The Vivaer® Procedure for Treatment of Nasal Airway Obstruction - A ProspecTive, Multicenter Randomized Controlled TriAl Comparing Vivaer to Sham Control (VATRAC)
Phase: NA
Conditions: Nasal Airway Obstruction
Sponsor: Aerin Medical

 
 
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CONFIDENTIAL 
 
The Vivaer® Procedure for Treatment of Nasal Airway Obstruction –  
A ProspecTive, Multicenter Randomized Controlled TriAl Comparing Vivaer 
to Sham Control (VATRAC) 
 
NCT# NCT04549545 
 
Protocol REV C. 
 
Amendment Date 15SEP2020 
 
 

 
 
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CONFIDENTIAL 
The Vivaer® Procedure for Treatment of Nasal Airway Obstruction –  
A ProspecTive, Multicenter Randomized Controlled TriAl Comparing Vivaer 
to Sham Control (VATRAC) 
 
Protocol Number: 
CTP1006 
Protocol Date: 
22 May 2020 
Amendment Date:  
15 Sep 2020 
Version: 
C 
Co-Principal 
Investigators: 
Joseph Han, MD 
EVMS Medical Group 
Ear, Nose and Throat Surgeons 
600 Gresham Drive, Suite 1100 
Norfolk, VA 23507 USA 
 
Phone: (757) 388-7823  
Email: hanjk@evms.edu  
Stacey Silvers, MD 
Madison ENT 
161 Madison Avenue, #11W 
New York, NY 10016 USA 
 
 
Phone: (212) 213-3339 
Email: ssilversmd@yahoo.com 
Sponsor: 
Aerin Medical, Inc. 
232 E. Caribbean Drive 
Sunnyvale, CA 94089 USA 
 
Contact: Anais Laborde, 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 (CIP) 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 .................................................................................................................... 6 
List of Abbreviations .............................................................................................................. 12 
1.0 Introduction and Background ........................................................................................ 14 
2.0 Purpose ........................................................................................................................... 16 
2.1 Device and Regulatory Status ............................................................................... 16 
2.2 Indications for Use (applicable to U.S. only) ....................................................... 17 
2.3 Intended and Indications for Use (applicable to European Union only) .............. 17 
2.4 Rationale ............................................................................................................... 17 
3.0 Study Objectives ............................................................................................................ 17 
3.1 Primary Objective ................................................................................................. 17 
3.2 Secondary Objectives ............................................................................................ 18 
3.3 Safety and Risk Profile ......................................................................................... 19 
4.0 Study Plan ...................................................................................................................... 19 
4.1 Study Design ......................................................................................................... 19 
4.2 Study Population ................................................................................................... 20 
4.2.1 Inclusion Criteria .......................................................................................20 
4.2.2 Exclusion Criteria ......................................................................................21 
4.3 Enrollment and Randomization ............................................................................ 22 
4.4 Blinding................................................................................................................. 22 
4.5 Outcome Measures................................................................................................ 23 
4.5.1 Nasal Assessment.......................................................................................23 
4.5.2 Nasal Obstruction Symptom Evaluation (NOSE) Scale ............................23 
4.5.3 Pain – Visual Analog Scale Pain Score .....................................................24 
4.5.4 Ease of Breathing – Visual Analog Scale Breathing Score .......................24 
4.5.5 Epworth Sleepiness Scale (ESS) ................................................................24 
4.5.6 Participant Satisfaction Assessment ..........................................................25 
4.5.7 Change in amount of PRN medication/device use for nasal 
obstruction symptoms ................................................................................25 
4.5.8 Medication and Other Therapies for Symptoms of Nasal Obstruction ......25 
4.5.9 Adverse Events ..........................................................................................25 
4.6 Success/Failure Criteria ........................................................................................ 25 
4.6.1 Participant Success .....................................................................................25 
4.6.2 Participant Failure ......................................................................................25 
4.6.3 Study Success.............................................................................................25 
4.7 Duration of the Study ............................................................................................ 26 
4.8 Site Staffing and Responsibilities of Study Personnel .......................................... 26 
4.9 Device Description ................................................................................................ 26 
4.10 Risk/Benefit Analysis ......................................................................................... 28 
4.10.1 Risks ...........................................................................................................28 
4.10.2 Potential Risks to Participant Confidentiality ............................................30 
4.10.3 Mitigation of Risks ....................................................................................30 
4.10.4 Study Justification in Relation to Risk.......................................................31 
4.10.5 Benefits ......................................................................................................31 

 
 
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5.0 Study Schedule and Procedures ..................................................................................... 32 
5.1 Schedule of Events ................................................................................................ 32 
5.2 Participant Flowchart ............................................................................................ 33 
5.3 Enrollment and Baseline Assessment ................................................................... 34 
5.4 Treatment Visit and Procedure ............................................................................. 36 
5.5 Postprocedure Assessments and Care ................................................................... 38 
5.6 Follow-up Evaluations and Study Exit ................................................................. 38 
5.7 Product Handling and Accountability ................................................................... 40 
6.0 Statistical Considerations ............................................................................................... 40 
6.1 Study Design ......................................................................................................... 40 
6.2 Study Hypotheses.................................................................................................. 40 
6.3 Sample Size Estimate ............................................................................................ 41 
6.4 Timing of Analysis ............................................................................................... 42 
6.5 Analysis Populations ............................................................................................. 42 
6.6 Missing Data ......................................................................................................... 42 
6.7 Pooling .................................................................................................................. 42 
6.8 Participant Disposition .......................................................................................... 42 
6.9 Demographics and Characteristics ........................................................................ 43 
6.10 Primary Endpoint Analysis ................................................................................. 43 
6.11 Secondary Endpoint Analyses ............................................................................ 43 
6.12 Other Outcome Measures Analyses .................................................................... 44 
6.13 Safety Analysis ................................................................................................... 45 
6.14 Extension Phase Analysis ................................................................................... 45 
6.15 Standard Methods of Report ............................................................................... 46 
7.0 Adverse Events and Product Complaints / Device Deficiencies ................................... 46 
7.1 Adverse Events ..................................................................................................... 46 
7.1.1 Definitions..................................................................................................46 
7.1.2 Documentation and Reporting of Adverse Events .....................................49 
7.2 Product Complaints / Device Deficiencies ........................................................... 49 
7.2.1 Definitions..................................................................................................49 
7.2.2 Documentation and Reporting of Complaints / Device Deficiencies ........50 
8.0 Study Administration ..................................................................................................... 50 
8.1 Investigator Training ............................................................................................. 51 
8.2 Study Monitoring .................................................................................................. 51 
8.3 Documentation of Study Findings ........................................................................ 51 
8.3.1 Data Management ......................................................................................51 
8.3.2 Case Report Forms .....................................................................................52 
8.3.3 Investigator Responsibilities, Records, and Reports ..................................53 
8.3.4 Retention of Study Records .......................................................................55 
8.3.5 Data Quality Assurance .............................................................................55 
8.3.6 Confidentiality ...........................................................................................55 
8.3.7 Publication Policies ....................................................................................56 
8.4 Study Suspension or Early Termination ............................................................... 56 
9.0 Ethics.............................................................................................................................. 57 
9.1 Institutional Review Board/Ethics Committee ..................................................... 57 

 
 
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9.2 Ethical Conduct of the Study ................................................................................ 57 
9.3 Participant Privacy ................................................................................................ 58 
9.4 Participant Insurance ............................................................................................. 58 
9.5 Participant Reimbursement ................................................................................... 58 
9.6 Participant Withdrawal ......................................................................................... 58 
9.7 Protocol Modifications.......................................................................................... 59 
9.8 Protocol Adherence and Deviations ...................................................................... 59 
9.8.1 Definition ...................................................................................................59 
9.8.2 Documentation and Reporting of Deviations ............................................59 
10.0  References ...................................................................................................................... 60 
 
 
 

 
 
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Protocol Summary 
Title of Study: 
The Vivaer® Procedure for Treatment of Nasal Airway Obstruction -  
A ProspecTive, Multicenter Randomized Controlled TriAl Comparing 
Vivaer to Sham Control (VATRAC) 
Purpose: 
The purpose of this study is to compare the Vivaer procedure for 
treatment of nasal airway obstruction (NAO) with a sham procedure that 
simulates the actual procedure as closely as possible absent the delivery 
of radiofrequency (RF) energy to the nasal tissue. 
Study Device: 
Vivaer® ARC Stylus 
  
Indications for 
Use (U.S.):  
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 by shrinking submucosal tissue, including 
cartilage in the internal nasal valve area. 
The Aerin Console is an electrosurgical system intended to generate 
radiofrequency (RF) electrical current for the use of an Aerin Medical 
Stylus. The Aerin Console is indicated for use in small clinic, office or 
hospital environments. 
Intended and 
Indications for 
Use (European 
Union): 
The Vivaer ARC Stylus is intended to improve nasal breathing by 
modifying the soft tissues of the nasal airway. It is indicated for use in 
patients who experience poor nasal breathing or chronic nasal 
obstruction. 
The Aerin Console is an electrosurgical system intended to generate 
radiofrequency (RF) electrical current for modification of soft tissues 
during ear, nose and throat procedures, when used with an Aerin 
Medical Stylus. It is indicated for use in delivering radio-frequency 
energy to tissues as part of ear, nose and throat procedures in small 
clinic, office or hospital environments. 
Study 
Objective: 
The primary objective is to assess the performance of the Vivaer 
procedure compared to a sham procedure with respect to individual 
participant success rates when used as a treatment for nasal airway 
obstruction. 
Individual participant success (“responder”) is defined as at least 1 
Nasal 
Obstruction 
Symptom 
Evaluation 
(NOSE) 
Scale 
class 
improvement or an improvement (decrease) in NOSE Scale score of 
20% or more from baseline at the 3-month evaluation. 

