Safety and Effectiveness Evaluation of the Sinusway™ Device for Endoscopy of the Nasal Cavity and Paranasal Sinuses in Conjunction With Sinus Balloon Dilation
Phase: NA
Conditions: Sinusitis
Sponsor: 3NT Medical Ltd.

 
3NT Medical - Confidential 
 
Page 1 of 29 
 
 
 
 
 
 
 
Title of the study: Safety and Effectiveness Evaluation of the 
Sinusway™ Device for Endoscopy of the Nasal Cavity and 
Paranasal Sinuses in Conjunction with Sinus Balloon Dilation 
NCT No. : NCT03390257 
Date of document: July 3rd, 2017 

 
3NT Medical - Confidential 
 
Page 2 of 29 
 
 
 
 
Clinical Protocol 
 
Version Date 
July 3rd, 2017 
Amendment No. 
1 
Protocol Number 
SD-001  
Protocol Title 
Safety and Effectiveness Evaluation of the Sinusway™ Device for 
Endoscopy of the Nasal Cavity and Paranasal Sinuses in 
Conjunction with Sinus Balloon Dilation 
 
 
Approvals: 
Site 
Sponsor 
 
 ______________________________________  
Principal Investigator                            Date
Signature 
 
______________________________ 
Hadas Weiss                               Date   
CT & RA Manager 
3NT MEDICAL 
 

 
3NT Medical - Confidential 
 
Page 3 of 29 
 
 
 
A Feasibility study to Evaluate the Safety and Initial Effectiveness of the Sinusway™ Device for 
Endoscopy of the Nasal Cavity and Paranasal Sinuses in Conjunction with Sinus Balloon Dilation 
 
 
 
 The Indications for Use claim for this system is –  
The 3NT endoscopy system is intended to visualize the internal cavities of the ear, airways, nose and 
sinus cavities during diagnostic and therapeutic endoscope procedures.  
 
Protocol Number: 
SD-001 
Date: 
July 3, 2017 
 
 
3NT Medical 
22 Hamelacha St., POB 11384, 
 Rosh Ha’ayin, 4809169 
 Israel 
 

 
3NT Medical - Confidential 
 
Page 4 of 29 
 
 
 
Table of Content 
1 
LIST OF ABBREVIATIONS .......................................................................................................... 6 
2 
SYNOPSIS ......................................................................................................................................... 7 
3 
BACKGROUND ............................................................................................................................... 9 
3.1 
Nasal Endoscopy .....................................................................................................................................9 
3.2 
Functional Endoscopic Sinus Surgery (FESS) and Balloon Sinus Dilation (BSD) ..........................10 
3.3 
The Sinusway Device ............................................................................................................................10 
3.4 
Clinical Experience with Sinusway ......................................................................................................13 
4 
OBJECTIVES .................................................................................................................................. 13 
4.1 
Safety assessment ..................................................................................................................................13 
4.2 
Performance assessment .......................................................................................................................13 
4.3 
Study End Points ...................................................................................................................................14 
5 
DESCRIPTION OF PATIENT POPULATION ............................................................................ 14 
5.1 
Patient Selection ....................................................................................................................................14 
5.2 
Subject Enrollment ...............................................................................................................................14 
5.3 
Inclusion Criteria ..................................................................................................................................15 
5.4 
Exclusion Criteria .................................................................................................................................15 
6 
INVESTIGATION PLAN ................................................................................................................ 15 
6.1 
Study Design ..........................................................................................................................................15 
6.2 
Study Procedures ..................................................................................................................................16 
6.3 
Methods and Timing for assessments ..................................................................................................17 
7 
STATISTICAL CONSIDERATIONS AND SAMPLE SIZE ......................................................... 19 
Statistical Considerations ..................................................................................................................................19 
Sample Size .........................................................................................................................................................19 
8 
RISK ANALYSIS ............................................................................................................................. 19 
8.1 
Potential risks – (Sinusway): ................................................................................................................19 
8.2 
Definitions of Adverse Device Events and Adverse Events ...............................................................21 
8.3 
Definitions of Serious Adverse Device Effects and device deficiencies .............................................22 
8.4 
Unanticipated Serious Adverse Device Effect (USADE) ...................................................................23 
8.5 
Adverse Effects and Precautions .........................................................................................................23 
8.6 
Adverse Event Reporting .....................................................................................................................23 
9 
DATA MANAGEMENT .................................................................................................................. 24 

 
3NT Medical - Confidential 
 
Page 5 of 29 
 
 
 
10 MONITORING PLAN ..................................................................................................................... 24 
11 INVESTIGATOR RESPONSIBILITIES ..................................................................................... 25 
12 AMENDMENTS TO THE PROTOCOL ..................................................................................... 25 
13 DEVIATION FROM THE STUDY PLAN .................................................................................. 25 
14 DEVICE ACCOUNTABILITY ..................................................................................................... 26 
15 VULNERABLE POPULATION ................................................................................................... 26 
16 SUBJECT CONFIDENTIALITY ................................................................................................. 26 
17 SUBJECT WITHDRAWAL OR DISCONTINUATION ........................................................... 26 
18 SUSPENSION OR PREMATURE TERMINATION OF THE STUDY................................... 26 
19 PUBLICATION POLICY .............................................................................................................. 27 
20 REFRENCES .................................................................................................................................. 27 
21 APPENDICES ................................................................................................................................. 28 
 

 
3NT Medical - Confidential 
 
Page 6 of 29 
 
 
 
1 LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
CRF 
Case Report Form 
CV 
Curriculum Vitae 
EC 
Ethic Committee 
ENT 
Ear Nose and Throat 
ID 
Identification 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedures 
RS 
Rhinosinusitis 
CRS 
Chronic Rhinosinusitis 
FESS 
BSD 
EC 
IRB 
Functional Endoscopic Sinus Surgery 
Balloon Sinus Dilation 
Ethics Committee 
Institutional Review Board 
 
 

 
3NT Medical - Confidential 
 
Page 7 of 29 
 
 
 
