Identify the Epidural Space With EpiFaith Syringe in Air and Saline Based Procedures
Phase: NA
Conditions: Epidural Localization
Sponsor: Flat Medical Co., Ltd

Protocol no.: EPS01  
CONFIDENTIAL 
3.0/ March 15, 2019 
 
 
 
 
 
 
Identify the Epidural Space with EpiFaithTM Syringe in Air and Saline 
based Procedures 
 
 
 
Short Title: EpiFaithTM Syringe for Epidural Space Detection 
Indication: Epidural space localization 
Protocol Number: EPS01 
Version/Date: 3.0/ March 15, 2019 
Study Site: Taipei Veterans General Hospital 
Sponsor: Flat Medical Co., Ltd. 
 
 
 
 
This protocol is the confidential information of Flat Medical Co., Ltd. and is intended solely for the 
guidance of the clinical investigation. This protocol may not be disclosed to parties not associated 
with the clinical investigation or used for any purpose without the prior written consent of Flat 
Medical Co., Ltd. 
 
 

Protocol no.: EPS01  
CONFIDENTIAL 
3.0/ March 15, 2019 
 
 
 
Study Title: 
Identify the Epidural Space with EpiFaithTM Syringe in Air and Saline based Procedures 
Objective:  
Clinical Study Protocol 
 
 
I have read the protocol and agree to conduct this clinical study in accordance with all stipulations of 
the protocol, with applicable law and regulations and in accordance with the ethical principles outlined 
in the Declaration of Helsinki. 
 
 
Principal Investigator: 
 
 
Chien-Kun Ting, M.D., Ph. D.  
Taipei Veterans General Hospital 
Date 
 
 
 

Protocol no.: EPS01  
CONFIDENTIAL 
3.0/ March 15, 2019 
 
 
 
 
Study Title: 
Identify the Epidural Space with EpiFaithTM Syringe in Air and Saline based Procedures 
Objective:  
Clinical Study Protocol 
 
 
I have read the protocol and agree to conduct this clinical study in accordance with all stipulations of 
the protocol, with applicable law and regulations and in accordance with the ethical principles outlined 
in the Declaration of Helsinki. 
 
 
Sponsor: 
 
 
Flat Medical Co., Ltd. 
Date 

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SYNOPSIS 
I. Protocol Title:  
Identify the Epidural Space with EpiFaithTM Syringe in Air and Saline based Procedures. 
II. Objectives:  
The objective of the study is to verify the efficacies of both air and saline based procedure of 
EpiFaith syringe for assisting the needle localization of the epidural space. 
III. Test device:  
1. Name: EpiFaith syringe 
2. Manufacturer: Flat Medical Co., Ltd. 
3. Method of use: EpiFaith Syringe can provide a visual signal to assist anesthesiologists to 
localize the epidural space. 
4. Device category: Class II 
IV. Study design: 
1. ■ Controlled: 
■ Same device  
 
□ other:  
□ Uncontrolled 
2. Blinding 
□ Open label 
□ Evaluator blind 
■ Single blind 
 
□ Double blind      □ Double dummy □ Other 
3. Randomized:  
■ Yes 
□ No 
4. ■ Parallel 
□ Cross-over 
□ Other 
5. Duration of treatment:  30 minutes  
6. Titration:  
□ Forced 
□ Optional 
 ■ None 
7. 
 □ Multi-national     □ Multi-center (Taiwan)  
■ Single center  
V. Endpoints: 
1. Primary Endpoint(s): 
 
Success of epidural localization  
2. Secondary Endpoints 
 
Time to identify the epidural space  
 
Duration of the epidural space localization procedure 
 
Number of attempts 
 
Number of the occurrence of false positive 
 
The distance from the skin to the epidural space 
 
Number of change insertion segment 

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VI. Selection criteria:  
 Main Inclusion Criteria 
1. 
20 years and older 
2. 
Surgery requiring epidural anesthesia or analgesia 
3. 
ASA Physical Status 1 to 3 
 Exclusion Criteria 
1. 
Bleeding and clotting disorders 
 Platelet count < 100,000 / mm3 
 International normalized ratio (INR) > 1.5 
2. 
History of peripheral neuropathy 
3. 
Neuromuscular or neuropsychiatric disease 
4. 
Marked spinal deformities or a history of spinal instrumentation 
5. 
Systemic infection 
6. 
Skin infection at the injection site 
7. 
Significant heart failure, e.g. New York Heart Association (NYHA) Functional 
Classification 3 or 4 
VII. Study procedures:  
This is a single blind, randomized study. Subjects who will receive a surgery requiring epidural 
anesthesia or analgesia and meet all of the study criteria will be enrolled in the study. All subjects 
must sign an informed consent and receive a copy of the signed and dated informed consent form 
prior to participation in the trial.  
The study consists of 2 study visits: Visit 1 (Screening Visit) and Visit 2 (Operative Visit). After 
screening, eligible subject will be randomly assigned to one of the following groups: Group A: 
detection by EpiFaith syringe with air; Group S: detection by EpiFaith syringe with saline with a 
1:1 ratio. In Visit 2, the following variables will be recorded and rated during the process of 
epidural space localization: Success of epidural localization, time to identify the epidural space, 
duration of the epidural space localization procedure, number of attempts, Number of the 
occurrence of false positive, the distance from the skin to the epidural space, and number of change 
insertion segment. Adverse events and concomitant treatments will be also recorded. 
VIII. Concomitant therapy: 
1. Prohibited therapy: 
The following medications are prohibited within 5 days prior to epidural localization: 
 
Anti-coagulants (e.g., Warfarin, Heparin, Plavix)  
 
Antiplatelet 
2. All concomitant therapies related to epidural localization should be recorded, including AE 
treatment. 
IX. Statistics: 
1. Primary hypothesis:  
□ Superiority 
□ Non-inferiority 
 
□ Equivalence 
■ Other 
2. Sample size:  
 

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Considering the recommendation given by Lancaster, Dodd &Williamson. A total of 60 
subjects (30 subjects per group) will be required in this study to obtain parameters such as ratio, 
mean and standard deviation which will be used in a sample size calculation for the full-scale 
trial, and to estimate the rate of participants who drop out of the trial.  
3. Efficacy population:  
■ITT 
□PP 
□Other 
Safety population: 
□ITT 
□PP 
■Other  
4. Statistical method(s) for efficacy/safety evaluations: 
Statistical analyses will be reported using summary tables, graphs, and data listings. Analysis 
are performed with SPSS, Version 20.0 (IBM Corporation, Armonk, NY, USA). The analysis 
population will be summarized by A and S groups. For categorical variables, frequencies and 
percentages will be summarized; continuous data will be shown as descriptive statistics. The 
variables within a normal distribution will be compared using Student’s t-tests, and those 
without a normal distribution will be compared using the Mann-Whitney U test. The number 
of patients will be compared between the groups using the Fisher’s exact test. All information 
will be summarized and presented in statistical analysis tables. As for data of efficacy and safety 
variables, no imputation method is applied. 
Incidence of the adverse events will be summarized. In the case of CTCAE grade summaries, 
the most severe event will be presented in summary tables in the case of multiple occurrences 
per patient. The frequency and the percentage of each category will be presented. All safety 
parameters, including adverse events, adverse device effect, serious adverse event, serious 
adverse device effects and unanticipated adverse device effect will be listed by A and S groups. 
The Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary will be 
used to map verbatim adverse events to preferred terms and system organ class. Fisher’s exact 
test will be applied for comparing the incidences of adverse events between treatment groups. 
5. Planned interim analysis:  □Yes    ■No   
 
