regulations, Part 54 concerning financial disclosure by clinical investigators, Part 58 
and 820 concerning Good Laboratory Practice (GLP) for nonclinical laboratory studies and 
quality system and applicable sections of US 21 CFR Part 812 and/or Part 312 
 
The protocol, informed consent form(s) (ICFs), recruitment materials, and all participant materials 
will be submitted to the Institutional Review Board (IRB)/Ethics Committee (EC) for review and 
approval.  Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled.  Any amendment to the protocol will require review and approval by the IRB 
before the changes are implemented to the study. In addition, all changes to the consent form will 
be IRB-approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 

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Evaluation the Non-Inferiority of Airmod to Capnostream™35 on Respiratory Rate Monitoring and User Experience Clinical 
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Protocol No.: HF-AM-01-2021 
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2 
1 
PROTOCOL SUMMARY 
 
1.1 
SYNOPSIS  
 
Title: 
Evaluation the Non-Inferiority of Airmod to Capnostream™35 on 
Respiratory Rate Monitoring and User Experience Clinical Evaluation  
 
Study Description: 
This is a prospective, multi-center, pivotal study. The purpose of this 
study is to evaluate the non-inferiority of Airmod to Capnostream™35 for 
respiratory rate monitoring and user experience clinical evaluation. 
 
Objectives: 
 
The objective of this study is to demonstrate that the performance and 
safety of Airmod in monitoring respiratory rate is non-inferior to 
Capnostream™35. 
 
 
Primary Objective:   
To evaluate accuracy and performance of respiratory rate (RR) 
measurement from Airmod compared to Capnostream™35. The primary 
objective is to establish the non-inferiority. 
 
 
 
Secondary Objectives:  
1. To assess the accuracy of respiratory rate measurement by Airmod 
in comparison with manual-scored auscultation sound during the 
less sensitive period of Capnography on Capnostream™35. 
2. To measure the agreement between AirRR and ManCRR.  
3. To evaluate the response time of the first breath detection followed 
by administration of jaw thrust during the apnea period. The 3rd 
secondary objective is to compare the response time of Airmod 
versus Capnography. 
4. To compare the influence of subjects to variated breath rates on 
respiratory rate monitoring in bpm as measured by Airmod, manual-
scored and Capnostream™35. 
5. To evaluate the safety and usability of Airmod. 
 
Manual-scored Capnography (ManCRR) originated from 
CapnostreamTM35 (K150272, Medtronic) 
Machine-scored Capnography (CapRR) generated from 
CapnostreamTM35 (K150272, Medtronic) 
Manual-scored auscultation sound (ManARR) originated from AS-101 
Airmod-scored auscultation sound (AirRR) generated from AS-101  
 
Endpoints: 
Primary Endpoint: 
The difference between AirRR and ManCRR, which is greater than -3 
under to establishes non-inferiority. The unit in this calculation is bpm 
and sampling rate is 1 Hz. 
 
 
Secondary Endpoints: 
1. The accuracy of inhalation classification in the segmentation basis is 
greater than 82.5% at the 95% CI. The performance metrics (F1-

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Protocol No.: HF-AM-01-2021 
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socre, MAPE) at event level will be demonstrated and target for F1-
score > 0.8, MAPE < 0.5. 
2. To measure the agreement of AirRR and ManCRR on concordance 
correlation coefficient, and on their mean and bias by Bland-Altman 
analysis.  
3. Use paired t-test to compare the response time of Airmod versus 
Capnography on Capnostream™35 after administration of jaw thrust. 
In the target of p<0.05 indicates significance. 
4.1. The difference of ManCRR minus AirRR and ManCRR minus CapRR  
indicates non-inferiority at margin of 3 bpm (M1) and sampling rate 
1Hz. 
4.2. The difference of ManCRR minus AirRR and ManCRR minus CapRR 
indicates non-inferiority at margin of 2 bpm (M2) and sampling rate 
1Hz.  
5. The absence of unanticipated serious adverse device effect (USADE) 
during study period and the questionnaire. 
 
[Time Frame:  
Non-Anesthesia Stage: Up to 40 patients will be randomly assigned to 
non-anesthesia stage assessment, the measurement will be evaluated 
after enrollment with ICF, at the non-operating room (NOR) area. (5~30 
minutes) 
Procedure Stage: From firstly anesthetic administration to end of 
procedure. (Depends on procedure 10mins ~ few hours) 
Non-operating room area (NORA) stage : From transportation of subjects 
to  PACU to discharge from PACU (PAR or PADSS score ≥ 9) (At least 15 
minutes) ] 
The information of patient monitoring period refers to 10.2.1. 
 
Study Population: 
By referencing predicate device clinical trials on respiratory rate 
monitoring in the hospital setting, most of the cases recruited 120+ 
patients. Considering a 40% withdrawal/dropout rate, we proposed a 
total enrollment of 300 subjects at the operation room (OR) and NOR 
area in the hospital. Further information refers to 10.2.2. 
 
Inclusion Criteria: 
1. Provision of signed and dated informed consent form. 
2. Stated willingness to comply with all study procedures and 
availability for the duration of the study. 
3. Male or female with at least 20 years of age. 
4. Fit for intravenous general anesthesia (IVG) as assessed by pre-
anesthesia evaluation. 
Details of 3 & 4 refer to 10.2.3. 
 
Exclusion Criteria: 
1. Presence of neck pain or injuries. 
2. Under the use of high-flow nasal cannula ventilation. Other examples 
refer to 10.2.4. 
3. Unable to wear Airmod and Capnostream™35 device related 
accessories at the investigator’s discretion. 

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4. As a vulnerable population, including legal incapacity or evidence 
that a subject cannot understand the purpose and risks of the study, 
regardless of authorized representative support. 
5. Unwilling or unable to comply fully with study procedures (including 
non-toleration of the capnography cannula) due to any disease 
condition which can raise doubt about compliance and influencing 
the study outcome. 
6. The patient who can’t receive operation under IVG anesthesia that 
suggest by the evaluation of preoperative assessment. 
 
Phase: 
Pivotal 
 
Description of 
Sites/Facilities 
Enrolling Participants: 
 
This study is intended to conduct in 3 sites in Taiwan, with an equal 
number of patients will be expected to enroll in all sites but competitive. 
 
