A Phase 4 Randomized Trial Comparing Varithena to Endothermal Ablation for the Treatment of the Great Saphenous Vein
Phase: PHASE4
Conditions: Varicose Veins
Sponsor: Boston Scientific Corporation

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Protocol Number: 
S2473 
Protocol Short Title: 
Varithena versus Endothermal Ablation of the Great Saphenous Vein 
(VERITAS) 
Protocol Name: 
A Phase 4 Randomized Trial Comparing Varithena to Endothermal 
Ablation for the Treatment of the Great Saphenous Vein 
Global Sponsor: 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752, United States 
Global Principal 
Investigators: 
Steven Elias, MD 
Englewood Health 
Englewood, NJ 07631, United States 
Antonios Gasparis, MD 
Stony Brook Medicine 
Stony Brook, NY 11794, United States 
Physician Advisor: 
Nick Morrison, MD 
Arizona, United States 
Protocol Medical Safety 
Director: 
Anna Chavez, MD 
Boston Scientific 
Anna.Chavez@bsci.com 
Product: 
Varithena (polidocanol injectable foam) 1% 
Protocol ver.1.0 Approval 
Date:  
23Feb2022 
Protocol Amendment 
ver.1.2 Approval Date: 
17Aug2023 
This document is the confidential property of the Sponsor. No part of it may be transmitted, reproduced, 
published, or used by other persons without prior written permission.  
NCT 05312970

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Table 1: Protocol Revision History 
VERSION 
NUMBER 
AMENDMENT 
APPROVAL 
DATE 
BRIEF DESCRIPTION OF CHANGES 
1.0 
23Feb2022 
Original protocol 
1.1 
18Oct2022 
Updated Table 2, clarified treatment groups-control arm, clarified Section 
3.2 Description of Varithena, clarified Section 6.1.2 Retreatment Criteria, 
updated Section 7.3.15 Duplex Ultrasound reference, updated Section 
11.8 End of Study now termed Trial Completion with expanded definitions, 
updated Varithena USPI references, clarified rVCSS assessment, updated 
Varithena complaint reporting mailbox address 
1.2 
17Aug2023 
Revised Informed Consent Process to standard Boston Scientific Informed 
Consent language Section 7.3.1, Clarified Point of Enrollment Section 
7.3.8, added Point of Treatment 7.3.10, and updated references to 
enrollment, randomization, and treatment throughout. 
 
 

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TABLE OF CONTENTS, LISTS OF TABLES & FIGURES 
Table of Contents 
1 
SCHEMA .......................................................................................................................................... 12 
2 
SCHEDULE OF VISITS .................................................................................................................... 14 
3 
BACKGROUND ................................................................................................................................ 15 
3.1 
Disease background ............................................................................................................... 15 
3.2 
General Description of Varithena ............................................................................................ 16 
3.3 
Clinical Summary of Varithena ................................................................................................ 16 
4 
STUDY OBJECTIVE and PURPOSE ............................................................................................... 18 
4.1 
Study Objective ....................................................................................................................... 18 
4.2 
Study Design ........................................................................................................................... 18 
4.3 
Randomization ........................................................................................................................ 18 
4.4 
Primary Endpoint ..................................................................................................................... 18 
4.5 
Additional Assessments .......................................................................................................... 19 
5 
PATIENT SELECTION ..................................................................................................................... 19 
5.1 
Patient Population ................................................................................................................... 19 
5.2 
Patient Selection ..................................................................................................................... 19 
5.2.1 Inclusion Criteria .......................................................................................................... 19 
5.2.2 Exclusion Criteria ......................................................................................................... 20 
5.3 
Patient Completion .................................................................................................................. 20 
5.4 
Patient Withdrawal .................................................................................................................. 20 
5.5 
Patients “Lost to Follow-Up” prior to the Last Scheduled Visit ................................................ 21 
6 
TREATMENT OF PATIENTS ........................................................................................................... 21 
6.1 
Varithena Product Description ................................................................................................ 21 
6.1.1 Dosage & Administration ............................................................................................. 21 
6.1.2 Retreatment Criteria .................................................................................................... 22 
6.1.3 Safety Criteria for Adjusting or Stopping Treatment(s) ................................................ 22 
6.1.4 Post-treatment Management ....................................................................................... 22 
6.1.5 Duration of Treatment and Follow up .......................................................................... 22 
6.1.6 Concomitant Therapies or Interventions ...................................................................... 22 
6.2 
Product Labelling / Packaging / Storage / Handling ................................................................ 22 
6.2.1 Labelling and Packaging ............................................................................................. 22 
6.2.2 Storage and Handling .................................................................................................. 22 
7 
MEASUREMENTS AND EVALUATIONS ........................................................................................ 22 
7.1 
Study Blinding and Treatment Group Assignment .................................................................. 22 
7.2 
Time and Event Schedule ....................................................................................................... 23 
7.2.1 Screening Visit ............................................................................................................. 23 
7.2.2 Index Procedure Visit .................................................................................................. 23 