 
 

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X. Schedule of Assessments 
Procedures 
Screening(3) 
Operative period 
Visit 1 
Visit 2 
Informed Consent 
X 
 
Inclusion/Exclusion Criteria(1) 
X 
X 
Medical History 
X 
 
Demography 
X 
 
Physical Examination 
X 
 
Randomization 
 
X 
Epidural Space Localization Planning 
 
X 
Epidural Space Localization with Study Test 
Device 
 
X 
Concomitant Therapy 
 
X 
Adverse Events(2) 
 
X 
(1): For exclusion criteria #1, platelet count and INR in admission medical record are acceptable. 
(2): The AEs and SAEs will be recorded from the start to the end of epidural space localization. 
(3): All activities listed for the Screening Visit should be accomplished prior to those listed in the 
Operative Visit. 
 
 

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TABLE OF CONTENTS 
SYNOPSIS ............................................................................................................................................ 1 
TABLE OF CONTENTS .................................................................................................................... 5 
LIST OF ABBREVIATIONS ............................................................................................................. 8 
1. 
INTRODUCTION ......................................................................................................................... 9 
2. 
OBJECTIVE ................................................................................................................................ 10 
3. 
STUDY DESIGN......................................................................................................................... 10 
3.1. Overall Study Design ........................................................................................................... 10 
3.2. Study Population .................................................................................................................. 10 
3.2.1. Subject number ........................................................................................................ 10 
3.2.2. Inclusion criteria ...................................................................................................... 10 
3.2.3. Exclusion criteria ..................................................................................................... 11 
3.3. Withdrawal of Subjects from Therapy or Assessment ........................................................ 11 
3.4. Method of assigning subjects to treatment groups ............................................................... 11 
3.5. Blinding................................................................................................................................ 12 
3.6. Concomitant therapy ............................................................................................................ 12 
3.6.1. Components and Accessories .................................................................................. 13 
4. 
TEST DEVICE ............................................................................................................................ 13 
4.1. Detail of test device ............................................................................................................. 13 
4.1.1. Detail description of the principle of EpiFaith Syringe ........................................... 13 
4.1.2. Use direction ............................................................................................................ 15 
4.1.3. Associated consumables .......................................................................................... 17 
4.1.4. Biocompatibility Evaluation .................................................................................... 17 
4.2. Indication for Use ................................................................................................................ 17 
4.3. Packing and labeling ............................................................................................................ 18 
4.4. Handling and storage ........................................................................................................... 18 

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5. 
STUDY CONDUCT .................................................................................................................... 18 
5.1. Visit Schedule ...................................................................................................................... 18 
5.1.1. Schedules ................................................................................................................. 18 
5.1.2. Eligibility and inform consent ................................................................................. 19 
5.1.3. Visit 1 – Screening Visit .......................................................................................... 19 
5.1.4. Visit 2 – Operative Visit (End of Treatment/Study) ................................................ 19 
5.2. Procedures ............................................................................................................................ 20 
5.2.1. Informed Consent..................................................................................................... 20 
5.2.2. Eligibility ................................................................................................................. 20 
5.2.3. Demographic data and medical history.................................................................... 20 
5.2.4. Physical examination ............................................................................................... 22 
5.2.5. Epidural anaesthesia procedure ................................................................................ 22 
5.3. Data management................................................................................................................. 24 
5.3.1. Data Collection ........................................................................................................ 24 
5.3.2. Data Quality Assurance ........................................................................................... 24 
6. 
ADVERSE EVENTS ................................................................................................................... 25 
6.1. Adverse Events .................................................................................................................... 25 
6.1.1. Adverse Event (AE) ................................................................................................. 25 
6.1.2. Serious Adverse Event (SAE) .................................................................................. 25 
6.1.3. Severity of Adverse Events ...................................................................................... 27 
6.1.4. Associated with the Use of the Test Device ............................................................ 27 
6.1.5. Reporting Procedure ................................................................................................ 28 
7. 
STUDY ENDPOINTS ................................................................................................................. 29 
7.1. Primary Endpoint ................................................................................................................. 30 
7.2. Secondary Endpoint ............................................................................................................. 30 
8. 
STATISTICAL METHODS ........................................................................................................ 30 

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8.1. Planned sample size ............................................................................................................. 30 
8.2. Statistical Methods ............................................................................................................... 30 
9. 
ETHICAL AND LEGAL ASPECTS........................................................................................... 32 
9.1. Good Clinical Practice ......................................................................................................... 32 
9.2. Delegation of Investigator Responsibilities ......................................................................... 32 
9.3. Subject Information and Informed Consent ......................................................................... 33 
9.4. Subject rights and confidentiality ........................................................................................ 33 
9.4.1. Subject Confidentiality ............................................................................................ 33 
9.4.2. Study Discontinuation .............................................................................................. 33 
9.5. Protocol Amendments .......................................................................................................... 34 
9.6. Approval of the Study Protocol and Amendments .............................................................. 34 
9.7. Payment to Subjects/Families .............................................................................................. 35 
9.8. Publication policy ................................................................................................................ 35 
10. REFERENCES ............................................................................................................................ 36 
 

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LIST OF ABBREVIATIONS 
Abbreviations 
Terms and Definitions 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ARD 
Acute Respiratory Disease 
ASA 
American Society of Anesthesiologists 
CAD 
Coronary Artery Disease 
COPD 
Chronic Obstructive Pulmonary Disease 
CRA 
Clinical Research Associate 
CRF 
 
Case Report Form 
CVA 
Cerebrovascular Accident 
DIC  
Disseminated Intravascular Coagulation 
DM 
Diabetes Mellitus 
ES 
Epidural space 
ESRD 
End-stage renal disease 
GCP 
Good Clinical Practice 
HTN 
Hypertension 
ICH 
International Conference of Harmonisation  
LOR 
Loss of resistance 
MI 
Myocardial infarction 
PCA 
Post Conceptional Age 
SDE 
Serious Adverse Event 
TIA 
Transient Ischemic Attack 
 