 
 
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Study Design: 
The study is designed as a multicenter (up to 20 sites), prospective, 
randomized, controlled superiority trial with a one-way crossover 
component available to participants randomized to the control arm. A 
2:1 site-stratified randomization will be used to allocate participants 
with NAO to either the active treatment arm (Vivaer procedure) or the 
control arm (sham procedure) to provide up to 120 total participants in 
the following groups: 
o 80 active treatment (Vivaer procedure) 
o 40 inactive treatment (sham procedure) 
All participants will be evaluated in-office prior to treatment and 
following treatment at week 4 (1 month) and week 13 (3 months). The 
3-month evaluation will be used for the primary endpoint analysis. 
Active treatment participants (Vivaer procedure) will have an extended 
follow-up with evaluations conducted in-office at 6 months (26 weeks) 
and remotely at 12 months (52 weeks) and 24 months (104 weeks). 
Participants receiving the sham procedure may elect to crossover to the 
active treatment arm (Vivaer procedure) within 30 days after the 3-
month follow-up evaluation provided they still meet all eligibility 
criteria. Continued follow-up will be conducted at 1, 3, 6, 12, and 24 
months after the Vivaer procedure to provide additional information on 
longer-term efficacy and duration of treatment effect. Participants that 
received the sham procedure and do not elect to crossover or no longer 
meet all eligibility criteria will be exited from the study following the 3-
month evaluation. 
Active 
Treatment 
Arm  
(Vivaer 
procedure): 
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 in this study will undergo bilateral 
treatment of the nasal valves in a single study session. Each side of the 
nose will be treated with up to four (4) non-overlapping applications of 
RF energy at the junction of the upper and lower lateral cartilage on the 
lateral nasal wall. 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 (24 
months). 
Control Arm 
(Sham 
procedure): 
The sham procedure will be performed in the study clinic using the 
Vivaer ARC Stylus while audible sounds that accurately simulate the 
Aerin Console’s active treatment are produced even though RF energy 
is not being generated or delivered. All other aspects of the procedure 
will be the same as used for the active treatment, including 
administration of anesthetic agent(s). 

 
 
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Primary Study 
Hypothesis: 
The proportion of participants in the active treatment arm (Vivaer 
procedure) with a successful outcome (responders) will exceed the 
proportion of participants in the control arm (sham procedure) with a 
successful outcome (responders) at 3 months postprocedure. 
Primary 
Endpoint: 
The primary endpoint is the responder rate at 3 months after the 
procedure for the randomized participants.  
Secondary 
Endpoints: 
• Mean change in NOSE Scale scores from baseline to 3 months after 
procedure. 
• Frequency of device-related and procedure-related serious adverse 
events through the 3-month evaluation. 
Other 
Effectiveness 
and Safety 
Measures: 
Adverse events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
Nasal Assessment - The target nasal valve area within each nostril will 
be visually assessed at baseline, just prior to treatment (if screening and 
procedure occur on different days), immediately after treatment, at 1 
month, 3 months, and 6 months after the procedure. The use of an 
endoscope for visual assessment is required. Representative video of 
each nasal passage will be captured for each assessment. 
NOSE Scale score:  
• Mean and mean change from baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
• Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, and 24-month 
follow-up evaluations. 
• Mean, change from baseline 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-, and 24-month 
follow-up evaluations. 
• Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, and 24-month follow-up evaluations. 
Visual analog scale (VAS) for pain - perception of pain associated with 
the procedure on a 0 to 100 mm scale with 0 indicating no pain and 100 
indicating the worst pain imaginable assessed immediately after 
treatment, and at 1-month and 3-month follow-up evaluations. 
Visual analog scale (VAS) for ease of breathing - perception of the 
ability to breathe through the nose on a 0 to 100 mm scale with 0 
indicating no difficulty and 100 indicating extreme difficulty assessed at 
baseline, 1-month, 3-month, and 6-month follow-up evaluations.  

 
 
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Epworth Sleepiness Scale (ESS) - mean and change from baseline in the 
ESS score at each evaluation. The ESS evaluates the self-reported 
likelihood of dozing or falling asleep in 8 daytime situations with 
likelihood rated No Chance (0), Slight (1), Moderate (2), or High 
Chance (3) administered at baseline and the 1-, 3-, 6-, 12-, and 24-
month follow-up evaluations. 
Participant Satisfaction Assessment - Five question self-reported survey 
of satisfaction with the procedure and recommendation to others 
administered at the 3-, 6-, 12-, and 24-month follow-up evaluations. 
Change in amount of “as needed” (PRN) medication/device use for 
nasal obstruction symptoms - Self-reported assessment of an increase, 
no change, or decrease in as needed medications and/or devices being 
used for treatment of nasal symptoms at each evaluation compared to 
use prior to the procedure administered at the 1- 3-, 6-, 12-, and 24-
month follow-up evaluations. 
Medications - Medications associated with relief or treatment of nasal 
airway obstruction symptoms will be documented at baseline and 
updated as necessary at each evaluation. In addition, medications 
associated with treatment of adverse events will be documented.  
Duration of 
Study: 
The primary endpoint will be evaluated at 3 months. In addition, 
evaluations at 6, 12, and 24 months after treatment will extend follow-
up to 2 years for evaluation of longer-term efficacy. Participants 
receiving the sham procedure and meeting all eligibility requirements 
may elect to crossover and receive the active Vivaer procedure within 
30 days after the 3-month evaluation with continued follow-up for 24 
more months for a total of 28 months of follow-up. Study enrollment is 
anticipated to be completed within 12 months. Therefore, total study 
duration is anticipated to be approximately 40 months. 
Study Centers: 
Up to 20 sites in the United States (U.S.) and Europe 
Participants: 
120 
 
Inclusion 
Criteria: 
1. Age 18 to 85 years (inclusively). 
2. Willing and able to provide informed consent. 
3. Willing and able to comply with the subject-specific requirements 
outlined in the Study Protocol. 
4. Seeking treatment for nasal obstruction and willing to undergo an 
office-based procedure. 
5. Baseline Nasal Obstruction Symptom Evaluation (NOSE) Scale 
score ≥ 55. 

 
 
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6. Nasal valve is a primary or significant contributor to the patient's 
nasal obstruction as determined by the study investigator (based on 
clinical presentation, physical examination, nasal endoscopy, etc.) 
and the patient has a positive response to any of the following 
temporary measures (based on patient history or office exam): 
• Use of external nasal dilator strips (eg, Breathe Right Strips) 
• Use of internal nasal dilator cones 
• Modified Cottle Maneuver (manual elevation of the lateral 
nasal wall using a small instrument or cotton-tipped applicator 
to open the nasal valve) 
• Cottle Maneuver (manual lateral retraction of the cheek to 
open the nasal valve) 
7. Dissatisfaction with medical management as judged by the patient. 
Defined as failed medical therapy (eg, decongestants, antihistamines, 
and/or nasal sprays for an appropriate period of time), but a positive 
response to internal or external nasal dilators.  
Exclusion 
Criteria: 
1. Prior surgery of the lateral nasal wall, including cephalic resection 
of the lower lateral cartilage, dome division or suture plication, alar 
graft or spreader graft placement. 
2. Rhinoplasty, septoplasty, inferior turbinate reduction or functional 
endoscopic sinus surgery (FESS) within the preceding 3 months. 
3. Severe case of any of the following: septal deviation, turbinate 
hypertrophy, polyps, or ptotic nose tip believed to be the primary 
contributor to the patient’s nasal obstruction symptoms and 
warranting surgical intervention. 
4. Any adjunctive surgical nasal procedure planned on the same day 
or within 6 months after the Vivaer procedure. 
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 patient to poor wound healing or increased 
surgical risk, or poor compliance with the requirements of the 
study. 
 
 

 
 
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Schedule of Events 
 
 
Treatment 
Follow-up 
(office) 
Extended 
Follow-up 
(remote) 
Screening 
  Procedure 
    Immediate 
Postprocedure 
1 Month 
(4 weeks)  
  3 Months1, 2  
  (13 weeks) 
  6 Months 
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 7) 
(± 14) (± 30) (± 30) (± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal Assessment (physical, endoscopic) 
X 
X3 
X 
X 
X 
X 
 
 
Current medication use (study relevant) 
X 
X3 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
NOSE Scale 
X 
 
 
X 
X 
X 
X 
X 
VAS nasal pain  
 
 
X 
X 
X 
 
 
 
VAS ease of breathing 
X 
 
 
X 
X 
X 
 
 
Epworth Sleepiness Scale 
X 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
X 
X 
X 
X 
Adverse Events 
X 
X3 
X 
X 
X 
X 
X 
X 
1Primary analysis endpoint. 
2 Control participants eligible to crossover and receive Vivaer procedure. 
3Repeat on day of treatment if screening and procedure occur on different days. 
 