2 SYNOPSIS 
Protocol 
Number 
SD-001 
Protocol Title 
Safety and Effectiveness Evaluation of the Sinusway™ Device for Endoscopy of the 
Nasal Cavity and Paranasal Sinuses in Conjunction with Sinus Balloon Dilation 
Participating 
Countries 
USA 
Clinical Phase 
Open, multi - center, prospective, feasibility study 
Investigational 
Study Device  
Sinusway™, a flexible, steerable endoscope, by 3NT Medical Ltd. 
Study 
Procedures 
 
Up to 15 Patients scheduled for sinus balloon dilation will be examined with 
Sinusway™ before and as part of balloon sinus dilation in the operation room (OR) 
or office setting (Office). The patients will attend the following: 
1. Visit 1: Screening and Enrollment, as part of pre-operative visit 
2. Visit 2: Sinusway evaluation at the time of the procedure 
Study 
Population 
15 adult patients, male or female, scheduled for Sinus Balloon Dilation. 
Study Purpose 
To assess the safety and initial performance of Sinusway™ in patients in terms of 
access and visualization of the nasal anatomy and paranasal sinuses, usability (alone 
and in conjunction with balloon dilation instruments), visualization quality, and 
irrigation.
Study Endpoints
Primary – Safety Endpoints:  
 
Device related adverse events  
 
Secondary – Performance Endpoints: 
 
To evaluate the ability to access and visualize the nasal anatomy including the 
maxillary, frontal, and sphenoid sinuses. 
 
To evaluate usability by filling a user questionnaire 
 
To evaluate irrigation of the nasal anatomy
Inclusion/ 
Exclusion 
Criteria 
Inclusion Criteria: 
1. Male or female patient indicated for balloon sinus dilation procedure by the 
ENT specialist 
2. Patient age: adult (>18 years old) 
3. Patients in general good health in the opinion of the investigator as determined 
by medical history and physical examination

 
3NT Medical - Confidential 
 
Page 8 of 29 
 
 
 
4. A patient who is able to understand the requirements of the study, is willing to 
comply with its instructions and schedules, and agrees to sign the informed 
consent 
 
Exclusion Criteria: 
1. Known history of any significant medical disorder, which in the investigator’s 
judgment contraindicates the patient's participation 
2. Patients with known current or previous bleeding disorder receiving 
anticoagulants (e.g., chronic Coumadin treatment) 
Study Duration 
Per Patient: between 1 day and 30 days, depending on the interval between pre-
operative visit (inclusion) and day  
of procedure. 
Total 10 months to recruit and treat 15 patients. 
Statistical 
Analysis Plan 
NA 
 

 
3NT Medical - Confidential 
 
Page 9 of 29 
 
 
 
 
3 BACKGROUND  
3.1 
 Nasal Endoscopy  
The paranasal sinuses are 4 pairs of air-filled bony spaces that surround the nasal cavity and are 
lined with mucous membrane densely covered with cilia that facilitates mucociliary clearance and 
drainage into the nasal cavity. Infection of sinuses, or rhinosinusitis (RS), is caused when 
mucociliary functionality is compromised and/or the sinus ostia is compromised causing the 
sinuses to become congested and eventually blocked. RS is a severely debilitating quality of life 
condition, which is characterized by throbbing headaches and facial pressure, purulent nasal 
discharge, and nasal obstruction. Chronic rhinosinusitis (CRS) is a chronic disease that involves 
long-term inflammation of the nasal and paranasal sinus mucosa with a minimum duration of 12 
weeks. CRS causes not only physical suffering, but also impacts psychological wellbeing and 
daily functioning.  CRS is an extremely common condition, affecting 29.2 million (14.2%) US 
adults. 
Nasal endoscopy is the most important diagnostic tool currently available to otolaryngologists to 
diagnose sino-nasal disorders [1]. Current endoscopes perform well at allowing otolaryngologists 
to evaluate the nasal cavity. When anatomy is favorable, endoscopes also visualize regions 
externally adjacent to the sinus ostia, but do not allow visualization, culture, or lavage of the sinus 
cavity without extensive prior surgical opening.   
The endpoints of nasal endoscopy include the ability to diagnose the patient’s condition and obtain 
a nasal culture that has some correlation with the sinus cavity contents [2]. The limitations include 
the inability to steer into or around narrow anatomy, to obtain an intra-sinus culture, and to 
visualize the sinus cavity.  
A CT scan is required when diagnosing chronic sino-nasal disorders like CRS. A CT scan 
provides information as to whether the sinus is clear or opacified, but is often limited in providing 
information as to what is opacifying the sinus cavity [3]. Most importantly, CT scan is associated 
with radiation exposure harmful to the patient and should be avoided if possible.  
Sinusway, a flexible, steerable endoscope, overcomes current technological limitations by 
providing sinus visualization, and irrigation. Sinusway does not pose any risk additional to the 
minor risks already associated with current sino-nasal endoscopy; furthermore, the risks of 
bleeding, pain are reduced due to the flexibility and small profile of the device which minimizes 
contact with the anatomy.  The risk of infection is eliminated as the intra-nasal component of the 
device is a one-time single use disposable and does not require re-sterilization between patients. 