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1. INTRODUCTION 
Locating the epidural space is an indispensable part of obstetrical analgesia, surgical anesthesia, 
postoperative analgesia, and chronic pain control. 
The traditional method of locating the position of the needle tip is loss of resistance technique (i.e., the
“LOR”), which is based on detecting the pressure drop occurring at the moment the needle tip 
reaching the epidural space. Because the pressure of the epidural space is lower than the cavities of 
others tissue, a free injection of air or liquid from the syringe can be induced, resulting in a sudden 
loss of resistance of the plunger. Thus, the anesthesiologist can detect the pressure drop by feeling the 
resistance of pushing the plunger of the attached syringe. 
The epidural space is a very thin area near the spinal cord. The advance of needle must be stopped 
right after the needle tip reaches the epidural space to prevent accidental dural puncture, which may 
lead to cerebrospinal fluid leakage followed by intractable headache and injuries of the spinal nerves. 
However, the current incidence rates of accidental dural punctures are 0.19-3.6%1. 
Using the LOR hand feeling to locate epidural space relies on manual skill of the operator and the 
considerable experiences. Choosing air or saline for LOR technique depends on personal experiences 
of the operator. The variety of LOR techniques has increased the difficulty of learning2. 
Some objective and confirmatory devices based on LOR technique are developed, such as Episure and 
Epidrum, and have been discuss under clinical trial3-5. The results show a lower failure rate and a 
shorter time needed to identify the epidural space. However, the restriction of the media and the 
actuating pressure selection will deprive the anesthesiologists’ habit.    
The EpiFaith syringe is an improved LOR device with the ability to warn and help physicians to 
achieve the safe insertion is required. EpiFaith syringe provides objective, and quantitative pressure 
information as well as a visual signal which is triggered at the moment the needle tip enters the epidural 
space. Hence, the anesthesiologist can get a clear endpoint for the advancing of the needle easily. The 
advantages of EpiFaith syringe including that the anesthesiologist can control the epidural needle with 
both hands and achieve the real- time pressure detection. 
The trial quantity of EpiFaith syringe were finished, as well as the biocompatibility testing to ISO 
10993, the connector testing to ISO80369-7, epidural simulated testing on ex-vivo and in-vivo porcine 
spine were performed. Results of testing demonstrate that the EpiFaith syringe meets its performance 
specifications and is safe and effective for its intended use. 

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The aim of this study is to evaluate using the EpiFaith syringe with two different sensing medians for 
epidural localization. The hypothesis of the study is that EpiFaith syringe can detect LOR of epidural 
space effectively with its achievable pressure. It is beneficial to both junior and senior physicians by 
transforming the process into a safe and convenient procedure. 
2. OBJECTIVE 
The objective of the study is to verify the efficacies of both air and saline based procedure of 
EpiFaith syringe for assisting the needle localization of the epidural space. 
3. STUDY DESIGN 
3.1. Overall Study Design 
This is a single blind, randomized study. Subjects who will receive a surgery requiring combined spinal 
-epidural technique and meet all of the study criteria will be enrolled in the study. All subjects must 
sign an informed consent and receive a copy of the signed and dated informed consent form prior to 
participation in the trial.  
The study consists of 2 study visits: Visit 1 (Screening Visit) and Visit 2 (Operative Visit). After 
screening, eligible subject will be randomly assigned to one of the following groups: Group A: 
detection by EpiFaith syringe with air, or Group S: detection by EpiFaith syringe with saline with a 
1:1 ratio. In Visit 2, the following variables will be recorded and rated during the process of epidural 
space localization: Success of epidural localization, time to identify the epidural space, duration of the 
epidural space localization procedure, number of attempts, Number of the occurrence of false positive, 
the distance from the skin to the epidural space, and number of change insertion segment. Adverse 
events and concomitant treatments will be also recorded. 
3.2. Study Population 
3.2.1. Subject number 
Recruitment will stop when approximately 60 subjects are included.  
3.2.2. Inclusion criteria 
Subjects meeting all of the following criteria will be considered for enrollment into the study: 
1. 
20 years and older  

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2. 
Surgery requiring epidural anesthesia or analgesia 
3. 
ASA Physical Status 1 to 3 
3.2.3. Exclusion criteria 
Subjects who meet any of the following criteria will be not enrolled in the study: 
1. 
Bleeding and clotting disorders 
 
Platelet count < 100,000 / mm3 
 
International normalized ratio (INR) > 1.5 
2. 
History of peripheral neuropathy 
3. 
Neuromuscular or neuropsychiatric disease 
4. 
Marked spinal deformities or a history of spinal instrumentation 
5. 
Systemic infection 
6. 
Skin infection at the injection site 
7. 
Significant heart failure, e.g. New York Heart Association (NYHA) Functional 
Classification 3 or 4 
3.3. Withdrawal of Subjects from Therapy or Assessment 
Each subject has the right to withdraw study at any time. In addition, the investigator may terminate a 
subject's participation from the study at any time if the investigator considers it necessary for any 
reason including: 
 Consent withdrawn 
The reasons for withdrawal will be recorded in the CRF.  
3.4. Method of Assigning Subjects to Treatment Groups 
Subjects will be randomized to one of the two groups (A group – EpiFaith syringe with air or S group 
– EpiFaith syringe with saline) at the ratio of 1:1. The randomization method will result in sealed, 
opaque envelopes containing the computer- generated, random assignment. Randomization will occur 
in blocks so that blocks of equal numbers of subjects will be used to avoid potential runs of 
assignments. The randomization code will be generated specifically for each center. 
Screening number will be assigned once subject signed the inform consent. Only eligible subjects at 
Visit 2 will receive a randomization number at randomization. The subject will receive the 

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corresponding test devices assigned in the randomization envelope according to the randomization 
number. The number will be maintained by the investigator throughout the study. For any reason that 
a subject withdraws from the study prematurely after the randomization, his/her randomization number 
will not be reused. The next eligible subject will receive the lowest available randomization number. 
3.5. Blinding 
In order to eliminate a potential for bias, all subjects will be blinded to their treatment assignment. The 
investigator and research staffs will not know the randomization assignment at the time of subject 
enrollment to ensure that they do not accidentally notify the patient of their assignment until anesthesia. 
At Visit 2, the investigator will be informed of the randomized treatment assignment from 
randomization envelops. Subjects will remain blinded to their treatment assignment during study 
period. 
The treatment codes are not to be prematurely broken to subjects unless an emergency situation, when 
the appropriate management of the subject necessitated acknowledge of the treatment allocation 
occurs. In such cases, the sponsor will be notified immediately, and the date, time, and the reason for 
breaking the blind as well as the individual who breaks the code must be documented. 
3.6. Concomitant Therapy 
(1) Prohibited therapy: 
The following medications are prohibited within 5 days prior to epidural localization: 
 
Anti-coagulants (e.g., Warfarin, Heparin, Plavix)  
 
Antiplatelet 
(2) All concomitant therapies related to epidural space localization procedure, including AE 
treatment, should be recorded.  
(3) Preoperative fasting is mandatory to reduce the risk of aspiration at least 6-8 hours prior to 
anesthesia, including solid and liquid food. Prescribed medications which be allowed by 
investigator should be to taken with a sip of water less than two hours prior to anesthesia unless 
otherwise directed. 