 
 

 
 
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List of Abbreviations 
ADE – Adverse Device Effect 
AE – Adverse Event 
ANOVA – analysis of variance 
BMI – Body Mass Index 
CPAP – Continuous Positive Airway Pressure 
CRF (eCRF) – Case Report Form (electronic Case Report Form) 
CTA – Clinical Trial Agreement 
EC – Ethics Committee 
EDC – Electronic Data Capture 
ENT – Ear, Nose, Throat; medical field of otorhinolaryngology (otolaryngology) 
FDA – Food and Drug Administration 
FESS – Functional Endoscopic Sinus Surgery 
FWA – Federalwide Assurance for the Protection of Human Subjects 
GCP – Good Clinical Practice 
HIPAA – Health Insurance Portability and Accountability Act 
ICH – International Council for Harmonisation 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 
ITT – Intent-To-Treat 
MDD – Medical Device Directive 
NAO – Nasal Airway Obstruction 

 
 
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NOSE – Nasal Obstruction Symptom Evaluation Scale  
OTC – Over-The-Counter (nonprescription) 
PRN – Pro Re Nata (as needed or as required) 
QOL – Quality of Life 
RF – Radiofrequency 
RFTR – Radiofrequency turbinate reduction 
SAE – Serious Adverse Event 
SADE – Serious Adverse Device Effect 
SD – standard deviation 
UADE – Unanticipated Adverse Device Effect 
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 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 
hypertrophy, nasal septal deviation, and nasal valve angle changes, narrowing or 
collapse.1,4- 7 
Treatment strategies 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, and the caudal end of the upper lateral cartilage. 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. 
Multiple devices designed to increase the size of the nasal passage at the nasal valve 
area are available over-the-counter (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 inferior turbinates. 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.8, 
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- 23  
Radiofrequency (RF) energy has been used for decades in the fields of 
otorhinolaryngology (ENT), neurosurgery, cardiology, urology and general surgery. 

 
 
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The ability of radiofrequency, electrical current, or laser-mediated heating to reshape 
cartilage has been shown in ex-vivo studies on rib and septal cartilage.24-26 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.27 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.28 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.29  
Targeted radiofrequency heating of the lateral cartilaginous nasal wall has also been 
used in patients with inspiratory nasal valve collapse; however, an incisional 
approach was required.30 In this investigation, 3 treatments were applied per side with 
intent to produce tissue retraction and volume reduction. Participants (n=28) were 
asked to evaluate their nasal blockage on a visual analog scale (VAS) from 0 to 10, 
with 10 indicating total blockage and 0, no sensation of blockage. At 16 weeks the 
mean VAS for the left nostril had decreased from 8.2 to 3.4 and decreased for the 
right nostril from 8.9 to 4.1. There were no major complications during or after the 
procedure. 
The Vivaer procedure has previously been investigated in a prospective, 
nonrandomized multicenter study with 50 participants that supported regulatory 
clearance of the Vivaer ARC Stylus.31 Participants exhibited significant symptoms of 
nasal obstruction attributed to internal nasal valve dysfunction with Nasal Obstruction 
Symptom 
Evaluation 
(NOSE) 
Scale 
score 
≥60. 
Temperature-controlled 
radiofrequency treatment was applied intranasally using a bipolar stylus to the 
internal nasal valve region. Under local anesthesia, radiofrequency energy along with 
outward pressure was applied to the mucosa at the region of the caudal end of the 
weakened upper lateral cartilage to induce mechanical deformation and potentially 
change the shape of the lateral nasal wall. Contraction of the treated area during the 
healing process would serve to curve the treated portion of the upper lateral cartridge, 
creating a wider nasal airway and a stiffer nasal valve wall. Forty-nine participants 
were available for the primary analysis at the 6-month evaluation. No device or 
procedure-related serious adverse events occurred. There were 36 adverse events 
reported from 20 participants. None of the events were considered related to the 
device, although 13 were considered related to the procedure. Most events occurred in 
the period from the procedure to 4 weeks. Soreness, edema, and crusting resolved by 
4 weeks. The mean baseline NOSE Scale score was 79.9 (SD 10.8, range 60-100), 
and all participants had severe or extreme nasal obstruction. At 6 months, mean 
NOSE Scale score improved to 24.7 (SD 20.4, range 0-90) with an average decrease 

 
 
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of 54.5 (68.6%). The severe and extreme nasal obstruction categories were reduced to 
10%. At 12 weeks, all participants (100%) were treatment responders, defined as 
participants with at least a 15-point decrease in the NOSE Scale score, and at 6 
months there were 3 nonresponders for a 94% responder rate. The decrease in NOSE 
Scale score did not differ significantly between patients who did or did not have prior 
nasal surgery. 
Thirty-nine of this study’s participants enrolled in a long-term follow-up study to 
assess NOSE score and quality of life through 2 years with evaluations at 12, 18, and 
24 months. The mean NOSE Scale score at baseline was 80.8 (SD 10.7) for 
participants in the follow-up study. The mean NOSE Scale score for participants in 
this study improved to 24.9 (SD 21.3) at the 26-week endpoint of the pivotal study 
with a mean change from baseline of 55.9 (SD 23.6). Improvement in mean NOSE 
Scale score was maintained through the 12-, 18-, and 24-month evaluations (27.5, 
32.7, and 26.5, respectively). At 6 months, severe and extreme nasal obstruction rates 
had decreased from 100% to 10% (4 of 39) of participants, and at 12-, 18-, and 24-
months, 17%, 26% and 17% of participants had severe or extreme nasal obstruction, 
respectively. Using the definition of responder of at least a 15-point improvement in 
NOSE Scale score, 92% of participants in this study were classified as responders at 6 
months and at 12 months 94% were classified as responders (3 participants were not 
evaluated at 12 months). All 39 participants were evaluated at 18 months with a 
responder rate of 87% and at 24 months, 36 of 39 participants were evaluated and had 
a responder rate of 97%. Participants in the study also responded favorably to the 
Aerin Medical Quality of Life survey showing improvement in areas such as sleep 
quality, energy and productivity, wellbeing and emotions, less sickness, and less 
frequent use of medication compared to prior to having the procedure. Treatment for 
symptoms of nasal obstruction attributed to internal nasal valve dysfunction with the 
Vivaer procedure was demonstrated to provide durable relief through 24 months. 
Response to the Aerin Medical Quality of Life survey provided additional support for 
the durability and benefits of the treatment. 
2.0 
Purpose 
The purpose of this study is to compare the Vivaer procedure for treatment of nasal 
airway obstruction with a sham procedure that simulates the actual procedure as 
closely as possible absent the delivery of radiofrequency energy to the nasal tissue.  
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.  
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. Both devices are also CE-marked in the European 
Union. 

 
 
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2.2 Indications for Use (applicable to U.S. only) 
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 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 Intended and Indications for Use (applicable to European Union only) 
The Vivaer ARC Stylus is intended to improve nasal breathing by modifying the 
soft tissues of the nasal airway. It is indicated for use in patients who experience 
poor nasal breathing or chronic nasal obstruction. 
The Aerin Console is an electrosurgical system intended to generate radiofrequency 
(RF) electrical current for modification of soft tissues during ear, nose and throat 
procedures, when used with an Aerin Medical Stylus. It is indicated for use in 
delivering radio-frequency energy to tissues as part of ear, nose and throat 
procedures in small clinic, office or hospital environments. 
2.4 Rationale 
Patients suffering from symptoms attributed to nasal airway obstruction 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 nasal airway obstruction. 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 
using the randomized, controlled trial, “gold standard” study design.   
3.0 
Study Objectives 
3.1 Primary Objective 
The primary objective is to assess the performance of the Vivaer procedure 
compared to a sham procedure with respect to individual participant success rates 
when used as a treatment for nasal airway obstruction. 

 
 
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Individual participant success (“responder”) is defined as at least 1 Nasal 
Obstruction Symptom Evaluation (NOSE) Scale class improvement or an 
improvement (decrease) in NOSE Scale score of 20% or more from baseline at the 
3-month evaluation.   
The primary objective will be assessed through evaluation of the primary endpoint 
defined as the responder rate at 3 months after the procedure for the randomized 
participants. 
3.2 Secondary Objectives 
Additional objectives include assessment and comparison of secondary and 
informational outcome measures between the groups receiving the Vivaer 
procedure and the sham procedure. 
Secondary endpoints are: 
• Mean change in NOSE Scale scores from baseline to 3 months after 
procedure. 
• Frequency of device-related and procedure-related serious adverse events 
through the 3-month evaluation. 
Other Effectiveness and Safety Measures include: 
• Adverse events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
• Nasal Assessment - The target nasal valve area within each nostril will be 
visually assessed at baseline, just prior to procedure (if screening and 
procedure occur on different days), immediately after procedure, at 1 
month, 3 months and 6 months after procedure. The use of an endoscope 
for visual assessment is required. Representative video of each nasal 
passage will be captured for each assessment. Endoscopic video of subject 
holding breath and during maximal inhalation to capture dynamic changes. 
• NOSE Scale score:  
o Mean and mean change from baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
o Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, and 24-month follow-
up evaluations. 
o Mean, change from baseline 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-, and 24-month follow-
up evaluations. 
o Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, and 24-month follow-up evaluations. 