Description of Study 
Intervention: 
The investigational product (IP), ‘Airmod’, is intended to provide 
professionally trained health professionals with continuous non-invasive 
measurement and monitoring of respiratory rate in adult patients. It is 
designed to detect inhalation acoustics and provides respiratory rates 
based on the analysis of the acoustic signals of breathing sounds 
collected by the electronic stethoscope. The device is intended for use in 
hospitals, hospital-type facilities, during intra-hospital transport, and 
out-of-hospital emergency medical service (EMS) applications that 
include ground and air transport. The intended for use is further 
described in 10.2.5. 
 
Study Duration: 
Estimated 12 months 
 
Participant Duration: 
Approximate 1.5 months for each individual subject to complete all 
participant visits. 
 
 
1.2 
SCHEMA 
 
Study Flow diagram 
 
Screening 
Visit 1, Day -28 ~ -1 
 
Total 300:  Obtain informed consent.  
Screen potential participants by inclusion and exclusion criteria.  
Obtain medical history and demographic data. 
Perform physical examination and vital signs. 
Refer to Section 1.3, Schedule of Activities 
 
 
 
 
 
 

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Treatment 
Visit 2, Day 1 + 14 
 
Administer study intervention. 
Refer to Section 1.3, Schedule of Activities 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening a 
Treatment a 
Visit Number 
1 
2 
Visit Days 
-28 ~ 1 
1 
Allowed visit window (days) 
 
+14 
Informed consent 
X 
 
Criteria evaluation 
X 
 
Medical history 
X 
 
Demographic data b 
X 
 
Physical examination c 
X 
 
Vital signs d 
X 
 
Study intervention administration 
 
X e 
PAR assessment f 
 
X g 
PADSS assessment f 
 
X g 
Adverse event review and evaluation 
 
X 
a. 
Screening and treatment can be the same day. 
b. 
Demographic data include date of birth and gender. 
c. 
Physical examination includes general appearance, weight and height, HEENT (head, eyes, ears, nose, and throat), 
mouth, skin, neck (including thyroid), lymph nodes, spine, cardiovascular system, respiratory system, gastro-
intestinal system, nervous system, musculoskeletal system, blood and blood forming organs, mental status, and 
other body systems if applicable. 
d. 
Vital signs include body temperature, sitting blood pressure and pulse rate. 
e. 
The administered anesthetic medication and dosage, surgery type, start and stop time of surgery will also be 
collected. 
f. 
Post Anesthetic Recovery (PAR) and Post Anesthetic Discharge Scoring System (PADSS) will be assessed upon 
admission and every 15 minutes after transferring to post anesthesia care unit (PACU). 
g. 
Subject will be discharged when PAR or PADSS score ≥ 9, consider as complete the study. 
 
 
 
 

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2 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
 
Longitudinal general population-level estimates of sedative medication use are lacking. There are a 
few studies that show the use of sedative medications has substantially risen among various countries 
across the population [1-3], which gender and age disparities with respect to sedative use [1, 4-6].  
 
Sedation is widely used in the reduction of irritability or agitation, which could be performed in OR or 
NOR, by relieving anxiety, reducing pain, and providing amnesia, sedation techniques have the 
potential to render potentially uncomfortable diagnostic and therapeutic procedures more 
comfortable and acceptable for patients [7]. Sedation for medical procedures is provided in a variety 
of clinical settings by medical personnel with differing levels of education and training, although 
generally a safe practice, there is a degree of risk associated with sedation practice [8]. This is because 
sedation is a continuum and it is not possible to predict how an individual patient will respond. At a 
certain level of sedation, the natural drive to breathe can be inhibited, therefore an adequate 
ventilation of the patient is important [7, 8]. These risks have been recognized but the incidence of 
significant morbidity or mortality is difficult to ascertain. 
 
One of the key components of managing sedation is knowing how to manage the patient’s airway, 
while monitoring using capnography is the most reliable method, making sure that patients are 
properly ventilating [9, 10]. Adverse events could be preventable with the adequate monitoring.  
 
Respiratory rate (RR) is among the first vital signs to reflect the change in patient’s condition and is 
usually assessed clinically, by counting chest wall movements. This is time consuming, may be difficult 
to perform in busy post-anesthesia care units, and is limited by its intermittent nature. Monitoring RR 
using continuous end-tidal carbon dioxide (EtCO2), by capnography for the early detection of 
respiratory changes during the sedation is then highly useful [8, 11].  
 
There is an urgent need for a robust, low-cost method that can help frontline healthcare workers to 
measure RR quickly. An effective way for improving efficiency of rate estimations is incremental and 
continuous analysis of time intervals instead of counting events in a fixed time interval, thus, using 
deep learning to assist with such tasks. 
 
The purpose of this study is to compare the respiratory rate assessment in adult patients at hospital, 
on the deep learning-enable RR monitor software, Airmod, to the commercial respiratory monitor, 
Capnostream™35, to indicate non-inferiority. 
 
 

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2.2 
BACKGROUND  
 
Sedation is commonly prescribed to reduce the patient’s anxiety, discomfort and pain during certain 
procedures. All sedatives suppress the central nervous system in a dose-dependent manner, usually 
accompanied by a reduction in CO2 responsiveness in the medullary respiratory center. One of the 
most common adverse effect associated with sedation is respiratory depression, and the greater the 
degree of sedation, the greater the degree of respiratory depression observed [12]. 
 
Monitoring of sedation is of great importance, not only avoid inadequate or over sedation, also 
assuring quality care and minimizing risk of adverse events [8, 13]. Given that capnography is the most 
reliable method to confirm airway device placement and monitor ventilation, as the current gold 
standard method [9, 14]. After initial placement, loss of the waveform can indicate movement of the 
tube, possible esophageal placement or circuit disconnection, which provides a continuous assurance 
of functional tube placement. In a 2001 study of 345 intubations, capnography had a sensitivity and 
specificity of 100% for correct placement [15].  
 
The capnography waveform represents air movement in the lungs, starts at the beginning of 
exhalation, and senses air from dead space in the upper airway and bronchi. As carbon dioxide (CO2) 
is a product of metabolism transported via perfusion and expelled through ventilation, the End-tidal 
carbon dioxide (EtCO2) waveform adds an objective measurement on counting the respiratory rate 
(RR), where it increases as CO2 rises, and decreases as CO2 falls [16]. This provided real-time feedback 
on the patient’s conditions, indicating the response to a treatment, where plans can be quickly 
adjusted when capnography is used to monitor trends. 
 
The importance of monitoring respiratory rate as a key vital sign has been well defined in medicine 
[17]. An abrupt alteration in respiratory rate can help detect changes in the status of a patient during 
a crucial period where modifications in management might be needed. Respiratory monitoring is 
important for both patients receiving general anesthesia as well as for those who require sedation 
[17]. 
 
