The Vivaer Procedure for Treatment of the Septal Swell Bodies for Airway Obstruction - A Prospective Open-Label Multicenter Study (SWELL)
Phase: NA
Conditions: Nasal Obstruction
Sponsor: Aerin Medical

 
 
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CONFIDENTIAL 
The Vivaer® Procedure for Treatment of the Septal Swell Bodies for 
Airway Obstruction - A Prospective Open-Label Multicenter Study 
(SWELL) 
Protocol Number: 
CTP1125 
Protocol Date: 
27 Jul 2021 
Amendment Date:  
31 Aug 2021 
Version: 
C 
Principal Investigator: 
Jordan Pritikin, MD 
Chicago Nasal & Sinus Center 
111 W Washington Street, Suite 903  
Chicago, IL 60602 
Phone: (312)-372-9355 
Email: jpritikinmd@gmail.com 
Sponsor: 
Aerin Medical, Inc. 
232 E. Caribbean Drive 
Sunnyvale, CA 94089 USA 
 
Contact: Anais Laborde, Senior Director of Clinical Affairs 
Phone: 650-518-9624 
Email: alaborde@aerinmedical.com   
Sponsor 
Representative: 
<If the sponsor is not a resident in the country(ies) in which the clinical 
investigation is to be carried out, the name and address of a representative in 
that country (those countries) can be required according to national or regional 
regulations> 
 
INVESTIGATOR 
I, the undersigned, certify that I have reviewed this Clinical Investigational Plan and agree to abide by the 
terms of the study described herein and within the Investigator Agreement, Clinical Trial Agreement and 
according to the Declaration of Helsinki and The Belmont Report as well as any conditions imposed by the 
reviewing Institutional Review Board, Ethics Committee, U.S. FDA or other regulatory agency. 
Site Name:  
 
Print Name: 
 
Signature: 
 
Date: 
 
 
This protocol contains proprietary and confidential information of Aerin Medical, Inc. and should be restricted in its 
distribution to investigators, subinvestigators, and reviewing Institutional Review Boards/Ethics Committees.  Do not 
copy, distribute, or share with others without prior written authorization from Aerin Medical Inc. 
 
 

 
 
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Table of Contents 
 
Protocol Summary .................................................................................................................... 5 
Activity / Assessment ...................................................................................................... 9 
Screening.......................................................................................................................... 9 
Treatment ......................................................................................................................... 9 
Follow-up ......................................................................................................................... 9 
(in-office) ......................................................................................................................... 9 
Extended Follow-up (remote) .......................................................................................... 9 
List of Abbreviations .............................................................................................................. 10 
1.0 Introduction and Background ........................................................................................ 12 
2.0 Purpose ........................................................................................................................... 14 
2.1 Device and Regulatory Status ............................................................................... 14 
2.2 Indications for Use ................................................................................................. 14 
2.3 Rational ................................................................................................................... 14 
3.0 Device and Procedure Description ................................................................................. 14 
4.0 Study Objectives ............................................................................................................ 16 
4.1 
Primary Objective .............................................................................................. 16 
4.2 
Secondary Objective .......................................................................................... 17 
5.0 Study Plan ...................................................................................................................... 18 
5.1 
Study Design ...................................................................................................... 18 
5.2 
Study Population ................................................................................................ 18 
5.2.1 Inclusion Criteria .....................................................................................19 
5.2.2 Exclusion Criteria ....................................................................................19 
5.3 
Study Entry and Enrollment ............................................................................... 20 
5.4 
Outcome Measures............................................................................................. 20 
5.4.1 Nasal Assessment .....................................................................................20 
5.4.2 CT Assessment – Substudy – Selected Sites Only .................................21 
5.4.3 Nasal Obstruction Symptom Evaluation (NOSE) Scale .......................22 
5.4.4 Visual Analog Scale (VAS) for Nasal Pain ............................................22 
5.4.5 Ease of Breathing Through the Nose – Numeric Rating Scale 
(NRS) Breathing Score ............................................................................22 
5.4.6 Sino-Nasal Outcomes Test 22 (SNOT-22) ..............................................23 
5.4.7 Participant Satisfaction Assessment .......................................................23 
5.4.8 Medications for Symptoms of Nasal Obstruction .................................23 
5.4.9 Adverse Events .........................................................................................24 
5.5 
Success/Failure Criteria ..................................................................................... 24 
5.5.1 Participant Success ..................................................................................24 
5.5.2 Study Success ............................................................................................24 
5.6 
Duration of the Study ......................................................................................... 24 
5.7 
Site Staffing and Responsibilities of Study Personnel ....................................... 24 
5.8 
Risk/Benefit Analysis ........................................................................................ 25 
5.8.1 Risks ..........................................................................................................25 
5.8.2 Potential Risks to Participant Confidentiality ......................................26 

 
 
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5.8.3 Mitigation of Risks ...................................................................................26 
5.8.4 Study Justification in Relation to Risk...................................................27 
5.8.5 Benefits ......................................................................................................27 
6.0 Study Schedule and Procedures ..................................................................................... 27 
6.1 Schedule of Events ......................................................................................................... 28 
Activity / Assessment .................................................................................................... 28 
Screening........................................................................................................................ 28 
Treatment ....................................................................................................................... 28 
Follow-up ....................................................................................................................... 28 
(in-office) ....................................................................................................................... 28 
Extended Follow-up (remote) ........................................................................................ 28 
6.2 
Participant Flowchart ......................................................................................... 29 
6.3 
Enrollment and Screening Assessment .............................................................. 29 
6.4 
Treatment Visit and Procedure (Day 0) ............................................................. 31 
6.5 
Postprocedure Assessments and Care ................................................................ 34 
6.6 
Follow-up Evaluations and Study Exit .............................................................. 34 
6.7 
Product Handling and Accountability ................................................................ 36 
7.0 Statistical Considerations ............................................................................................... 36 
7.1 
Study Design ...................................................................................................... 36 
7.2 
Study Hypotheses............................................................................................... 37 
7.3 
Power Analysis and Sample Size Estimate ........................................................ 37 
7.4 
Timing of Analysis ............................................................................................ 38 
7.5 
Analysis Populations .......................................................................................... 38 
7.6 
Missing Data ...................................................................................................... 39 
7.7 
Pooling ............................................................................................................... 39 
7.8 
Participant Disposition ....................................................................................... 39 
7.9 
Demographics and Baseline Characteristics ...................................................... 39 
7.10 
Primary Endpoint Analysis ................................................................................ 39 
7.11 
Secondary Endpoint Analysis ............................................................................ 39 
7.12 
Other Outcome Measures Analyses ................................................................... 40 
7.13 
Subgroup Analysis ........................................................................................... 41 
7.14 
Safety Analysis ................................................................................................. 41 
7.15 
Follow-up Phase Analysis.................................................................................. 42 
7.16 
Standard Methods of Report .............................................................................. 42 
8.0 Adverse Events and Product Complaints / Device Deficiencies ................................... 42 
8.1 
Adverse Events .................................................................................................. 42 
8.1.1 Definitions .................................................................................................42 
8.1.2 Documentation and Reporting of Adverse Events ................................45 
8.2 
Product Complaints / Device Deficiencies ........................................................ 46 
8.2.1 Definitions .................................................................................................46 
8.2.2 Documentation and Reporting of Complaints / Device 
Deficiencies ...............................................................................................46 
9.0 Study Administration ..................................................................................................... 46 
9.1 
Investigator Training .......................................................................................... 47 
9.2 
Study Monitoring ............................................................................................... 47 

 
 
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9.3 
Documentation of Study Findings ..................................................................... 48 
9.3.1 Data Management ....................................................................................48 
9.3.2 Case Report Forms ..................................................................................48 
9.3.3 Investigator Responsibilities, Records, and Reports ............................50 
9.3.4 Retention of Study Records.....................................................................52 
9.3.5 Data Quality Assurance ...........................................................................52 
9.3.6 Confidentiality ..........................................................................................52 
9.3.7 Publication Policies ..................................................................................53 
9.4 
Study Suspension or Early Termination ............................................................ 53 
10.0 Ethics.............................................................................................................................. 54 
10.1 
Institutional Review Board ................................................................................ 54 
10.2 
Ethical Conduct of the Study ............................................................................. 54 
10.3 
Participant Privacy ............................................................................................. 54 
10.4 
Participant Insurance .......................................................................................... 55 
10.5 
Participant Reimbursement ................................................................................ 55 
10.6 
Participant Withdrawal ...................................................................................... 55 
10.7 
Protocol Modifications....................................................................................... 55 
10.8 
Protocol Adherence and Deviations ................................................................... 56 
10.8.1 Definition ..................................................................................................56 
10.8.2 Documentation and Reporting of Deviations ........................................56 
11.0  References ...................................................................................................................... 57 
 
 
 

 
 
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Protocol Summary 
Title: 
The Vivaer® Procedure for Treatment of the Septal Swell Bodies for 
Airway Obstruction - A Prospective Open-Label Multicenter Study 
(SWELL) 
Purpose: 
The purpose of this study is to assess the clinical use of the Vivaer ARC 
Stylus to treat Septal Swell Bodies (SSB) to improve symptoms in adults 
diagnosed with nasal obstruction attributed to SSB.  
Indications 
for Use:  
The Vivaer ARC Stylus is indicated for use in otorhinolaryngology 
(ENT) surgery for the coagulation of soft tissue in the nasal airway, to 
treat nasal airway obstruction (NAO) by shrinking submucosal tissue, 
including cartilage in the internal nasal valve area. 
The Aerin Console is an electrosurgical system intended to generate 
radiofrequency electrical current for the use of an Aerin Medical Stylus. 
The Aerin Console is indicated for use in small clinic, office or hospital 
environments. 
Study 
Objectives: 
The primary objective of this study is to determine the efficacy of treating 
the nasal septal swell body area with temperature-controlled 
radiofrequency (RF) using the Vivaer system for the treatment of NAO.  
The  secondary objective is to evaluate the durability of the treatment 
effect in an extended follow-up period of 36 months. . 
Study Design: 
The study is designed as a multicenter, prospective, open-label, single-
arm study. 
All participants will be evaluated prior to treatment and following 
treatment at week 1 and week 13 (3 months). The 3-month evaluation will 
be used for the primary endpoint analysis. 
The study will have an extended follow-up phase with evaluations 
conducted at 26 weeks (6 months), 52 weeks (12 months), 104 weeks (24 
months) and 156 weeks (36 months) to provide additional information on 
longer-term efficacy and duration of treatment effect. 
A subset of study sites will be selected to participate in a substudy of the 
use of computed tomography (CT) imaging to assess changes in the SBB 
after treatment. 
Vivaer 
Treatment: 
The Vivaer procedure will be performed in the study clinic using the 
Vivaer ARC Stylus and Aerin Console. The Vivaer ARC Stylus is a 
disposable handheld device capable of delivering bipolar radiofrequency 
energy to tissue when connected to the Aerin Console radiofrequency 
generating device. Participants will undergo bilateral treatment of the 
nasal airway in a single study procedure session. Each side of the nose 
will be treated as follows: 

 
 
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• Two (2) to six (6) nonoverlapping applications of RF energy 
are performed at the SSB per nostril. 
The default treatment settings will be used for the study: temperature 60° 
C, power 4 watts, treatment time 18 seconds, and cooling time 12 
seconds. No repeat (“touch up”) procedures will be permitted after the 
initial procedure through the end of the study (36 months). 
 
Primary 
Endpoint: 
The primary endpoint is improvement in self-reported Nasal Obstruction 
Symptom Evaluation (NOSE) Scale score from baseline recorded at the 
screening evaluation to 13 weeks after the procedure.  
Secondary 
Endpoints: 
• Responder percent: A responder is defined as at least 1 NOSE Scale 
class improvement or an improvement (decrease) in NOSE Scale 
score of 20% or more from baseline to 13 weeks after the procedure. 
• Frequency of device-related and procedure-related serious adverse 
events, including frequency of septal perforation during the 
procedure, through the 3-month evaluation. 
Study 
Hypotheses 
Primary hypothesis: mean improvement in NOSE Scale score from 
screening  to 13 weeks will exceed 25 points. 
Other hypothesis: the treatment effects will be maintained through the 
extended follow-up period of 36 months. 
Other 
Outcome 
Measures: 
Adverse Events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
Nasal Assessment - The target SSB within each nostril will be visually 
assessed at screening, prior to the procedure, immediately after the 
procedure, and 3 months after the procedure. The use of an endoscope for 
visual assessment is required. Representative endoscopic video of each 
nasal passage will be captured for each assessment. Endoscopic nasal 
assessment will include assignment of an SSB grading score.36CT 
Assessment - A subset of study sites will be selected to participate in a 
substudy of the use of computed tomography (CT) imaging to assess 
changes in the SBB after treatment. Radiographic changes, including 
change in size of the SSB, will be assessed using CT imaging prior to the 
procedure and at 3 months after the procedure. 
NOSE Scale Score:  
• Mean and mean change from screening at the 3-, 6-, 12-, 24- and 
36-month follow-up evaluations. 
• Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, 24- and 36-month 
follow-up evaluations. 