 
 
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• Visual analog scale (VAS) for pain - perception of pain associated with 
the procedure on a 0 to 100 mm scale with 0 indicating no pain and 100 
indicating the worst pain imaginable assessed immediately after 
procedure, and at 1-month and 3-month follow-up evaluations. 
• Visual analog scale (VAS) for ease of breathing - perception of the ability 
to breathe through the nose on a 0 to 100 mm scale with 0 indicating no 
difficulty and 100 indicating extreme difficulty assessed at baseline, 1-
month, 3-month and 6-month follow-up evaluations. 
• Epworth Sleepiness Scale (ESS) - mean and change from baseline in the 
ESS score at each evaluation. The ESS evaluates the self-reported 
likelihood of dozing or falling asleep in 8 daytime situations with 
likelihood rated No Chance (0), Slight (1), Moderate (2), or High Chance 
(3) administered at baseline and the 1-, 3-, 6-, 12-, and 24-month follow-
up evaluations. 
• Participant Satisfaction Assessment - Five question self-reported survey of 
satisfaction with the procedure and recommendation to others 
administered at the 3-, 6-, 12-, and 24-month follow-up evaluations. 
• Change in amount of “as needed” (PRN) medication/device use for nasal 
obstruction symptoms - Self-reported assessment of an increase, no 
change, or decrease in as needed medications and/or devices being used 
for treatment of nasal symptoms at each evaluation compared to use prior 
to the procedure administered at the 1-, 3-, 6-, 12-, and 24-month follow-
up evaluations. 
• Medications - Medications associated with relief or treatment of nasal 
airway obstruction symptoms will be documented at baseline and updated 
as necessary at each evaluation. In addition, medications associated with 
treatment of adverse events will be documented.  
3.3 Safety and Risk Profile 
The safety and risk profile of the Vivaer procedure relative to the sham procedure 
will be evaluated with respect to overall incidence of adverse events and treatment-
related adverse events. 
4.0 
Study Plan 
4.1 Study Design 
The study is designed as a multicenter (up to 20 sites in the U.S. and Europe), 
prospective, randomized, controlled superiority trial with a one-way crossover 
component available to participants randomized to the control arm. A 2:1 site-
stratified randomization will be used to allocate participants with NAO to either the 
active treatment arm (Vivaer procedure) or the control arm (sham procedure) to 
provide up to 120 total participants in the following groups: 

 
 
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o 80 active treatment (Vivaer procedure) 
o 40 inactive treatment (sham procedure) 
All participants will be evaluated in-office prior to treatment and following 
treatment at week 4 (1 month) and week 13 (3 months). The 3-month evaluation 
will be used for the primary endpoint analysis.  
Active treatment participants (Vivaer procedure) will have an extended follow-up 
with evaluations conducted in-office at 6 months (26 weeks) and remotely at 12 
months (52 weeks) and 24 months (104 weeks). 
Participants receiving the sham procedure may elect to crossover to the active 
treatment arm (Vivaer procedure) within 30 days after the 3-month follow-up 
evaluation provided they still meet all eligibility criteria. Continued follow-up will 
be conducted at 1, 3, 6, 12, and 24 months after the Vivaer procedure to provide 
additional information on longer-term efficacy and duration of treatment effect.  
Participants that received the sham procedure and do not elect to crossover or no 
longer meet all eligibility criteria will be exited from the study following the 3-
month evaluation. 
4.2 Study Population 
The target population for this study is adults suffering from symptoms attributed to 
nasal airway obstruction primarily due to internal nasal valve dysfunction, rather 
than hypertrophied turbinates. This study requires severe or extreme symptoms 
demonstrated by a NOSE Scale score ≥ 55 and determination by the investigator 
that the nasal valve is the primary or significant contributor to the nasal obstruction.  
Patients who have had previous surgical treatment of the nasal valve are not eligible 
to enroll in this study; however, it is anticipated that many patients will have 
already undergone rhinoplasty, septoplasty, inferior turbinate 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 patient from 
enrolling in this study. However, to ensure that changes in NOSE Scale score over 
the course of follow-up are the result of the Vivaer procedure, prior surgical 
procedures must have been performed at least 3 months before the patient is 
enrolled in this study and no additional procedures should take place on the day of 
the Vivaer procedure or in the next 6 months.   
Patients must meet all inclusion and exclusion criteria listed below for participation 
in the study. 
4.2.1 Inclusion Criteria 
1. Age 18 to 85 years (inclusively). 
2. Willing and able to provide informed consent.  
3. Willing and able to comply with the subject-specific requirements outlined 
in the Study Protocol. 

 
 
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4. Seeking treatment for nasal obstruction and willing to undergo an office-
based procedure. 
5. Baseline Nasal Obstruction Symptom Evaluation (NOSE) Scale score ≥ 
55. 
6. Nasal valve is a primary or significant contributor to the patient's nasal 
obstruction as determined by the study investigator (based on clinical 
presentation, physical examination, nasal endoscopy, etc.) and the patient 
has a positive response to any of the following temporary measures (based 
on patient history or office exam): 
• Use of external nasal dilator strips (eg, Breathe Right Strips) 
• Use of internal nasal dilator cones 
• Modified Cottle Maneuver (manual elevation of the lateral nasal 
wall using a small instrument or cotton-tipped applicator to open 
the nasal valve) 
• Cottle Maneuver (manual lateral retraction of the cheek to open the 
nasal valve) 
7. Dissatisfaction with medical management as judged by the patient. 
Defined as failed medical therapy (eg, decongestants, antihistamines, 
and/or nasal sprays for an appropriate period of time), but a positive 
response to internal or external nasal dilators. 
4.2.2 Exclusion Criteria 
1. Prior surgery of the lateral nasal wall, including cephalic resection of the 
lower lateral cartilage, dome division or suture plication, alar graft or 
spreader graft placement. 
2. Rhinoplasty, septoplasty, inferior turbinate reduction or functional 
endoscopic sinus surgery (FESS) within the preceding 3 months. 
3. Severe case of any of the following: septal deviation, turbinate 
hypertrophy, polyps, or ptotic nose tip believed to be the primary 
contributor to the patient’s nasal obstruction symptoms and warranting 
surgical intervention. 
4. Any adjunctive surgical nasal procedure planned on the same day or 
within 6 months after the Vivaer procedure. 
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 patient to poor wound healing or increased surgical risk, or 
poor compliance with the requirements of the study. 

 
 
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4.3 Enrollment and Randomization 
Patients must be diagnosed with NAO prior to entry into the study. The use of 
diagnostic procedures and screening tests to determine a diagnosis and assess 
whether patients are appropriate candidates for inclusion in the study is an 
appropriate pre-entry activity. All participants must provide written informed 
consent before undergoing any study related procedures. A participant will be 
considered enrolled after signing and dating the IRB/EC approved informed consent 
form. If a participant is enrolled in the study but subsequently does not meet the 
eligibility criteria, participation in the study will be terminated and the data may be 
excluded from all analysis. 
Randomization will occur after the participant is enrolled, met all eligibility criteria, 
and prior to the treatment procedure allowing sufficient time to prepare the required 
treatment. The randomized assignment (active treatment arm or control arm) will be 
determined using a web-based service. Once the baseline assessments have been 
completed and if patient meets eligibility, results must be entered into the electronic 
data capture (EDC) system before the system will randomize the participant to a 
study assignment group. Participants will be assigned to the active treatment arm 
(Vivaer procedure) or the control arm (sham procedure) in a 2:1 allocation, using 
the computer-generated randomization scheme stratified by site. To help assure 
balance in treatment assignment within sites a block randomization scheme will be 
implemented. Sites will be trained at site initiation to follow detailed randomization 
instructions to assure strict adherence to the randomization process. 
4.4 Blinding 
It will not be possible to blind the investigator administering the treatment because 
of obvious differences in the active application of the RF energy versus the sham 
control. However, every effort should be made to keep the participant blinded as to 
the treatment received.  Steps to help maintain blinding include: 
• Following the same preparation procedures for all cases, including 
administration of anesthetics (topical and local). 
• Application of the Vivaer ARC Stylus in the same manner (pressure, locations, 
timing) for both the active and sham procedures. 
• Simulation of RF energy being applied by having the Aerin Console appear to 
make audible sounds even though RF energy is not being generated or delivered 
for the sham procedure. 
• Use of a blinded evaluator (nontreating physician) to conduct the follow-up visit 
nasal assessment when feasible; however, this is not required. Medical 
personnel who are unaware of the treatment received are also preferred for 
overseeing and coordinating the collection of the participant reported outcome 
measures during the follow-up evaluations. At a minimum, the treating 
physician should not be present when the participant reported outcomes are 
being collected. Site training will include the importance of maintaining the 

 
 
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blinded nature of the study and caution against inadvertent revelation of the 
treatment assignment by study personnel. 
4.5 Outcome Measures 
4.5.1 Nasal Assessment 
The target nasal valve area within each nostril will be visually assessed for 
this study. The use of an endoscope for visual assessment is required. 
Observations are categorized as not present, mild, moderate, or severe. 
Representative video of each nasal passage will be captured for each 
assessment.  Endoscopic video of subject holding breath and during maximal 
inhalation to capture dynamic changes. 
Assessments include: 
• Saddle nose deformity 
• Bruising around orbital area 
• Soreness, pain 
• Numbness 
 