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4. TEST DEVICE 
4.1. Detail of Test Device 
4.1.1. Components and accessories 
The schematic views of EpiFaith Syringe are shown in Figure 1. The components are listed in Table 
1. 
 
Figure 1. The schematic view of the EpiFaith Syringe with Luer slip connector. 
 
Figure 2. Explosion drawing of EpiFaith syringe 
 
Table 1.  Parts of EpiFaith Syringe 

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Parts of EpiFaith Syringe 
Plunger 
Spring 
Indicator 
Color ring 
Fixator 
Low friction rubber 
Syringe barrel 
The indicator, combined with a low friction rubber and a color ring, is connected to the plunger that 
allowing relatively co-axial movement of the two parts. The spring is placed inside the two parts. 
Decreasing the distance between the indicator and the plunger will compress the pre-load spring, as 
shown in Figure 2, leading to a spring force delivered to both indicator and the plunger. The relative 
position of the two parts is a result of force balance between the spring force and the pressure in the 
syringe, as principle described later. A fixator is attached to the plunger to increase the friction force 
between the plunger and the syringe barrel. The friction force can help to hold the position of the 
plunger without being moved by the spring force. 
4.1.2. Detail description of the principle of EpiFaith Syringe 
EpiFaith Syringe is based on the LOR technique, which means the visual signal is triggered by the 
pressure change occurring at the moment the needle tip arrives the epidural space. 
EpiFaith Syringe should be connected to a 16-18 gauge epidural needle to locate the epidural space. 
After the needle is inserted to an appropriate depth and the stylet is removed, the EpiFaith Syringe can 
be connected to it. The initial pressure is induced by pushing the plunger and the fixator can hold the 
position of the plunger to maintain the pressure.  
The spring is compressed due to the initial pressure and constantly delivers force to the content in the 
syringe (sensing material such as air or normal saline). Because of the spring force, the ejection of the 
sensing material will happen when the LOR occurring, resulting in the movement of the low friction 
rubber. It provides a visual signal to warn the anesthesiologists that the LOR has happened, which 
implies that the needle tip has arrives the epidural space. The parameters of the EpiFaith Syringe can 
be found in Figure 3. 
For more detail please see the demo video: https://tinyurl.com/y8serflu 

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Figure 3. The different states of EpiFaith Syringe. (a) The indicator is fully protruded and the spring 
is released. (b)&(c) The spring is compressed and the indicator is covered by the plunger. The fixator 
can help to maintain the position of the rear plunger. Therefore, even though the spring constantly 
applies a spring force on both indicator and the plunger, the plunger will not be pushed back.  
4.1.3. Use direction  
All of the steps are performed under sterile conditions. The directions of using EpiFaith Syringe are 
shown in Figure 4.  

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Figure 4. The use direction of EpiFaith Syringe 

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4.1.4. Associated consumables 
Kit 
Portex CSE Minipack 
 
Figure 5. The associated consumables of this study 
4.1.5. Biocompatibility evaluation 
Based on the recommended biocompatibility testing addressed in FDA guidance “Use of International 
Standard ISO-10993”, Biological Evaluation of Medical Device part 1: Evaluation and Testing”, the 
following biological effect shall be evaluated: 
 
ISO10993-4 Selection of tests for interactions with blood 
 
ISO10993-5 Tests for in vitro cytotoxicity 
 
ISO10993-7 Ethylene oxide sterilization residuals 
 
ISO10993-10 Tests for irritation and skin sensitization 
 
ISO10993-11 Tests for systemic toxicity(acute systemic toxicity) 
 
USP<85> Bacterial endotoxins teat 
4.2. Indication for Use 
EpiFaith Syringe is intended for use with an epidural needle for detecting a loss of resistance, 
which aids a clinician in verifying needle tip placement in the epidural space. 

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4.3. Packing and Labeling 
Packaging: Flat Medical Co., Ltd. will carry out the preparation, packaging and distribution of the 
test devices.  
Labeling: All test devices will must also be labeled "for use in clinical trials only" and be supplied in 
identical package with the protocol number, randomization number, expiration dates, the name of the 
sponsor, and information sufficient to identify the trial site and research personnel involved. 
4.4. Handling and Storage 
The test devices will be handled by the investigator or the designated pharmacist for management and 
dispensation. All supplies for this study should be kept under adequate security and storage conditions.  
5. STUDY CONDUCT 
5.1. Visit Schedule 
5.1.1. Schedules  
The following table details the study schedule of procedures: 
Table 2. Schedule of Assessments 
Procedures 
Screening(3) 
Operative period 
Visit 1 
Visit 2 
Informed Consent 
X 
 
Inclusion/Exclusion Criteria(1) 
X 
X 
Medical History 
X 
 
Demography 
X 
 
Physical Examination 
X 
 
Randomization 
 
X 
Epidural Space Localization Planning 
 
X 
Epidural Space Localization with Study Test 
Device 
 
X 
Concomitant Therapy 
 
X 
Adverse Events(2) 
 
X 
(1): For exclusion criteria #1, platelet count and INR in admission medical record are acceptable. 
(2): The AEs and SAEs will be recorded from the start to the end of epidural space localization. 
(3): All activities listed for the Screening Visit should be accomplished prior to those listed in the 
Operative Visit. 

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5.1.2. Eligibility and inform consent 
Subjects will be screened prior to the start of the study treatment. All assessments will be performed 
after the subjects have signed and dated the inform consent form. 
The investigator or a designee will explain the nature of the study to subjects who will undergo surgery 
requiring epidural space localization. The subject will be given an informed consent form to be read 
carefully before agreeing to take part in the study and before the study-specific procedures take place. 
The informed consent form should be reviewed, signed, and dated by the subject and counter-signed 
by the investigator. A copy of the statement will be given to the subject, and the original should be 
maintained by the investigator in the site master file. After informed consent being obtained, designed 
procedures and assessments will be initiated to determine eligibility. 
5.1.3. Visit 1 – Screening Visit 
After a subject has signed the informed consent document, he or she will be enrolled after screening 
for selection criteria. The following assessments should be evaluated at this visit: 
 Sign informed consent.  
 Check subject’s eligibility: inclusion and exclusion criteria.  
 Collect significant medical history and ASA physical status.  
 Collect demographic data. 
 Conduct physical exam: At enrollment, it should be also recorded a complete physical exam, 
height, and weight.  
5.1.4. Visit 2 – Operative Visit (End of Treatment/Study) 
All activities listed for the Screening Visit should be accomplished prior to those listed in the Operative 
Visit. The following assessments should be evaluated in operative Visit: 
 Check subject’s eligibility: exclusion #5 should be excluded. Platelet count, INR, and skin 
infection at injection site must be re-checked before epidural space localization. 
 Randomization and assign randomization number. 
 Decide the procedure of epidural space localization. 
 Measure all designated outcomes of epidural space localization as following: 
 
Success of epidural localization   
 
Time to identify the epidural space  
 
Duration of the epidural space localization procedure 
 
Number of attempts 
 
Number of the occurrence of false positive 

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 
The distance from the skin to the epidural space 
 