Capnostream™35 is a commercially available device (cleared by FDA, MHLW/PMDA, TFDA and CE-
Marked), a portable respiratory monitor that offers comprehensive respiratory monitoring which 
helps medical expert to respond earlier and intervene sooner if the patient is showing signs of 
respiratory compromise. The monitor provides information to help support clinical decisions and may 
improve workflow [18].  
 
Airmod is a software application designed to aid healthcare professionals by monitoring a patient’s 
breathing in real time. It can detect inhalation acoustics and provides respiratory rates based on the 
analysis of the acoustic signals of breathing sounds collected by the electronic stethoscope. The noise-
cancelling technology in the Airmod helps to reduce ambient noises and acoustic feedback. The AS-
101, a digital stethoscope,  performs sound processing, with the bandwidth covering the frequency 
range of 20-2000Hz. Auscultation sound is then transferred to the headphone or the mobile device 
speaker allowing the user to switch among four channels to listen to and view the spectrogram coming 
from different auscultation locations. 
 
 
 
 

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9 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
To evaluate accuracy 
and performance of 
respiratory rate (RR) 
measurement from 
Airmod compared to 
Capnostream™35. 
The primary 
objective is to 
establish the non-
inferiority. 
The difference between AirRR and 
ManCRR, which is greater than -3 under 
establishes non-inferiority. The unit in 
this calculation is bpm and sampling 
rate is 1 Hz. 
 
[Time Frame:  
Non-Anesthesia Stage: Up to 40 
patients will be randomly assigned to 
non-anesthesia stage assessment, the 
measurement will be evaluated after 
enrollment with ICF, at the NOR area. 
(5~30 minutes) 
Procedure Stage: From firstly anesthetic 
administration to end of procedure. 
(Depends on procedure 10mins ~ few 
hours) 
NORA stage : From transportation of 
subjects to PACU to discharge from 
PACU (PAR or PADSS score ≥ 9) (At least 
15 minutes) ] 
The information of patient monitoring 
period refers to 10.2.1. 
 
Secondary 
 
 
To assess the 
accuracy of 
respiratory rate 
measurement by 
Airmod in 
comparison with 
manual-scored 
auscultation sound 
during the less 
sensitive period of 
Capnography on 
Capnostream™35. 
The accuracy of inhalation classification 
in the segmentation basis is greater 
than 82.5% at the 95% CI. The 
performance metrics (F1-socre, MAPE) 
at event level will be demonstrated and 
target for F1-score > 0.8, MAPE < 0.5. 
The principal investigator and 
research members will 
determine the less sensitive 
period. 
To assess the precision and 
recall rate of Airmod deep 
learning algorithm, the F1-
score build up and bind the 
hierarchy positive and negative 
metrics all together. It is 
generally described the 
harmonic mean of the two. 
Besides, the MAPE enhanced 
the difference power of error 
prediction by keep positive and 
negative errors from cancelling 
out each other. The relative 
errors are independent with 
the scale of target.   
To measure the 
agreement between 
AirRR and ManCRR.  
To measure the agreement of AirRR and 
ManCRR on concordance correlation 
Bland-Altman analysis is used 
to measure the consistency of 
continuous data from two 

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coefficient, and on their mean and bias 
by Bland-Altman analysis. 
[Time Frame:  
Non-Anesthesia Stage: Up to 40 
patients will be randomly assigned to 
non-anesthesia stage assessment, the 
measurement will be evaluated after 
enrollment with ICF, at the NOR area. 
(5~30 minutes) 
Procedure Stage: From firstly anesthetic 
administration to end of procedure. 
(Depends on procedure 10mins ~ few 
hours) 
NORA stage : From transportation of 
subjects to PACU to discharge from 
PACU (PAR or PADSS score ≥ 9) (At least 
15 minutes) ] 
The information of patient monitoring 
period refers to 10.2.1. 
distinct measurements. 
Therefore, the likelihood of 
AirRR and ManCRR will be 
quantified and visualized on 
the assumption of fixed 
observer and pairs Bland-
Altman analysis. 
Further information refers to 
10.2.6. 
To evaluate the 
response time of the 
first breath 
detection followed 
by administration of 
jaw thrust during the 
apnea period. The 
3rd secondary 
objective is to 
compare the 
response time of 
Airmod versus  
Capnography. 
Use paired t-test to compare the 
response time of Airmod versus 
Capnography on Capnostream™35 after 
administration of jaw thrust. In the 
target of p<0.05 indicates significance. 
The principal investigator and 
research members will 
determine the apnea period 
and the first effective breath.  
To compare the 
influence of subjects 
to variated breath 
rates on respiratory 
rate monitoring in 
bpm as measured by 
Airmod, manual-
scored and 
Capnostream™35.  
1. The difference of ManCRR minus 
AirRR and ManCRR minus CapRR 
indicates non-inferiority at margin of 3 
bpm (M1) and sampling rate 1Hz.  
2. The difference of ManCRR minus 
AirRR and ManCRR minus CapRR 
indicates non-inferiority at margin of 2 
bpm (M2) and sampling rate 1Hz.   
[Time Frame:  
Non-Anesthesia Stage: Up to 40 
patients will be randomly assigned to 
non-anesthesia stage assessment, the 
measurement will be evaluated after 
enrollment with ICF, at the NOR area. 
(5~30 minutes) 
Procedure Stage: From firstly anesthetic 
administration to end of procedure. 
(Depends on procedure 10mins ~ few 
hours) 
Capnography is inherently 
limited in certain 
circumstances which may 
cause ineffectively detecting 
CO2, including movement, 
nasal cannula drop, blocked, or 
other situations. Airmod is 
superior to capnography in 
these limitations since it 
detects and measure breath 
sound directly.  
 
1. The difference between 
ManCRR and AirRR is 
comparing with the difference 
between CapRR and ManCRR 
to indicate the bias of Airmod 
are non-inferior to the 
reference devices at the 

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NORA stage : From transportation of 
subjects to PACU to discharge from 
PACU (PAR or PADSS score ≥ 9) (At least 
15 minutes) ]           
The information of patient monitoring 
period refers to 10.2.1.                                  
margin of 3 bpm, which also 
demonstrates substantial 
equivalence. 
2. To evaluate whether Airmod 
can approach a strict standard 
suggested by clinicians, the 
difference between ManCRR 
and AirRR is comparing with 
the difference between CapRR 
and ManCRR to indicate the 
bias of Airmod are non-inferior 
to the reference devices at the 
margin of 2 bpm, which 
indicates the largest clinically 
acceptable difference. 
 