 
Endoscope required: 
• Inflammation / generalized redness 
• Swelling, edema  
• Blanching (generalized whiteness) 
• Bleeding at anesthetic injection site (not requiring physician 
intervention) 
• Bleeding at treatment site (not requiring physician intervention) 
• Nasal obstruction from tissue edema 
• Disruption of mucosal flow / crusting 
4.5.2 Nasal Obstruction Symptom Evaluation (NOSE) Scale 
Evaluation of nasal valve obstruction is based on clinical observations of signs 
and symptoms with no easily obtained, reproducible objective measurement 
techniques of the valve.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 subjective measures have generally been reported.32- 36 Since patient 
symptoms and perception of condition are the factors leading an individual to 
seek treatment, patient-reported subjective measures are cited as the most 
important determinates of treatment outcome.3,32,33 
To evaluate the significance of a patient’s nasal obstruction both before and 
after the procedure, this study will use the well-known subjective patient-

 
 
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reported Nasal Obstruction Symptom Evaluation (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 patients treated for nasal obstruction.37 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 survey.38 
Treatment responder based on NOSE Scale improvement 
Individual participant success (responder) is defined as at least 1 Nasal 
Obstruction Symptom Evaluation (NOSE) Scale class improvement, (eg, 
going from a score in the severe range (55-75) at baseline 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 baseline at the 3-month 
evaluation. 
4.5.3 Pain – Visual Analog Scale Pain Score 
A horizontal 100 mm visual analog scale (VAS)39 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.   
4.5.4 Ease of Breathing – Visual Analog Scale Breathing Score 
A horizontal 100 mm VAS anchored on the left with the words “No Difficulty 
Breathing” and on the right with the words “Extreme Difficulty Breathing”, 
will be used to assess the perception of the ability to breathe through the nose.  
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 assessment of ease of breathing. 
4.5.5 Epworth Sleepiness Scale (ESS) 
The ESS evaluates the self-reported likelihood of dozing or falling asleep in 8 
daytime situations with likelihood rated No Chance (0), Slight (1), Moderate 
(2), or High Chance (3).40 The total of the scores across the 8 questions can be 
categorized and interpreted as: 
• 0-7  
It is unlikely that you are abnormally sleepy. 
• 8-9  
You have an average amount of daytime sleepiness.   
• 10-15 You may be excessively sleepy depending on the situation. 
You may want to consider seeking medical attention.  
• 16-24 You are excessively sleepy and should consider seeking 
medical attention. 

 
 
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This measure is included in the study because results from at least 1 study 
suggest that chronic nasal obstruction impairs quality of life, at least partially, 
through excessive daytime sleepiness possibly caused by sleep-disordered 
breathing.1 Treatment effectiveness with the Vivaer procedure may be evident 
in improvement of the ESS score. 
4.5.6 Participant Satisfaction Assessment  
Five question self-reported survey of satisfaction using a 5-point scale to 
assess tolerability of the procedure, ease of recovery, breathing through nose, 
overall satisfaction with the procedure, and recommendation to others. 
4.5.7 Change in amount of PRN medication/device use for nasal obstruction 
symptoms  
Self-reported assessment of an increase, no change, or decrease from baseline 
in as needed medications and/or devices being used for treatment of nasal 
symptoms following the procedure. Medication/device use may be 
categorized for reporting purposes.   
4.5.8 Medication and Other Therapies for Symptoms of Nasal Obstruction 
The current use of medication, devices or other therapies for symptoms of 
nasal obstruction, medication name, frequency, and dose will be recorded at 
each evaluation visit. Medications may be categorized for reporting purposes. 
4.5.9 Adverse Events 
Adverse events will be documented according to Section 7.1.2. 
4.6 Success/Failure Criteria 
Determinations of the overall success of treatment will be based on two levels: (1) 
the individual participant level and (2) the overall treatment group success relative 
to the sham control group.  Each level has its own criteria for success. 
4.6.1 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 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). 
4.6.2 Participant Failure 
A participant will be considered a nonresponder at the 3-month evaluation if 
neither success criterion has been attained. 
4.6.3 Study Success 
The study will be considered a success if the proportion of participants in the 
active treatment arm achieving a successful outcome (responder) is 
statistically significantly greater than the proportion of participants in the 

 
 
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control arm achieving a successful outcome when evaluated at 3 months after 
the procedure.  
4.7 Duration of the Study 
The primary endpoint will be evaluated at 3 months.  In addition, evaluations at 6, 
12, and 24 months after treatment will extend follow-up to 2 years for evaluation of 
longer-term efficacy. Participants receiving the sham procedure and meeting all 
eligibility requirements may elect to crossover and receive the active Vivaer 
procedure within 30 days after the 3-month evaluation with continued follow-up for 
24 more months for a total of up to 28 months of follow-up. Study enrollment is 
anticipated to be completed within 12 months. Therefore, total study duration is 
anticipated to be approximately 40 months. 
4.8 Site Staffing and Responsibilities of Study Personnel 
The principal investigator is responsible for ensuring that s/he has sufficient and 
qualified staff to conduct the clinical study and that all study-related tasks have 
been appropriately delegated and documented. Roles may include: 
• Treating physician – The treating physician will perform the procedure and 
postprocedure assessments. The treating physician must be a medical doctor 
with experience in ENT procedures and trained in administering the Vivaer 
procedure.   
• Blinded physician evaluator (Not Required) – A physician experienced in 
ENT procedures, trained for participation in this study, and unaware of the 
treatment received, may be used to conduct the follow-up nasal assessment. 
The blinded evaluator may also be responsible for the assessment, treatment 
and/or management of adverse events; however, in some cases it may be 
necessary to refer the event to the treating physician. If a blinded evaluator 
is not available, the treating physician or principal investigator will conduct 
the follow-up assessments. 
• 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. Ideally, 
these individuals would be unaware of the treatment received by the 
participants. 
Due to differences between the active and sham control procedures, staff may also 
become aware of the treatment being administered. Staff with knowledge of the 
randomization assignment should not communicate any information to the 
participant or blinded evaluator (if used) in order to minimize any potential bias.  
4.9 Device Description 
The Vivaer procedure incorporates use of the Vivaer ARC Stylus (Model FG257), 
which is a cleared and CE-marked (FDA - K172529, CE 639608) disposable 
handheld device capable of delivering bipolar radiofrequency energy to tissue, and 

 
 
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the Aerin Console (Model FG226), a cleared and CE-marked (FDA - K162810, CE 
639608) RF generator with temperature control capable of delivering very low 
doses of energy. 
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 
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 pre-set maximum). 
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 radiofrequency energy 
generates heat within the tissue and creates a coagulation lesion. As the lesion 
heals, the tissue retracts and stiffens, thereby decreasing nasal airway obstruction 
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 patient.  
 
 
 
Figure 1.  Vivaer ARC Stylus 
 
②Connector 
①Cable 
③Stylus Handle 
⑥Stylus Shaft 
⑤Stylus Tip 
④Oval Depression – indicates electrode 
orientation 
 

 
 
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Figure 2.  Vivaer ARC Stylus Tip 
 
 
 
                    Figure 3.  Aerin Console with Vivaer ARC Stylus 
4.10 Risk/Benefit Analysis 
4.10.1 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. 

 
 
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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 
These observations will be assessed in the nasal assessment and recorded at 
study visits if they occur. Should any of the following 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 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 with relief at 3 months. 

 
 
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An additional risk to participants receiving the sham procedure is a potential 
for higher likelihood of the treatment not relieving their nasal obstruction 
symptoms compared to those receiving the Vivaer procedure. 
4.10.2 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 electronic case report forms (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. 
4.10.3 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)/Ethics Committee and conducted according to applicable 
regulations with ongoing review by the IRB/EC. 
• Careful consideration has been given to the inclusion/exclusion criteria 
in order to select appropriate candidates for treatment. 
• Patients 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 
Stylus for performing the Vivaer procedure will be permitted to 
participate in the study. 
• Study procedures, follow-up, and study monitoring are designed to 
closely manage adverse events in a timely manner. 

 
 
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• Participants receiving the sham control procedure will be offered the 
Vivaer procedure if they have not responded to the sham procedure by 
the 3-month evaluation. 
4.10.4 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. 
4.10.5 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 radiofrequency energy. The low-power 
radiofrequency energy generates heat within the tissue and creates a 
coagulation lesion. As the lesion heals, the tissue retracts and stiffens, thereby 
decreasing nasal airway obstruction 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. 
The procedure will be provided at no cost to participants. Participants 
randomized to the sham control procedure will be offered the opportunity to 
receive the Vivaer procedure within 30 days after the 3-month evaluation if 
the sham control procedure has not alleviated their symptoms.  

 
 
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5.0 
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. 
5.1 Schedule of Events 
 
 
Treatment 
Follow-up 
(office) 
Extended 
Follow-up 
(remote) 
Screening 
  Procedure 
    Immediate 
Postprocedure 
1 Month 
(4 weeks)  
  3 Months1, 2  
  (13 weeks) 
  6 Months  
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 7) 
(± 14) (± 30) (± 30) (± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal Assessment (physical, endoscopic) 
X 
X3 
X 
X 
X 
X 
 
 
Current medication use (study relevant) 
X 
X3 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
NOSE Scale 
X 
 
 
X 
X 
X 
X 
X 
VAS nasal pain  
 
 
X 
X 
X 
 
 
 
VAS ease of breathing 
X 
 
 
X 
X 
X 
 
 
Epworth Sleepiness Scale 
X 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
X 
X 
X 
X 
Adverse Events 
X 
X3 
X 
X 
X 
X 
X 
X 
1Primary analysis endpoint. 
2 Control participants eligible to crossover and receive Vivaer procedure. 
3Repeat on day of treatment if screening and procedure occur on different days. 
 