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7.2.3 7 Days (±3 Days), 3 Months (±14 Days), 12 Months (±30 Days), 24 Months (±30 Days), 
and 36 Months (±30 Days) Follow Up Visit ............................................................................. 23 
7.2.4 6 Months (±14 Days) Follow Up Visit ........................................................................... 24 
7.2.5 Early Discontinuation ................................................................................................... 24 
7.3 
Study Evaluations and Procedures ......................................................................................... 24 
7.3.1 Informed Consent Process .......................................................................................... 24 
7.3.2 Demographics ............................................................................................................. 25 
7.3.3 Medical History ............................................................................................................ 25 
7.3.4 Mapping of Superficial and Deep Veins ...................................................................... 26 
7.3.5 Physical Examination .................................................................................................. 26 
7.3.6 Pregnancy Test ........................................................................................................... 26 
7.3.7 Eligibility Review .......................................................................................................... 26 
7.3.8 Point of Enrollment ...................................................................................................... 26 
7.3.9 Randomization Event .................................................................................................. 26 
7.3.10 Point of Treatment ....................................................................................................... 26 
7.3.11 Treatment Record ........................................................................................................ 27 
7.3.12 Observation and Recording of Adverse Events ........................................................... 27 
7.3.13 Varicose Veins Symptoms Questionnaire (VVSymQ) ................................................. 27 
7.3.14 Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-
QOL/sym) ................................................................................................................................ 27 
7.3.15 Revised Venous Clinical Severity Score (rVCSS) ....................................................... 27 
7.3.16 5-level EQ-5D version (EQ-5D-5L) .............................................................................. 27 
7.3.17 Duplex Ultrasound ....................................................................................................... 28 
7.3.18 CEAP Clinical Condition Classification ........................................................................ 28 
8 
ADVERSE EVENTS ......................................................................................................................... 28 
8.1 
Adverse Event Definitions ....................................................................................................... 28 
8.1.1 Definitions of AE/ADR/SAE/SADR/SUSAR ................................................................. 28 
8.1.2 Recording Adverse Events .......................................................................................... 29 
8.2 
Causality Assessment ............................................................................................................. 30 
8.2.1 Criteria for Assessing the Relationship of Varithena, ETA Device, or Procedure to an 
Adverse Event ......................................................................................................................... 30 
8.3 
Submitting Safety Reports ...................................................................................................... 31 
8.4 
Periodic Safety Reporting ....................................................................................................... 32 
8.5 
Expected Adverse Events ....................................................................................................... 32 
8.6 
Adverse Events of Special Interest ......................................................................................... 32 
9 
STATISTICAL CONSIDERATIONS ................................................................................................. 33 
9.1 
Study Design and Determination of Sample Size ................................................................... 33 
9.2 
Statistical Populations and Sub-Groups .................................................................................. 33 
9.3 
Baseline and Demographic Characteristics ............................................................................ 33 
9.4 
Efficacy Analyses .................................................................................................................... 33 