 
 
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• Mean, change from screening in mean, and response distribution 
of the 5 components of the NOSE Scale score (nasal congestion, 
nasal blockage, trouble breathing, trouble sleeping, and getting 
enough air during exercise) at the 3-, 6-, 12-, 24- and 36-month 
follow-up evaluations. 
• Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, 24- and 36-month follow-up evaluations. 
Visual Analog Scale (VAS) for nasal pain - perception of pain associated 
with the procedure on a 0 to 100 mm scale (0 indicating no pain and 100 
indicating the worst pain ever) assessed immediately after treatment and 
at 1 week. 
Numerical Rating Scale (NRS) for ease of breathing through the nose - 
perception of the ability to breathe through the nose over the past week 
on a 0 to 10 scale (0 indicating no difficulty and 10 indicating severe 
difficulty) assessed at screening, 3, 6, 12, 24 and 36 months.  
Sino-Nasal Outcome Test (SNOT-22) - Participant-reported outcome 
measure for the prior 2 weeks of 22 symptoms related to both nasal and 
general health on a score of 0 (no problem) to 5 (problem as bad as it can 
be) and indicate up to 5 items they consider the most important items 
affecting their health. Scores range from 0 to 110, with higher numbers 
representing a significant problem for the participant. 
Participant Satisfaction Assessment - Five-question self-reported survey 
of satisfaction with the procedure and recommendation to others 
administered at the 3-, 6-, 12-, 24- and 36-month follow-up evaluations. 
Medications - Medication used for relief or treatment of NAO symptoms 
will be documented at screening and updated as necessary with new 
associated medications at each postprocedure evaluation through the End 
of Study visit. An increase, decrease, no change, starting new or stoppage 
of medication use compared to the first recorded use will be documented. 
Length of 
Study: 
The primary outcome will be evaluated at 3 months. In addition, 
evaluations at 6, 12, 24 and 36 months after treatment will extend follow-
up to 3 years for evaluation of longer-term efficacy. Enrollment is 
anticipated to be completed within 6 months. Therefore, total study 
duration is anticipated to be approximately 42 months. 
Study 
Centers: 
up to 10  
 
Participants: 
up to 70 
 
Inclusion 
Criteria: 
1. Age 22 to 85 years (inclusively). 
2. Seeking treatment for nasal obstruction and willing to undergo 
an office-based procedure. 

 
 
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3. Baseline NOSE score ≥ 55. 
4. Presence of SSB hypertrophy limiting visualization of the middle 
turbinate (MT) by more than 50%.  
5. Reduction in size of the SSB after application of topical 
decongestant on a cotton plug directly to the SSB region.  
6. Improvement in the symptoms of nasal obstruction after SSB 
decongestion suggesting that the SSB may play a role in nasal 
obstruction. 
7. Willing and able to withhold anticoagulant medications during 
the perioperative period (3-day window on either side).  
8. Willing and able to provide informed consent.  
9. Willing and able to comply with the participant-specific 
requirements outlined in the study protocol.  
 
Exclusion 
Criteria: 
1. Rhinoplasty, septoplasty, inferior turbinate (IT) reduction, or 
other surgical nasal procedures within the preceding 6 months. 
2. Severe case of any of the following: septal deviation, turbinate 
hypertrophy, polyps, or ptotic nose tip believed to be the primary 
contributor to the participant’s nasal obstruction symptoms and 
warranting surgical intervention.  
3. Any adjunctive surgical nasal procedure planned on the same day 
or within 3 months after the Vivaer procedure.  
4. Known or suspected allergies or contraindications for any 
general or local anesthetic agents. 
5. Known or suspected to be pregnant or is lactating.  
6. Participating in another clinical research study. 
7. Other medical conditions which in the opinion of the investigator 
would predispose the participant to poor wound healing or 
increased surgical risk, or poor compliance with the requirements 
of the study. 
8. Known or suspected regular use of oxymetazoline (Afrin) nasal 
decongestant or oral steroids.  
9. For sites participating in the CT substudy only: Active sinus 
condition (eg, significant sinus diseases, infection or polyp 
formation) identified by CT. 
 
 
 

 
 
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SCHEDULE OF EVENTS 
 
 
 
Activity / Assessment 
Screening 
Treatment 
Follow-up  
(in-office) 
Extended Follow-up 
(remote) 
Preprocedure 
Procedure 
Immediate 
Postprocedure 
1 Week 
3 Months 
(13 weeks) 
6 Months 
(26 weeks) 
12 Months 
(52 weeks) 
24 Months 
(104 weeks) 
36 months 
(156 weeks) 
 Window (days) (-30) 
(0) 
(± 3) (± 14) (± 30) (± 30) (± 30) (± 30) 
Eligibility 
X 
 
 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
 
 
Nasal Assessment (visual, 
endoscopic) 
X 
X1 
 
X 
X 
X 
 
 
 
 
CT imaging of SSB 
X2 
 
 
 
 
X 
 
 
 
 
Current medication use (study 
relevant) 
X 
 
 
X3 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
NOSE Scale 
X4 
 
 
 
 
X5 
X 
X 
X 
X 
VAS nasal pain  
 
 
 
X 
X 
 
 
 
 
 
NRS ease of breathing 
X 
 
 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
 
X 
X 
X 
X 
X 
SNOT-22 
X 
 
 
 
 
X 
X 
X 
X 
X 
Study Procedure (includes 
anethesia) 
 
 
X 
 
 
 
 
 
 
 
Adverse Events 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
1 Nasal Assessment do not need to be repeated if Screening and Treatment visits occur on the same day. 
2CT should only be performed if your site was selected for the CT substudy and only after all other screening procedures and 
participant eligibility is confirmed. 
3Add any postprocedure medications to the medication log. 
4Baseline NOSE Scale Score for analysis is defined as the Screening score. 
5Primary analysis endpoint evaluation.  
 
 
 

 
 
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List of Abbreviations 
ADE – Adverse Device Effect 
AE – Adverse Event 
BMI – Body Mass Index 
CFR – Code of Federal Regulations 
CPAP – Continuous Positive Airway Pressure 
CRF (eCRF) – Case Report Form (electronic Case Report Form) 
CT (CAT)– Computed Tomography (Computed Axial Tomography) 
CTA – Clinical Trial Agreement 
DICOM – Digital Imaging and Communication in Medicine 
EDC – Electronic Data Capture 
ENT – Ear, Nose, Throat; medical field of otorhinolaryngology (otolaryngology) 
FDA – Food and Drug Administration 
FDAAA – Food and Drug Administration Amendments Act 
FOV – Field of View 
FWA – Federal Wide Assurance for the Protection of Human Participants 
GCP – Good Clinical Practice 
HIPAA – Health Insurance Portability and Accountability Act 
ICH – International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use  
ICMJE – International Committee of Medical Journal Editors 
IFU – Instructions for Use 
IRB – Institutional Review Board 
ISO – International Organization for Standardization 
IT – Inferior Turbinate 

 
 
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KVp – kilovotage peak 
MPR – Multiplanar reformation 
MRI – Magnetic Resonance Imaging 
MT – Middle Turbinate 
NAO – Nasal Airway Obstruction 
NOSE – Nasal Obstruction Symptom Evaluation Scale  
NRS – Numeric Rating Scale 
SSB – Septal Swell Body 
OTC – Over-The-Counter (nonprescription) 
QOL – Quality of Life 
RF – Radiofrequency 
RFTR – Radiofrequency turbinate reduction 
SAE – Serious Adverse Event 
SADE – Serious Adverse Device Effect 
SD – standard deviation 
SNOT-22 – Sino-Nasal Outcomes Test 22 
UADE – Unanticipated Adverse Device Effect 
ULC – Upper Lateral Cartilage 
US – United States 
VAS – Visual Analog Scale 

 
 
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1.0 
Introduction and Background 
Nasal airway obstruction (NAO) is a highly prevalent disorder that affects the upper 
airway system causing restriction in normal airflow into the nasal cavity. Chronic nasal 
obstruction can elicit many symptoms, including congestion, stuffiness, headache, 
fatigue, sleep disturbance, daytime sleepiness, snoring and impairment of various daily 
and social activities leading to an overall decline in health-related quality of life 
(QOL).1-3 Given its high prevalence, treatment of NAO can be costly, with 
expenditures for prescriptions, over-the-counter (OTC) medications, and doctor’s 
visits. 
NAO can be mediated by a diversity of mucosal and structural disorders in the nasal 
cavity, including acute or chronic mucosal inflammation from infection, allergenic or 
non-allergenic irritants, or structural factors such as nasal masses or polyps, turbinate 
or septal swell body (SSB) hypertrophy, nasal septal deviation, and nasal valve angle 
changes, narrowing or collapse.1,4- 8 
Treatment strategies for NAO have included both noninvasive management and 
surgical treatment with recent focus on treatment of the nasal valve region. The nasal 
valve is defined by the caudal cartilaginous nasal septum, the anterior head of the 
inferior turbinate (IT), and the caudal end of the upper lateral cartilage (ULC). This 
region is critical in the development of nasal obstruction and represents the narrowest 
part of the nasal airway.3,8-10 As described by Poiseuille’s law, minute changes in the 
diameter of a tube will result in exponential changes in airflow11. Thus, any narrowing 
in the nasal valve region, such as that associated with septal deviation, turbinate 
hypertrophy, congestion of SSB, ULC collapse or insufficiency, nasal polyps, or 
structural changes after rhinoplasty, will change nasal breathing.11  
Multiple devices designed to increase the size of the nasal passage at the nasal valve 
area are available OTC for noninvasive management of NAO. These products are 
marketed to people with poor nasal breathing, snoring difficulties, and those with 
increased breathing demands, such as athletes. These devices include adhesive external 
nasal dilator strips and internal nasal dilators. Both internal and external dilators have 
been found to effectively dilate the nasal airway and reduce airway resistance.12- 15 
However, nasal dilating devices require significant patient involvement and 
compliance to be effective. 
Surgical treatment most commonly consists of repair of a deviated nasal septum and 
reduction of the IT. Surgical treatments may involve various suturing techniques used 
alone or in conjunction with grafting techniques using autologous cartilage typically 
harvested from the nasal septum or ear or synthetic biomaterials.9,16- 19 A new 
minimally invasive surgical procedure has also been introduced that uses an absorbable 
polymer blend nasal implant to support the upper and lower cartilage inside the lateral 
nasal wall similar to more traditional cartilage and nonabsorbable polymer grafts.20 
Surgical treatments are efficacious, but may require significant recovery periods with 
complication risks such as bleeding, intranasal adhesions, scarring, infection, and graft 
migration, resorption or extrusion.16,19  

 
 
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Radiofrequency (RF) energy has been used for decades in the fields of 
otorhinolaryngology (ENT), neurosurgery, cardiology, urology, and general surgery. 
ENT surgeons currently use radiofrequency energy in several nasal therapies. 
Numerous studies have demonstrated that radiofrequency therapy applied to tissue of 
the nasal passage can be safe and effective in improving nasal obstruction while 
preserving nasal function.21 Radiofrequency turbinate reduction (RFTR), for instance, 
is a minimally invasive surgical option that can reduce tissue volume in a precise, 
targeted manner. This technique uses radiofrequency to create heat within the 
submucosal tissue of the turbinate, reducing tissue volume with minimal impact on 
surrounding tissues. Radiofrequency turbinate reduction differs fundamentally from 
traditional surgical methods by using low-power radiofrequency energy to provide a 
relatively quick and painless treatment for tissue coagulation and/or ablation.22,23 There 
have been multiple studies analyzing the safety and outcomes of RFTR treatment. A 
systematic literature review of the RF ablation technique concluded that the technique 
is well tolerated and effective.24  
Targeted radiofrequency heating of the lateral cartilaginous nasal wall has also been 
used in patients with inspiratory nasal valve collapse. 25,26 The Seren procedure25 used 
an incisional approached to apply RF heating to the target tissue with the intent to 
produce tissue retraction and volume reduction. Significant improvement in Nasal 
Obstruction Symptom Evaluation (NOSE) Scale score was seen at 16 weeks. The 
Vivaer procedure26 applies radiofrequency energy along with outward pressure to the 
mucosa at the region of the caudal end of the weakened ULC to induce mechanical 
deformation and potentially change the shape of the lateral nasal wall. At 6 months, 
mean NOSE Scale score improved to 24.7 (SD 20.4, range 0-90) with an average 
decrease of 54.5 (68.6%). Improvement in mean NOSE Scale score was maintained 
through the 12-, 18-, and 24-month evaluations (27.6, 32.7, and 26.8, respectively).27  
As discussed above, typical medical, surgical, or radiofrequency treatments of nasal 
obstruction target the nasal septum, IT or nasal valve cartilage. However, SSBs also lie 
within the nasal airflow pathway and may be contributors to obstructed flow.10,28,29, but 
only minimal attention has been paid to them historically and few studies describe 
them. The SSB have also been referred to as septal turbinate, nasal swell bodies, 
Kiesselbach’s ridge, septal body, and septal tumescence since first being described by 
Wustrow.30 The SSB can be identified on rhinoscopy, endoscopy, and by computed 
tomography (CT) and magnetic resonance imaging (MRI), appearing as a widened 
portion of the anterior nasal septum. The SSB contains both glandular and vasoerectile 
tissues although the function of the SSB is not well described.10 A study of MRI brain 
studies from 54 patients with nonsinonasal complaints provided measures of the 
average length, width, and height of the SSB and further described them as a normal 
2x3-cm fusiform structure located anterior to the middle turbinate (MT) and superior 
to the IT approximately 2.5 cm above the nasal floor31 The study also concluded that 
the proximity of the SSB to the nasal valve region in conjunction with its composition 
of a large number of venous sinusoids suggested a role in nasal airflow regulation. The 
SSB has been found to be more prominent contralateral to a septal deviation32 and to 
be significantly larger among patients with allergic rhinitis and rhinosinusitis than in 

 
 