Part of the measurement result 
within subject will be censored 
and excluded in the paired 
non-inferiority test. The 
principle of exclusion is based 
on the failure event/period of 
Airmod or CapnostreamTM35 
reported by investigator. The 
report will be confirmed by the 
principal investigator, the data 
prior to discontinuation and 
after machine failure being 
fixed is still included.  
Examples of excluded 
measurement refer to 10.2.7.  
To evaluate the 
safety and usability 
of Airmod. 
The absence of unanticipated serious 
adverse device effect (USADE) during 
study period and the questionnaire. 
 
 
 
 
 
 
 
 
4 
STUDY DESIGN  
 

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4.1 
OVERALL DESIGN 
 
This is a prospective, multi-center, pivotal study. The purpose of this study is to evaluate the non-
inferiority of Airmod to Capnostream™35 for respiratory rate monitoring. Subgroup analyses will be 
performed, details are described in statistical analysis plan (SAP).In the total of 300 subjects enrolled 
at the OR and NOR area in the hospital, the interim analysis will be performed at the enrollment of 
150 subjects during study period. (using OBrien-Fleming to determine α=0.00153) 
 
Safety will be assessed by the investigator(s) and will be monitored until the end of the study. All 
Adverse Event(s) (AE) and Serious Adverse Event(s) (SAE) occurring during the study period will be 
followed until the event is considered stable or until full resolution. 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
A new simple tool to monitor patient’s respiratory rate is needed which benefits both patients and 
medical experts. The current standard for RR measurement is capnography (EtCO2). Capnostream™35, 
a commercially available device that provides functions that are required for the standard of care 
along with benefits that are conducive to the study (capnography, sufficient battery life, suitable in 
size and portable), is selected as the study control device. So, in order to establish whether Airmod is 
no worse than the commercially available device for which the performance of RR monitoring has 
been determined, the clinical study was planned. 
 
4.3 
JUSTIFICATION FOR DOSE 
 
Not applicable in this study. 
 
4.4 
END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.3. The end of the study is defined as the time point when the subject discharged from post 
anesthesia care unit (Post Anesthetic Recovery [PAR] or Post Anesthetic Discharge Scoring System 
[PADSS] score ≥ 9; these are assessed by the site staff upon admission and every 15 minutes after the 
subject transfer to PACU), or the end of non-anesthesia period determined by principal investigator. 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Provision of signed and dated informed consent form. 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study. 
3. Male or female with at least 20 years of age. 
4. Fit for intravenous general anesthesia (IVG) as assessed by pre-anesthesia evaluation. 
Details of 3 & 4 refer to 10.2.3. 

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5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Presence of neck pain or injuries. 
2. Under the use of high-flow nasal cannula ventilation. Other examples refer to 10.2.4. 
3. Unable to wear Airmod and Capnostream™35 device related accessories at the investigator’s 
discretion. 
4. As a vulnerable population, including legal incapacity or evidence that a subject cannot 
understand the purpose and risks of the study, regardless of authorized representative 
support. 
5. Unwilling or unable to comply fully with study procedures (including non-toleration of the 
capnography cannula) due to any disease condition which can raise doubt about compliance 
and influencing the study outcome. 
6. The patient who can’t receive operation under IVG anesthesia that suggest by the evaluation 
of preoperative assessment. 
 
5.3 
LIFESTYLE CONSIDERATIONS 
 
Not applicable in this study. 
 
5.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical study but are not 
enrolled in the study. A minimal set of screen failure information is required to ensure transparent 
reporting of screen failure participants, to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria. 
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
The recruitment of subjects will be conducted according to GCP and local regulations. Subjects will be 
recruited through appropriate measures, including but not limited to posters established for the 
specific purpose of recruiting. There will be a reimbursement for the participant at the time on signing 
informed consent form in order to keep the retention. 
 
 

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6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
The investigational product (IP), ‘Airmod’, manufactured by Heroic Faith Medical Science Co., Ltd., is 
intended to provide professionally trained health professionals with continuous non-invasive 
measurement and monitoring of respiratory rate in adult patients. It is designed to detect inhalation 
acoustics and provides respiratory rates based on the analysis of the acoustic signals of breathing 
sounds collected by the electronic stethoscope. The device is intended for use in hospitals, hospital-
type facilities, during intra-hospital transport, and out-of-hospital emergency medical service (EMS) 
applications that include ground and air transport. The intended for use is further described in 10.2.5. 
 
In this study, Airmod will be used along with AS-101 (AccurSound Electronic Stethoscope, a 
commercially available device in Taiwan). There are no known contraindications and are not designed 
for use in patients unable to be assessment by stethoscope such as who require the use of high-flow 
nasal cannula. 
 
Table 1 and 2 provides a list of devices and accessories components that may be used in the study. 
 
Table 1. Airmod and Accessory Components 
Product 
Model or Version or Material 
Airmod Software 
Airmod V1 
Additional Accessories 
Devices with operating system standard Android 10/11, RAM 8G, 
128G; chipset processing power equivalent or superior to 
Snapdragon™ 855. 
AccurSound Electronic Stethoscope model AS-101  
(herein referred to ‘AS-101’) 
Surgical tape 
 
Table 2. Capnostream™35 Devices and Accessory Components 
Product 
Model or Version or Material 
Hardware (monitor) 
Capnostream™35 Portable Respiratory Monitor PM35MN 
Capnostream™35 
Software 
Monitor: 01.00.06.05 
CO2: 01.14 
Unit dimensions 
(Height) 213 mm × (Width) 137 mm × (Depth) 55 mm 
Power supply 
Input Voltage 100-240 V, 50/60 Hz, ± 10% 
Waveform sampling rate  
20 samples/sec 
Additional Accessories 
‘Medtronic’ Microstream™ etCO2 Sampling Lines  
(Smart CapnoLine Plus O2, herein referred to ‘sampling lines’) 
 

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6.1.2 DOSING AND ADMINISTRATION 
 
Subjects will be monitored with the devices Airmod and Capnostream™35 simultaneously on Visit 2; 
both devices should be ready and apply correctly on the subject before sedation. 
 
● Airmod administration procedure 
 
Preparation 
1. The device with Airmod should have enough battery life that last for the whole study process. 
Attach the device with Airmod with the AS-101 using type- C to type-C cable.  
2. Place the auscultation sensor on the patient neck (left or right-side plain area of thyroid 
cartilage), secure with surgical tape. 
3. Click on the ‘Airmod’ on the screen of the device to enter the software interface. When the 
device with Airmod and AS-101 are properly connected, an indicator light should come up, 
and then are able to click on the start/stop button to start monitoring.  
4. By clicking the start/stop button, immediately breathing sound and spectrogram should be 
presented via speaker and display screen respectively, and if the signal or reception is 
unstable, adjust the auscultation sensor or secure with surgical tape to improve. 
 