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9.4.1 Handling of Missing Data ............................................................................................. 33 
9.4.2 Primary Efficacy Endpoint Analysis ............................................................................. 33 
9.4.3 Secondary Efficacy Endpoint Analysis ........................................................................ 33 
9.5 
Safety Analyses ...................................................................................................................... 34 
9.6 
Other Analyses ........................................................................................................................ 34 
9.7 
Interim Analyses ...................................................................................................................... 34 
10 
DATA MANAGEMENT ..................................................................................................................... 34 
10.1 Image Management System ................................................................................................... 35 
11 
LEGAL/ETHICS and ADMINISTRATIVE PROCEDURES .............................................................. 35 
11.1 Good Clinical Practice/Regulatory Compliance ...................................................................... 35 
11.2 Study Site and Investigator Qualification ................................................................................ 35 
11.2.1 Investigator Responsibilities ........................................................................................ 36 
11.2.2 Investigator CV ............................................................................................................ 37 
11.2.3 Investigator Agreement Form (Form FDA 1572) ......................................................... 37 
11.2.4 Financial Agreements and Financial Disclosure .......................................................... 37 
11.2.5 Site Qualifications ........................................................................................................ 37 
11.3 Institutional Review Board (IRB)/Independent Ethics Committees (IEC) ................................ 38 
11.3.1 Institutional Approval of the Protocol ........................................................................... 38 
11.3.2 Ethics/IRB Committee Membership Roster ................................................................. 38 
11.4 Patient Privacy and Confidentiality .......................................................................................... 38 
11.5 Study Monitoring ..................................................................................................................... 39 
11.6 Modification of the Protocol ..................................................................................................... 39 
11.7 Suspension or Termination of Study ....................................................................................... 39 
11.8 Trial Completion ...................................................................................................................... 39 
11.9 Clinical Study Report ............................................................................................................... 40 
11.10 Departure from Protocol .......................................................................................................... 40 
11.10.1 Protocol Deviations .................................................................................................. 40 
11.11 Recording, Access to and Retention of Source Data .............................................................. 40 
11.12 Electronic Case Report Forms ................................................................................................ 41 
11.13 Publications ............................................................................................................................. 41 
11.14 Audit/Inspections ..................................................................................................................... 41 
12 
BIBLIOGRAPHY .............................................................................................................................. 41 
13 
SUPPLEMENTS/APPENDICES ...................................................................................................... 42 
Protocol Approval & Release Signature Page .................................................................................. 43 
Principal Investigator Protocol Review Statement ............................................................................ 44 
VVSymQ ........................................................................................................................................... 45 
 
LIST OF TABLES 
Table 1: Protocol Revision History .................................................................................................................. 2 

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Table 2: Terms, Acronyms, Abbreviations ...................................................................................................... 7 
Table 3: Pre-Treatment VVSymQ ................................................................................................................. 45 
Table 4: Post-Treatment VVSymQ ............................................................................................................... 46 
  
 

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Table 2: Terms, Acronyms, Abbreviations 
The following abbreviations and specialist terms are used in this protocol. 
AASV 
Anterior Accessory Saphenous Vein  
ABPI 
Ankle-Brachial Pressure Index  
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
CEAP 
Clinical condition, etiological, anatomical location, and pathophysiological 
CFR 
Code of Federal Regulation 
CI 
Confidence Interval 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CV 
Curriculum Vitae 
CVD 
Chronic Venous Disease  
CVI 
Chronic Venous Insufficiency  
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EQ-5D 
EuroQoL-5D  
ETA 
Endothermal Ablation  
EVLA 
Endovenous Laser Ablation  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GSV 
Great Saphenous Vein 
HASTI 
Heaviness, Achiness, Swelling, Throbbing, and Itching 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IFU 
Instruction for Use 
IPR-V3 
Independent Photographic Review Visible Varicose Veins  
IRB 
Institutional Review Board 

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ISO 
International Organization for Standardization 
LOCF 
Last non-missing post-baseline observation carried forward 
mL 
millilitre 
PA-V3 
Patient Assessment of Visible Varicose Veins  
PCF 
Physician-Compounded Foam  
PI 
Principal Investigator 
QOL 
Quality of Life 
RFA 
Radiofrequency Ablation  
rVCSS 
revised Venous Clinical Severity Score  
SADR 
Serious Adverse Drug Reaction 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SFJ 
Saphenofemoral Junction  
SoC 
Standard of Care 
SSV 
Small Saphenous Vein  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
USPI 
United States Prescribing Information 
VCSS 
Venous Clinical Severity Score 
VEINES-QOL/Sym 
Venous insufficiency Epidemiological and Economic Study – Quality of 
Life/Symptoms  
ver. 
Version 
VTU 
Varithena Transfer Unit  
VVSymQ 
Varicose Veins Symptoms Questionnaire  
WHO 
World Health Organization 
WOCP 
Women of Child-bearing Potential 
 