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control patients without those conditions.33 The SSB are known to swell in the presence 
of histamine.34 A decrease in the size of the anterior nasal septum after application of a 
topical decongestant has been observed through MRI.35  Preliminary studies indicate 
that radiofrequency energy can be used to reduce swell body size.36,37 
2.0 
Purpose  
The purpose of this study is to assess the clinical use of the Vivaer ARC Stylus to treat 
Septal Swell Bodies (SSB) to improve symptoms in adults diagnosed with nasal 
obstruction.  
2.1 Device and Regulatory Status  
The Vivaer procedure will be performed in the study clinic using the Vivaer ARC 
Stylus and Aerin Console. The Vivaer ARC Stylus is a disposable handheld device 
capable of delivering bipolar radiofrequency energy to tissue when connected to the 
Aerin Console radiofrequency generating device with temperature control capable of 
delivering very low doses of energy.  
The Vivaer ARC Stylus was cleared for use in the United States (U.S.) by the Food and 
Drug Administration (FDA) under 510(k) K172529 and the Aerin Console was cleared 
under 510(k) K162810. 
2.2 Indications for Use 
The Vivaer ARC Stylus is indicated for use in otorhinolaryngology (ENT) surgery for 
the coagulation of soft tissue in the nasal airway, to treat nasal airway obstruction 
(NAO) by shrinking submucosal tissue, including cartilage in the internal nasal valve 
area. 
The Aerin Console is an electrosurgical system intended to generate radiofrequency 
electrical current for the use of an Aerin Medical Stylus. The Aerin Console is indicated 
for use in small clinic, office, or hospital environments. 
2.3 Rational  
Patients suffering from symptoms attributed to NAO primarily due to internal nasal 
valve dysfunction, rather than hypertrophied turbinates, have treatment options ranging 
from OTC devices and medications to surgical procedures that have varying degrees of 
effectiveness, discomfort, and potential complications. There remains a significant 
need for a simple, safe, nonsurgical, minimally invasive treatment that can provide 
sustained relief for patients suffering with symptoms of NAO. The Vivaer procedure 
using RF technology has been shown to be safe, effective, and durable in a single-arm 
trial comparing pretreatment condition with posttreatment condition. This study is 
being undertaken to provide additional evidence of the effectiveness of the procedure 
when treating the SSB tissue.  
3.0 
Device and Procedure Description 
The Vivaer ARC Stylus (Figure 1) consists of a handle, shaft and treatment tip. An 
array of bipolar electrodes is positioned on a nonconductive tip (Figure 2) that is 
attached to the handle via a nonconductive shaft. A temperature sensor is located on 

 
 
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the Stylus tip to monitor tissue temperature during RF energy delivery. The Stylus is 
powered by an external temperature-controlled radiofrequency generator via a flexible 
cable (Figure 3). The Stylus incorporates features to allow compatibility with and 
authentication by only the Aerin Console. The connector for the Vivaer ARC Stylus 
has a pin configuration that prevents its use with other RF generators, making it only 
compatible with the Aerin Console. Authentication of the Stylus is achieved via a 
crypto chip that is built into the Stylus handle assembly. The chip is read and written 
to by the Aerin Console. Information stored on the chip includes the Stylus model 
information, treatment parameters, usage timestamp data, and a count of the remaining 
treatment cycles (based upon preset maximum). 
  
 
Figure 1.  Vivaer ARC Stylus 
 
 
 
 
Figure 2.  Vivaer ARC Stylus Tip 

 
 
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Figure 3.  Aerin Console with Vivaer ARC Stylus 
The Vivaer ARC Stylus is temporarily inserted into the nose to access the treatment 
area. The Stylus requires the application of conductive media (eg, saline gel) to the tip 
prior to use. The conductive media helps to ensure good contact with tissue at all points 
of the treatment tip to facilitate energy transmission. Application of the RF energy is 
controlled by a foot switch connected to the Aerin Console. The Vivaer ARC Stylus 
improves nasal breathing by modifying the tissues of the nasal airway using low doses 
of radiofrequency energy. The low-power RF energy generates heat within the tissue 
and creates a coagulation lesion. As the lesion heals, the tissue retracts and stiffens, 
thereby decreasing NAO and improving airflow.  
The procedure requires local anesthesia only. The Stylus is manufactured and supplied 
sterile and for single use only by Aerin Medical and may be used to treat both nostrils 
of the participant. 
4.0 
Study Objectives 
4.1 Primary Objective 
The primary objective of this study is to determine the efficacy of treating the nasal 
septal swell body area with temperature-controlled radiofrequency (RF) using the 
Vivaer system for the treatment of NAO.  
The primary objective will be assessed through evaluation of the primary endpoint, 
defined as change in mean participant NOSE Scale score at 3 months after the 
procedure, and the secondary endpoints of responder percent at 3 months and 
frequency of septal perforation, and other device-related and procedure-related 
serious adverse events through 3 months. 

 
 
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4.2 Secondary Objective 
The secondary objective is to evaluate the durability of the treatment effect in an 
extended follow-up period of 36 months.  
In addition to the primary and secondary endpoints, both the primary and secondary 
objectives will be supported by assessment of several other effectiveness and safety 
measures that will include: 
• Adverse events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
• Nasal Assessment - The target SSB within each nostril will be visually 
assessed at screening, prior to the procedure, immediately after the 
procedure, and 3 months after the procedure. The use of an endoscope for 
visual assessment is required. Representative endoscopic video of each 
nasal passage will be captured for each assessment. Endoscopic nasal 
assessment will include assignment of an SSB grading score.36 
• CT Assessment – A subset of study sites will be selected to participate in a 
substudy of the use of CT imaging to assess changes in the SBB after 
treatment. Radiographic changes, including change in size of the SSB, will 
be assessed using CT imaging prior to the procedure and at 3 months after 
the procedure. 
• NOSE Scale score:  
o Mean and mean change from screening at the 3-, 6-, 12-, 24- and 
36-month follow-up evaluations. 
o Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, 24- and 36-month 
follow-up evaluations. 
o Mean, change from screening in mean, and response distribution of 
the 5 components of the NOSE Scale score (nasal congestion, nasal 
blockage, trouble breathing, trouble sleeping, and getting enough air 
during exercise) at the 3-, 6-, 12-, 24- and 36-month follow-up 
evaluations. 
o Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, 24- and 36-month follow-up evaluations. 
• Visual Analog Scale (VAS) for nasal pain - perception of pain associated 
with the procedure on a 0 to 100 mm scale (0 indicating no pain and 100 
indicating the worst pain ever) assessed immediately after treatment and at 
1 week. 
• Numeric Rating Scale (NRS) for ease of breathing through the nose - 
perception of the ability to breathe through the nose over the past week on 
a 0 to 10 scale with 0 indicating no difficulty and 10 indicating extreme 

 
 
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difficulty assessed at screening and the 3-, 6-, 12-, 24- and 36-month follow-
up evaluations. 
• Sino-Nasal Outcome Test (SNOT-22) - Participant-reported outcome 
measure for the prior 2 weeks of 22 symptoms related to both nasal and 
general health on a score of 0 (no problem) to 5 (problem as bad as it can 
be) and indicate up to 5 items they consider the most important items 
affecting their health. Scores range from 0 to 110, with higher numbers 
representing a significant problem for the participant. 
• Participant Satisfaction Assessment - Five-question self-reported survey of 
satisfaction with the procedure and recommendation to others administered 
at the 3-, 6-, 12-, 24- and 36-month follow-up evaluations. 
• Medications - Medication used for relief or treatment of NAO symptoms 
will be documented at screening and updated as necessary with new 
associated medications at each postprocedure evaluation through the End of 
Study visit. An increase, decrease, no change, starting new or stoppage of 
medication use compared to the first recorded use will be documented.  
5.0 
Study Plan 
5.1 Study Design 
The study is designed as a multicenter, prospective, open-label, single-arm study 
involving up to 10 sites in the US.  
All participants will be evaluated in-office prior to treatment and following treatment 
at weeks 1 and 13 (3 months). The 3-month evaluation will be used for the primary 
endpoint analysis.  
Participants will have an extended follow-up with evaluations conducted remotely at 
6 months (26 weeks), 12 months (52 weeks) 24 months (104 weeks) and 36 months 
(156 weeks).  
A subset of study sites will be selected to participate in a substudy of the use of 
computed tomography (CT) imaging to assess changes in the SBB after treatment. 
5.2 Study Population 
The target population for this study is adults suffering from symptoms attributed to 
NAO with evidence of SSB obstruction of the airway which may or may not include 
hypertrophied turbinates. This study requires severe or extreme symptoms 
demonstrated by a NOSE Scale score ≥ 55 and determination by the investigator that 
the SSBs are the primary or significant contributor to the nasal obstruction.  
Participants who have had previous surgical treatment of the nasal valve in the past 
6 months are not eligible to enroll in this study; however, it is anticipated that many 
participants will have already undergone rhinoplasty, septoplasty, IT reduction or 
other surgical procedures prior to being approached for participation in this study. 
Therefore, a history of those types of procedures does not exclude a participant from 
enrolling in this study. However, to ensure that changes in NOSE Scale score over 

 
 
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the course of follow-up are the result of the Vivaer procedure, prior surgical 
procedures must have been performed at least 6 months before the participant is 
enrolled in this study and no additional procedures should take place on the day of 
the Vivaer procedure or in the next 3 months.  
Participants must meet all inclusion and no exclusion criteria listed below for 
participation in the study. 
5.2.1 Inclusion Criteria 
1. Age 22 to 85 years (inclusively). 
2. Seeking treatment for nasal obstruction and willing to undergo an office-
based procedure. 
3. Baseline NOSE score ≥ 55. 
4. Presence of SSB hypertrophy limiting visualization of the middle turbinate 
(MT) by more than 50%.  
5. Reduction in size of the SSB after application of topical decongestant on a 
cotton plug directly to the SSB region.  
6. Improvement in the symptoms of nasal obstruction after SSB decongestion 
suggesting that the SSB may play a role in nasal obstruction. 
7. Willing and able to withhold anticoagulant medications during the 
perioperative period (3-day window on either side). 
8. Willing and able to provide informed consent.  
9. Willing and able to comply with the participant-specific requirements 
outlined in the study protocol.  
5.2.2 Exclusion Criteria 
1. Rhinoplasty, septoplasty, inferior turbinate (IT) reduction, or other surgical 
nasal procedures within the preceding 6 months. 
2. Severe case of any of the following: septal deviation, turbinate hypertrophy, 
polyps, or ptotic nose tip believed to be the primary contributor to the 
participant’s nasal obstruction symptoms and warranting surgical 
intervention. 
3. Any adjunctive surgical nasal procedure planned on the same day or within 
3 months after the Vivaer procedure. 
4. Known or suspected allergies or contraindications for any general or local 
anesthetic agents. 
5. Known or suspected to be pregnant or is lactating.  
6. Participating in another clinical research study. 

 
 
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7. Other medical conditions which in the opinion of the investigator would 
predispose the participant to poor wound healing or increased surgical risk, 
or poor compliance with the requirements of the study. 
8. Known or suspected regular use of oxymetazoline (Afrin) nasal decongestant 
or oral steroids is exclusionary. 
9. For sites participating in the CT substudy only: Active sinus condition (eg, 
significant sinus diseases, infection, or polyp formation) identified by CT. 
5.3 Study Entry and Enrollment 
Participants will be considered entered into the study upon signature of the informed 
consent document. All participants must provide written informed consent before 
undergoing any study-related procedures. Participants must be diagnosed with NAO 
prior to entry into the study and it is expected that participants will have undergone 
standard evaluations for the diagnosis of NAO as part of their regular care. 
Participants will be considered enrolled in the study upon introduction of anesthetic 
into the nasal cavity for the purpose of the study procedure. 
5.4 Outcome Measures 
5.4.1 Nasal Assessment 
The targeted nasal area within each nostril will be visually assessed for this 
study. The use of both visual and endoscope assessment is required. 
Observations are categorized as not present, mild, moderate, or severe. 
Representative endoscopic video of each nasal passage will be captured for each 
assessment.  
General assessments include: 
• Saddle nose deformity 
• Bruising around orbital area 
• Soreness, pain 
• Numbness. 
 
 
Endoscopic assessments: 
• Inflammation / generalized redness 
• Swelling, edema  
• Blanching (generalized whiteness) 
• Bleeding at anesthetic injection site (not requiring physician 
intervention) immediately postprocedure only 
• Bleeding at treatment site (not requiring physician intervention) 
immediately postprocedure only 
• Nasal obstruction from tissue edema 

 
 
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• Disruption of mucosal flow / crusting 
• SSB endoscopy grading score. The SSB endoscopy grading scale was 
developed by Catalano et al.36 to complement the more subjective NOSE 
Scale for the purpose of evaluating the degree of reduction of the SSB as 
seen clinically and is based on the ability to see the middle turbinate from 
the most anterior nares during endoscopy. Scores are assigned as: 
1 = visualization of >50% of the ipsilateral middle turbinate 
2 = visualization of <50% of the middle turbinate 
3 = no visualization of the middle turbinate. 
5.4.2 CT Assessment – Substudy – Selected Sites Only 
A subset of study sites will be selected to participate in a substudy of the use of 
CT imaging to assess changes in the SBB after treatment. 
CT imaging will be conducted prior to the procedure and at 3 months after the 
procedure using the following specifications:  
• 120 kilovoltage peak (KVp) 
• Dose reduction technique according to manufacturer 
• Anatomical Scan Range: paranasal sinus 
• Slice thickness 0.4mm minimum 
• Scan Field of View (FOV) – 15cm 
• Reformat technique – Multiplanar reformation (MPR) 
• Contrast – none  
• Save file identified with participant ID and date of scan to DICOM 
format 
• Upload DICOM images to the designated secure cloud content 
management system. 
SSB measurement adapted from Gelera et al.33 Thickness of 3 segments of the 
SSB will be measured by an independent board certified radiologist:  
• the anterior part located anterior and superior to the IT, 
• the middle or widest part located anterior to middle turbinate and 
superior to IT, and 
• the posterior part located within the anterior 1/3 of the middle turbinate 
not going beyond the crista galli.  
The posterior part of septum will be measured at the area of horizontal 
attachment of middle turbinate to the lateral nasal wall and superior turbinate 
to represent the less vasoactive part of the septum.  
Other structures or anatomy that may contribute to nasal airway passage 
compromise at or about the SSB such as nasal septal deviation, turbinate 
hypertrophy/concha bullosa, polyp/cyst, will be entered into electronic Case 
Report Form (eCRF). 