Monitoring (start time) 
5. To start recording the monitoring for the study, on the display screen, select start/ stop button 
and entering the patient ID.  
 
Monitoring (end time) 
6. To end monitoring and terminate the saving process, on the display screen, select the 
start/stop button. This procedure should be done at the time point where the subject is ready 
to discharge from post anesthesia care unit (PACU) or the end of non-anesthesia period, which 
compliance with the criteria PAR or PADSS score ≥ 9 or determined termination by principal 
investigator. 
 
● Capnostream™35 administration procedure 
 
Preparation 
1. Capnostream™35 should have enough battery life that last for the whole study process. 
2. To set up for the subject, on the monitoring display screen, select menu -> action -> patient 
admin -> insert the subject number.  
3. Connect the sampling line to the monitor, rotate it clockwise until it can no longer be turned; 
and also connect the sampling line to the subject nostril, adjust the tightness at the lower 
band to fit on the subject. When properly connected, the monitor will immediately begin to 
search breaths, then present EtCO2 value and waveform on the display screen after 3.4 ~ 5.0 
second. 
4. Connect the pulse oximetry line to the monitor and clip the pulse oximetry probe onto the 
finger of subject. When properly connected, the monitor will present SPO2 value on the 
display screen after 3.4 ~ 5.0 second. 
5. To start storing the report and output to SD card, on the monitoring display screen, select 
menu -> report -> store report -> real-time full continuous transfer -> choose to save in SD 
card or USB drive -> save report. 
 
Monitoring (start time) 
6. The monitoring period starts once the last step (save report) has been done.  

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Monitoring (end time) 
7. To end monitoring and terminate the saving process, on the monitoring display screen, select 
menu -> report -> store report -> active report -> stop. This procedure should be done at the 
time point where the patient is ready to discharge from PACU or the end of non-anesthesia 
period, which compliance with the criteria PAR or PADSS score ≥ 9 or determined termination 
by principal investigator. 
 
 
The administered anesthetic medication and dosage, surgery type, start and stop time of surgery will 
be collected during surgery. 
 
The medical records of subjects will be confirmed on allowed visit window (within 14 days). 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
The investigator and study staff will be responsible for the accountability of all clinical supplies 
(dispensing, inventory, and record keeping) following the Sponsor’s instructions. In this matter, the 
investigator and study staff must adhere to GCP guidelines, as well as national requirements. Under 
no circumstances will the investigator allow the investigational product to be used other than as 
directed by this protocol. Clinical supplies will be dispensed only by an appropriately qualified person 
and will not be dispensed to any individual who is not enrolled in the study. An accurate and timely 
record of the receipt of all clinical supplies and dispensing of investigational product to the subject 
must be maintained. 
 
The supplies and inventory records must be made available, on request, for inspection by the Sponsor 
(or its designee) or a representative of a regulatory authority. All unused investigational product is to 
be returned to the Sponsor at the conclusion of the study, unless provision is made by the Sponsor for 
destruction of supplies at the study site. On completion of investigational product accountability and 
reconciliation procedures by study site personnel and documentation procedures by Sponsor 
personnel, investigational product that is to be returned to the Sponsor, if necessary, must be boxed 
and sealed and shipped back to the Sponsor following all local regulatory requirements. 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
The investigational materials will be obtained and/or packaged and labeled in a manner consistent 
with the study design including but not limited to product name, model number, lot number, quantity, 
shelf life, manufacturing date, company name, company address, manufacturer name and 
manufacturer address.  
 
Labels will be non-removable in nature. Sample labels for the primary package containing the 
investigational products are including but not limited to product name, model number, material, lot 
number, quantity, shelf life, manufacturing date, company name, company address, manufacturer 
name, manufacturer address, study number and storage condition. 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
The investigational product will be stored in accordance with labelled storage conditions. The 
investigation products (IPs) must be kept strictly separate and in a different location than non-study 

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commercially available product. The IP should be kept at 0°C to 40°C (32°F to 104°F) and humidity 
level 15% to 90% until time of use. No damage should appear on the packaging and/or device before 
using. 
 
Temperature monitoring is required at the storage location to ensure that the investigational product 
is maintained within an established temperature range. The investigator is responsible for ensuring 
that the temperature is monitored throughout the total duration of the study and that records are 
maintained; the temperature should be monitored continuously by using either an in-house validated 
data acquisition system, a mechanical recording device, such as a calibrated chart recorder, or by 
manual means, such that minimum and maximum thermometric values over a specific time period 
can be recorded and retrieved as required.  
 
6.2.4 PREPARATION 
 
Set up for the device with Airmod and Capnostream™35 is required, manual book and a quick guild 
card along with the product information will be provided for the user included in the study training 
materials. The device data transfer process will be tested and verified during the site initiation 
process.  
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
This study will not be randomized and blinded. 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
 
Records of treatment administration for each subject will be kept during the study. 
 
6.5 
CONCOMITANT THERAPY 
 
Not applicable in this study. 
 
6.5.1 RESCUE MEDICINE 
 
Not applicable in this study. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
If subject discontinued without administered study intervention, no further evaluations are needed. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request.  
An investigator may discontinue or withdraw a participant from the study for the following reasons: 

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● Participant unable to receive Airmod and/or Capnostream™35 and their device related 
accessories. 
● After adjustment, noises (such as those caused by air leak continue to pronounce-affect signal 
quality) continue to be pronounced, and cannot be resolved. 
● The anesthesiologists determine that the participant is at risk of hypoxemia or other life-
threatening conditions. 
● If any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interest of the participant. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Case 
Report Form (CRF). Subjects who signed the informed consent form (ICF) and subsequently withdraw, 
or discontinued from the study, will not be replaced. 
 
7.3 
LOST TO FOLLOW-UP 
 
Not applicable in this study. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
 
During the study visit 2 (Day 1), the breathing sound and partial pressure of CO2 will be recorded using 
the device with Airmod and Capnostream™35 respectively. The breathing sounds is obtained from the 
device with Airmod as a wav file, while the partial pressure of CO2 (with sampling rate of 20 Hz) is 
obtained from Capnostream™35 as a txt file. 
 
Accurate time frame is required as is the factor which may affect the endpoint. Both devices should 
start and end the recording at the same time in a specific time point, as below. 
 