 
 

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PROTOCOL SYNOPSIS  
Protocol Number 
S2473 
Protocol Short Title 
Varithena versus Endothermal Ablation of the Great Saphenous Vein 
(VERITAS) 
Protocol Title 
A Phase 4 Randomized Trial Comparing Varithena to Endothermal Ablation for 
the Treatment of the Great Saphenous Vein 
Product 
Varithena® (polidocanol injectable foam) 1% 
Type of Protocol 
Phase 4 
Study Rationale 
The purpose of this study is to observe insights into the benefits of Varithena 
compared to Endothermal Ablation (ETA) in the treatment of the great 
saphenous vein 
Study Objectives 
To collect comparative evidence on patient reported outcomes of Varithena 
compared to ETA when used to treat the incompetent great saphenous vein 
(GSV).  ETA will include either radiofrequency ablation or endovenous laser 
ablation according to the site’s standard practice. To provide long term (1-year, 
2-year, and 3-year) outcomes. 
Primary Endpoint 
Change in Varicose Veins Symptoms Questionnaire (VVSymQ) between 
baseline and 3-month post treatment 
Additional 
Assessments 
• 
Change from baseline in revised Venous Clinical Severity Score (rVCSS) at 
7-day, 3-month, 6-month, 12-month, 24-month, and 36-month post 
treatment 
• 
VEINES-QOL/Sym and EQ-5D at 7-day, 3-month, 6-month, 12-month, 24-
month, and 36-month post treatment 
• 
Clinical condition, etiological, anatomical location, and pathophysiological 
(CEAP) clinical condition classification at 7-day, 3-month, 6-month, 12-
month, 24-month, and 36-month post treatment 
• 
Varithena, ETA, and Procedure related serious adverse events (SAE) 
• 
Healthcare resource utilization for treated limb venous disease at 12-month, 
24-month, and 36-month post treatment 
Study Duration 
Enrollment is estimated to take 9 months. The study will be considered 
complete with regard to the primary endpoint after all subjects have completed 
the 3-month follow-up. It is estimated that it will take approximately 4 years to 
complete this trial. 
Study Design 
Multicenter, randomized, controlled, open-label, parallel group trial. 
Study Population 
Patients with GSV incompetence, defined as reflux > 0.5 seconds on duplex 
ultrasound in a single limb.  
Number of Patients 
Approximately 100 randomized and treated subjects 
Number & Location of 
Sites 
Up to 15 sites located in the United States 

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Treatment Groups – 
Control arm 
FDA approved (PMA) or cleared (510k) ETA systems, including 
Radiofrequency ablation (RFA) systems or Endovenous laser ablation (EVLA) 
systems. 
Treatment Groups – 
Investigational arm 
Varithena® (polidocanol injectable foam) 1% 
Multiple Interventions 
During Treatment 
Additional interventions or treatments of the treated vein are not allowed during 
the index procedure or at any time until after the 3-month (primary endpoint) 
visit.  Additional veins cannot be treated until after the 3-month timepoint. 
Inclusion / Exclusion 
Criteria 
Inclusion Criteria 
1. 
Age ≥ 18  
2. 
Primary GSV incompetence, defined as reflux > 0.5 seconds on Duplex 
ultrasound in a single limb (Note the contralateral limb can have 
varicosities or SVI if intervention is not required within 3 months i.e. 
asymptomatic) 
3. 
Failed conservative therapy (compression, diet, exercise, leg elevation) 
4. 
CEAP Clinical Condition Classification C2 - C6 
5. 
Vein diameter 5-10mm, inclusive 
6. 
GSV treatable length > 10cm 
7. 
Superficial venous disease manifest by clinical symptoms (rVCSS ≥ 4) 
8. 
Able to comprehend and sign an informed consent document and 
complete written study questionnaires 
9. 
Willing and able to return for scheduled follow-up visits (7-days, 3-
months, 6-months, 12-months, 24-months, and 36-months post-
procedure) 
10. Willingness to comply with post-treatment compression protocol 
Exclusion Criteria    
11. Allergy to polidocanol, xylocaine, or epinephrine 
12. Deep vein thrombosis or pulmonary embolism within 3 months prior to 
randomization or hypercoagulable disorder 
13. Post thrombotic deep vein disease above the calf veins 
14. Pregnancy or lactating (within 30 days of randomization) 
15. Symptomatic peripheral arterial disease or ankle-brachial pressure index 
(ABPI) < 0.8 
16. Previous treatment to targeted incompetent GSV or previous superficial 
thrombophlebitis in targeted GSV 
17. Previous venous intervention in affected limb in past 3 months 
18. Local aneurysmal GSV segments 
19. Inability to walk unaided 
20. Inability to wear post-procedure compression bandaging and stockings 
21. Patients with clinically significant reflux of the small saphenous vein 
(SSV) or anterior accessory saphenous vein (AASV) 