 
3NT Medical - Confidential 
 
Page 10 of 29 
 
 
 
3.2 
Functional Endoscopic Sinus Surgery (FESS) and Balloon Sinus Dilation (BSD) 
The objective of FESS is to open the natural pathways to the sinuses. Once an improved drainage 
system is achieved, the diseased sinus mucosa has an opportunity to return to normal. FESS 
involves the insertion of endoscope into the nose for a direct visual examination of the openings 
into the sinuses.  Diseased or obstructive sinus tissue may be removed resulting in improved 
natural sinus drainage. 
There are several sinus surgery options that can be performed in a hospital operating room or 
doctor’s office. Balloon sinus dilation (BSD) is a minimally invasive surgery that can be 
performed in both settings. A small balloon is inserted into the nose; once in the right spot, it is 
inflated to open and drain blocked sinus pathways. The goal of balloon sinus surgery is to unblock 
sinus pathways and improve symptoms, reduce infections, minimize sinus headaches and restore 
quality of life. When performed in the doctor's office, it offers faster recovery times and may allow 
eligible patients to have a lower out-of-pocket cost. 
3.3 
The Sinusway Device 
Sinusway, developed by 3NT Medical, is a single-use disposable handheld endoscope 2.3mm in 
diameter that provides a means to visualize the internal cavities of the ear, airways, nose and sinus 
cavities during diagnostic and therapeutic endoscope procedures.  
An ENT specialist may use the device in an operating room (OR) or an office setting, for 
visualization and for irrigation at anatomic landmarks, including the sinuses cavities, currently 
inaccessible by existing endoscopes without significant surgical resection of bone and tissue.  
3NT endoscopy system (See figure 1 below) includes: 
1. A Multi-use handle accessory (re-processible and auto-clavable) – engages the single-use 
endoscope component and allows the user to mechanically control its articulation through 
dedicated levers. (see Figure 1, Reusable Handle) 
2. A Single-use flexible endoscope (provided sterile) – includes a distal tip CMOS imager and an 
integrated working channel which allows irrigation through a single channel. It is the only part that 
comes in contact with the patient and is disposed of at the end of the procedure. (see Figure 2, 
Disposable Endoscope). 
3. A Camera control unit (CCU) – includes a video processor and a white LED light source. The 
CCU includes an attachment cable which connects to the single-use endoscope, receives video 
images from the endoscope, and delivers LED light to the endoscope. 
 

 
3NT Medical - Confidential 
 
Page 11 of 29 
 
 
 
 
Figure 1 - Reusable Handle 
 
 
 
 
 
Figure 2 - Disposable Endoscope  
 
The Sinusway endoscope contains an articulation mechanism that supports angulation of 125˚ and 
advancement of the insertion tube over the angulated section and beyond it, effectively keeping the 
angulated section stationary with respect to the anatomy (See Figure 3). 

 
3NT Medical - Confidential 
 
Page 12 of 29 
 
 
 
 
 
 
 
 
 
 
Figure 3 Angulation and advancement of the flexible endoscope 
 
 
 
Figure 4 Assembled Endoscope 
 
When used in conjunction with a commercially available balloon dilation device, the Sinusway may 
facilitate minimally invasive endoscopic sinus surgery with less post-operative nasal bleeding, faster 
recovery time, shorter duration of prescription medication use and short term symptom improvement 
than traditional FESS. [4] 

 
3NT Medical - Confidential 
 
Page 13 of 29 
 
 
 
3.4 
Clinical Experience with Sinusway 
3NT Medical is currently conducting a clinical study in Belgium and Israel to assess the safety and 
initial performance of Sinusway. The study evaluates the ability of the endoscope to access and 
visualize the nasal anatomy and paranasal sinuses, the endoscope usability, visualization quality, 
and irrigation in patients undergoing FESS surgery.  
The Sinusway endoscope was evaluated during eleven (11) functional endoscopic sinus surgeries 
(FESS) occurring in the operating room under general anesthesia. Six (6) cases were performed in 
two sites in Israel: Assuta M.C.(3) and Rabin M.C.(3).  Five cases were performed at the 
University of Ghent, Belgium. Mean Subject age was 44.3 Years [23-60 yrs], 6 males, 5 females. 
No major technical issues were observed during the operation of the system. No adverse event 
reported. Device operation and physician feedback were satisfactory. 
4 OBJECTIVES 
The objective of this study is to assess the safety and initial performance of Sinusway in patients in 
terms of access and visualization of the nasal anatomy and paranasal sinuses, usability (alone and in 
conjunction with balloon dilation instruments), visualization quality, and irrigation. 
For this study, up to 15 patients scheduled for sinus balloon dilation will be examined with Sinusway 
before and as part of balloon dilation in the operation room (OR) or office setting (Office). Additional 
endoscopes as available in the procedure room and as commonly used by the ENT specialist may be 
used. 
4.1 
Safety assessment  
Safety assessment will be based upon monitoring the adverse device effects, which will be collected 
throughout the procedure. 
All adverse events and serious adverse events will be reported in accordance with reviewing Ethics 
Committee /Institutional Review Board (IRB), FDA and Competent authority requirements. 
4.2 
Performance assessment 
1. Ability to access the nasal anatomy and paranasal sinuses: Ability to access and visualize 
anatomic landmarks, including the maxillary, frontal and sphenoid sinuses, will be recorded. 
Successful access will be confirmed by direct visualization and transillumination where 
applicable. 
 
2. Usability evaluation 
 
3. Irrigation evaluation  
4. Nasal cavity and sinuses inflammation evaluation  

 
3NT Medical - Confidential 
 
Page 14 of 29 
 
 
 
 
5. Patient pain score and tolerability, when applicable  
4.3 
Study End Points 
 
Primary - Safety 
All adverse device effects will be captured and summarized as defined in Section-8.  Adverse device 
effects (type, frequency, severity) are expected to be similar to those reported in literature for Nasal 
Endoscopy (section 8).  
For this study, the Safety comparison with the data of Nasal Endoscopy reported in literature will be 
descriptive with no statistical endpoints.   
 
Secondary - Performance 
 
To evaluate the ability to access and visualize the nasal anatomy including the maxillary, 
frontal, and sphenoid sinuses (according to physician discretion).  This ability will be verified 
by observing anatomic landmarks and transillumination (as Done/Not Done/Failed). 
 
 
To evaluate usability and user satisfaction-  by filling a usability questionnaire regarding the 
device, including assessment of visualization quality. Will be completed by the user 
 
 
Other Measurement – Performance 
 
To evaluate irrigation of the nasal anatomy (as Done/Not Done, which sinus was irrigated) 
 
To evaluate nasal cavity inflammation and sinuses inflammation using Lund Mackay CT score 
and Lund Kennedy Endoscopic scoring 
 
Patient tolerability and Pain assessment will be recorded by a 0-10 scale (when applicable) 
 
 
5 DESCRIPTION OF PATIENT POPULATION    
5.1 
Patient Selection   
Patients indicated for balloon sinus dilation procedure by the ENT specialist. 
5.2 
Subject Enrollment 
a)  
Patients who appear to be eligible will be asked if they would like to participate in this study.  
b) 
Written informed consent will be obtained from each participating patient prior to collecting a 
patient history or other testing. The patient will be counseled concerning the research nature of this 
study, and the risks and possible benefits to participation. Participation is fully voluntary.  