 

 
 
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5.2 Participant Flowchart 
 
 
No 
No 
Yes 
Yes 
Consented Participants 
Vivaer procedure 
Sham procedure 
Randomization 2:1 
4-week Follow-up 
(Office) 
13-week Follow-up 
(Office) 
4-week Follow-up 
(Office) 
13-week Follow-up 
(Office) 
Meets 
eligibility 
criteria 
Primary Endpoint 
Extended Follow-up 
(Remote) 
 
12 months 
 
24 months 
Exit Study 
Elects 
Vivaer 
procedure 
Follow-up (Office) 
4 weeks 
 
13 weeks 
 
26 weeks 
 
Extended Follow-up  
(Remote) 
 
12 months 
 
24 months 
26-week Follow-up 
(Office) 

 
 
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5.3 Enrollment and Baseline Assessment 
Screening 
The investigator or designated research staff will perform an evaluation of the study 
candidate for study eligibility, which may include a history and physical 
examination of the nasal area, review of overall medical history, understanding of 
general health and discussion of any conservative measures used for nasal airway 
obstruction.  
Patients must be diagnosed with nasal airway obstruction prior to entry into the 
study. The use of diagnostic procedures and screening tests to determine a diagnosis 
and assess whether patients are appropriate candidates for inclusion in the study is 
an appropriate pre-entry activity. 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 of determining eligibility to 
participate in the study. Once the pretreatment assessments are completed the study 
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/EC 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 patient must be fully counseled with an explanation 
of the study background, 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 
patient 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 patient to participate in the study, 
• ensure the patient understands that their legal rights are not waived at any 
time, 
• use language at a level the patient can understand, and  
• ensure the patient understands that after providing signature on the informed 
consent, the patient may still withdraw at any time before, during or after 
study treatment. 

 
 
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Evaluation of inclusion and exclusion criteria 
The Screening Visit / Study Eligibility eCRF will be used to document the 
participant’s eligibility status.   
Pretreatment (baseline) data and assessments 
The following data will be obtained prior to treatment and recorded on the Baseline 
Visit – Demographics & Treatment History eCRF: 
• Demographics 
o Sex 
o Height (inches) 
o Weight (pounds) 
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, non-allergic), sinus disease, and/or 
obstructive sleep apnea 
o Medication/treatments used to address nasal obstruction and/or 
related symptoms (including CPAP) 
o 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 (physical and endoscopic exam) for each nostril 
including video. Representative video of each nasal passage will be 
captured for this assessment. Endoscopic video of subject holding breath 
and during maximal inhalation to capture dynamic changes. If treatment is 
not provided the same day as screening, then this assessment will be 
repeated on the day of the procedure immediately prior to treatment.  
• Current use of medication, devices or other therapies for symptoms of 
nasal obstruction, including medication name, frequency, and dose will be 
detailed on the Concomitant Medication Log. 
• NOSE Scale score (completed by participant).   
• VAS ease of breathing score (completed by participant). 
• Epworth Sleepiness Scale (completed by participant). 

 
 
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5.4 Treatment Visit and Procedure 
Randomization will occur after the participant is enrolled, met all eligibility criteria, 
and prior to performing the procedure allowing enough time for preparation of the 
selected treatment.  
The treatment procedure is summarized below. Consult the Vivaer procedure 
Investigator’s Brochure and the Vivaer ARC Stylus and Aerin Console Instructions 
for Use (IFUs) for full detail of the treatment procedure and step-by-step 
instructions for preparation and use of the Vivaer ARC Stylus and Aerin Console. 
Preparation  
The procedure will be performed in the study clinic. The participant will be 
positioned in the exam chair according to personal comfort and study physician’s 
preference (eg, upright, reclined or supine). A nasal assessment (physical and 
endoscopic exam) will be performed on each side of the nose and for each nostril, 
including video (only required if screening and procedure occur on different days). 
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) and to allow the study physician to map out and plan the areas of 
treatment. Participants will undergo bilateral treatment of the nasal valves in a 
single study procedure session. Each side of the nose will be treated with up to four 
(4) non-overlapping applications of RF energy at the junction of the upper and 
lower lateral cartilage on the lateral nasal wall.  
 
Figure 4.  Vivaer ARC Stylus at the nasal valve 
The study physician will anesthetize the treatment area by using a topical 
swab/gauze or spray of lidocaine to numb the mucosal tissue, wait approximately 
20 minutes, and then inject anesthesia to the treatment area after initial numbness 
has occurred. The control group will undergo the same anesthetic protocol as the 
active treatment group. 

 
 
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Treatment Administration 
A nasal speculum is inserted into the nostril and opened to visualize the treatment 
area on the lateral nasal wall. 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.    
The default settings for the Vivaer ARC Stylus will be used for the study:  
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 lateral nasal wall in the desired treatment location, the 
foot pedal is depressed and the Stylus is used to both gently displace the cartilage 
and mucosa of the lateral nasal wall and 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; this tone stops when the pedal is released and 
RF energy is no longer delivered. 
When conducting a sham control procedure, the study physician will activate an 
audible tone mimicking the activation of the Aerin Console; however, no energy 
will be transmitted to the Stylus. The study physician should apply the Stylus to the 
lateral nasal wall in a similar fashion as would be done if energy was actually being 
delivered.  
No repeat ("touch-up") procedures will be permitted during the study 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: 
• Preprocedure nasal assessment (physical and endoscopic exam) for each 
nostril including video (only required if screening and procedure occur on 
different days).  
• Procedure type, date of procedure 
• Preprocedure and procedure medications 
• Vivaer ARC Stylus and Aerin Console information 
• Procedure start and end times 
• Aerin Console settings 
• Treatment duration 
• Number of sites treated 

 
 
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• Occurrence of device malfunctions, protocol deviations, and/or adverse 
events 
• Postprocedure nasal assessment (physical and endoscopic exam) for each 
nostril including video 
5.5 Postprocedure Assessments and Care 
Immediately postprocedure, a nasal assessment (physical and endoscopic exam) for 
each nostril including 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 (vertical line marked on the 100 mm line) on the Pain VAS CRF. 
At the discretion of the study physician, the following care may be provided: 
• Apply compression to the treatment area internally for 5 minutes. 
• Apply petroleum jelly to the treatment area as needed.  
• Use of nasal saline spray or ointment as needed 
• The participant should be instructed not to manipulate the treatment site for 
24 hours with the exception of any necessary hemostasis. 
Participants should have their first follow-up visit (4 weeks) scheduled within the 
visit window prior to release. 
Participants should not receive other concomitant nasal treatment therapies or 
interventions after the procedure or during the study follow-up period 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. Therapies, interventions, and pain medication will be monitored at 
follow-up evaluations.   
5.6 Follow-up Evaluations and Study Exit 
Follow-up visit dates will be calculated from the study procedure date. Follow-up 
visits should be scheduled within the specified visit windows described in the 
Schedule of Events (Section 5.1) and Table 1 (Section 8.3.2). In-office follow-up 
evaluations are scheduled for 4 weeks (1 month), 13 weeks (3 months) and 26 
weeks (6 months) after the procedure. In addition, follow-up evaluations at 12 and 
24 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 nonstudy visits should be 
evaluated for possible adverse events and an Adverse Event Report eCRF should be 
submitted if appropriate. 
Participants randomized to the control arm (sham procedure) may elect to crossover 
to the active treatment arm (Vivaer procedure) within 30 days after the 3-month 

 
 
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evaluation, once they have undergone their scheduled 3-month evaluation and 
continue to meet all of the eligibility criteria, including NOSE Scale score of ≥ 55. 
New baseline information will be collected prior to the Vivaer procedure. Crossover 
participants who choose to have the Vivaer procedure will maintain their original 
study ID and will follow the same pretreatment, treatment, and follow-up processes 
as any newly enrolled participant.  
All participants who receive the Vivaer procedure, as well as sham procedure 
participants who choose to have the Vivaer procedure after their 3-month 
evaluation, should be followed through the final follow-up evaluation at 2 years 
postprocedure regardless of their success/failure classification. Sham procedure 
participants who choose not to have the Vivaer procedure or who fail to meet 
inclusion and exclusion criteria will be exited from the study following the 3-month 
evaluation. Every effort should be made to avoid having participants withdraw from 
the study (Section 9.6). 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 
point and recorded on the Follow-up Visit eCRF: 
In-office evaluations: 4-Weeks (1-month), 13-Weeks (3-month) and 26-weeks (6-
months) follow-up: 
• Nasal assessment (physical and endoscopic exam) for each nostril including 
video 
• Current use of medication, devices or other therapies for symptoms of nasal 
obstructions, including medication name, frequency, and dose  
• Participant reported change in use of as needed medications and devices for 
nasal obstruction symptoms (completed by participant)  
• NOSE Scale score (completed by participant) 
• VAS pain score  (completed by participant) (4-weeks and 13-weeks only) 
• VAS ease of breathing score (completed by participant)  
• Epworth Sleepiness Scale (completed by participant) 
• Participant Satisfaction Survey (completed by participant) (13-weeks and 
26-weeks only) 
• Adverse events  
Remote (telephone) evaluations: 12-month (52-Weeks) and 24-month (104-Weeks) 
follow-up: 
• Current use of medication, devices or other therapies for symptoms of nasal 
obstruction, including medication name, frequency, and dose (study staff 
follow-up required if participant indicates change) 