● Non-Anesthesia Stage: Up to 40 patients will be randomly assigned to non-anesthesia stage 
assessment, the measurement will be evaluated after enrollment with ICF, at the NOR area. 
(5~30 minutes) 
● Procedure Stage: From firstly anesthetic administration to end of procedure. (Depends on 
procedure 10mins ~ few hours) 
● NORA stage: From transportation of subjects to PACU to discharge from PACU (PAR or PADSS 
score ≥ 9) (Ideally keep following to 15 minutes) 
 
o Post Anesthesia Recovery (PAR) score 
The information of patient monitoring period refers to 10.2.1. 
 
The Post Anesthesia Recovery (PAR) score (Miller’s Anesthesia, 9th Edition) will be performed and 
recorded by relevant personnel after the transfer of care through the PACU. Subjects are 
evaluated upon admission and every 15 minutes until a score of ≥ 9 is reached. Elements include: 

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Activity 
Muscle activity is assessed by observing the ability of the patient to 
move his/ her extremities spontaneously or on command. 
Respiration 
Respiratory efficiency evaluated in a form that permits accurate and 
objective assessment without complicated physical tests. 
Circulation 
A measurement of cardiovascular homeostasis and a comparison with 
previous blood pressures. 
Consciousness 
Determination of the patient's level of consciousness. 
Oxygen saturation 
Measurement of arterial oxygen saturation using pulse oximetry. 
 
o Post Anesthesia Discharge Scoring System (PADSS) 
The Post Anesthesia Discharge Scoring System (PADSS) (Miller’s Anesthesia, 9th Edition) will be 
performed and recorded by relevant personnel after the transfer of care through the PACU. 
Subjects are evaluated upon admission and every 15 minutes until a score of ≥ 9 is reached. 
Elements include: 
 
Vital signs 
A measurement of cardiovascular homeostasis and a comparison with 
previous blood pressures. 
Activity level 
Prior to discharge home, the patient’s activity level must be at 
baseline.  Patient must be able to ambulate at preoperative level. 
Nausea and 
vomiting 
Prior to discharge, the patient must have minimal to no nausea and 
vomiting. 
Pain 
Pain/discomfort must be at a level identified by the patient as 
tolerable. The location, type and intensity of pain should be consistent 
with anticipated postoperative discomfort. 
Surgical bleeding 
The surgical site must be free from excessive or unexpected bleeding/ 
drainage. 
 
The breathing sounds and the partial pressure of CO2 will then convert to the breathing counts and 
CO2 waveform respectively using self-developed software written from Python and Matlab, the data 
will be recorded in Microsoft Excel and RR will eventually be calculated manually by trained personnel 
for each result. 
 
During the study, if the study staff indicates the breathing sounds or the partial pressure of CO2 is 
affected, for instance, an obviously external sound, moving the patient, nasal cannula drop, blocked, 
or other situation identify by the investigator. Such start/stop time of event(s) will be recorded in CRF, 
accurate to second. Such affected data or missing data will be excluded in the final comparison as such 
event(s) may be affecting the study result, determined by the investigator during the monitoring 
period.  
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 
● Safety Assessment 
The adverse events will be reviewed and evaluated by investigator throughout the study period (after 
enrollment to end of study). All adverse events will be recorded on the CRF.  
 

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● Medical History 
A complete medical history will be reviewed at Screening. Medical history within 3 months prior to 
Screening will be recorded. Medical conditions occurring more than 3 months prior to Screening will 
not be recorded, unless they are judged by the principal investigator(s) to be significant. 
 
● Demographic Data 
Demographic information for each participant, including birth date and gender will be collected and 
recorded at Screening. 
 
● Physical Examination 
A full physical examination will be performed at Screening. Items will include: general appearance, 
weight and height, HEENT (head, eyes, ears, nose, and throat), mouth, skin, neck (including thyroid), 
lymph nodes, spine, cardiovascular system, respiratory system, gastro-intestinal system, nervous 
system, musculoskeletal system, blood and blood forming organs, mental status, and other body 
systems if applicable for describing the status of participant’s health. 
 
● Vital Signs 
Vital signs include body temperature (°C), blood pressure (including systolic and diastolic blood 
pressure, unit: mmHg), and pulse rate (times/minute) will be performed at Screening. Results will be 
documented in the CRF. Vital signs should be evaluated after the participant has rested in a sitting 
position for at least 3 minutes. Note that study site staff should measure ear temperature of the 
participant if possible. If tympanic or axillary methods are used, the same method should be used 
consistently throughout the study. 
   
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
  
Primary Analysis: 
 
In this study, all the measurements were conducted in the same subject, and the clocking variance 
would be limited by investigator justification procedure to acquire the utmost matching recording. 
The study design is a paired non-inferiority test to evaluate accuracy and performance of respiratory 
rate (RR) measurement from Airmod compared to Capnostream™35. The primary objective is to 
establish the non-inferiority. The primary end goal is to test the entire effect at the margin of 3 breaths 
per minute (bpm). The non-inferiority is a directional (one-sided) test. The null hypothesis (H0) and 
alternative (H1) are defined as: 
 
H0: µAirRR- µManCRR < -3 ; 
H1: µAirRR- µManCRR ≥ -3. 
 
 
Details refer to the SAP. 
 
9.2 
SAMPLE SIZE DETERMINATION 
 

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By referencing predicate device clinical trials on respiratory rate monitoring in the hospital setting, 
most of the cases recruited 120+ patients. Considering a 40% withdrawal/dropout rate, we proposed 
a total enrollment of 300 subjects. 
 
Details refer to the SAP. 
 
 
9.3 
POPULATIONS FOR ANALYSES 
 
The analysis will test the performance and safety using the Per-Protocol (PP) and Intention-to-Treat 
(ITT). The PP population is defined to be evaluable subjects who complete the entire study procedure 
without major protocol violations. The ITT population is defined to be all treated subjects who are 
administered using the device with Airmod and Capnostream™35. 
 
Details refer to the SAP. 
 
9.4 
STATISTICAL ANALYSES 
 
Details refer to the SAP. 
 
9.4.1 GENERAL APPROACH 
 
For descriptive statistics, continuous variables will be presented as N, mean, median, SD, maximum 
and minimum, while categorical variables will be presented as N and percentiles.  
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
In this study, all the measurements were conducted in the same subject, and the clocking variance 
would be limited by investigator justification procedure to acquire the utmost matching recording. 
The study design is a paired non-inferiority test to evaluate accuracy and performance of respiratory 
rate (RR) measurement from Airmod compared to Capnostream™35. The primary objective is to 
establish the non-inferiority. The primary end goal is to test the entire effect at the margin of 3 breaths 
per minute (bpm). The non-inferiority is a directional (one-sided) test. The null hypothesis (H0) and 
alternative (H1) are defined as: 
 
H0: µAirRR- µManCRR < -3; 
H1: µAirRR- µManCRR ≥ -3. 
 