 
 
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All CTs will be reviewed by a central reviewer.  The central reviewer is a board-
certified radiologist. 
5.4.3 Nasal Obstruction Symptom Evaluation (NOSE) Scale 
Evaluation of NAO is based on clinical observations of signs and symptoms 
with no easily obtained, reproducible objective measurement techniques of the 
airway.3 Poor correlation and uncertainty between more objective measures of 
nasal patency (eg, nasal inspiratory peak flow, acoustic rhinometry, 
rhinomanometry, CT scans, physician assessment of anatomy) and 
participantive measures have generally been reported.38- 42 Since participant 
symptoms and perception of condition are the factors leading an individual to 
seek treatment, participant-reported participantive measures are cited as the 
most important determinates of treatment outcome.3,38,39 
To evaluate the significance of a participant’s nasal obstruction both before and 
after the procedure, this study will use the well-known participant-reported 
NOSE Scale for determining the primary endpoint of the study. The NOSE 
Scale is a validated disease-specific health status instrument used by clinicians 
to measure the outcome of participants treated for nasal obstruction.43 The 
NOSE Scale consists of 5 items, each scored using a 5-point Likert scale to 
make a total score range of 0 through 100, where higher scores indicate worse 
obstruction. Severity of symptoms can be classified as mild (range, 5-25), 
moderate (range, 30-50), severe (range, 55-75), or extreme (range, 80-100) 
nasal obstruction, based on responses to the NOSE Scale survey.44 
Treatment responder based on NOSE Scale score improvement: 
A responder is defined as 1 NOSE Scale class improvement (eg, going from a 
score in the severe range (55-75) at preprocedure to a score in the moderate 
range (30-50) at the 3-month evaluation), or an improvement (decrease) in 
NOSE Scale score of 20% or more from screening at the 3-month evaluation. 
5.4.4 Visual Analog Scale (VAS) for Nasal Pain   
A horizontal 100 mm VAS45 anchored on the left with the words “No Pain” and 
on the right with the words “Worst Pain Imaginable”, will be used to measure 
nasal pain associated with the procedure. Scores are obtained by measuring the 
distance in millimeters from the left origin of the line (0) to the point indicated 
with a vertical slash placed by the participant to indicate their current level of 
pain in and around the nose. 
5.4.5 Ease of Breathing Through the Nose – Numeric Rating Scale (NRS) 
Breathing Score 
Participants will be asked to describe their perception of their ability to breathe 
through the nose over the past week on a NRS from 0 to 10 where 0 is defined 
as “No Difficulty Breathing” and 10 is defined as “Extreme Difficulty 
Breathing”. 

 
 
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5.4.6 Sino-Nasal Outcomes Test 22 (SNOT-22) 
The SNOT-22 is a disease-specific, 22-item, participant-reported outcome 
measure of the prior 2 weeks of symptoms originally developed and validated 
specifically for rhinosinusitis46 that has also been described and used in the 
context of NAO.47,48 participants rate 22 different symptoms related to both 
nasal and general health on a 6-point Likert scale of no problem (0), very mild 
problem (1), mild or slight problem (2), moderate problem (3), severe problem 
(4), and problem as bad as it can be (5) and indicate up to 5 items they consider 
the most important items affecting their health. Scores on the SNOT-22 are 
scaled from 0 to110, with higher numbers representing a significant problem to 
a participant’s life. Individual studies have consistently shown that SNOT-22 
scores improve after endoscopic sinus surgery in adults with chronic 
rhinosinusitis with the minimal clinically important difference commonly 
considered to be a change of 8.9 points; however, the magnitude of changes 
across studies is quite variable.49 
The SNOT-22 has also been shown to measure 5 underlying domains, each of 
which may be impacted differently depending on the therapy or intervention 
involved.50. The domains are 3 sinus-specific symptom domains (Rhinologic, 
Extra-nasal rhinologic and Ear/Facial symptoms) and 2 general health-related 
QOL domains (Psychological and Sleep dysfunction). The domains are defined 
by grouping individual items from the 22 total items: 
• Rhinologic symptoms - Items 1, 2, 3, 6, 21, 22 (0-30 score) 
• Extra-nasal rhinologic symptoms - Items 4, 5, 6 (0-15 score) 
• Ear/Facial symptoms - Items 2, 7, 8, 9, 10 (0-25 score) 
• Psychological dysfunction - Items 14, 15, 16, 17, 18, 19, 20 (0-35 score) 
• Sleep dysfunction - Items 11, 12, 13, 14, 15 (score 0-25). 
Reporting individual domain scores may help improve the sensitivity and 
usefulness of the SNOT-22 for the specific procedure in this study.  
5.4.7 Participant Satisfaction Assessment  
Five-question self-reported survey of satisfaction using a 5-point scale to assess 
tolerability of the procedure, ease of recovery, change in breathing through 
nose, overall satisfaction with the procedure, and recommendation to others. 
5.4.8 Medications for Symptoms of Nasal Obstruction 
Medication used for relief or treatment of NAO symptoms will be documented 
at screening and updated as necessary with new associated medications at each 
postprocedure evaluation through the End of Study visit. An increase, decrease, 
no change, starting new or stoppage of medication use compared to the first 
recorded use will be documented.  

 
 
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5.4.9 Adverse Events 
Adverse events will be documented according to Section 8.1. 
5.5 Success/Failure Criteria 
Determinations of the overall success of treatment will be based on 2 levels: (1) the 
individual participant level and (2) the overall treatment success. Each level has its 
own criteria for success. 
5.5.1 Participant Success 
The primary outcome success measure for a participant in this study is based 
on an improvement (decrease) in the NOSE Scale score after the procedure 
compared to the baseline (screening) score. The improvement must reflect at 
least one category improvement or ≥ 20% decrease in score at the 3-month 
evaluation for the participant to be considered a success (responder). A 
participant will be considered a nonresponder (failure) at the 3-month 
evaluation if neither success criterion has been attained. 
5.5.2 Study Success 
The study will be considered a success if the mean improvement in NOSE Scale 
score from baseline (screening) to 13 weeks exceeds 25 points.  
5.6 Duration of the Study 
The primary endpoint will be evaluated at 3 months. In addition, evaluations at 6, 12, 
24 and 36 months after treatment will extend follow-up to 3 years for evaluation of 
longer-term efficacy. Study enrollment is anticipated to be completed within 6 
months. Therefore, total study duration is anticipated to be approximately 42 months. 
5.7 Site Staffing and Responsibilities of Study Personnel 
The principal investigator is responsible for ensuring that they have sufficient and 
qualified staff to conduct the clinical study and that all study-related tasks have been 
appropriately delegated and documented. Roles may include: 
• Investigator/Treating Physician - The Investigator/Treating Physician will 
perform the procedure and postprocedure assessments. The treating physician 
must be a medical doctor with experience in ENT procedures and trained on 
study procedures, including the administration of the Vivaer procedure for 
treatment of SSB. 
• Oversight of participant-reported outcomes and other data collection – 
Medical or office staff with relevant knowledge and experience as determined 
by the principal investigator to interact with study participants to ensure 
collection of study data and participant-reported outcomes. 

 
 
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5.8 Risk/Benefit Analysis 
5.8.1 Risks 
Potential risks associated with the use of the Vivaer ARC Stylus do not differ 
from commonly used devices and treatments for nasal obstruction and snoring, 
but due to the nonsurgical nature of the therapy, small treatment area, low 
energy delivery, and lack of need for general anesthesia, the overall risk to the 
participant may be less than presented by other surgical treatments such as RF 
turbinoplasty, septoplasty, or functional rhinoplasty. 
Potential risks associated with the use of the Vivaer ARC Stylus and the 
associated local anesthetics are listed below. participants will be monitored 
closely as part of this study to allow for early detection of potential problems 
and prompt treatment if required. 
Anticipated adverse events or side effects that may occur as a result of the 
treatment include:  
• Infection 
• Bleeding (other than during the treatment at treatment sites and greater 
than anticipated by the investigator)  
• Mucosal changes  
• Scar formation leading to nasal obstruction  
• External deformity 
• Sensory changes at treatment site   
• Bruising including around the orbital area (black eyes) 
Anticipated observations that are expected in and around the treatment area and 
are considered minor include: 
• Inflammation / generalized redness 
• Temporary swelling, edema 
• Blanching (generalized whiteness) 
• Temporary numbness/tingling 
• Temporary soreness/pain 
• Mild bleeding at anesthetic injection and/or treatment site (not requiring 
physician-level intervention, such as cautery) 
• Temporary nasal obstruction from tissue edema  
• Disruption of mucosal flow/intranasal crusting 
• Scab formation 

 
 
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These observations will be assessed in the nasal assessment and recorded at 
study visits if they occur. Should any of the events above require mitigation by 
the treating physician or be greater in severity or degree of incidence than 
anticipated, they will be considered an adverse event and will be recorded on 
the study Adverse Event Report electronic case report forms (eCRF). 
Symptomatic improvements may not be achieved in all participants receiving 
the Vivaer procedure and may not be durable beyond the 3-month evaluation in 
all participants who achieved relief at 3 months. 
5.8.2 Potential Risks to Participant Confidentiality  
In all clinical studies, confidentiality of protected health information may be 
breached due to study-related activities beyond those of routine clinical care. 
This risk will be minimized by not entering personally identifying information 
into the EDC system through the study’s eCRF. Risks to participant 
confidentiality are further minimized by allowing only authorized individuals 
to access the EDC system and the database that stores the electronically entered 
data. The 21 CRF Part 11 compliant and validated system maintains audit trails 
on all entries, changes or corrections to eCRFs. If a person with authority to 
complete but not sign eCRFs makes changes to an already signed eCRF, the 
investigator will be required to resign the eCRF, thereby protecting the integrity 
of the data collection process and the data. 
5.8.3 Mitigation of Risks 
The study was developed based on previous preclinical and clinical experience 
and includes a number of steps to minimize any additional risks to participants 
in the study: 
• Preclinical mechanical and bench evaluations have been conducted to 
demonstrate that the design characteristics of the study device are 
appropriate for reliable clinical use of the device. 
• The Vivaer ARC Stylus and Console have been cleared for use by the 
FDA based in part on prior clinical studies demonstrating safety and 
efficacy of their use and are CE-marked in the European Union. 
• The study will be reviewed and approved by an Institutional Review 
Board(s) and conducted according to applicable regulations with 
ongoing review by the IRB. 
• Careful consideration has been given to the inclusion/exclusion criteria 
in order to select appropriate candidates for treatment. 
• Participants will be fully informed of the study requirements prior to 
enrollment. 
• Only physicians with experience in nasal surgical and minimally 
invasive procedures, and with specific training using the Vivaer ARC 

 
 
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Stylus for performing the Vivaer procedure will be permitted to 
participate in the study. 
• Study procedures, follow-up, and study monitoring are designed to 
identify and closely manage adverse events in a timely manner. 
5.8.4 Study Justification in Relation to Risk 
The sponsor believes that any additional risks presented by participating in this 
study are very low and that adequate testing, safeguards, and risk monitoring 
have been incorporated into the study to further minimize and mitigate the risks 
relative to the potential benefits, including relief from symptoms of nasal 
obstruction, that may be realized by participation in this study. 
5.8.5 Benefits 
The potential benefit associated with the Vivaer procedure is to offer a 
minimally invasive treatment method that has been shown in a previous study 
to help alleviate symptoms of nasal obstruction and which has been cleared for 
use by the FDA and is CE-marked in the European Union. The Vivaer ARC 
Stylus improves nasal breathing by modifying the tissues of the nasal airway 
using low doses of RF energy. The low-power RF energy generates heat within 
the tissue and creates a coagulation lesion. As the lesion heals, the tissue retracts 
and stiffens, thereby decreasing NAO and improving airflow. In addition to 
symptom relief after correcting nasal obstruction, participants may also 
experience better sleep function and better psychological function. (eg, 
concentration, productivity, and frustration). These benefits may last beyond 
the length of the study. 
6.0 
Study Schedule and Procedures  
This section provides summaries of the study Schedule of Events and flow of 
participants through the study, as well as more detailed information on study 
procedures and processes. 

 
 
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6.1 Schedule of Events 
 
 
 
Activity / Assessment 
Screening 
Treatment 
Follow-up  
(in-office) 
Extended Follow-up 
(remote) 
Preprocedure 
Procedure 
Immediate 
Postprocedure 
1 Week 
3 Months 
(13 weeks) 
6 Months 
(26 weeks) 
12 Months 
(52 weeks) 
24 Months 
(104 weeks) 
36 months 
(156 weeks) 
 Window (days) (-30) 
(0) 
(± 3) (± 14) (± 30) (± 30) (± 30) (± 30) 
Eligibility 
X 
 
 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
 
 
Nasal Assessment (visual, 
endoscopic) 
X 
X1 
 
X 
X 
X 
 
 
 
 
CT imaging of SSB 
X2 
 
 
 
 
X 
 
 
 
 
Current medication use (study 
relevant) 
X 
 
 
X3 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
NOSE Scale 
X4 
 
 
 
 
X5 
X 
X 
X 
X 
VAS nasal pain  
 
 
 
X 
X 
 
 
 
 
 
NRS ease of breathing 
X 
 
 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
 
X 
X 
X 
X 
X 
SNOT-22 
X 
 
 
 
 
X 
X 
X 
X 
X 
Study Procedure (includes 
anethesia) 
 
 
X 
 
 
 
 
 
 
 
Adverse Events 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
1 Nasal Assessment do not need to be repeated if Screening and Treatment visits occur on the same day. 
2CT should only be performed if your site was selected for the CT substudy and only after all other screening procedures and 
participant eligibility is confirmed. 
3Add any postprocedure medications to the medication log. 
4Baseline NOSE Scale Score for analysis is defined as the Screening score. 
5Primary analysis endpoint evaluation.  
 