 
3NT Medical - Confidential 
 
Page 15 of 29 
 
 
 
5.3 
Inclusion Criteria 
1. Male or female patient indicated for balloon sinus dilation procedure by the ENT specialist 
2. Patient age: adult (>18 years old) 
3. Patients in general good health in the opinion of the investigator as determined by medical 
history and physical examination 
4. A patient who is able to understand the requirements of the study, is willing to comply with its 
instructions and schedules, and agrees to sign the informed consent 
5.4 
Exclusion Criteria 
1. Known history of any significant medical disorder, which in the investigator’s judgment 
contraindicates the patient's participation 
2. Patients with known current or previous bleeding disorder receiving anticoagulants (e.g., chronic 
Coumadin treatment) 
6 INVESTIGATION PLAN 
6.1 
Study Design 
 
Type of Study 
This is an open, multi-center, prospective, feasibility study in which the investigational device, the 
Sinusway, will be tested in a single group of adult patients, male or females. 
The rationale behind this feasibility study is to show that access and visualization of the nasal anatomy 
and paranasal sinuses (Maxillary, Frontal and Sphenoid sinuses) in conjunction with Balloon Sinus 
Dilation in patients suffering from symptoms attributable to sinusitis is feasible in the office and 
operating room settings; This is an essential step in the development of a combined dilation and 
visualization system that will allow visualization, dilation and lavage of the sinuses via their  natural 
ostia during an office visit, and minimize radiation exposure, antibiotic use, multiple office visits, and 
cost. 
This study is proposed after completing a series of clinical cases, which demonstrated that the system is 
safe and performed well to physician's satisfaction (detailed information on the studies is provided in the 
Investigator’s Brochure). 

 
3NT Medical - Confidential 
 
Page 16 of 29 
 
 
 
 
Measures to Minimize Bias 
No control groups and no randomization will be utilized in this study since its primary objectives are to 
obtain information on safety, tolerability and usability which may serve as a basis for modification (if 
required) and future controlled studies. 
6.2 
Study Procedures 
 
Visits 1: Screening 
 Screening will take place within 1 day-30 days before the procedure. 
 Patients potentially qualifying for the study will be offered an Informed Consent to sign prior to 
further evaluation.   Any patients not qualifying will be exited from the study as screening 
failures and will not be included in the safety/effectiveness analyses.   
 The following screening assessments will be performed at pre-study for each patient: 
- Medical history (including concomitant medications) 
- Sino-Nasal outcome test (SNOT-20)  
- Vital signs (optional) 
- CT 
- Laboratory blood work within 6 months including Hematocrit, White Blood Cells , PT, PTT, 
INR, Creatinine and Glucose (optional, only if done prior to surgery) 
- Compliance with inclusion/exclusion criteria  
- Patients found eligible to participate in the study in the initial screening will be scheduled to 
undergo the Sinusway evaluation. 
 
 
 
Visit 2: Procedure and Study Termination 
 
Before the procedure: 
- Eligible subject/s will attend the Medical Center at the day of procedure and will be inquired by 
the PI regarding changes to their health status since the screening visit. If at this point it is 
determined that the patient does not meet all Inclusion and Exclusion criteria and cannot be 
treated, the patient will be exited from the study.  These patients will be considered screening 
failures, and will not be included in any of the safety or efficacy endpoint analyses.   
 
Endoscopy: 
1. Patients may undergo BSD under local anesthesia, intravenous sedation and local anesthesia or 
under general anesthesia, at physician discretion.  
2. The Sinusway device will be prepared for use per its instructions for use. 
 
3. Evaluation of the patient with physician’s typical rigid endoscope(s). Visualization of the 
sinuses (frontal, maxillary, sphenoid) will be recorded as performed/failed and an Image of the 
anatomic landmark will be taken.  

 
3NT Medical - Confidential 
 
Page 17 of 29 
 
 
 
4. Following the Evaluation with physician’s typical rigid endoscope(s) the evaluation will be 
repeated using the Sinusway endoscope. Access to the sinuses (frontal, maxillary, sphenoid) 
will be recorded as performed/failed and an Image of the anatomic landmark will be taken. 
Nasal Cavity and sinuses inflammation score will be captured using the Lund Mackay CT and 
endoscopy score. 
5. BSD procedure will be performed with either endoscope.  
6. Irrigation of the nasal anatomy will be performed and recorded as Done/Not Done and which 
sinus was irrigated. 
7. Following the BSD procedure, repeated evaluation of patient's sinuses and nasal cavity will be 
performed using the Sinusway endoscope 
8. Usability assessment will be completed by physician. 
9. If applicable, patient pain assessment using a 0-10 pain Scale and patient tolerability will be 
captured (Office procedures only) 
 
After the procedure: 
- The patient will recover from the procedure per physician’s common practice. Before patient's 
release, recording of AE, if any, will be performed. Patient will exit the study. 
6.3 
Methods and Timing for assessments 
Schedules of assessments are listed in Table No. 1 below. 