Number of change insertion segment 
 Record concomitant therapy. 
 Record adverse events, if AEs occur. 
5.2. Procedures 
5.2.1. Informed consent 
The subjects must personally sign and date the latest approved version of the informed consent form 
before any study specific procedures are performed. 
Written versions of the subject information and informed consent will be presented to the subjects 
detailing no less than: the exact nature of the study; the implications and constraints of the protocol; 
the known side effects and any risks involved in taking part.  It will be clearly stated that the subject 
is free to withdraw from the study at any time for any reason without prejudice to future care, and with 
no obligation to give the reason for withdrawal.  
The subject will be allowed as much time as wished to consider the information, and the opportunity 
to question to decide whether they will participate in the study.  Written informed consent will then be 
obtained by means of subject dated signature and dated signature of the person who presented and 
obtained the informed consent. The person who obtained the consent must be suitably qualified and 
experienced, and have been authorized to do so by the principal investigator. A copy of the signed 
informed consent will be given to the subjects.  The original signed form will be retained at the study 
site. 
5.2.2. Eligibility 
Eligibility will be evaluated at Visit 1 and Visit 2. Subjects must meet all of the inclusion and none of 
the exclusion criteria to be considered eligible for the study. 
5.2.3. Demographic data and medical history 
Demographic data and medical history will be collected.  
The significant medical history should be recorded, including chronic diseases, allergic history, and 
surgical history. The medical history will be tracked back for 3 months prior to surgery. The ASA 
physical status should be also noted. 

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5.2.3.1. ASA physical status classification system 
The ASA physical status classification system (October 15, 2014) is a system for assessing the fitness 
of patients before surgery. 
Table 3. The ASA Physical Status Classification System  
ASA PS Classification 
Definition 
Examples, including, but not limited to: 
ASA I 
A normal healthy patient 
Healthy, non-smoking, no or minimal alcohol 
use 
ASA II 
A patient with mild 
systemic disease 
Mild diseases only without substantive 
functional limitations. Examples include (but 
not limited to): current smoker, social alcohol 
drinker, pregnancy, obesity (30 < BMI < 40), 
well-controlled DM/HTN, mild lung disease 
ASA III 
A patient with severe 
systemic disease 
Substantive functional limitations; One or more 
moderate to severe diseases. Examples include 
(but not limited to): poorly controlled DM or 
HTN, COPD, morbid obesity (BMI ≥40), active 
hepatitis, alcohol dependence or abuse, 
implanted pacemaker, moderate reduction of 
ejection fraction, ESRD undergoing regularly 
scheduled dialysis, premature infant PCA < 60 
weeks, history (>3 months) of MI, CVA, TIA, 
or CAD/stents. 
ASA IV 
A patient with severe 
systemic disease that is a 
constant threat to life 
Examples include (but not limited to): recent ( < 
3 months) MI, CVA, TIA, or CAD/stents, 
ongoing cardiac ischemia or severe valve 
dysfunction, severe reduction of ejection 
fraction, sepsis, DIC, ARD or ESRD not 
undergoing regularly scheduled dialysis 
ASA V 
A moribund patient who is 
not expected to survive 
without the operation 
Examples include (but not limited to): ruptured 
abdominal/thoracic aneurysm, massive trauma, 
intracranial bleed with mass effect, ischemic 
bowel in the face of significant cardiac 
pathology or multiple organ/system dysfunction 
ASA VI 
A declared brain-dead 
patient whose organs are 
being removed for donor 
purposes 
  
The addition of “E” to the ASAPS (e.g., ASA 2E) denotes an emergency surgical procedure. The ASA defines an emergency as existing 
“when the delay in treatment of the patient would lead to a significant increase in the threat to life or body part.” 
Abbreviations used: ASA: American Society of Anesthesiologists, DM: diabetes mellitus; HTN: hypertension; COPD: chronic 
obstructive pulmonary disease; ESRD: end-stage renal disease; PCA: post conceptional age; MI: myocardial infarction; CVA: 
cerebrovascular accident; TIA: transient ischemic attack; CAD: coronary artery disease; DIC: disseminated intravascular coagulation; 
ARD: acute respiratory disease. 

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5.2.4. Physical examination 
A complete physical examination will be performed at the screening visit, including the examination 
of general appearance, skin, cardiovascular, pulmonary, abdomen, neurological system and 
musculoskeletal/joints. Height and weight will be also collected at Visit 1.  
5.2.5. Epidural space localization procedure 
Subjects will undergo the surgical procedure using epidural space localization in a medical center with 
appropriate facilities and by appropriately trained personnel. 
Epidural space localization planning will be completed before the epidural space localization. The plan 
should be recorded, and the records should include surgery name, insertion segment. 
During epidural space localization, the subject are in the lateral position. After cleaning and draping 
the area, a local anesthetic is infiltrated at the insertion site of epidural needle.  
Anesthesiologist inserted the epidural needle at least 3cm to pass the subcutaneous tissue. Pull out the 
stylet and attach the filled EpiFaith syringe. In Group A, the EpiFaith syringe is filled with air; in 
Group S, the EpiFaith syringe is filled with saline. Then, push the plunger to create a continuous 
pressure inside the syringe. When the needle arrived the epidural space, due to LOR occurred, the 
piston of EpiFaith syringe will move forward. The clear visual signal can warn the operator the 
localization of needle tip.  After the detection of LOR, the catheter will be inserted though the 
needle. When the catheter can protrude from the needle tip at least 3cm, which can be identified 
by the graduations on its surface, the test dose (2 ml of 2% lidocaine) of anesthetic will be 
injected. After  injection for 15min, the cold sensation test will be performed, by comparing the 
perception of cold of alcohol sponges between the blocked dermatomes and face. The tests will 
be bilaterally, and repeated 3 times in 3 difference dermatomes on each side. 
If the visual signal occurs but the catheter cannot be inserted to protrude the needle tip at least 
3 cm, which means the false positive occurs.  
If the catheter is inserted successfully and the test dose of anesthetic is injected, but the result of 
cold sensation test shows the perception of cold exists in the blocked dermatomes by cold 
sensation test and exclude the reason is due to dose and drug failure, which also means the false 
positive occurs.  

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If the inadvertent dural puncture occurs, the success of epidural localization will be recorded 
failed. There is no necessary to record all secondary outcome. The physician can use the 
traditional LOR syringe or other method to compete the procedure.   
The process of epidural space localization will be simultaneously recorded by video. 
5.2.5.1. The duration and attempt of epidural localization  
The designated assessments of duration and attempt of epidural space localization are defined as 
below:  
 
Success of epidural localization is defined as the catheter can be inserted into epidural space 
successfully, no cold perception in the blocked dermatomes after the injection of anesthetic 
by cold sensation test, and no occurrence of inadvertent dural puncture. 
 
The time to identify the epidural space is defined as the time of the successful localization from 
the syringe attached to the Tuohy needle to the occurrence of LOR signal. 
 