 
 
 
 
 
 
 
 

 
 
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6.2 Participant Flowchart 
 
 
6.3 Enrollment and Screening Assessment 
Screening 
During screening, the investigator or designated research staff will perform an 
evaluation of the study candidate for study eligibility, which will include a history 
and physical examination of the nasal area bilaterally, review of overall medical 
history, history of allergies, understanding of general health and discussion of any 
conservative measures used for NAO.  
Participants must be diagnosed with NAO prior to entry into the study. While the 
availability of the study may be discussed with a prospective participant without first 
obtaining consent, informed consent must be obtained prior to initiation of any 
clinical procedures dictated by the protocol that are performed solely for the purpose 
Consented Participants 
Vivaer procedure 
1-week follow-up 
Primary Endpoint 
Extended follow-up 
6 months 
 
12 months 
 
24 months 
 
36 months 
13-week follow-up 
Enrolled 
Participant 

 
 
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of determining eligibility to participate in the study. A participant will be considered 
as being entered into the study once informed consent is provided. Once the 
participant is entered into the study, screening assessments are completed, and the 
study treatment (preprocedure, procedure and immediate post procedure) should be 
completed within 30 days.  
Informed Consent 
Informed consent must be obtained in accordance with FDA regulation 21 CFR Part 
50 and ISO 14155. The investigator or designated staff member is responsible for 
ensuring that IRB current and approved informed consent is obtained for each 
participant prior to participation in the study, or before undergoing any procedure 
specific to the clinical investigation. The participant must be fully counseled with an 
explanation of the study background, non-randomized nature of the study, study 
procedure, follow-up schedule, and informed of their options, risks and benefits, and 
have every opportunity to ask questions about participation in the study. Any new 
information obtained during the course of the study that may affect the health of the 
participant or their decision to continue in the study will be provided to the 
participant. This process includes a thorough explanation of the informed consent 
document that the participant will be asked to sign and date acknowledging that they 
understand and desire to participate in the study. The explanation and discussion 
should be conducted in such a way as to: 
• answer the participant’s questions, 
• avoid coercion or influence of participant to participate in the study, 
• ensure the participant understands that their legal rights are not waived at any 
time, 
• use language at a level the participant can understand, and  
• ensure the participant understands that after providing signature on the 
informed consent, the participant may still withdraw at any time before, 
during or after study treatment. 
A copy of the signed informed consent document should be provided to the 
participant. 
Evaluation of Inclusion and Exclusion Criteria 
The Screening Visit / Study Eligibility eCRF will be used to document the 
participant’s eligibility status.   
Screening Data and Assessments 
The following data will be obtained at Screening and recorded on the Screening Visit 
– Demographics, Treatment History and Nasal Exam eCRF: 
• Demographics 
o Sex 
o Height (inches) 

 
 
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o Weight (pounds) 
o BMI 
o Date of birth 
o Race / Ethnicity 
• Medical history, Nasal Symptoms, History of Treatments, General Nasal 
Exam 
o History (duration) of nasal obstruction 
o History of nasal trauma 
o Related nasal symptoms  
o History of rhinitis (allergic, nonallergic), sinus disease, and/or 
obstructive sleep apnea 
o participant-reported, Medication/treatments used to address nasal 
obstruction and/or related symptoms, including continuous positive 
airway pressure (CPAP) 
o Evaluation of significant anatomic conditions that could affect 
treatment outcome (eg, severe septal deviation, turbinate enlargement, 
nasal polyps, ptotic nasal tip, and/or other external nasal deformity) 
• Nasal assessment (visual and endoscopic exam) for each nostril including 
representative video of each nasal.  
• (Selected sites only)CT to assess changes in the SSB after treatment will be 
collected at a subset of study sites. 
• Current use of medication for symptoms of nasal obstruction will be 
detailed on the Nasal Medication Log 
• Current use of devices, or other therapies. 
• Screening NOSE Scale score (completed by participant).   
• NRS ease of breathing score (completed by participant). 
• SNOT-22 (completed by participant). 
• Adverse Events. 
6.4 Treatment Visit and Procedure (Day 0) 
The treatment is summarized below and is comprised of the preprocedure, procedure 
and postprocedure as indicated on the Schedule of Events (Section 6.1). The 
treatment visit should occur within 30 days of the Screening Visit (study entry), once 
all inclusion and exclusion criteria have been met. Consult the Aerin Console 
Instructions for Use (IFU) for full detail of the standard treatment procedure and step-
by-step instructions for preparation and use of the Vivaer ARC Stylus and Aerin 
Console. 

 
 
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Preparation (preprocedure) 
The treatment will be performed in the study clinic within 30 days of study entry. 
The participant will be seated and positioned in the exam chair according to personal 
comfort and study physician’s preference (eg, upright, reclined or supine). A nasal 
assessment (visual and endoscopic exam) will be performed on each side of the nose 
and for each nostril, including endoscopic video. This is to assess the configuration 
of the structural components of the lateral nasal wall (including the upper and lower 
lateral cartilage, their junction and the overlying mucosa), location of SSB and the 
MT to allow the study physician to map out and plan the areas of treatment. If the 
Screening and Treatment visits occur on the same day, the nasal assessment does not 
need to be repeated for Preprocedure. 
Following the nasal assessment, it is recommended the study physician prepare the 
treatment area with a topical anesthetic agent (eg, lidocaine, tetracaine, etc.) and 
applying via spray, gel, or saturated pledget placed within the nose. After an 
appropriate amount of time, the SSB is then visualized with an endoscope and 
infiltrated in a submucosal plane with a small amount of local anesthetic to provide 
adequate tissue analgesia as well as tumescence to facilitate radiofrequency energy 
transfer. For example, cottonoid pledgets saturated with 4% lidocaine are placed in 
the nasal passages adjacent to the septum; after 5 minutes, these pledgets are removed 
and the swell body is injected bilaterally with 0.4 cc of 1% lidocaine with 1:100,000 
epinephrine on each side.  
Treatment administration 
Once the nasal cavities have been anesthetized, participants will undergo bilateral 
treatment of the SSB in a single study procedure session. Each side of the nose will 
be treated as follows 
• A nasal speculum is inserted into the nostril and opened to visualize the 
treatment area. The Vivaer ARC Stylus will then be inserted to access the 
treatment area. The Stylus will be connected to the Aerin Console generator and 
the RF energy level will be set on the generator. 
• Two (2) to six (6) nonoverlapping applications of RF energy are performed at 
the SSB per nostril. 
• For the SSB, Vivaer ARC stylus default settings will be employed. (Figure 4). 
 

 
 
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Figure 4. Vivaer ARC Stylus applied at SSB  
 
The default settings for the Vivaer ARC Stylus: 
Temperature  
60° C 
Power  
 
4 Watts 
Treatment Time 
18 secs 
Cooling Time  
12 secs 
The Aerin Console is activated by depressing the foot pedal. With the Vivaer ARC 
Stylus pressed against the tissues in the desired treatment locations, the foot pedal is 
depressed, and the Stylus is gently pressed against the nasal tissues to deliver RF 
energy to the tissues consistent with the IFU. A tone sounds when the Console is 
activated, signifying that energy is being delivered through the Stylus. The tone stops 
when the pedal is released, and RF energy is no longer being delivered.  
No repeat ("touch-up") procedures will be permitted during the study follow-up 
period. Additionally, for the purposes of this study, no other concomitant treatments 
are permitted during this treatment or the follow-up period. 
Procedure data collection 
Data relating to the procedure and the products used will be recorded on the Study 
Procedure eCRF. The following information will be recorded: 
• Date of procedure. 
• Procedure and postprocedure medications (including anesthesia). 
• Aerin Console serial number. 
• Procedure start and end times. 
• Aerin Console settings. 
• Treatment duration and number  of sites treated for SSB. 
• Occurrence of device malfunctions, protocol deviations, and/or adverse 
events. 

 
 
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6.5 Postprocedure Assessments and Care 
Immediately postprocedure, a nasal assessment (visual and endoscopic exam) for 
each nostril including endoscopic video will be conducted prior to discharging the 
participant and reported on the Study Procedure eCRF.   
Participants will be asked to indicate the pain level experienced during the study 
procedure from anesthesia delivery to procedure completion using the VAS pain 
score instrument on the Pain VAS CRF. 
At the discretion of the study physician, the following care may be provided and 
should be documented: 
• Use of nasal saline spray and antibiotic ointment 2 to 3 times daily for 1 week. 
• The participant should be instructed not to manipulate the treatment site (i.e., 
no nose blowing) for 24 hours with the exception of any necessary 
hemostasis. 
• Remind participant to continue to hold all anticoagulants for 3 days post 
procedure. 
Participants should have their first study follow-up visit (1 week +/- 3 days) 
scheduled within the visit window prior to release. 
Participants should not receive other concomitant nasal treatment therapies (other 
than those specified above) or interventions after the procedure through the 36-month 
follow-up to avoid confounding the evaluation of the effect of the treatment, unless 
the additional care is in response to an adverse event or is considered in the best 
interest of the participant. Should a treatment or procedure be in the best interest of 
the participant, it must be documented in the source.  The participant will remain in 
the study and be followed through 36 months. Concomitant nasal treatments will be 
monitored at follow-up evaluations.   
6.6 Follow-up Evaluations and Study Exit 
Follow-up visit dates will be calculated from the study procedure date (Day 0). 
Follow-up visits should be scheduled within the specified visit windows described in 
the Schedule of Events (Section 6.1) and Table 1 (Section 9.3.2). An in-office follow-
up evaluation is scheduled for 1 week and 13 weeks (3 months) after the procedure. 
In addition, follow-up evaluations at 26 weeks (6 months), 52 weeks (12 months), 
104 weeks (24 months) and 156 weeks (36 months) after the treatment procedure will 
be conducted remotely as a telephone assessment by site personnel. The timing of all 
follow-up evaluations is based on the date of the procedure and should not be altered 
based on the actual time of preceding follow-up visits. Participants who make non-
study visits should be evaluated for possible adverse events and an Adverse Event 
Report eCRF should be submitted if appropriate. 
All participants should be followed through the final follow-up evaluation at 156 
weeks (36 months) postprocedure regardless of their earlier success/failure 
classification. Every effort should be made to avoid having participants withdraw 

 
 
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from the study (Section 10.6). If a participant does choose to withdraw from the 
study, it is very important to record information regarding the reason(s) and the last 
known status of the participant. 
The following assessments will be conducted as indicated for each follow-up time 
points and recorded on the Follow-up Visit eCRF: 
In-office evaluation - 1 Week: 
• Nasal assessment (visual and endoscopic exam) for each nostril including 
endoscopic video. 
• Current use and any change in use of medication. 
• VAS for pain score (completed by participant). 
• Adverse events. 
In-office evaluation - 3-month (13 Weeks): 
• Nasal assessment (visual and endoscopic exam) for each nostril including 
endoscopic video. 
• Review of current use and change in use of medication for symptoms of nasal 
obstructions. 
• NOSE Scale score (completed by participant). 
• NRS ease of breathing score (completed by participant). 
• SNOT-22 (completed by participant).  
• CT imaging (Substudy – selected sites only). 
• Participant Satisfaction Survey (completed by participant). 
• Adverse events. 
Remote evaluations - 6-month (26 Weeks), 12-month (52-Weeks), 24-month (104-
Weeks) and 36-month (156-Weeks) follow-up: 
• Current use and participant-reported change in use of medication, and other 
therapies for symptoms of nasal obstruction and participant-reported changes 
in frequency of use. 
• NOSE Scale score (verbal administration by site personnel). 
• NRS ease of breathing score (verbal administration by site personnel). 
• SNOT-22 (verbal administration by site personnel). 
• Participant Satisfaction Survey (verbal administration by site personnel).  
• Adverse events (study staff follow-up required if participant indicates an 
event). 

 
 
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Study exit: 
Participants meeting the study requirements as planned will be exited from the study 
upon completion of the 36-month follow-up evaluation. If a participant reaches the 
36-month follow-up evaluation and is experiencing a new or ongoing adverse event, 
the study sponsor should be contacted to discuss the need and/or methods for 
continued surveillance of the event. 
Study exit applies to those participants where data is no longer collected for a study 
participant. A Study Exit form should be completed and entered into the electronic 
data capture (EDC) Systems in the following cases: 
• Completion of 36 month participant questionnaires 
• Signed consent but no procedure took place (eg, screen failure) 
• Participant was unable to complete the follow-up visits 
• Withdrawal of informed consent 
• Physician exited participant based on medical or surgical necessity or 
other reason  
• Participant received treatment outside of the study that, in the opinion 
of the investigator, would affect the study results. 
• Lost to follow-up (3 attempts should be made and documented in the 
participant’s record indicating due diligence by the site) 
o If a participant misses a questionnaire window and cannot be 
contacted, the participant may remain in the study, as contact may be 
re-established for a future questionnaire window period. (Any missed 
study assessment is considered a protocol deviation.)Participant 
withdrawal should be reported within 5 days of site becoming aware. 
participant death should be reported within 24 hours to Aerin Medical.  
• Participant Death 
6.7 Product Handling and Accountability 
A system that allows tracking of orders, shipping and returns will be used to control 
the Vivaer ARC Stylus inventory. The devices will be packaged and labeled to clearly 
indicate that they are for clinical study use only and must only be used for participants 
enrolled in this study. All devices not used must be returned to the sponsor disposed 
of in accordance with the sponsor’s instructions. The investigator is responsible for 
adequate record keeping regarding the receipt, use, and final disposition of study 
inventory. 
7.0 
Statistical Considerations 
7.1 Study Design 
This is a prospective, multicenter, open-label, single-arm study to assess the Vivaer 
procedure for treatment of SSB to improve symptoms in those diagnosed with NAO. 
This study is designed to assess improvement in symptoms from prior to the 
procedure to a primary endpoint at 3 months after the procedure and out to 36 months. 