 
3NT Medical - Confidential 
 
Page 18 of 29 
 
 
 
 
Table 1: Study visit schedule 
Study Activities 
Session I:  
Screening and Inclusion V-1 
 
Session II: 
Procedure V-2 
Within 30 days post screening 
Informed Consent
x
Demographic Data 
x
Medical History 
x
SNOT 20
x
Concomitant medication
x
Physical Examination 
x
Laboratory test (Optional as 
commonly done for BSD)
x 
 
Vital Signs (optional)
x
Inclusion/exclusion criteria
x
CT scan (as commonly done for 
BSD)
x 
 
Lund Mackay/Kennedy 
inflammation score
x 
x 
Endoscopy with Sinusway and 
Commercially Available 
Endoscope
 
x 
Balloon sinus dilation Followed 
by Sinusway Endoscopy 
 
x 
User questionnaire 
x
Patient tolerability and pain 
score 
 
x 
AEs/SAEs
x
Patient Exit
 
x
 

 
3NT Medical - Confidential 
 
Page 19 of 29 
 
 
 
7 STATISTICAL CONSIDERATIONS AND SAMPLE SIZE 
Statistical Considerations 
No statistical analysis will be used as this is a feasibility safety study. 
Sample Size 
Up to Fifteen (15) patients are expected to complete the study at all sites 
8 RISK ANALYSIS 
Risk analysis for The Sinusway device has been conducted as part of FDA 510k submission (K162916).  
This risk analysis is applicable to the proposed clinical investigation.  The potential risks described 
below will be explained to the subject in the informed consent process. 
8.1 
Potential risks – (Sinusway): 
Endoscopy is a minimally invasive, diagnostic medical procedure.   Overall, nasal endoscopy is a safe 
and low risk procedure. Nonetheless, potential complications such as mucosal trauma and bleeding may 
occur, particularly in susceptible patients with increased risk of bleeding, such as those receiving aspirin 
or other anticoagulant medications (i.e. Plavix, Coumadin, etc.). In addition, adverse reactions to the 
topical decongestants or anesthetic provided prior to the procedure may occur.  
Since the Sinusway endoscope will be used in conjunction with balloon sinus dilation, the following 
risks which are associated with BSD and/or endoscopic sinus surgery are presented. 
Risk associated with Endoscopic Sinus Surgery  
Surgeons performing routine endoscopic interventions are faced with minor complications in 5% and 
major complications in 0.5–1% [21] 
 
Infection-  A patient with sinusitis is at risk of developing infection (abscesses, meningitis, etc.) 
Infection risk increases with the invasiveness of the intervention. The rate of intracranial infections 
where the intervention is maximized is 1.6% and the rate of infection-related mortality is 0.125%. 
It is comparable to the one of transcranial surgeries not involving the use of an endoscope [5,6,7]. 
The Risk of Infection following Sinusway use is mitigated since the Sinusway endoscope is a 
disposable intended for single use only.   
 
Bleeding- Bleeding may occur, particularly in susceptible patients with increased risk of bleeding, 
such as those receiving aspirin or other anticoagulant medications (i.e. Plavix, Coumadin, etc.) 
[20]. The rate of peri- or postoperative bleeding is around 2% altogether; transfusions were 
required in about 0.2% of cases [8,9]. 

 
3NT Medical - Confidential 
 
Page 20 of 29 
 
 
 
 
Nasomucosal injury- Nasomucosal injury may occur during transnasal endoscopy. Nasomucosal 
injury was assessed in 1569 patient that underwent unsedated transnasal 
esophagogastroduodenoscopy (EGD), at termination of the procedure. Normal mucosa was 
observed in 68% of cases, redness of mucosa was observed in 19% of cases, oozing hemorrhage 
was observed in 12% of cases and overt bleeding was observed in 2% of cases. The hemorrhage 
was self-limiting and no patient required nasopharyngeal treatment [10].  
 
CSF leakage - Small and isolated CSF fistulas, which are treated at once successfully, are 
considered as minor complication in sinus surgeries [11]. These particular incidents are not rare – 
in a survey, 25% of American otorhinolaryngologists had experienced at least one unexpected 
CSF fistula intraoperatively during endoscopic sinus surgeries within 5 years [12]. The rate of 
unexpected dura exposure is reported with a percentage of 0.2% [8]. The number of minimal, 
temporary and occult leakage of cerebrospinal fluid ceasing spontaneously without clinical 
relevance, is significantly higher [13]. Once a small cerebrospinal fluid leak is confirmed, 
references recommend conservative treatment to begin with [12, 14, 15, 16]. In a few cases lumbar 
drainage was solely carried out [17]. However, in case of a persisting leak encountered during 
routine sinus surgeries or e.g. after rhino-neurosurgical procedures, surgical treatment should be 
pursued even with small defects.  
 
Orbital hematoma -  The incidence of orbital hematomas is around 0.1% in all procedures [18, 19]. 
Visual loss and blindness have been reported but are extremely rare. Another uncommon problem 
is damage to the muscles that move the eye, leading to double vision, which can be temporary or 
permanent. In certain circumstances, there may be a change in the function of the tear ducts 
causing excessive tearing. Since the eye is in close proximity to the sinuses, a major orbital 
complication or blindness could possibly occur even without surgery for patients with severe or 
refractory sinus infections. 
 
Voice changes - One of the functions of the sinuses is to affect resonance, therefore, there is a 
potential change in the voice after sinus surgery. 
 
Impaired sense of taste or smell - The sense of smell usually improves after the procedure because 
airflow is restored, although in sporadic cases it could worsen depending on the extent of swelling, 
infection, or allergy. This impairment is often temporary but can be prolonged. 
 
Nasal obstruction, dryness and pain - Although preventative measures are performed by the 
surgeon at the time of procedure, the cartilage may move after the surgery which may rarely lead 
to persistent blockage. Surgery typically improves airflow, but in some patients, it may not 
improve or rarely may worsen. Small scar bands may also occur in the nose and require removal 
by the surgeon at postoperative visits. Over-aggressive resection of the turbinate structures may 
leave some patients with the sensation of being overly dry or even cause chronic pain. 
 
 Adverse reactions to the topical decongestants or anesthetic provided prior to the procedure may 
occur. Thus, before administering these topical medications, patients’ allergies should be verified 

 
3NT Medical - Confidential 
 
Page 21 of 29 
 
 
 
8.2 
Definitions of Adverse Device Events and Adverse Events 
 
Adverse Device Effect (ADE) 
 
An "Adverse Device Effect" is an adverse event related to the use of an investigational medical 
device.  
 