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22. In the clinical judgement of the investigator, patient who will require 
ipsilateral deep venous intervention within 3 months following 
randomized treatment 
23. In the clinical judgement of the investigator, patient who will require 
contralateral venous intervention (superficial or deep) within 3 months 
following randomized treatment 
24. Patient on therapeutic anticoagulants 
25. Active malignancy 
26. Life expectancy < 2 years 
27. Documented COVID-19 infection currently or within 2 months prior to 
randomization 
28. Enrollment in another clinical trial that could confound the endpoint within 
3 months prior to screening or within 3 months following enrollment 
Sample Size 
Justification 
The objective of the study is to measure the change in VVSymQ score for both 
treatment groups within the same patient population in the same clinical setting, 
and the study is not powered to detect a difference between treatments. 
Whilst there is no pre-specified hypothesis relating to the comparison between 
treatment groups, a sample size of approximately 100 patients would allow a 
minimally detectable absolute difference of 2.0 points in a t-test with 2-sided 
alpha level of 0.05, assuming a standard deviation of 5.0 points in both arms. 
The assumption for the standard deviation is based on baseline standard 
deviation values observed in the Vanish 1 and Vanish 2 studies (4.96 and 4.55, 
respectively). 
Statistical Methods 
The absolute change in VVSymQ score between baseline and 3-month follow-
up will be evaluated for each subject.  Changes in scores will be summarized 
by treatment group (n, mean, standard deviation, min, max, and 95% 
confidence interval) and compared using a two-sample t-test. 
Procedures in 
Screening/Baseline 
Period 
The following assessments are collected or obtained during the screening and 
baseline period: 
• 
Informed consent 
• 
Demographics and medical history 
• 
Duplex ultrasound 
• 
Mapping of superficial and deep veins 
• 
VVSymQ 
• 
VEINES-QOL/sym 
• 
rVCSS 
• 
CEAP Clinical Classification  
• 
EQ-5D 
Randomization 
After written informed consent has been obtained, patients will be randomized 
1:1 to either Varithena or ETA. Randomization will be performed by a 
computer-generated block randomization scheme. The EDC system will be 
used to randomize patients by site into the trial. 

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Study Visits and 
Follow-up 
Subject visits will occur at baseline and at the treatment procedure, with follow-
up visits at 7-days, 3-months, 6-months, 12-months, 24-months, and 36-
months post-procedure. 
Assessment of the primary endpoint will occur at 3-months post-procedure. 
All follow-up visits will be conducted in the office/clinic with the exception of the 
6-months post-procedure which may be conducted either in the office/clinic or 
via telephone contact. 
The study will be conducted and documented in accordance with the current Declaration of Helsinki, the 
protocol, standards of Good Clinical, applicable laws and regulatory requirements specified in the protocol, 
and the stipulations of the clinical study agreement. 
 
 

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Page 13 of 46 
1 
SCHEMA 
 
 
  

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2 
SCHEDULE OF VISITS 
 
Procedure/Assessment 
Screening 
Index 
procedure 
(Treatment) 
Follow-up Visits 
7 days post 
procedure  
(± 3 days) 
office visit 
3 months 
post 
procedure  
(± 14 days) 
office visit 
6 months 
post 
procedure  
(± 14 days) 
office visit or 
telephone 
12 months 
post 
procedure  
(± 30 days) 
office visit 
24 months 
post 
procedure  
(± 30 days) 
office visit 
36 months 
post 
procedure  
(± 30 days) 
office visit 
Informed consent process 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
 
 
 
 
 