 
 
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7.2 Study Hypotheses 
The primary endpoint hypothesis for the primary study objective is designed to 
demonstrate that the mean improvement in participant NOSE Scale score from the 
baseline assessment at screening to 13 weeks exceeds 25 points. Note that 
improvement is represented by a decrease in NOSE score. The null hypothesis (H0) 
is that the decrease in mean NOSE Scale score will be less than 25 points and the 
alternative hypotheses (H1) is that the decrease will be more than 25 points: 
H0: µd ≥ −25.0 
H1: µd < −25.0,  
where µd represents the mean change in NOSE Scale score from baseline to 13 weeks 
(13-week NOSE Scale score − baseline NOSE Scale score). Rejection of the null 
hypothesis in favor of the alternative hypothesis (H1) means that there is evidence for 
a statistically significant reduction in mean NOSE Scale score from baseline to 13 
weeks postprocedure. 
The secondary endpoint hypothesis for the primary study objective is designed to 
show that the proportion (percent) of participants meeting the responder definition 
will exceed 0.55 (55%) at 13 weeks. The null hypothesis (H0) is that the proportion 
of responders will be equal to .55 (55%) and the alternative hypotheses (H1) is that 
the proportion of responders will exceed 0.55 (55%): 
H0: p0 = 0.55 
H1: p > 0.55,  
where p0 represents the targeted minimum responder proportion at 13 weeks and p 
represents the expected proportion at 13 weeks.  
7.3 Power Analysis and Sample Size Estimate 
The study will enroll up to 70 participants. The power analysis was performed such 
that there is adequate power to reject the null hypothesis for both the primary 
effectiveness endpoint and for the principal secondary endpoint. 
The statistical power (1 – β) for the primary effectiveness endpoint that, on average, 
there is at least a 25-point improvement in the NOSE Scale score from the 
pretreatment assessment to the assessment at 13 weeks: 
Statistical Hypothesis: 
H0: µd > -25.0 versus H1: µd < -25.0 
where µd is the average change from screening (baseline) 
in the NOSE Scale score at 13 weeks post treatment 
Statistical Methodology: 
Single-sample paired t-test 
Expected µd: 
-50 
Standard Deviation: 
20 
Significance Level: 
One-sided α = .025 

 
 
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Minimum Sample Size: 
70 Participants  
Statistical Power: 
0.99 
The statistical power (1 – β) for the secondary endpoint is such that at least 55% of 
the treated participants respond to treatment, defined as either at least one NOSE 
Scale class improvement, or at least a 20% improvement in the NOSE Scale score, 
both assessed at 13 weeks posttreatment: 
Statistical Hypothesis: 
H0: π < 0.55 versus H1: π > 0.55 
where π is the proportion of participants responding to 
treatment 13 weeks posttreatment 
Statistical Methodology: 
Single-sample chi-square test 
Expected π: 
0.80 
Significance Level: 
One-sided α = .025 
Minimum Sample Size: 
70 Participants  
Statistical Power: 
0.99 
With at least 70 treated participants, we can be 95% confident that we will observe 
at least one unexpected serious device-related event when the underlying incidence 
of that event is at least 2.3%. 
It is anticipated that participants will be enrolled at sites on a competitive basis; 
however, a reasonable balance of participants among sites may be maintained by 
potentially capping enrollment at individual sites based on the final number of 
participating sites. 
7.4 Timing of Analysis 
The primary evaluation phase of the study lasts until all participants have reached the 
primary endpoint at 13-weeks (3-month) postprocedure. The primary and secondary 
endpoints will be analyzed using the data from the primary evaluation phase for an 
interim study report when these data become available. Informational outcomes will 
be analyzed and may be included in interim reports after all participants have reached 
each of the successive follow-up time points. A final study report will be provided 
after all participants have reached the final 36-month follow-up evaluation of the 
extended follow-up phase of the study. 
7.5 Analysis Populations 
All enrolled participants entered in the study will comprise the safety population and 
will be subject to all safety analyses. All enrolled participants undergoing the 
procedure (initiation of anesthesia) represent the evaluable study population. For 
some evaluations, summaries will be presented by nostril. The per-protocol 
population is defined as all participants who received treatment, with 13-week (3-
month) follow-up data and no major protocol deviations. 

 
 
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7.6 Missing Data 
Every effort will be made to obtain complete follow-up data for all participants, and 
it is anticipated that analysis of the primary and secondary endpoint hypotheses will 
be conducted using all available complete data. The effect of missing data will be 
examined by imputing missing NOSE scores as no change from baseline and as 
nonresponders.  
Other outcome measures will be analyzed by using available data only. 
7.7 Pooling 
All study data will be pooled across study sites to facilitate hypothesis testing in 
accordance with the sample size estimation and power analysis (Section 7.3). 
Comparability between study sites may be shown using summary statistics calculated 
by site. 
7.8 Participant Disposition 
A detailed description of participant disposition will be provided using a CONSORT 
diagram and summaries of participants falling in various subgroups of interest, such 
as, consented but not treated, discontinued, major protocol deviations, deaths, and 
withdrawals. All study population exclusions and reasons will be summarized. All 
participants entered in the study will be accounted for in the summary. Follow-up by 
visit will be presented, showing theoretical, expected, and actual follow-up visits. 
7.9 Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized using frequencies and 
percentages for categorical factors and mean, median, SD, minimum and maximum 
for continuous factors.  
7.10 Primary Endpoint Analysis 
The primary endpoint hypothesis of change from baseline to the 13-week endpoint 
will be analyzed using a paired t-test at the 1-sided alpha .025 level and presented as 
the mean change with associated 1-sided lower confidence bound. 
7.11 Secondary Endpoint Analysis 
The secondary endpoint hypothesis will be tested only after the primary endpoint of 
the study is met. The secondary hypothesis will be evaluated using the proportion of 
responders on the primary outcome measure at 13 weeks. A responder is defined as 
having improvement in NOSE Scale score of ≥ 20% from baseline or at least one 
NOSE Scale class improvement.  
The hypothesis will be tested at the 1-sided alpha .025 level with a single proportion 
binomial test. The responder proportion (percent) will be presented with the 
associated 95% confidence interval. The secondary endpoint will be met if the lower 
bound of the confidence interval exceeds 0.55 (55%). 
The frequency (proportion) of septal perforation will be calculated along with the 
95% confidence interval along with a summary of each event. 

 
 
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The frequency (proportions) of serious device-related adverse events and procedure-
related adverse events will be calculated along with the 95% confidence interval 
along with a summary of each serious event. 
7.12 Other Outcome Measures Analyses 
Additional outcome measures will be collected for information and hypothesis 
generating purposes. The primary analysis methods will be descriptive and 
exploratory and presented by evaluation to more completely understand the time 
course of treatment effect. Measures will be summarized using frequencies and 
percentages for categorical measures and mean, median, SD, minimum and 
maximum for continuous factors. Statistical comparisons will either not be performed 
or used for information purposes. Proportions may be compared using exact tests, 
chi-square tests, or general linear models. Continuous outcomes may be compared 
using t-tests or nonparametric equivalents. Repeated measures linear mixed models 
may be used for longitudinal analysis across evaluations. 
Other outcome measures include: 
• Nasal Assessment - The visual and endoscopic assessment factors will be 
summarized to include frequency and percentage of responses in each 
category for each component of the nasal assessment by treatment group at 
screening, just prior to procedure (if screening and procedure occur on 
different days), immediately after procedure and at 3 months. The 
distribution of SSB grades prior to the procedure and at each follow-up will 
be summarized along with the mean scores and change from screening. 
• Radiographic Imaging - A subset of study sites will be selected to 
participate in a substudy of the use of CT imaging to assess changes in the 
SBB after treatment. SSB measures from CT scans will be summarized and 
presented as means at screening and at 3 months and as the mean change 
from screening to 3 months.  
• NOSE Scale score - Categorical responses and scores on the NOSE Scale 
and its individual components will be subject to multiple summary methods 
and analyses including the:  
o Mean and mean change from preprocedure at the 3-, 6-, 12-, 24- and 
36-month follow-up evaluations. 
o Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, 24- and 36-month 
follow-up evaluations for each group. 
o Mean, change from preprocedure in mean, and response distribution 
of the 5 components of the NOSE Scale score (nasal congestion, 
nasal blockage, trouble breathing, trouble sleeping, and getting 
enough air during exercise) at the 3-, 6-, 12 24- and 36-month 
follow-up evaluations for each group. 

 
 
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o Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, 24- and 36-month follow-up evaluations for 
each group. 
• VAS for nasal pain- Summary will include mean NRS pain scores assessed 
postprocedure. 
• NRS for ease of breathing - Summary will include mean and mean change 
from baseline (screening) of ease of breathing scores assessed at screening 
and at each follow-up evaluation. 
• SNOT-22 - mean and change from baseline (screening) in mean SNOT-22 
score and individual domain scores will be summarized at the 3-, 6-, 12-, 
24- and 36-month follow-up evaluations. 
• Participant Satisfaction Assessment - mean response for each of the 5 
survey questions will be summarized at the 3-, 6-, 12-, 24- and 36-month 
follow-up evaluations. 
• Medications - Medication, and other therapies associated with relief or 
treatment of NAO symptoms will be documented at screening and updated 
as necessary with changes to any treatment and any new associated 
medications at each postprocedure evaluation. An increase or decrease in 
frequency of use or dose, no change, starting new or stoppage of medication 
use compared to the first recorded use will be documented.  
7.13 Subgroup Analysis 
A subgroup analysis of primary and secondary efficacy measures based on allergic 
or nonallergic classification will be performed for the 3-month endpoint using a 2-
sample t-test to compare changes in mean NOSE Scale score between the 2 groups 
and a 2 sample binomial or exact test to compare the responder percents between the 
2 groups.  
Other exploratory subgroup analyses may be performed based on demographic, 
procedural, or other identified characteristics. Potential baseline covariates with 
possible impact on outcomes at 3 months are: 
• Age  
• Race 
• Sex 
• BMI 
7.14 Safety Analysis 
All adverse events, collected from the time of study consent (study entry) until the 
end of the study will be analyzed for all participants. Adverse events may occur 
during the treatment phase or during the follow-up phase. AEs occurring after the 
screening assessment but before the procedure (application of anesthesia) will be 

 
 
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documented in the participant’s medical record and EDC but will not count as related 
to the study device or procedure. Adverse events will be coded using a custom Aerin 
Medical dictionary so that adverse events may be categorized for analysis at an 
appropriate level of detail. Listings will be provided to detail individual events. The 
number of participants, number of AEs, and the proportion of participants reporting 
each AE will be summarized. Seriousness and severity of AEs and their relationship 
to the device and procedure will be summarized. A time course of adverse events will 
be presented. Any unexpected adverse device experiences or adverse events that 
occur at an unexpectedly high incidence rate will receive detailed analyses. 
Narratives will be presented for all deaths, serious adverse events, unexpected 
adverse device experiences, and participants withdrawn due to an adverse event. 
7.15 Follow-up Phase Analysis 
The follow-up phase analyses will be similar to those detailed above with a particular 
emphasis on the summarization of all adverse events occurring throughout the entire 
study and the maintenance of the treatment effect over time. Missing data analyses 
and imputation will not be performed on data collected during the extension phase. 
7.16 Standard Methods of Report 
Summary descriptive statistics including means, medians, standard deviations and 
histograms for continuous measures, and frequencies and percentages for categorical 
outcomes will be presented for all variables of interest. Outcome measures (primary, 
secondary, and informational) will be presented by evaluation. 
8.0 
Adverse Events and Product Complaints / Device Deficiencies 
8.1 Adverse Events 
All adverse events, collected from the time of study consent (study entry) until the 
end of the study will be analyzed for all participants. Adverse events may occur 
during the treatment phase or during the follow-up phase. AEs occurring after the 
screening assessment but before the preprocedure (application of anesthesia) will be 
documented in the participant’s medical record and EDC but will not count as related 
to the study device or procedure.   
8.1.1 Definitions 
Following are definitions associated with AEs: 
Adverse Event - any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory or image 
findings) in participants, users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated (per 
ISO 14155) 
Note: This definition includes events related to the investigational medical 
device or the comparator. This definition also includes events related to the 
procedures involved. For users or other persons, this definition is restricted to 
events related to the use of investigational medical devices.   