This includes any adverse event resulting from insufficiencies or inadequacies in the instructions 
for use, the deployment, the implantation, the installation, the operation, or any malfunction of 
the investigational medical device. 
 
This includes any event that is a result of a use error or intentional misuse. 
 
"Adverse Events" are defined as any untoward medical occurrence, unintended disease or injury 
or any untoward clinical signs (including an abnormal laboratory finding) in subjects, users or 
other persons whether or not related to the investigational medical device. 
 
This includes events related to the investigational device. 
 
This includes events related to the procedures involved (any procedure in the clinical 
investigation plan). 
 
For users or other persons this is restricted to events related to the investigational medical device. 
 
All Adverse device effects must be recorded in the CRF. A description of the event, including 
the start date, resolution date, action taken, and the outcome should be provided. 
 
All adverse events will be graded for severity as follows: 
Grade 
Degree 
Description 
1 
Mild 
Symptom(s) barely noticeable to patient or does not make patient uncomfortable; 
does not influence performance or functioning; prescription drug not ordinarily 
needed for relief of symptom(s) but may be given because of personality of patient.
2 
Moderate 
Symptom(s) of a sufficient severity to make patient uncomfortable; performance of 
daily activity is influenced; patient is able to continue in study; treatment for 
symptom(s) may be needed.
3 
Severe 
Cause severe discomfort; symptoms cause incapacitation or significant impact on 
patient’s daily life; severity may cause cessation of treatment with study device; 
treatment for symptom(s) may be given and/or patient hospitalized.
4 
Life-threatening 
May result in death if not promptly treated and reversed. 
5 
Fatal 
Results in death 
 
Relationship -whether or not the test procedure/device caused the adverse event 
 
Degree 
Description 
Definitely 
There is evidence of exposure to the test procedure/device , the AE is most likely to be 
explained by the test procedure / device than by another cause; the challenge is 
positive; rechallenge (if feasible) is positive; the AE shows a pattern consistent with 
previous knowledge of the test procedure / device.

 
3NT Medical - Confidential 
 
Page 22 of 29 
 
 
 
Degree 
Description 
Probably 
There is evidence of exposure to the test procedure / device; the temporal sequence of 
the AE onset relative to the test procedure / device is reasonable; the AE is more likely 
explained by the test procedure / device than by another cause.
Possibly 
There is evidence of exposure to the test procedure / device; the temporal sequence of 
the AE relative to the test procedure / device is reasonable; the AE could have been due 
to another equally likely cause; 
Probably not 
There is evidence of exposure to the test procedure / device; there is another more 
likely cause of the AE
Definitely not 
The patient did not receive the test procedure / device; or temporal sequence of the AE 
onset relative to test procedure / device is not reasonable; or there is another obvious 
cause of the AE.
 
Action taken - whether or not the adverse event caused the subject to be discontinued from the 
study. 
Clinical Outcome – whether the adverse event was resolved or ongoing. 
All adverse events, including a worsening of physical examination findings, in comparison with 
baseline values, must be followed until the event resolves, the condition stabilizes, the event is 
otherwise explained, or the patient is lost to follow-up. 
 
 Anticipated adverse events  
Anticipated adverse device effects include Infection, Excessive Bleeding, Nasomucosal injury, 
CSF leakage, Orbital hematoma, Voice changes, Impaired sense of taste or smell, Nasal 
obstruction, dryness and pain and Adverse reactions to the topical decongestants or anesthetic 
provided prior to the procedure. Please refer to section 8.1 above 
 
8.3 
Definitions of Serious Adverse Device Effects and device deficiencies 
  
Serious Adverse Device Effect (SADE) 
A "Serious Adverse Device Effect" is an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
 
Serious Adverse Event (SAE) 
A "Serious Adverse Event” is an adverse event that: 
a)  
led to a death (Note: In the event of subject death during the conduct of the study, efforts 
should be made to perform an autopsy.) 
b)   led to a serious deterioration in health that either: 

 
3NT Medical - Confidential 
 
Page 23 of 29 
 
 
 
1)   resulted in a life-threatening illness or injury, or 
2)   resulted in a permanent impairment of a body structure or a body function, or 
3)  
required in-patient hospitalization or prolongation of existing hospitalization, or 
4)  
resulted in medical or surgical intervention to prevent life threatening illness or injury 
or permanent impairment to a body structure or a body function   
c)   
led to fetal distress, fetal death or a congenital abnormality or birth defect.  
 This includes device deficiencies that might have led to a serious adverse event if a) 
suitable action had not been taken or b) intervention had not been made or c) if 
circumstances had been less fortunate. These are handled under the SAE reporting 
system. 
 A planned hospitalization for pre-existing condition, or a procedure required by the 
Clinical Investigation Plan, without a serious deterioration in health, is not considered 
to be a serious adverse event. 
 
8.4 
Unanticipated Serious Adverse Device Effect (USADE)                                                  
Serious adverse device effect which by its nature, incidence severity or outcome has not been 
identified in the current version of the risk analysis report.   
Anticipated: an effect which by its nature, incidence, severity or outcome has been previously 
identified in the literature. For example minor bleeding. 
Please note: All procedures carry some risk but ENT endoscopy is very safe. Minor complications 
are uncommon and major complications are very rare. 
8.5 
Adverse Effects and Precautions 
The subjects will be counseled concerning what to expect during the procedure and the importance 
of communicating any problems to the investigator. 
8.6 
Adverse Event Reporting 
It is the responsibility of the investigator to document all treatment related and device related 
Adverse Events (ADE’s), which occur during the course of the study.  All ADEs will be recorded 
on the adverse events page of the CRF. Severity and relationship to study device will be assigned 
by the investigator as described in the section above. ADEs will be recorded after the subject has 
been admitted to the clinic Visit-2. 
Any SAE, whether deemed device-related or not, must be reported to the site Ethics Committee 
and to the sponsor as soon as possible after the investigator has become aware of its occurrence 
even if not all the information is available at the time of initial contact. 