 
 
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• Participant reported change in use of as needed medications and devices for 
nasal obstruction symptoms (verbal administration by site personnel)  
• NOSE Scale score (verbal administration by site personnel) 
• Epworth Sleepiness Scale (verbal administration by site personnel) 
• Participant Satisfaction Survey (verbal administration by site personnel)  
• Adverse events (study staff follow-up required if participant indicates 
changes) 
 
Study Exit 
Participants meeting the study requirements as planned will be exited from the 
study upon completion of the 24-month follow-up evaluation. If a participant 
reaches the 24-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.   
5.7 Product Handling and Accountability 
A system that allows tracking of orders, shipping and returns will be used to control 
Vivaer ARC Stylus and Aerin Console 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 or 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. 
6.0 
Statistical Considerations 
6.1 Study Design 
This is a prospective, multicenter, randomized, sham-controlled study to compare 
the Vivaer procedure for treatment of nasal airway obstruction with a sham 
procedure that simulates the actual procedure as closely as possible absent the 
delivery of radiofrequency (RF) energy to the nasal tissue. A 2:1 site-stratified 
randomization will be used to allocate participants with NAO to either the Vivaer 
procedure (active treatment) or a sham procedure (control). This study is designed 
to demonstrate the superiority of the active Vivaer treatment compared to the sham 
control. 
6.2 Study Hypotheses 
The null hypothesis (H0) for this superiority study is that there is no difference 
between the success (responder) rate for the sham control and the success 
(responder) rate for the Vivaer procedure: 
H0: πC - πT = 0 vs. H1: πC - πT ≠ 0 
where: 

 
 
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πC=proportion of responders in the sham procedure control group 
πT=proportion responders in the Vivaer procedure treatment group 
Rejection of the two-sided null hypothesis in favor of the alternative (H1) 
hypothesis means that there is evidence for a statistically significant difference in 
responder rates between the two groups.   
6.3 Sample Size Estimate 
The study will enroll up to 120 participants. The power analysis was performed 
such that there is adequate power to reject the null hypothesis of no difference 
between treatments. Sample size estimation was based on the test for differences 
between two proportions41 using an Exact test and on the following assumptions: 
• Significance level α = 0.05 (two-sided) 
• Power = 80% 
• πC = 0.50 (allowance for a 50% control responders) 
• πT = 0.80 (assumed 80% responders in the treated group) 
• Treatment allocation is 2:1 
• 10% dropout and nonevaluable 
The 80% responder rate assumed for the active Vivaer procedure group is a 
conservative estimate based on the prior clinical study of this procedure in which all 
50 participants were responders at 12 weeks and 46 of 49 (94%) were responders at 
26 weeks. The lower 95% confidence bound on the estimate of 94% is 83.5%, 
which supports the conservative estimate of 80% responders assumed for the 
purpose of sample size calculation. The 50% responder rate assumed for the sham 
control procedure is based on literature for placebo and sham controls in therapeutic 
and device studies suggesting from 30% to 60% responder rates, with device studies 
tending to be at the higher end of the range42. A randomized study of a 
bioabsorbable implant treatment for nasal valve collapse reported a 54.7% 
responder rate in the sham procedure arm of the study.20  
The minimum number of participants to achieve 80% power with a 2:1 active 
treatment to sham control allocation is 66 in the active treatment group and 33 in 
the sham. The sample size, allowing for 10% loss (nonevaluable) in each group and 
adjusting for a balanced distribution across 20 sites is 120 participants (80 active 
treatment (Vivaer procedure), 40 sham procedure control). 
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.   

 
 
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6.4 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 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 24-month (104-week) follow-
up evaluation of the extended follow-up phase of the study, including sham 
procedure control participants who subsequently received the Vivaer procedure. 
6.5 Analysis Populations 
The primary endpoint analysis will be based on the intent to treat (ITT) principle.  
Participants will be analyzed in the originally randomized treatment group 
regardless of actual treatment received. The effects of protocol deviations will only 
be examined when the validity of the study conclusion is in question. All secondary 
and other analyses and reports will include an ITT population analysis. Following 
data reporting conventions, statistics on the per protocol population will also be 
reported. The per protocol population is defined as all participants who received 
treatments, with 13-week (3-month) follow-up data and no major protocol 
deviations. 
6.6 Missing Data 
All missing data in each treatment group will be imputed for the primary endpoint 
by assuming the missing outcomes are nonresponders. In addition, a post hoc 
sensitivity analyses may be performed, including a worst-case analysis (all missing 
primary outcomes in the Vivaer procedure group are considered nonresponders and 
all missing outcomes in the sham procedure control group are responders) and/or a 
change-point analysis, to assess the effect of missing data on the primary analysis. 
The results of the sensitivity analysis will not be used to adjust the conclusions 
drawn from the primary analysis. 
Secondary outcome measures and additional observational measurements will be 
analyzed by using available data only. 
6.7 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 6.3).  
Comparability between study sites may be shown using summary statistics 
calculated by site.   
6.8 Participant Disposition 
A detailed description of participant disposition will be provided by treatment group 
using a CONSORT diagram and summaries of participants falling in various 
subgroups of interest, such as, enrolled but not treated with any study treatment, not 
treated as randomized, discontinued, excluded from ITT, protocol deviations, 

 
 
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deaths, and withdrawals. All study population exclusions and reasons will be 
summarized. All randomized 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. 
6.9 Demographics and Characteristics 
Demography, baseline characteristics and the comparability of active treatment 
group and sham control group participants will be summarized using frequencies 
and percentages for categorical factors and mean, median, standard deviation, 
minimum and maximum for continuous factors. Demographic characteristics will 
be reported to describe the profile of samples. Comparability between treatment 
groups will not be statistically assessed in this prospective randomized clinical trial.  
There are no preplanned subgroup analyses; however, potential baseline covariates 
with possible impact on outcomes at 3 months are: 
• Age  
• Race 
• Sex 
• BMI 
• Allergic status (allergic rhinitis - nonallergic rhinitis) 
Results may be evaluated by allergic status if sufficient numbers are obtained in 
both categories. 
6.10 Primary Endpoint Analysis 
Primary efficacy will be evaluated using the proportions of successful outcomes 
(responders) on the primary outcome measure (1 NOSE class improvement or 
improvement (decrease) in NOSE Scale score of ≥ 20% from baseline) at 13 weeks. 
The proportions of successful participants at 13 weeks in each group will be 
compared using Fisher’s Exact test. 
Confidence intervals (95%) will be provided for all proportions and comparisons. 
6.11 Secondary Endpoint Analyses 
Secondary endpoints will be tested only after the primary objective of the study is 
met. Confidence intervals (95%) will be included for all secondary outcome 
measures. 
• NOSE Scale score change from baseline to 13 weeks 
The mean changes from baseline at 13 weeks in each group will be 
compared with a 2-sided t-test with a null hypothesis of no difference 
between groups. 

 
 
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• Device-related and procedure-related serious adverse events through 13 
weeks 
The proportions of device-related and procedure-related serious adverse 
events through 13 weeks in each group will be compared using Fisher’s 
Exact test. 
6.12 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, standard deviation, 
minimum and maximum for continuous factors. Confidence intervals for 
differences between treatment groups will be included where appropriate. Statistical 
comparisons will either not be performed or used for information purposes.  
Proportions may be compared using exact tests or chi-square tests. Continuous 
outcomes may be compared using t-tests, ANOVA or nonparametric equivalents. 
Repeated measures ANOVA may be used for longitudinal analysis across 
evaluations. 
Other outcome measures include: 
• Nasal Assessment - The visual physical 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 baseline, just prior to procedure (if screening and procedure occur 
on different days), immediately after procedure, at 1 month, 3 months, and 
at 6 months after the procedure. 
• 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 baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
o Distribution of NOSE Scale score severity categories (mild, 
moderate, severe, extreme) at the 3-, 6-, 12-, and 24-month follow-
up evaluations for each group. 
o Mean, change from baseline 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-, and 24-month follow-
up evaluations for each group. 
o Proportion of responders based on improvement in NOSE Scale 
score at the 3-, 6-, 12-, and 24-month follow-up evaluations for 
each group. 

 
 
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• Visual analog scale (VAS) for pain - Summary will include mean VAS 
pain scores assessed postprocedure, 1 month, and at 3 months for both 
groups. 
• Visual analog scale (VAS) for ease of breathing - Summary will include 
mean ease of breathing scores assessed at baseline, 1 month, 3 months, 
and at 6 months for both groups. 
• Epworth Sleepiness Scale (ESS) - mean and change from baseline in mean 
ESS score and categorical responses will be summarized for both groups 
at baseline and the 1-, 3-, 6-, 12-, and 24-month follow-up evaluations. 
• Participant Satisfaction Assessment - mean response for each of the five 
survey questions will be summarized by group at the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
• Change in amount of PRN medication/device use for nasal obstruction 
symptoms - Proportions of participants reporting increase, decrease, or no 
change in use the categories of PRN medication or devices prior to 
procedure will be summarized by group at the 1-, 3-, 6-, 12-, and 24-
month follow-up evaluations.  
• Medications - Medications associated with relief or treatment of nasal 
airway obstruction symptoms or associated with the treatment of adverse 
events will be provided by group and documented at baseline and updated 
as necessary at each evaluation. Medication use by categories may also be 
presented as percentages of participants in each group.  
6.13 Safety Analysis 
All adverse events will be analyzed for all participants. 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. 
6.14 Extension Phase Analysis 
The extension 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. 