 
 
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Serious Adverse Event (SAE) - an adverse event that led to any of the following 
(per ISO 14155) 
a) death, 
b) serious deterioration in the health of the participant, users or other 
persons as defined by one or more of the following:  
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function 
including chronic disease, or  
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure or 
a body function, 
c) fetal distress, fetal death, or a congenital abnormality, or birth defect 
including physical or mental impairment. 
Note: Planned hospitalization for a pre-existing condition, or a procedure 
required by the protocol, without serious deterioration in health, is not 
considered a serious adverse event.  
Adverse Device Effect (ADE) – adverse event related to the use of an 
investigational medical device.  
Note: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. This 
definition also includes any event resulting from use error or from intentional 
misuse of the investigational medical device. This includes comparator if the 
comparator is a medical device  
Serious Adverse Device Effect (SADE) – an adverse device effect that has 
resulted in any of the consequences characteristic of a serious adverse event 
(per ISO 14155). 
Unanticipated Adverse Device Effect (UADE) - any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan 
or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of participants (21 CFR 812.3(s)). 
Relationship to device and procedure 
The potential relationship of the event to the device or procedure will be 
categorized by the investigator as follows: 

 
 
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• Not related 
An adverse event for which sufficient information exists to indicate that 
there is no causal connection between the event and the device or 
procedure. The adverse event is due to and readily explained by the 
participant’s underlying disease state or is due to concomitant 
medication or therapy not related to the use of the device or the 
procedure. In addition, the adverse event may not follow a reasonable 
temporal sequence following the procedure. 
• Unlikely 
The relationship with the use of the device or procedure seems not 
relevant and/or the adverse event can be reasonably explained by 
another cause, but additional information may be obtained.  
• Possibly related 
There is a reasonable possibility that the adverse event may have been 
primarily caused by the device or procedure. The adverse event has a 
reasonable temporal relationship to the use of the device or the 
procedure and follows a known or expected response pattern to the 
device or procedure, but alternative etiology is equally or more likely 
compared to the potential relationship to the use of the device or the 
procedure. 
• Probably related 
There is a reasonable probability that the adverse event may have been 
primarily caused by the device or procedure. The adverse event has a 
reasonable temporal relationship to the use of the device or the 
procedure and follows a known or expected response pattern to the 
device or procedure, and an alternative etiology is unlikely or 
significantly less likely. 
• Definitely related 
The adverse event has a strong causal relationship to the device or 
procedure. The adverse event follows a strong temporal relationship to 
the use of the device or the procedure, follows a known response pattern 
to the device or procedure, and cannot be reasonably explained by 
known characteristics of the participant’s clinical state or other 
therapies. 
Every effort should be made to determine the cause of each adverse event, 
because a judgment must be made as to the relationship to the device or 
procedure. If an investigator cannot assign a causality category the event will 
be considered possibly related for reporting and analysis. 

 
 
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Note: The occurrence of a diagnostic or elective surgical procedure for a pre-
existing condition, unless the condition becomes more severe or increases in 
frequency, would not be considered procedure- or device-related. 
Intensity of adverse events:  
• Mild 
The adverse event is noticeable to the participant but does not interfere 
with routine activity. 
• Moderate 
The adverse event interferes with routine activity but responds to 
symptomatic therapy or rest. 
• Severe 
The adverse event significantly limits the participant's ability to perform 
routine activities despite symptomatic therapy. The adverse event 
requires medical or surgical treatment or results in hospitalization. 
8.1.2 Documentation and Reporting of Adverse Events 
All adverse events will be monitored from the time of study entry through study 
exit. All adverse events must be reported on the Adverse Event Report eCRF. 
A description of the event, including onset date, resolution date, action taken, 
and the outcome should be provided. All adverse events will be followed until 
they are adequately resolved or reach a chronic, stable state.  If a participant 
reaches the 36-month follow-up visit and is experiencing a new or ongoing 
adverse event, the sponsor should be contacted to discuss the need and/or 
methods for continued surveillance of the event. Adverse events will be 
evaluated by the investigator and differentiated by: 
• Seriousness 
• Intensity (mild, moderate, severe) 
• Causality (in relation to the device or procedure) 
• Unexpectedness  
Signs and symptoms considered normal postprocedure recovery (eg, 
postprocedure pain, transient sensory symptoms, fever, postanesthesia 
symptoms) do not have to be reported as adverse events. If these events require 
treatment outside that which is considered normal or if the event lasted longer 
in duration than normal, they should be reported as adverse events.   
All adverse events classified as an Unanticipated Adverse Device Effect, 
Serious Adverse Device Effect, or Serious Adverse Event must be reported 
to the sponsor within 24 hours of learning of the event.  
Sponsor Contact: Anais Laborde  
Phone: 650-518-9624 
Email: alaborde@aerinmedical.com  

 
 
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Investigators must also report promptly all unanticipated problems to their 
IRB/EC and/or regulatory authority involving risks to participants or others and 
report adverse events according to the local or national reporting requirements. 
Reporting instructions and contact information will be provided in the site’s 
Regulatory Binder for this study. 
8.2 Product Complaints / Device Deficiencies 
8.2.1 Definitions 
Product Complaint - Any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness, or performance of an Aerin product (medical device) after it is 
released for distribution (per 21 820.3(b)). 
Complaint – written, electronic or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, usability, safety or 
performance of a medical device that has been released from the organization's 
control or related to a service that affects the performance of such medical 
device (per ISO 13485). 
Reportable Complaint – Any product complaint that represents an event, which 
must be reported to a regulatory agency including: 
• US FDA (per 21 CFR Part 803) 
• A Competent Authority within the European Community or a Notified 
Body (MDD) 
• The Canadian HPFB 
• Any regulatory agency, within the country of distribution 
Device Deficiency – inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, usability, safety or performance. 
Note: Device deficiencies include malfunctions, use errors, and inadequacy in 
the information supplied by the manufacturer including labeling. This 
definition includes device deficiencies related to the investigational medical 
device or the comparator (per ISO 14155). 
8.2.2 Documentation and Reporting of Complaints / Device Deficiencies 
All product complaints, deficiencies and malfunctions associated with devices 
will be documented on the appropriate eCRF and/or communicated to the 
sponsor within 24 hours of first becoming aware of the event.  
9.0 
Study Administration 
This study will be conducted in accordance with elements of ICH E6 Guideline for 
GCP, Abbreviated Requirements of 21 CFR 812 for nonsignificant risk device studies, 
the European Standard ISO 14155, the Declaration of Helsinki, the Belmont Report, 
and any applicable regional or national regulations. 

 
 
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The sponsor has the overall responsibility for the conduct of the study according to all 
applicable regulatory requirements. The sponsor will have certain direct 
responsibilities and will delegate other responsibilities to the investigator and study 
site. The sponsor and investigator will ensure that the study is conducted according to 
all applicable regulations. All personnel participating in the conduct of this study will 
be qualified by education and experience to perform their tasks. 
The sponsor, treating physician, or any person acting for or on behalf of the sponsor or 
investigator shall act in accordance the applicable standards, guidelines and 
regulations. 
This study is funded by Aerin Medical. The Clinical Trial Agreement (CTA), mutually 
signed by the study site and Aerin Medical, describes the agreement between sponsor 
and site with respect to study financing. 
9.1 Investigator Training 
Site initiation training will occur prior to the first procedure at a site. Investigators 
will be trained on the procedure and use of the Vivaer ARC Stylus and Aerin Console. 
All study staff will be trained, as necessary, to ensure compliance with the protocol 
and regulatory requirements, as well as to ensure accurate data collection. Site 
training will include a detailed review of this protocol, use of the EDC system, eCRF 
completion instructions, adverse event reporting, product handling and inventory, 
monitoring logistics, and regulatory requirements. 
9.2 Study Monitoring 
Study monitoring will be carried out in compliance with FDA regulations, ISO 
14155, and Good Clinical Practice (GCP) guidelines. The monitoring for this study 
will be carried out by monitors qualified by experience and training who are Aerin 
Medical employees or individuals contracted by Aerin to conduct monitoring 
activities. The study monitors will oversee the conduct of the study either on-site or 
remotely and evaluate compliance with the protocol, any specific recommendations 
made by the site’s IRB and the signed Investigator Agreement. During the study, 
phone contacts and site visits will be conducted to ensure protocol compliance. 
Monitoring will include a verification the informed consent was properly obtained 
for all study participants, a review of clinical records for accuracy and completeness, 
resolution of missing or inconsistent results, a review of source documents, and 
ensuring adverse events, protocol deviations and device usage are properly 
documented. The monitor will conduct source data verification by verifying eCRFs 
are consistent with source documents. The investigator will make available to the 
monitor for review the informed consent forms, source documents, and any other 
relevant records for all study participants at the site. The investigator and other site 
personnel will be accessible to the monitor during visits whether on-site or remote 
and sufficient time is provided to conduct the visits and address questions. If the 
monitor becomes aware of any deficiencies during the course of the study, the 
monitor will discuss with the sponsor and investigator to ensure compliance is 
maintained. A final close-out monitoring visit will occur when the study has been 
completed or terminated. 

 
 
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9.3 Documentation of Study Findings 
9.3.1 Data Management 
A secure EDC and management system will be used for entry, storage, review, 
and management of study data. The system will use the Medrio EDC platform 
(Medrio, Inc. San Francisco, CA) and be compliant with applicable GCP and 
regulatory requirements. Investigators are responsible for accurate completion 
and timely submission of the data collected during the study. Sites will be 
trained in the use of the system for entering study data and uploading supporting 
documents and will be given access for this purpose. Data monitoring will be 
performed to identify missing data, verify data accuracy, and ensure queries are 
resolved. Any data issues are to be promptly addressed with the investigator. 
Quality assurance procedures will be established to ensure that complete, 
accurate and timely data are submitted, protocol requirements are followed, and 
that complications, adverse events and adverse device effects are correctly 
reported and investigated as appropriate. The management and retention of 
these data will be compliant with applicable regulatory requirements.   
9.3.2 Case Report Forms 
Standardized electronic case report forms (eCRFs) will be used at all 
participating study sites to collect complete and accurate records of the clinical 
data. All study data will be entered by study personnel through eCRFs for each 
participant screened in the study. A unique ID number will be assigned to each 
participant.  
The following eCRFs and logs will be used in this study and submitted at the 
intervals outlined in Table 1: 
• Screening Visit / Study Eligibility (01) 
• ICF Checklist (01A) 
• Screening Visit – Demographics, Treatment History & Nasal Exam 
(02) 
• CT Settings Checklist (02A) (selected sites only) 
• NOSE Scale (03) 
• NRS Ease of Breathing– Participant form (04) 
• SNOT-22 (05) 
• Preprocedure (06A) 
• Anesthesia and Procedure (06B) 

 
 
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• Immediate Postprocedure (06C) 
 
• VAS for nasal pain – Participant form (07A) 
• VAS for nasal pain – Site form (07B) 
• Follow-up Visit (08) 
• Participant Satisfaction Survey (09) 
• Study Exit (10) 
• Device Malfunction Report (11) 
• Protocol Deviation (12) 
• Adverse Event Report (13A) (reference AE Code List [13B]) 
• Serious Adverse Event / Unanticipated Adverse Device Effect  
• (SAE / UADE) Report (14) 
• Medication Log (15) 
• Unscheduled Visit (16) 

 
 
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Table 1.  Schedule of case report forms and related materials. 
Visit 
Visit Window 
(days) 
eCRF 
Other 
Screening 
n/a 
01, 01A,02, 
02A*,03, 04, 05, 15 
Informed Consent 
Nasal assessment images† 
CT imaging* 
Study Procedure 
(preprocedure/anesthesia/treatment) 
within 30 days of 
Screening 
06A, 06B,  
Nasal assessment images† 
Nasal assessment does not 
get repeated Preprocedure 
if the Screening and 
Treatment visits occur on 
the same day 
Postprocedure 
0 
06C, 07A, 07B, 15 
Nasal assessment images† 
1-Week (In-office) 
+3 
07A, 07B, 08, 15 
Nasal assessment images† 
13-Week (In-office) 
±14 
02A*,03, 04, 05, 
08, 09, 15 
Nasal assessment images† 
CT imaging* 
6-Month (Remote) 
±30 
03, 04, 05, 08, 09, 
15 
 
12-Month (Remote) 
±30 
03, 04, 05, 08, 09, 
15  
 
24-Month (Remote) 
±30 
03, 04, 05, 08, 09, 
15 
 
36-Month (Remote) 
±30 
03, 04, 05, 08, 09, 
10, 15 
 
As Needed 
n/a 
10, 11, 12, 13A, 
13B, 14, 16 
 
†Copy de-identified endoscopic video/images collected for study records to USB flash drive and provide to Sponsor. 
*Sites selected for substudy only 
9.3.3 Investigator Responsibilities, Records, and Reports 
Responsibilities 
The investigator is responsible for ensuring that the study is conducted 
according to the protocol and all IRB requirements. In addition, the investigator 
is responsible for obtaining participant’s written informed consent and written 
authorization for disclosure and use of health information as required under the 
Health Insurance Portability and Accountability Act (HIPAA); 45 CFR Parts 
160 and 164), or other documentation as required by the IRB and national 
regulations. 
Records 
The investigator will maintain complete, accurate and current study records.  
Investigator records including: 
1. Relevant communication that documents any agreements or significant 
discussions regarding trial administration, protocol violations, trial 
conduct, or adverse event reporting, including that with the IRB, the 
sponsor, the study monitors, other investigators, and regulatory 
agencies. 

 
 
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2. Participant records, including the participant’s informed consent form, 
case history, procedure dictation, adverse events, progress notes, 
follow-up evaluations, case report forms and all supporting documents, 
such as diagnostic studies.  
3. Study protocol, amendments, and documentation (dates and reasons) of 
any deviations from the protocol. 
4. IRB records, including original and ongoing study approvals, all 
correspondence, and the approved informed consent form(s). 
5. IRB membership list, Federal Wide Assurance for the Protection of 
Human participants (FWA) as applicable, statement of compliance and 
written procedures pertaining to AE and Protocol Deviation reporting 
(if available).  
6. Study agreement, curricula vitae of investigator(s), financial disclosure, 
signature authorization log (delegation of responsibility), protocol 
signature page, and participant screening/enrollment log. 
7. Reports (including safety reports, progress reports and a final report 
from the investigator). 
8. Any other records, as required by the IRB and the sponsor. 
Reports 
Investigators are required to prepare and submit the following reports in a 
complete, accurate, and timely fashion: 
1. In the event of an adverse experience that is serious or unanticipated, or 
which requires action by sponsor to prevent an unreasonable risk of 
substantial harm to public health, notice shall be given immediately (but 
in no event later than 24 hours after learning of such experience) by 
telephone or email to the sponsor and the IRB. Any notices made by 
telephone shall be confirmed in writing within 2 days of the initial 
notification. The site shall provide all associated documentation (eg, lab 
reports, death summary, operative reports, etc.) for each adverse 
experience. 
2. Unanticipated adverse device effects and serious adverse events should 
be reported to the sponsor within 24 hours of event discovery. If the 
adverse event is alarming, the investigator shall report the event 
immediately. 
3. Investigators shall promptly report to the IRB all changes in the research 
activity and all unanticipated problems involving risk to participants and 
others, and that s/he will not make any changes in the research without 
IRB approval, except where necessary to eliminate apparent hazards to 
the participants. 