Duration of the epidural space localization procedure is defined as the time from the first 
puncture of skin to the successful insertion of the epidural catheter. 
 
Number of attempts is defined as a new puncture of the skin. 
 
Number of the occurrence of false positive is defined as the insertion of the epidural catheter is 
unsuccessful or the perception of cold exists in the blocked dermatomes after the injection 
of anesthetic by cold sensation test. 
 
The distance from the skin to the epidural space. 
 
Number of change insertion segment 
 
 
Fig. 6. The definition of the outcome measurement of this study 

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5.3. Data Management  
5.3.1. Data collection 
Source documents are original documents, data, and records from which subjects’ CRF data are 
obtained. All documents will be stored safely in confidential conditions. On all study-specific 
documents, other than the signed consent, the subject will be referred to by the study screening and 
randomization number/code, not by name. 
Designated investigator staff must enter the information required by the protocol onto the Case Report 
Forms (CRFs) that are printed on 3-part, non-carbon required paper. Field monitors will review the 
CRFs for completeness and accuracy, and instruct site personnel to make any required corrections or 
additions. The CRFs are forwarded to the Medical Documents Reception Center of sponsor or a 
Contract Research Organization (CRO) by field monitors or by the investigational site, one copy being 
retained at the investigational site. Once the CRFs are received by sponsor or the CRO, their receipt is 
recorded, the original copy is placed in Central Files and the non-carbon required copy is forwarded 
to the responsible medical data management staff for processing. All CRFs sent to sponsor or the CRO 
by investigational sites are reviewed upon receipt for any serious adverse events. 
5.3.2. Data quality assurance 
Data items from the CRFs will be entered into the study database. Subsequently, Data Management 
staff, using error messages printed from validation programs and database listings, will systematically 
check the information entered into the database. The data manager will correct obvious errors. Other 
errors or omissions will be sent electronically to the CRA via a Clarification Form to be reconciled 
with the investigational site. The CRA will obtain the resolution and submit the Clarification Form 
back to Data Management where the updates will be made to the database. A copy of the Data 
Clarification Form with the corrected entry will then be printed and sent back to the CRA to obtain the 
appropriate signatures from the site. The signed Clarification Form will be sent back to Data 
Management to be filed with the original CRFs. Quality control audits of all key safety and efficacy 
data in the database will be made after entering data from each visit. 
When the database has been declared to be complete and accurate, the database will be locked. Any 
changes to the database after that time can only be made by joint written agreement between the 
Clinical Trial Leader, the Trial Statistician and the Data Manager. 
If requested, the investigator is to provide to the sponsor, applicable regulatory agencies, and/or 
applicable ethical review boards, direct access to original source documents. The sponsor or its 

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representatives will periodically check a sample of the recorded subject data against source documents 
at the study site. 
6. ADVERSE EVENTS 
6.1. Adverse Events 
6.1.1. Adverse event (AE) 
An AE or adverse event is: 
Any untoward medical occurrence in a patient or other clinical investigation subject taking part in a 
trial of a medical device, which does not necessarily have to have a causal relationship with the device 
under investigation.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the use of the device, whether or not 
considered related to the device. 
6.1.1.1. Adverse device effect (ADE) 
All untoward and unintended responses to the medical device.  
The phrase "responses to a medical device" means that a causal relationship between the device under 
investigation and an AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or the sponsor as having a 
reasonable suspected causal relationship to the device qualifies as a device effect.   
This also includes any event resulting from insufficiencies or inadequacies in the instruction for use or 
deployment of the device and includes any event that is a result of a user error. 
All AEs will be reported from the start of epidural space localization to the end of epidural space 
localization. 
6.1.2. Serious adverse event (SAE) 
 
Led to death  
 
Led to fetal distress, fetal death or congenital abnormality or birth defect.  
 
Led to serious deterioration in the health of the subject that  
 
Resulted in a life-threatening illness or injury 

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NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
subject is at risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it are more severe. 
 
Resulted in a permanent impairment of a body structure or a body function  
 
Required in-patient hospitalization or prolongation of existing hospitalization  
 
Resulted in medical or surgical intervention to prevent permanent impairment to a body 
structure or a body function  
 
Other important medical events* 
*Other events that may not result in death, are not life threatening, or do not require hospitalization, 
may be considered a serious adverse event when, based upon appropriate medical judgement, the 
event may jeopardize the patient and may require medical or surgical intervention to prevent one of 
the outcomes listed above 
To ensure no confusion or misunderstanding of the difference between the terms "serious" and 
"severe", which are not synonymous, the following note of clarification is provided: 
The term "severe" is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache).  This is not the same as "serious," which is based on 
patient/event outcome or action criteria usually associated with events that pose a threat to a subject's 
life or functioning.  Seriousness (not severity) serves as a guide for defining regulatory reporting 
obligations. 
All SAEs will be reported from the start of epidural space localization to the end of epidural space 
localization. 
6.1.2.1. Serious adverse device effects (SADE) 
A serious adverse device effect (SADE) is any untoward medical occurrence seen in a patient that can 
be attributed wholly or partly to the device which resulted in any of the characteristics or led to a 
characteristics of a serious adverse event.  
SADE is also any event that may have led to these consequences if suitable action had not been taken 
or intervention had not been made or if circumstances has been less opportune.  
All cases judged by either the reporting medically qualified professional or the sponsor. 

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6.1.2.2. Unanticipated adverse device effect (UADE) 
Any serious adverse device effect on health or safety or any life-threatening problem or death caused 
by, or associated with a device, if that effect, problem, or death was not previously identified in nature, 
severity or degree of incidence in the investigational plan or application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with a device that related 
to the rights, safety or welfare of the subject. 
6.1.3. Severity of adverse events  
The grade refers to the severity of the AE using CTCAE Version 4.03 (published on June 14, 2010). 
The CTCAE displays Grade 1 to 5 with unique clinical descriptions of severity for each AE as shown 
in below: 
Table 4. Grading scales of AEs 
Grades of AEs 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL* 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, 
limiting self-care ADL** 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
* 
Instrumental activities of diary living (ADL) refer to preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc. 
** 
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medication, 
and not bedridden. 
6.1.4. Associated with the use of the test device  
An adverse event is considered associated with the use of the device if the attribution is certain, 
probably/likely, possible, or unlikely by the definitions listed as follows. The causal relationship 
between AEs and study device refers to WHO-UMC system for standardized case causality 
assessment.  
 