 
 
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6.15 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 treatment 
group and time. 
7.0 
Adverse Events and Product Complaints / Device Deficiencies 
7.1 Adverse Events 
Adverse events (AEs) may occur during the treatment phase or during the follow-up 
phase. Adverse events occurring after the baseline assessment but before the 
procedure will be documented in the participant’s medical record but will not count 
as related to the study device or procedure.   
7.1.1 Definitions 
Following are definitions associated with adverse events: 
Adverse Event (AE) - any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) 
in subjects, users or other persons, whether or not related to the investigational 
medical device and whether anticipated or unanticipated (per ISO 
14155:2020).  
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.   
Serious Adverse Event (SAE) - an adverse event that led to any of the 
following (per ISO 14155:2020): 
a) death, 
b) serious deterioration in the health of the subject, 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 

 
 
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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 (per ISO 14155:2020). 
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 14155:2020). 
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 subjects (per 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: 
• 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 

 
 
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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. 
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. 

 
 
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7.1.2 Documentation and Reporting of Adverse Events 
All adverse events will be monitored from the time of enrollment 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 24-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  
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. 
7.2 Product Complaints / Device Deficiencies 
7.2.1 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 

 
 
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organization's control or related to a service that affects the performance of 
such medical device (per ISO 13485:2016). 
Reportable Complaint – Any product complaint that represents an event, 
which must be reported to a regulatory agency including: 
• US Food and Drug Administration (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 14155:2020). 
7.2.2 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.  
8.0 
Study Administration 
This study will be conducted in accordance with elements of ICH E6 Guideline for 
Good Clinical Practice, Abbreviated Requirements of 21 CFR 812 for NSR device 
studies, the European Standard ISO 14155, the Declaration of Helsinki, the Belmont 
Report, and any applicable regional or national regulations.  
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. 

 
 
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8.1 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, randomization instructions, monitoring logistics, and regulatory 
requirements. 
8.2 Study Monitoring 
Study monitoring will be carried out in compliance with FDA regulations, ISO 
14155, and 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 and evaluate compliance with the 
protocol, any specific recommendations made by the site’s IRB/EC 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 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. 
8.3 Documentation of Study Findings 
8.3.1 Data Management 
A secure Electronic Data Capture (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 

 
 
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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.   
8.3.2 Case Report Forms 
Standardized electronic case report forms 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 enrolled in the study. A unique ID number will be assigned to each 
participant.  
The following eCRFs and log will be used in this study and submitted at the 
intervals outlined in Table 1: 
• Screening Visit / Study Eligibility (01) 
• Baseline Visit – Demographics & Treatment History (02) 
• Nasal Obstruction Symptom Evaluation (NOSE) Scale (03) 
• Ease of Breathing VAS – Participant form (04A) 
• Ease of Breathing VAS – Site form (04B) 
• Epworth Sleepiness Scale (05) 
• Study Procedure (06) 
• Pain VAS – Participant form (07A) 
• Pain VAS – 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) 
• Concomitant Medication Log (L3) 

 
 
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Table 1.    Schedule of case report forms and related materials. 
Visit 
Visit Window (days) 
eCRF 
Other 
Screening / Baseline 
n/a 
01, 02, 03, 04A, 
04B, 05, L3 
Informed Consent 
Nasal assessment images† 
Study Procedure 
within 30 days of Baseline‡ 
06 
Nasal assessment images† 
Postprocedure 
0 
06, 07A, 07B 
Nasal assessment images† 
4-Week (In-office) 
±7 
03, 04A, 04B, 05, 
07A, 07B, 08 
Nasal assessment images† 
13-Week (In-office) 
±14 
03, 04A, 04B, 05, 
07A, 07B, 08, 09 
Nasal assessment images† 
6-Month (In-office) 
±30 
03, 04A, 04B, 05, 
08, 09 
Nasal assessment images† 
12-Month (Remote) 
±30 
03, 05, 08, 09,  
 
24-Month (Remote) 
±30 
03, 05, 08, 09, 10 
 
As Needed 
n/a 
11, 12, 13, 14, L3 
 
†Copy deidentified endoscopic video/images collected for study records to USB flash drive and provide to 
sponsor. 
‡If the procedure does not occur on the same day as screening, the Nasal Assessment will be repeated prior to the 
procedure.  
8.3.3 Investigator Responsibilities, Records, and Reports 
Responsibilities 
The investigator is responsible for ensuring that the study is conducted 
according to the protocol and all IRB/EC requirements. In addition, the 
investigator is responsible for obtaining participant’s written informed consent 
and for U.S. study sites, participant’s 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/EC 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/EC, 
the sponsor, the study monitors, other investigators, and regulatory 
agencies. 
2. Device accountability records that will track device usage for all study 
participants. Information tracked will include date of receipt, lot or 
serial number, expiration date, date of device usage, subject ID, and 
disposition of all study products, including the type and quantity of the 

 
 
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product, the dates of their return, if applicable, the occurrence of any 
device malfunctions, and initials of study personnel conducting device 
accountability.   
3. 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.  
4. Study protocol, amendments, and documentation (dates and reasons) 
of any deviations from the protocol. 
5. IRB/EC records, including original and ongoing study approvals, all 
correspondence, and the approved informed consent form(s). 
6. IRB/EC membership list, FWA# as applicable, statement of 
compliance and written procedures pertaining to AE and PD reporting 
(if available).  
7. Study agreement, curricula vitae of investigator(s), financial 
disclosure, signature authorization log (delegation of responsibility), 
protocol signature page, and patient screening/enrollment log. 
8. Reports (including safety reports, progress reports and a final report 
from the investigator). 
9. Any other records, as required by the IRB/EC 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 e-mail to the sponsor and the IRB/EC. 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/EC 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 

 
 
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research without IRB/EC approval, except where necessary to 
eliminate apparent hazards to the participants. 
4. Withdrawal of IRB/EC 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/EC at regular intervals 
dictated by the IRB/EC but no less than annually. 
6. A final report must be submitted to the IRB/EC 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/EC 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/EC 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. 
8.3.4 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 two 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. 
8.3.5 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. 
8.3.6 Confidentiality 
All information provided to investigators, IRBs/ECs, 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 

 
 
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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 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 patient 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.   
8.3.7 Publication Policies 
The Clinical Trial Agreement 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 Clinical Trial 
Agreement.  
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. 
8.4 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: 

 
 
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• 
Obtaining new scientific knowledge that shows that the study is no longer 
valid or necessary 
• 
Insufficient recruitment of patients 
• 
Unanticipated adverse device effect presenting an unreasonable  risk 
to 
 
patients 
• 
Persistent noncompliance with the protocol and/or IRB/EC 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/EC shall 
also be informed promptly and provided with the reason(s) for the termination or 
suspension by the sponsor. The investigator shall promptly inform enrolled 
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 subject to the same retention 
policy as detailed in Section 8.3.4.  
9.0 
Ethics 
9.1 Institutional Review Board/Ethics Committee 
This study may not be initiated at a site until applicable Institutional Review 
Board/Ethics Committee, 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/EC. Any additional 
requirements or conditions imposed by the IRB/EC or regulatory authority shall be 
followed, if appropriate.   
To assure proper review and study oversight, the IRB/EC 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/EC for review and approval in accordance with 
applicable regulations. The investigator is responsible for providing accurate, 
complete, and current information to the IRB/EC throughout the course of the 
study.  
9.2 Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, Good Clinical 
Practice (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 wellbeing of study subjects shall be protected 
consistent with these principles. 

 
 
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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.  
9.3 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 
Health Information, or in accordance with EC policies and national regulations. 
Each participant must give permission for use and disclosure of their information by 
signing the Authorization to Use and Disclose Health Information, or other 
document as required by the EC and/or regulatory authority. 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 Food and 
Drug Administration 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. 
9.4 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. 
9.5 Participant Reimbursement 
Participants may be reimbursed for their time for completing questionnaires as 
allowed by the IRB/EC and study site policies. Participants will not be reimbursed 
for questionnaires not completed. 
9.6 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 

 
 
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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.   
9.7 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 scientific soundness of the protocol; or the rights, safety, or welfare of the 
participants. All modifications must be reviewed and approved by the IRB/EC 
before implementation.   
9.8 Protocol Adherence and Deviations 
9.8.1 Definition 
Deviation – instance of failure to follow, intentionally or unintentionally, the 
requirements of the protocol (per ISO 14155:2020). 
 
9.8.2 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/EC, 
except when necessary to eliminate apparent immediate hazards to a 
participant. Investigators will also adhere to procedures for reporting study 
deviations to their IRB/EC in accordance with their specific IRB/EC 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, pre-approved, or performed to protect the participant in an 
emergency. The investigator will document and explain the reason for the 
deviation. Participant specific deviations will be reported using the Protocol 
Deviation eCRF.  
 
 

 
 
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