 
 
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4. Withdrawal of IRB approval reported to the sponsor within 5 working 
days. The report will include a complete description of the reason that 
approval was withdrawn. 
5. Progress reports must be submitted to the IRB at regular intervals 
dictated by the IRB/EC but no less than annually. 
6. A final report must be submitted to the IRB within 3 months after 1) 
termination or completion of the study; or 2) the investigator's work on 
the study ceases. 
7. Any deviation from the protocol to protect the life or physical well-
being of a participant in an emergency is to be reported to the sponsor 
and IRB no later than 5 working days after the emergency occurs.  
Deviations to the informed consent process (eg, use of study product 
without informed consent) must be reported to the sponsor and the IRB 
immediately but no later than 5 working days after the use occurs. 
Deviations from the randomization scheme must be reported to the 
sponsor as soon as possible after they are recognized. 
8. Other: upon request, the investigator will supply accurate, complete and 
current information about any aspect of the study to the sponsor. 
9.3.4 Retention of Study Records 
The sponsor must ensure that all study participant records are stored for at least 
2 years after the later of the following 2 dates: the date on which the study is 
terminated or completed (all study participants through final follow-up), or the 
date that the records are no longer required by the study site record retention 
policy or per applicable regulatory requirements. To avoid error, the site should 
contact the sponsor prior to the destruction of study records to ensure that they 
no longer need to be retained. In addition, the sponsor should be contacted if 
the study site is acquired or shuts down so that arrangements can be made for 
the handling or transfer of study records. 
9.3.5 Data Quality Assurance 
The sponsor, or the sponsor’s representative, may conduct audits at the study 
sites. Audits may include, but are not limited to, device supply, presence of 
required documents, the informed consent process, and comparison of eCRFs 
with source documents. The investigator agrees to participate with audits 
conducted at a reasonable time, in a reasonable manner. 
9.3.6 Confidentiality 
All information provided to investigators, IRBs, and generated in this study 
must be considered highly confidential and must not be disclosed to any persons 
not directly involved with the study without prior written permission from the 
sponsor. However, authorized regulatory officials and sponsor personnel (or 
their representatives) will be allowed full access to inspect and copy the records. 
All study products must be used solely in accordance with this protocol. Privacy 

 
 
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and confidentiality of information about each participant shall be preserved in 
the reports and in any publication. Each participant in this study will be assigned 
a unique identifier. All data will be tracked, evaluated, and stored using only 
this unique identifier. 
The study site will maintain a confidential list (paper or electronic) identifying 
all participants. This list will contain the assigned participant’s unique identifier 
and name. The investigator is responsible for keeping this list confidential. This 
list will not be provided to the study sponsor and is only to be used at the study 
site. 
Monitors and auditors will have access to the study participant list and other 
personally identifying information of participants to ensure that data reported 
corresponds to the person who signed the informed consent form and the 
information contained in original source documents. Such personal identifying 
information may include, but is not limited to the participant’s name, address, 
date of birth, gender, race and medical record number.   
9.3.7 Publication Policies 
The CTA, mutually signed by the investigator(s) and Aerin Medical, defines 
and describes the nature of the study agreement. The data and results from this 
study are the sole property of Aerin Medical. Aerin Medical shall have the right 
to access and use all data and results generated during the clinical investigations 
now and in the future for presentation or publication at the sponsor’s discretion 
or for submission to governmental agencies. Publication authorship will be 
established according to the International Committee of Medical Journal 
Editors (ICMJE) guidelines and Aerin Medical policy. Clinical study design 
will be publicly disclosed on ClinicalTrials.gov, and summary results posted 
per FDAAA 801 Requirements, and in accordance with national regulations as 
required by other regulatory agencies. Additionally, an investigator may only 
publish data generated by this trial in accordance with the terms of the CTA.  
It is Aerin Medical’s intent to encourage and facilitate the publications of 
scientifically important results, while simultaneously ensuring minimization of 
duplicative data publication and the priority publications of multicenter results 
ahead of single-center investigations.  
Aerin Medical intends to provide research sites with a standardized study report 
containing aggregated site study data. 
9.4 Study Suspension or Early Termination 
The study can be suspended or discontinued at the discretion of the sponsor for 
reasons including, but not limited to, the following: 
• 
Obtaining new scientific knowledge that shows that the study is no longer 
valid or necessary. 
• 
Insufficient recruitment of participants. 

 
 
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• 
Unanticipated adverse device effect presenting an unreasonable risk to 
participants. 
• 
Persistent noncompliance with the protocol and/or IRB or regulatory 
authority requirements. 
If the study is discontinued or suspended prematurely, the sponsor shall promptly 
inform all participating study sites and treating physicians of the termination or 
suspension and the reason(s) for the termination or suspension. The IRB shall also be 
informed promptly and provided with the reason(s) for the termination or suspension 
by the sponsor. The investigator shall promptly inform screened participants at 
his/her study site, if appropriate. Regulatory authorities and the personal physicians 
of the participants may also need to be informed if deemed necessary. All applicable 
study documents will be participant to the same retention policy as detailed in Section 
9.3.3 
10.0 Ethics 
10.1 Institutional Review Board 
This study may not be initiated at a site until applicable Institutional Review Board, 
or regulatory authority approval/favorable opinion is obtained. The study protocol, 
all study protocol amendments, written study participant information, informed 
consent form, and any other appropriate study-related information must be reviewed 
and approved by the IRB. Any additional requirements or conditions imposed by the 
IRB or regulatory authority shall be followed, if appropriate. 
To assure proper review and study oversight, the IRB must comply with the 
responsibilities, functions, and records requirements defined in U.S. FDA regulations 
(21 CFR Part 56) or per their regulatory authority. 
The investigator at each site is responsible for submitting the appropriate study 
documentation to the IRB for review and approval in accordance with applicable 
regulations. The investigator is responsible for providing accurate, complete, and 
current information to the IRB throughout the course of the study.  
10.2 Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, GCP, and all applicable 
regulatory requirements governing clinical studies of marketed products. Compliance 
with these requirements also constitutes conformity with the ethical principles that 
have their origin in the Declaration of Helsinki and the rights, safety and well-being 
of study participants shall be protected consistent with these principles. 
The sponsor will promptly review all information relevant to the safety of the product 
that is received and comply with all regulatory device safety reporting requirements.  
10.3 Participant Privacy 
The privacy of participants in this study will be protected by all reasonable means.  
The investigator is responsible for study records at the study site and must only 
disclose information as provided for in the site’s Authorization to Use and Disclose 

 
 
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Health Information. Each participant must give permission for use and disclosure of 
their information by signing the Authorization to Use and Disclose Health 
Information. This form may be a separate document from the informed consent form, 
or it may be contained within or as an addendum to the informed consent form. 
Although the sponsor is not a covered entity under HIPAA, access to study records, 
particularly participant information, will be strictly limited by the sponsor to the 
investigator, the sponsor’s clinical research personnel, authorized representatives of 
the sponsor, the FDA under applicable federal regulations, or other regulatory 
authority as required per national regulations. No public reporting or publications of 
the results of this study will contain identifiable references to individual participants 
in the study. 
10.4 Participant Insurance 
It is the responsibility of the sponsor to provide insurance covering the cost of 
treatment of participants in the event of clinical-investigation-related injuries, in 
accordance with the national regulations, as applicable. 
10.5 Participant Reimbursement 
Participants may be reimbursed for their time for completing questionnaires as 
allowed by the IRB and study site policies. Participants will not be reimbursed for 
questionnaires not completed. 
10.6 Participant Withdrawal 
Participants may voluntarily withdraw from the study at any time for any reason 
without impact to their future medical care at the study site. In addition, the 
investigator may withdraw a participant from the study, if in the investigator’s 
opinion, it is not in the best interest of the participant to continue in the study. Any 
participant withdrawing from the study for any reason will continue to receive 
medically necessary follow-up care as determined by the investigator. Every attempt 
should be made to follow a participant withdrawing either because they failed to 
obtain a desired effect or suffered an adverse event. 
When a participant chooses to withdraw, the investigator or designee will make all 
possible efforts to collect and report the final visit observations. If the investigator 
has made 3 documented attempts to contact the participant and received no response, 
the participant may be considered to be lost to follow-up. A participant who misses a 
study visit but attends a subsequent visit will no longer be considered lost to follow-
up. All reasons for withdrawals and documentation will be recorded in source 
documentation and the appropriate case report form. In addition, within the informed 
consent process, participants will be asked to provide consent for the study staff to 
contact them by mail or phone to follow up on safety-related issues as appropriate. 
10.7 Protocol Modifications 
This protocol shall not be amended without the approval of the sponsor. The sponsor 
may amend the protocol to clarify study procedures or to implement changes to the 
protocol that do not affect the validity of the data; the risk to benefit ratio; the 

 
 
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scientific soundness of the protocol; or the rights, safety, or welfare of the 
participants. All modifications must be reviewed and approved by the IRB before 
implementation.   
10.8 Protocol Adherence and Deviations 
10.8.1 Definition 
Deviation – instance of failure to follow, intentionally or unintentionally, the 
requirements of the protocol (per ISO 14155). 
10.8.2 Documentation and Reporting of Deviations 
The investigator(s) agree to conduct the study in accordance with this protocol. 
An investigator must not make any changes in the study without first receiving 
agreement by the sponsor and approval in writing from the IRB, except when 
necessary to eliminate apparent immediate hazards to a participant. 
Investigators will also adhere to procedures for reporting study deviations to 
their IRB in accordance with their specific IRB reporting policies and 
procedures. Deviations will also be reported to the regulatory authority as 
required per national regulations.  
Deviations must be reported to the sponsor regardless of whether medically 
justifiable, preapproved, or performed to protect the participant in an 
emergency. The investigator will document and explain the reason for the 
deviation. participant deviations will be reported using the Protocol Deviation 
eCRF.  
 
 

 
 
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11.0  References 
 
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2. 
Rhee, JS, Book DT, Burzynski M, Smith TL. Quality of life assessment in nasal 
airway obstruction. Laryngoscope 2003;113(7):1118-1122.  
3. 
Rhee JS, Weaver EM, Park SS, et al. Clinical consensus statement: Diagnosis and 
management of nasal valve compromise. Otolaryngol Head Neck Surg 
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4. 
Recker C, Hamilton G. Evaluation of the patient with nasal obstruction. Facial 
Plast Surg 2016;32(1):3-8. 
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Chandra R, Patadia M, Raviv J. Diagnosis of nasal airway obstruction. 
Otolaryngol Clin North Am 2009;42(2):207-225, vii. 
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Wittkopf M, Wittkopf J, Ries WR. The diagnosis and treatment of nasal valve 
collapse. Curr Opin Otolaryngol Head Neck Surg 2008;16(1):10-13. 
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Fraser L., Kelly G. An evidence-based approach to the management of the adult 
with nasal obstruction. Clin Otolaryngol 2009;34(2):151-155. 
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Cole P. The four components of the nasal valve. Am J Rhinol 2003;17(2):107-
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Barrett D, Casanueva F, Cook T. Management of the nasal valve. Facial Plast 
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10. Wexler DB, Davidson TM. The nasal valve: a review of the anatomy, imaging, 
and physiology. Am J Rhinol 2004;18(3):143-150. 
11. Bloching MB. Disorders of the nasal valve area. GMS Curr Top 
Otorhinolaryngol Head Neck Surg 2007;6:Doc07. 
12. Kirkness JP, Wheatley JR, Amis TC. Nasal airflow dynamics: mechanisms and 
responses associated with an external nasal dilator strip. Eur Respir J 
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13 
Peltonen LI, Vento SI, Simola M, Malmberg H. Effects of the nasal strip and 
dilator on nasal breathing--a study with healthy subjects. Rhinology 
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14. Roithmann R, Chapnik J, Cole P, et al. Role of the external nasal dilator in the 
management of nasal obstruction. Laryngoscope 1998;108(5):712-715. 
15. Ellegard E. Mechanical nasal alar dilators. Rhinology 2006;44(4):239-248. 
16. Khosh MM, Jen A, Honrado C, Pearlman SJ. Nasal valve reconstruction: 
experience in 53 consecutive patients. Arch Facial Plast Surg 2004;6(3):167-171. 
 

 
 
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17. 
Fischer H, Gubisch W. Nasal valves--importance and surgical procedures. Facial 
Plast Surg 2006;22(4):266-280. 
18. Spielmann PM, White PS, Hussain SS. Surgical techniques for the treatment of 
nasal valve collapse: a systematic review. Laryngoscope 2009;119(7):1281-1290. 
19. Rhee J, Arganbright J, McMullin B, Hannley M. Evidence supporting functional 
rhinoplasty or nasal valve repair: A 25-year systematic review. Otolaryngol Head 
Neck Surg 2008;139(1):1020. 
20. Stolovitzky P, Senior B, Ow RA, et al. Assessment of bioabsorbable implant 
treatment for nasal valve collapse compared to a sham group: a randomized 
control trial. Int Forum Allergy Rhinol 2019;9(8):850-856. 
21. Sapci T, Sahin B, Karavus A, Akbulut UG. Comparison of the effects of 
radiofrequency tissue ablation, CO2 laser ablation, and partial turbinectomy 
applications on nasal mucociliary functions. Laryngoscope 2003;113(3):514-
519. 
22. Coste A, Yona L, Blumen M, et al. Radiofrequency is a safe and effective 
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