 

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Table 5. Causality categories between AEs and study device 
Causality term 
Assessment criteria* 
Certain 
 
Event or laboratory test abnormality, with plausible time relationship 
to study device use 
 
Cannot be explained by disease or other medical interventions 
 
Response to withdrawal plausible (pathologically) 
 
Event definitive phenomenologically (i.e. an objective and specific 
medical disorder or a recognized phenomenon) 
 
Rechallenge satisfactory, if necessary 
Probable / Likely 
 
Event or laboratory test abnormality, with reasonable time relationship 
to study device use 
 
Unlikely to be attributed to disease or other medical interventions 
 
Response to withdrawal clinically reasonable 
 
Rechallenge not required 
Possible 
 
Event or laboratory test abnormality, with reasonable time relationship 
to study device use 
 
Could also be explained by disease or other medical interventions 
 
Information on withdrawal may be lacking or unclear 
Unlikely 
 
Event or laboratory test abnormality, with a time to study device use  
that makes a relationship improbable (but not impossible) 
 
Disease or other medical interventions provide plausible explanations 
* All points should be reasonably conformed. 
6.1.5. Reporting procedure 
6.1.5.1. Adverse event (AE) 
All AE’s occurring during the study observed by the investigator or reported by the subject, whether 
or not attributed to the device under investigation will be recorded on the CRF as specified in the 
protocol. All ADE’s will be recorded in the CRF.  
The following information will be recorded: description, date of onset and end date, severity, 
assessment of relatedness to device, other suspect drug or device and action taken. Follow-up 
information should be provided as necessary.  
The relationship of AEs to the device will be assessed by a medically qualified investigator or the 
sponsor/manufacturer and will be followed up until resolution or the event is considered stable.  
All ADEs that result in a subject’s withdrawal from the study or are present at the end of the study, 
should be followed up until a satisfactory resolution occurs. 
6.1.5.2. Serious adverse reaction  
As any SAE occurs, regardless of relationship with the procedure or the device, the investigational 
staff must inform sponsor or its delegate of their knowledge of the event by email, fax or telephone, 
and shall provide detailed, written reports as soon as possible.  

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Information regarding serious adverse events will be transmitted to the sponsor using the Serious 
Adverse Event Form, which must be signed by a member of the investigational staff.  The initial report 
of a serious adverse event may be made by email, and facsimile (fax).  In addition, the SAE may also 
be forwarded to the TFDA by the sponsor within the appropriate time frame as follows: 
If an adverse event results in death or is life-threatening, an SAE should be reported to TFDA within 
7 days after becoming aware of the event, and shall provide detailed written documents within 15 days 
after awareness. If an adverse event results in hospitalization, prolonged hospitalization, 
disability/incapacity, is a congenital anomaly/birth defect, or requires medical and/or surgical 
intervention, an SAE should be reported to TFDA within 15 days and provide detailed written 
document after awareness. Any SAE should be reported promptly according to the reporting procedure 
of each IRB(s). 
6.1.6. Managements of AE 
The using of EpiFaith syringe will not change the managements of AEs.  
Table 6. The managements of common AEs related the procedure of epidural localization. 
AEs 
Treatments 
Post puncture headache 
Supporting treatment such as rehydration, simple 
analgesics, opioids and anti‐emetics may control the 
symptoms in milder cases. Generally, >85% of 
headaches after lumbar puncture will resolve 
without any specific treatment. Depending on the 
severity of the headache, prolonged hospital stay for 
better care and procedure such as blood patch may 
be required.  
Accidental intravascular 
catheter placement 
The intravascular catheter can either be withdrawn 
(1 cm at a time then flushed with saline and 
aspirated) until no more blood is be aspirated, or it 
can be totally removed and replaced. 
Accidental subarachnoid 
catheter placement 
The risk of inadvertently administering an epidural 
dose intrathecally. The headache may occur, and 
prolong hospital stay for better care and procedure 
such as blood patch may be required.  
Bleed at needle entry area 
Clean the puncture area with sterile protocol. 
6.2. Data Safety Monitoring Plan 
An Independent safety monitor (anesthesiologist) will call for terminating the study early if more 
than 5 subjects experience inadvertent dural puncture.  

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7. STUDY ENDPOINTS 
7.1. Primary Endpoint 
 
Success of epidural localization  
(defined as the catheter can be inserted into epidural space successfully, no cold perception 
in the blocked dermatomes after the injection of anesthetic by cold sensation test, and no 
occurrence of inadvertent dural puncture.)  
7.2. Secondary Endpoint 
(1) The time to identify the epidural space (defined as the time of the successful localization from 
the first syringe attached to the Tuohy needle to the occurrence of LOR signal) 
(2) Duration of the epidural space localization procedure 
(defined as the time from the puncture of skin to the successful insertion of the epidural 
catheter) 
(3) Number of attempts  
(defined as a new puncture of the skin) 
(4) Number of the occurrence of false positive 
(defined as the insertion of the epidural catheter is unsuccessful or the perception of cold 
exists in the blocked dermatomes after the injection of anesthetic by cold sensation test ) 
(5) The distance from the skin to the epidural space 
(6) Number of change insertion segment 
8. STATISTICAL METHODS 
8.1. Planned Sample Size 
Considering the recommendation given by Lancaster, Dodd &Williamson. A total of 60 subjects (30 
subjects per group) will be required in this study to obtain parameters such as ratio, mean and standard 
deviation which will be used in a sample size calculation for the full-scale trial, and to estimate the 
rate of participants who drop out of the trial. 
8.2. Analysis Population 
Intent-to-Treat (ITT) Population: The ITT will consist of all participants who are randomly assigned 

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to receive study device and have received any study device, irrespective of their protocol adherence. 
All analyses using the ITT will group participants according to randomized treatment. The ITT will be 
used as the efficacy analysis set. 
Safety Set: The safety set will consist of all participants who received any study device. All analyses 
using the safety set will group participants according to treatment actually received. 
8.3. Demographics and Other Baseline Characteristics 
Demographics and other baseline characteristics will be summarized by descriptive statistics for two 
treatment groups. For continuous variables, the number, mean, standard deviation, median, minimum, 
and maximum values will be presented. A two sample independent t-test will be performed for 
continuous variables. For categorical variables, the numbers and percentages of subjects in each class 
will be listed, and the Fisher’s exact test for testing two treatment group comparison. 
8.4. Efficacy Assessment 
Statistical analyses will be reported using summary tables, graphs, and data listings. Analysis are 
performed with SPSS, Version 20.0 (IBM Corporation, Armonk, NY, USA). The analysis population 
will be summarized by A and S groups. For categorical variables, frequencies and percentages will be 
summarized; continuous data will be shown as descriptive statistics. The variables within a normal 
distribution will be compared using Student’s t-tests, and those without a normal distribution will be 
compared using the Mann-Whitney U test. The number of patients will be compared between the 
groups using the Fisher’s exact test. All information will be summarized and presented in statistical 
analysis tables. As for data of efficacy and safety variables, no imputation method is applied. 
8.4.1. Analysis of primary endpoint 
The primary endpoint is the success of epidural localization. The primary analysis will be conducted 
by Fisher’s exact test.  
8.4.2. Analysis of secondary endpoints 
Student’s t-test or Mann-Whitney U-test will be applied to test the comparison between A and S 
Groups for the time to identify the epidural space, duration of the epidural space localization procedure, 
the distance from the skin to the epidural space, and the distance from the needle tip to dura. 
Number of attempts, number of the occurrence of false positive, and number of change insertion 
segment will be compared between A and S groups using Fisher’s exact test. 