At the interim analysis, under 99.69% CI, when reject the null hypothesis (H0) indicates the non-
inferiority. 
At the final analysis, under 95.1% CI, when reject the null hypothesis (H0) indicates the non-inferiority. 
 
A subgroup analysis for those subjects with BMI ≥ 30 will follow the original study design in a stratified 
sample pool to test the non-inferiority at the margin of 3 bpm. 
 
According to 7.2, part of the measurement result within subject will be censored and excluded in the 
paired non-inferiority test. The principle of exclusion is based on the investigator reported failure 
event/period of Airmod or CapnostreamTM35, the report will be confirmed by the principal 
investigator. The data prior to discontinuation or following a fixed machine failure period will be 
included in the paired non-inferiority test.  

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9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
1. To assess the accuracy of respiratory rate measurement by Airmod in comparison with manual-
scored auscultation sound during the less sensitive period of Capnography on Capnostream™35, the 
accuracy of inhalation classification in the segmentation basis is greater than 82.5% at the 95% CI. 
The performance metrics (F1-socre, MAPE) at event level will be demonstrated and target for F1-
score > 0.8, MAPE < 0.5. 
The precision and recall rate of Airmod deep learning machine, the F1-score build up and bind the 
hierarchy positive and negative metrics all together. It is generally described the harmonic mean of 
the two. Besides, the MAPE enhanced the difference power of error prediction by keep positive and 
negative errors from cancelling out each other. The relative errors are independent with the scale of 
target. 
 
F1-score:  
 
 
MAPE: 
 
 

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The output size of our model is a 235 x 1 vector for a 15-second audio recording so that the duration 
of each time frame is about 0.064 second. During the inference process, the deep learning model 
determines whether a time frame belongs to an inhalation. After comparing the inference results 
with the manual-scored ground-truth labels, we can assign true positive (TP), false positive (FP), true 
negative (TN), or false negative (FN) to each time frame. Thus, the accuracy 
((TP+TN)/(TP+TN+FP+FN)) of inhalation detection in the segment level can be calculated. We use the 
accuracy of segment detection to evaluate the performance of the deep learning model. 
 
2. To measure the agreement of AirRR and ManCRR on concordance correlation coefficient, and on 
their mean and bias by Bland-Altman analysis. 
Bland-Altman analysis is used to measure the consistency of continuous data from two distinct 
measurements. Therefore, the likelihood of AirRR and ManCRR will be quantified and visualized on 
the assumption of fixed observer and pairs Bland-Altman analysis. It combines the quantitative 
analysis of LoA (limits of agreement) and the qualitative analysis of scatter plot to show an instinctive 
evaluation between two methods of their correlation. Each of the n samples is then represented on 
the graph by assigning the mean of the two measurements as the x-value, and the difference between 
the two values as the y-value. By this graphical method, we can extend a simple logarithmic 
transformation approach to data where there is a relationship between difference and magnitude.  
We discuss the importance of repeatability of RR measurements from each equipment and compare 
an estimate of this to the LoA. [20] In this case, if the difference of RR measured from two equipment 
are in the 95% LoA, we will say that RR measured from these two equipment are correlated and 
acceptable. 
 
𝑆(𝑥, 𝑦) = (∆G_A + ∆G_E
2
, ∆G_A −∆G_E) 
 
3. Use paired t-test to compare the response time of Airmod versus Capnography on 
Capnostream™35 after administration of jaw thrust. In the target of p<0.05 indicates significance. 
The principal investigator and research members will determine the apnea period and the first 
effective breath. 
The paired t test can be used when the two groups under comparison are dependent on each other. 
[21] By acquiring the T value from paired t-test, we can obtain the p value indicating the significant 
difference level via t-distribution table or Microsoft Excel. A p value less than 0.05 would indicate 
that Airmod is able to resume RR estimation after proper intervention faster than Capnostream™35. 
𝑡=
𝑋̅1−𝑋̅2
√(𝑠1
2+𝑠2
2)2𝜌𝑠1𝑠2
𝑛
 
 
4. Capnography is inherently limited in certain circumstances which may cause ineffectively 
detecting CO2, including movement, nasal cannula drop, blocked, or other situations. Airmod is 
superior to capnography in these limitations since it detects and measure breath sound directly. 
 
4.1 The difference of ManCRR minus AirRR and ManCRR minus CapRR indicates non-inferiority at 
margin of 3 bpm (M1) and sampling rate 1Hz.  
 
The difference between ManCRR and AirRR is comparing with the difference between CapRR and 
ManCRR to indicate the bias of Airmod are non-inferior to the reference devices  at the margin of 
3 bpm, which also demonstrates substantial equivalence. 
 
4.2 The difference of ManCRR minus AirRR and ManCRR minus CapRR indicates non-inferiority at 
margin of 2 bpm (M2) and sampling rate 1Hz. 
 

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To evaluate whether Airmod can approach a strict standard suggested by clinicians, the difference 
between ManCRR and AirRR is comparing with the difference between CapRR and ManCRR to 
indicate the bias of Airmod are non-inferior to the reference devices at the margin of 2 bpm, 
which indicates the largest clinically acceptable difference. 
 
 
According to 7.2, part of the measurement result within subject will be censored and excluded in 
the paired non-inferiority test. The principle of exclusion is based on the investigator reported 
failure event/period of Airmod or CapnostreamTM35, the report will be confirmed by the principal 
investigator. The data prior to discontinuation or following a fixed machine failure period will be 
included in the paired non-inferiority test. 
 
5. The usability questionnaire as reference [Usability_Airmod] and descriptive analysis will be 
performed and recorded. 
 
9.4.4 SAFETY ANALYSES 
 
All candidates who were subjected to the device with Airmod and Capnostream™35 will be included 
in the safety analyses (performed in the Safety population) and data will be summarized using 
descriptive statistics. By reporting the numbers of adverse events (AE)/severe adverse events(SAE) 
within the trial to indicate the incidence rate of safety issues. We will also present the total number 
of patients suffering from AE/SAE and its percentage of all population.  
 
The incidence of adverse events will be tabulated, summarized by intensity and relationship to the 
investigational product. 
 