 
3NT Medical - Confidential 
 
Page 24 of 29 
 
 
 
The investigator must complete a SAE Form, and send it to the Sponsor within 24 hours of 
becoming aware of the event. Accompanying documentation, such as copies of hospital case 
reports, autopsy report, and other documents when applicable, should be sent as soon as they are 
available. 
The site’s Ethics Committee must also be duly notified and dealt with, according to the Hospital 
and FDA/Ministry of Health regulations. Subjects who have had a SAE must be followed 
clinically until all parameters (including laboratory) have either returned to normal or are 
stabilized.  
9 DATA MANAGEMENT 
Data from each subject will be recorded in source data and transmitted to case report forms (CRFs) 
supplied by the Sponsor. The data will be inserted manually and quality check for errors and omissions 
will be performed to ensure the accuracy of the entered data. 
The source data should be completed during the study by qualified personnel. All data must be filled out 
using ball pens (not pencils), accurately and promptly following each relevant step of the study. The 
CRF should be completed in full, i.e., no fields should be left blank once the subject has completed the 
study. CRFs entries corrections must be made only by lining out (single line) incorrect data and writing 
in the revisions. All corrections must be initialed and dated by the individual performing/recording the 
correction. If the reason for the change is not obvious, an explanation for the change should be recorded 
and attached to the CRF. Blacking out or using correction fluid or an eraser is not allowed to correct or 
eliminate data. The investigator must review the CRFs for completeness and accuracy and must 
sign/date the forms where indicated. 
The investigator will retain originals of CRFs, subject consent forms, and study data as permanent 
records for a period of 2 years or until the data is no longer required for regulatory purposes (the longest 
between these two). 
10 MONITORING PLAN 
Clinical Monitoring for this study will be managed by 3NT Medical. The Clinical Monitor is qualified 
by training and experience to oversee the conduct of this study. The Clinical Monitor’s responsibilities 
include maintaining regular contact with each investigational site through telephone/email contact and 
on-site visits, to ensure that:  
 The trial is conducted according to FDA, ICH-GCP and EN ISO 14155:2011 requirements;  
 The Investigational Plan is followed;  
 Complete, timely, and accurate data are submitted;  
 Problems with inconsistent or incomplete data are addressed;  
 Complications and unanticipated adverse effects are reported to the Sponsor and the IRB;  
 The site facilities will be monitored to stay adequate to meet the requirements of the study.  

 
3NT Medical - Confidential 
 
Page 25 of 29 
 
 
 
The Clinical Monitor will initiate the Study during an on-site visit and will continue to perform on-site 
monitoring visits as frequently as deemed necessary. The first monitoring visit will usually be made as 
soon as possible after enrollment has been initiated. At this visit and all monitoring visits, the Clinical 
Monitor will compare the data entered onto the CRFs with the hospital or clinical records (source 
documents). Source documentation must be available to substantiate proper informed consent 
procedures, adherence to protocol procedures, adequate reporting and follow-up of AEs, and device 
procedure information. Findings from the review of CRFs and source documents during a monitoring 
visit will be discussed with the PI. Completed paper CRFs will be reviewed prior to data closure at each 
visit. The dates of the monitoring visits will be recorded in a Log to be kept at the clinical site. During 
monitoring visits, the Sponsor expects that the study coordinator and the PI will be available, the source 
documentation will be available, and a suitable environment will be provided for review of Study related 
documents.   
Monitoring procedures will follow the Sponsor SOPs. 
11 INVESTIGATOR RESPONSIBILITIES 
All principal investigators will be required to sign an Investigator Agreement  
12 AMENDMENTS TO THE PROTOCOL 
No alterations or changes to this protocol will be permitted. However, should there be question or 
consideration of deviation from the protocol, clarification and approval must be sought from the 
sponsor. 
Protocol modifications must be confirmed in writing prior to implementation. 
13 DEVIATION FROM THE STUDY PLAN 
All major protocol amendments must be approved by the EC/IRB prior to implementation. 
No protocol amendments should be adopted without prior written approval from the IRB except in the 
following cases: 
 
In order to eliminate immediate hazard to the subjects 
 
Changes involving only logistical or administrative aspects of the trial. 
The investigator should document and explain any deviation from the approved protocol and to file 
waivers received from the sponsor, if applicable. The reasons for it, and, if appropriate, the proposed 
protocol amendments should be submitted to: 
1. The Sponsor for agreement 
2. The EC/IRB 

 
3NT Medical - Confidential 
 
Page 26 of 29 
 
 
 
Any subject treated in a manner that deviates from the protocol, or who is admitted into the study but is 
not eligible according to the protocol, may be ineligible for analysis and thereby compromises the study. 
14 DEVICE ACCOUNTABILITY 
3NT Medical will provide the study site with Sinusway devices and imaging/recording system for the 
duration of the study. The systems will be marked “for investigational use” and the investigator is 
responsible for storing the systems in a secure place to avoid unauthorized use. 
Immediately upon completion of the study all systems and unused items will be returned to 3NT 
Medical. 
15 VULNERABLE POPULATION 
No vulnerable population will be included in this study. 
16 SUBJECT CONFIDENTIALITY 
Subject confidentiality will be maintained throughout this study, including all publications.  Data 
collected and entered into the CRFs are the property of the study sponsor.  Representatives from the 
study sponsor or authorized sponsor representatives, the Institutional Review Board (IRB), Ethics 
Committee, FDA may receive copies of the study records and may review medical records related to the 
study. 
17 SUBJECT WITHDRAWAL OR DISCONTINUATION 
Any patient will be informed of his right to withdraw from the study at any time and for any reason. 
The Investigator or Sponsor may withdraw a patient from the study at any time if he considers that 
remaining in the study compromises the patient’s health or the patient is not sufficiently cooperative. 
The reasons for any patient withdrawal will be recorded on the study completion form of the CRF.  
The investigator will inform the Sponsor in writing of the subject's early withdrawal for any reason. 
If withdrawal is caused by an adverse event that the investigator considers may be related to the device, 
it will be reported to the EC/IRB and to the Sponsor. 
18 SUSPENSION OR PREMATURE TERMINATION OF THE STUDY 
The Sponsor reserves the right to discontinue the study at any time for any reason based on (but not 
exclusively) the following criteria: 