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8.5. Safety Assessment 
Incidence of the adverse events will be summarized. In the case of CTCAE grade summaries, the most 
severe event will be presented in summary tables in the case of multiple occurrences per patient. The 
frequency and the percentage of each category will be presented. All safety parameters, including 
adverse events, adverse device effect, serious adverse event, serious adverse device effects and 
unanticipated adverse device effect will be listed by A and S groups. The Medical Dictionary for 
Regulatory Activities (MedDRA) adverse event dictionary will be used to map verbatim adverse 
events to preferred terms and system organ class. Fisher’s exact test will be applied for comparing the 
incidences of adverse events between treatment groups. 
9. ETHICAL AND LEGAL ASPECTS 
9.1. Good Clinical Practice 
This study must be carried out in compliance with the protocol and in accordance with sponsor/CRO 
standard operating procedures. These are designed to ensure adherence to Good Clinical Practice, as 
described in the following documents: 
1. 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice 2016. 
2. 
Declaration of Helsinki, concerning medical research in humans (Recommendations Guiding 
Physicians in Biomedical Research Involving Human Subjects, Helsinki 1964, amended Tokyo 
1975, Venice 1983, Hong Kong 1989, Somerset West 1996, Edinburgh, 2000, Washington 2002, 
Tokyo 2004, Seoul 2008, Fortaleza 2013). 
The investigator agrees, when signing the protocol, to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of Good Clinical Practice that it conforms to. 
9.2. Delegation of Investigator Responsibilities 
Responsibilities of the investigators conducting the study in addition to those stated before are 
enumerated below: 
 
Obtain Institutional Review Board (IRB) approval to conduct the clinical study. 
 
Provide sponsor with written documentation that the study protocol, any protocol amendments, 
and the informed consent form have received IRB approval. 
 
Provide sponsor with a list of IRB members, including their affiliations and qualifications. As an 
alternative, a General Assurance number (as assigned by the Department of Health and Human 
Services) fulfills this requirement. 

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 
Report to the IRB as required. The IRB must assume continued responsibility for the study and 
review the research on an annual basis.  
 
Maintain a file of all communications with the IRB on issues related to the clinical trial. 
 
Conduct the study according to the protocol, ICH - GCP guidelines and in accordance with the 
Declaration of Helsinki. 
9.3. Subject Information and Informed Consent 
Written informed consent must be obtained from all subjects prior to study participation. The informed 
consent form documents the information the investigator provides to the subject and the subject’s 
agreement to participate. The investigator will fully explain the nature of the study, along with the 
aims, methods, anticipated benefits, potential hazards, and discomfort that participation might entail. 
The informed consent must be signed and dated by each subject or legal representative before entering 
the study and prior to the performance of any study specific procedures. 
Investigational site must provide the sponsor (or designee) with a copy of the informed consent 
approved by that site’s Institutional Review Board (IRB), or Ethics Committee (EC). The subject or 
the subject’s legally authorized representative must sign the informed consent form. The original 
signed consent form will be retained in the subject’s study records, and a copy will be provided to the 
subject. The sponsor will assure that each informed consent meets the basic elements of informed 
consent. 
9.4. Subject Rights and Confidentiality 
9.4.1. Subject confidentiality 
The trial staff will ensure that the subjects’ anonymity is maintained.  The subjects will be identified 
only by initials and a subjects ID number on the CRF and any electronic database.  All documents will 
be stored securely and only accessible by trial staff and authorized personnel. The study will comply 
with the Data Protection Act 1998 which requires data to be anonymized as soon as it is practical to 
do so. 
9.4.2. Study discontinuation 
The study may be discontinued at any time by the IRB, the TFDA, or other government agencies as 
part of their duties to ensure that research subjects are protected. 

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9.5. Protocol Amendments 
The investigator is responsible for properly notifying the sponsor of protocol changes or revisions. The 
investigators without prior written authorization from the sponsor may make no changes to this 
protocol. 
9.6. Approval of the Study Protocol and Amendments 
Before the start of the study, the study protocol, informed consent document, and any other appropriate 
documents will be submitted to the independent ethics committee (IEC)/institutional review board 
(IRB) with a cover letter or a form listing the documents submitted, their dates of issue, and the site 
(or region or area of jurisdiction, as applicable) for which approval is sought. If applicable, the 
documents will also be submitted to the authorities, in accordance with local legal requirements. 
Test device can only be supplied to the investigator after the sponsor has received documentation on 
all ethical and legal requirements for starting the study. This documentation must also include a list of 
the members of the IEC/IRB and their occupations and qualifications. If the IEC/IRB will not disclose 
the names of the committee members, it should be asked to issue a statement confirming that the 
composition of the committee is in accordance with GCP. The IRB General Assurance Number may 
be accepted as a substitute for this list. Formal approval by the IEC/IRB should preferably mention the 
study title, study code, study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision is made and must be officially 
signed by a committee member. 
Before the first subject is enrolled in the study, all ethical and legal requirements must be met. 
The IEC/IRB and, if applicable, the authorities must be informed of all subsequent protocol 
amendments, in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the informed consent document should 
also be revised. 
The investigator must keep a record of all communication with the IEC/IRB and, if applicable, between 
a coordinating investigator and the IEC/IRB. This also applies to any communication between the 
investigator (or the coordinating investigator, if applicable) and the authorities. 

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9.7. Payment to Subjects/Families 
There will be no costs to subjects for any research related activities. All research-related costs 
will be paid by sponsor- Flat Medical Co., Ltd.(醫盟科技). If subjects do not finish the study, 
they will not be paid.  
9.8. Publication policy 
The results from this clinical trial will be published in the journal of Anesthesia & Analgesia. 

Protocol no.: EPS01  
CONFIDENTIAL 
3.0/ March 15, 2019 
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10. REFERENCES 
(1) C. M. Gleeson FR. Accidental dural puncture rates in UK obstetric practice. Inrernationol Journal 
of Obstetric Anesthesrn. 1998:242-246. 
(2) Antibas PL, do Nascimento Junior P, Braz LG, Vitor Pereira Doles J, Modolo NS, El Dib R. Air 
versus saline in the loss of resistance technique for identification of the epidural space. Cochrane 
Database Syst Rev. Jul 18 2014(7):CD008938. 
(3) Kartal, S., Kilinç, H., Muslu, B., Karabayirli, S., & Kösem, B. (2015). Comparison of the Use of 
Epidrum® with Air or Saline for Identifying the Epidural Space. Enliven: J Anesthesiol Crit Care 
Med, 2(6), 018. 
(4) Sawada A, Kii N, Yoshikawa Y, Yamakage M. Epidrum®: a new device to identify the epidural 
space with an epidural Tuohy needle. J Anesth. Apr 2012;26(2):292-295. 
(5) Riley ET, Carvalho B. The Episure syringe: a novel loss of resistance syringe for locating the 
epidural space. Anesth Analg. Oct 2007;105(4):1164-1166.