Details refer to the SAP. 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
Demographic data, physical examination, vital signs, the administered anesthetic medication and 
dosage, surgery type, start and stop time of surgery will be summarized. For continuous demographic 
variables, results will be summarized and presented as N, mean, SD, median, and minimum and 
maximum values. For categorical (nominal or ordinal) variables, the number and percentage of 
subjects will be used. No statistical testing will be performed. 
 
9.4.6 PLANNED INTERIM ANALYSES  
 
In the non-blinded total of 300 subjects enrolled, the interim analysis will be performed at the 
enrollment of 150 subjects (at least 30   non-anesthesia patients enrolled) during the study period. at 
the nominal significance level using OBrien-Fleming to determine α=0.00153. The final analysis will be 
performed at the end of 300 subjects enrolled. The nominal significance level is using OBrien-Fleming 
to determine  α=0.02450. 
9.4.7 SUB-GROUP ANALYSES 
 
The primary endpoint will be analyzed based on different subgroups; details are described on SAP. 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
No individual participant data will be listed by measure and time point. 
 

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10 SUPPORTING DOCUMENTATION 
10.1 ABBREVIATIONS 
AE 
Adverse Event 
AirRR 
Airmod-scored auscultation sound generated from AS-101 
BMI 
Body Mass Index 
bpm 
breaths per minute 
CapRR 
 
CE 
Machine-scored Capnography (CapRR) generated from CapnostreamTM35 (K150272, 
Medtronic) 
Communate Europpene 
CFR 
Code of Federal Regulations 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DBP 
Diastolic Blood Pressure 
DSMB 
Data and Safety Monitoring Board 
EC 
Ethics Committee 
EMS 
Emergency Medical Service 
EtCO2 
End-tidal Carbon Dioxide 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practices 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
IVG 
Intravenous General Anesthesia 
LOA 
Limits of Agreement 
MHLW 
Ministry of Health, Labour and Welfare 
ManARR 
ManCRR 
 
NOR 
Manual-scored auscultation sound originated from AS-101 
Manual-scored Capnography (ManCRR) originated from CapnostreamTM35 (K150272, 
Medtronic) 
Non-operating Room 
OR 
Operating Room 
PACU 
Post Anesthesia Care Unit 
PADSS 
Post Anesthetic Discharge Scoring System 
PAR 
Post Anesthetic Recovery 
PI 
Principal Investigator 
PMDA 
Pharmaceutical and Medical Devices Agency 
PP 
Per Protocol 
QC 
Quality Control 
RMSD 
Root Mean Square Difference 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SoA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
TFDA 
Taiwan Food and Drug Administration 
USADE 
Unanticipated Serious Adverse Device Effect 
US 
United States 
WMA 
World Medical Association 

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10.2 SUPPLEMENTARY 
10.2.1 PATIENT MONITORING PERIOD (TIME FRAME) 
Device installation is done in the preparation period and trial will start upon sedation until discharge 
from the post-anesthesia care unit (PACU). A small group of patients (at least 40 patients) will also 
be evaluated for 15 to 30 minutes prior sedation or past discharge. 
 
10.2.2 STUDY POPULATION 
The population will be consisted with the study, to cover a wide range of health conditions, 
comorbidity, and risk, we proposed to enroll at least 40 non-anesthesia patients in a total of 300 
sedative/ anesthesia patients from pre-anesthesia evaluation clinics. 
10.2.3 INCLUSION CRITERIA 
The compared digital stethoscope, AS-101, is not limited to patient age. 
We will include patients eligible for procedure sedation/analgesia and have the target level from 
minimal to moderate and deep sedation/ analgesia. The enrolled patients' pre-anesthesia evaluation 
(followed ASA guidance) and their medical history will be recorded. We will also ensure that the 
patient group is wide enough to cover various common medical disorders. 

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10.2.4 EXCLUSION CRITERIA 
Patients with advanced airway management equipment will be excluded. (For instance, Supraglottic 
airway device, LMA, Endotracheal tube.) 
Some equipment, such as High Flow Nasal Cannula (HFNC), CPAP, suction machine, could continually 
make noise in the patient’s airway, affecting auscultation and RR measurement. These conditions 
will also be excluded. 
10.2.5 INTENDED FOR USE 
The Airmod is an Android based software intended to be used with a legally marketed digital 
stethoscope as input sensor for the continuous, non-invasive monitoring of respiratory rate (RR) in 
patients aged 20 years and older who are subjected to procedural sedation in which the depth of 
sedation ranges from minimal to moderate and deep sedation/anesthesia. It is intended for use by 
healthcare professionals in hospitals and healthcare facilities performing procedural 
sedation/anesthesia. 
10.2.6 SAP ABSTRACT 
The primary objective is evaluating the non-inferiority of Airmod to Capnostream™35 for respiratory 
rate monitoring and user experience clinical evaluation, these results will be included in the clinical 
study report. In a total of 300 patients enrolled, Airmod and Capnostream™35 recorded the 
respiratory rate concurrently. The demographic of patients and their Charleson comorbidity in the 
statistical analysis are collected to describe the patient population in our study. We will further 
analyze the primary and secondary end goal in the records to show non-inferiority of respiratory 
rate estimation, agreement, and the excellence event detection of Airmod to Capnostream™35. The 
subgroup analysis in each period and particular BMI patient group will indicate the statistical power 
of our study and provide further information on the substantial equivalence performance in 

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respiratory rate measurement. We will also record all the adverse events during the procedure for 
analysis of device-related hazards or adverse events for the submission documents. 
10.2.7 EXAMPLES OF EXCLUDED MEASUREMENT 
The principle of exclusion is based on the failure event/period of Airmod or CapnostreamTM35 
reported by investigator. Events such as EtCO2 oversaturated period of CapnostreamTM35 or noises 
unable to be eliminated by the noise-cancelling technology and bias the respiratory rates. The report 
will be confirmed by the principal investigator, data apart from these events is still included. 
EtCO2 oversaturated period of CapnostreamTM35: 
 
*ORS: Operation start; EHV: Patient exhausting voice; EMF: CapnostreamTM35 failure determined by Investigator  
Noises unable to be eliminated by the noise-cancelling technology and bias the respiratory rates: 
 
*PAM: Patient movement; BDM: Sickbed movement start; FCV: Friction voice; BDE: Sickbed movement end; AAV: 
Abnormal acoustic sound produced by upper GI endoscope. 
 
10.3 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
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Minor fixed of description (no 
effect with study design) and 
added supplementary section 
(10.2). 
Found some description errors 
(no effect with study design). 
Meanwhile, give further 
information to complement 
the protocol. 

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