 
3NT Medical - Confidential 
 
Page 27 of 29 
 
 
 
 Technical problems in the device. 
 Unanticipated Serious adverse device effect (USADE) 
 The Principal Investigator's or the Ethics Committee recommendation 
 Poor performance or compliance of the clinical site 
 Company considerations 
In case of premature termination of the study, the Ethics Committee will be duly informed according to 
the local regulations. 
19 PUBLICATION POLICY 
Any presentation/publication of complete or partial study data by the Investigators or any other party is 
stipulated by written authorization from the sponsor. 
20 REFRENCES 
1 
Josef Shargorodsky, MD, MPH, et al.: What is the Role of Nasal Endoscopy in the Diagnosis of 
Chronic Rhinosinusitis? The Laryngoscope (2012), The American Laryngological Rhinological and 
Otological Society, Inc . 
2 
Michael S. Benninger, MD, et al.: Endoscopically Directed Middle Meatal Cultures versus 
Maxillary Sinus Taps in Acute Bacterial Maxillary Rhinosinusitis: A Meta-Analysis, 
Otolaryngology–Head and Neck Surgery (2006) 134, 3-9 
3 
Use of Diagnostic Imaging Studies and Associated Radiation Exposure for Patients Enrolled in 
Large Integrated Health Care Systems, 1996-2010, JAMA, June 13, 2012—Vol 307, No. 22 
4 
Jeffrey Cutler, M.D., Nadim Bikhazi, et al.: Standalone balloon dilation versus sinus surgery for 
chronic rhinosinusitis: A prospective, multicenter, randomized, controlled trial, Am J Rhinol 
Allergy 27, 2013, 416–422 
5 
Hosemann, W., & Draf, C. (2013). Danger points, complications and medico-legal aspects in 
endoscopic sinus surgery. GMS current topics in otorhinolaryngology, head and neck surgery, 12. 
6 
Kassam, A. B., Prevedello, D. M., Carrau, R. L., Snyderman, C. H., Thomas, A., Gardner, P., & 
Horowitz, M. B. (2011). Endoscopic endonasal skull base surgery: analysis of complications in the 
authors' initial 800 patients: a review. Journal of neurosurgery, 114(6), 1544-1568. 
7 
Kramer, A., Kohnen, W., Israel, S., Ryll, S., Hübner, N. O., Luckhaupt, H., & Hosemann, W. 
(2015). Principles of infection prevention and reprocessing in ENT endoscopy. GMS current topics 
in otorhinolaryngology, head and neck surgery, 14. 
8 
Dalziel, K., Stein, K., Round, A., Garside, R., & Royle, P. (2006). Endoscopic sinus surgery for the 
excision of nasal polyps: A systematic review of safety and effectiveness. American journal of 
rhinology, 20(5), 506-519. 

 
3NT Medical - Confidential 
 
Page 28 of 29 
 
 
 
9 
Vleming, M., Middelweerd, R. J., & de Vries, N. (1992). Complications of endoscopic sinus 
surgery.Archives of Otolaryngology–Head & Neck Surgery,118(6), 617-623. 
10 Mori, A., Ohashi, N., Maruyama, T., Ito, M., Miyawaki, T., & Okuno, M. (2008). A proposal for 
grading nasomucosal injury as a complication of transnasal endoscopy. Endoscopy, 40(S 02), E60-
E60 
11 Rombout, J., & de Vries, N. (2001). Complications in sinus surgery and new classification 
proposal.American journal of rhinology, 15(6), 363-370. 
12 Platt, M. P., Shaye, D., & Parnes, S. M. (2007). Management of unexpected cerebrospinal fluid 
fistulae during endoscopic sinus surgery. American journal of rhinology, 21(5), 611-614. 
13 Bachmann, G., Djenabi, U., Jungehülsing, M., Petereit, H., & Michel, O. (2002). Incidence of occult 
cerebrospinal fluid fistula during paranasal sinus surgery. Archives of Otolaryngology–Head & 
Neck Surgery, 128(11), 1299-1302. 
14 Hegazy, H. M., Carrau, R. L., Snyderman, C. H., Kassam, A., & Zweig, J. (2000). Transnasal 
Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea: A Meta‐Analysis. The Laryngoscope,110(7), 
1166-1172. 
15 Casiano, R. R., & Jassir, D. (1999). Endoscopic cerebrospinal fluid rhinorrhea repair: is a lumbar 
drain necessary?. Otolaryngology--Head and Neck Surgery, 121(6), 745-750. 
16 DelGaudio, J. M., & Ingley, A. P. (2010). Treatment of pneumocephalus after endoscopic sinus and 
microscopic skull base surgery. American journal of otolaryngology, 31(4), 226-230. 
17 Warnecke, A., Averbeck, T., Wurster, U., Harmening, M., Lenarz, T., & Stöver, T. (2004). 
Diagnostic relevance of β2-Transferrin for the detection of cerebrospinal fluid fistulas. Archives of 
Otolaryngology–Head & Neck Surgery, 130(10), 1178-1184. 
18 Bhatti, M. T., & Stankiewicz, J. A. (2003). Ophthalmic complications of endoscopic sinus surgery. 
Survey of ophthalmology, 48(4), 389-402. 
19 Ramakrishnan, V. R., & Palmer, J. N. (2010). Prevention and management of orbital 
hematoma.Otolaryngologic Clinics of North America, 43(4), 789-800. 
20 Soudry, E., & Nayak, J. V. (2015, February 17). Nasal Endoscopy. Retrieved August 21, 2016, 
from http://care.american-rhinologic.org/nasal_endoscopy 
21 W. Hosemann, C. Draf, . (2013). Danger points, complications and medico-legal aspects in 
endoscopic sinus surgery, Head and Neck Surgery, Vol. 12 
 
21 APPENDICES 
Appendix-A:  Informed Consent 
Appendix-B: Case Report Forms 
 

 
3NT Medical - Confidential 
 
Page 29 of 29