Duplex ultrasound 
X 
 
X 
X 
 
X 
X 
X 
Mapping of superficial and deep 
veins 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
Varithena or ETA procedure 
 
X 
 
 
 
 
 
 
VVSymQ 
X 
 
X 
X 
X 
X 
X 
X 
VEINES-QOL/sym 
X 
 
X 
X 
X 
X 
X 
X 
rVCSS 
X 
 
X 
X 
X 
X 
X 
X 
EQ-5D 
X 
 
X 
X 
X 
X 
X 
X 
CEAP Clinical Classification 
X 
 
X 
X 
X1 
X 
X 
X 
Adverse event assessment 
 
X 
X 
X 
X 
X 
X 
X 
1Performed only if patient returns for office visit

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3 
BACKGROUND 
3.1 Disease background 
The exact etiology and pathophysiology of varicose veins remains elusive, however, valvular dysfunction 
leading to valvular reflux is thought to be the underlying cause.1 Varicose veins due to failure of the terminal 
(proximal) valve of the great saphenous vein (GSV) at the saphenofemoral junction (SFJ) is commonly 
seen, affecting up to 25% of the adult population in the United States with the prevalence and severity 
increasing with age.2 More than 30 million adults in the United States aged 18 to 70 have varicose veins, 
with women twice as likely as men to develop varicosities. Varicose veins often require treatment for 
symptoms, including leg pain, aching, heaviness, restless legs, cramps, throbbing, fatigue, itchiness, 
tingling, and edema. These symptoms are frequently the cause of absenteeism from work, disability, and 
decreased quality of life.3 Symptoms motivate patients to seek treatment, with >400,000 patients treated in 
the US each year.4 
Current therapeutic approaches for the treatment of chronic venous insufficiency (CVI) and varicose veins 
include compression treatment, open venous surgery, endovenous thermal ablation (ETA; which includes 
both endovenous laser ablation using a laser or radiofrequency ablation using radio waves), ambulatory 
phlebectomy, liquid sclerotherapy, and foam sclerotherapy, with treatment strategy largely dependent on 
clinical class, etiology, anatomy, and pathophysiology of the chronic venous disease (CVD).3 Historically, 
open venous surgery comprised of ligation and stripping was the standard treatment, however, given that 
these procedures were found to be invasive, painful, cause an increased complication rate, lead to long 
recovery times, and result in high rates of recurrence, minimally invasive procedures replaced surgical 
stripping as the standard of care for varicose veins and CVI. Endovenous thermal ablation is one such 
minimally invasive treatment method that has demonstrated benefits over conventional open venous 
surgery. These catheter-based procedures require threading a relatively inflexible catheter through long 
segments of incompetent vein and are better suited to the larger diameter saphenous veins above the knee 
and less suitable in areas with significant venous tortuosity. Thermal ablation requires the use of tumescent 
anesthesia to be injected around the vein as a heat sink, therefore, it is not used for visible varicosities 
(subcutaneous veins) due to the risk of skin burn and inability to cannulate these veins. Furthermore, 
thermal ablation below the knee is thought to be associated with thermal injury to the saphenous nerve; 
thus, thermal ablation is generally more effective when confined to above the knee.  
In 2016, The American College of Phlebology Guidelines Committee identified ETA as one of the preferred 
methods for treatment of symptomatic incompetence of the accessory GSVs.5 However, for harder to treat 
varicose veins (i.e., most located below the knee and visible varicosities), supplemental treatments such as 
ambulatory phlebectomy (invasive) and liquid sclerotherapy (minimally invasive), or foam sclerotherapy 
(minimally invasive), have been utilized.3 Sclerotherapy involves destruction of the vein using a chemical 
sclerosant under ultrasound guidance. While the solution can be delivered in either a foam or liquid form, 
foam allows for prolonged contact time increasing the effectiveness of the procedure and therefore is used 
more frequently. However, physician-compounded foam (PCF) uses liquid sclerosants that are not FDA-
approved and because there is no standard formulation, this can result in inconsistencies in the stability, 
bubble size, and density that can lead to rare but serious adverse events. Varithena (Polidocanol Injectable 
Foam) attempts to address this issue using a standardized low-nitrogen foam for consistent performance. 

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3.2 General Description of Varithena 
Varithena (polidocanol injectable foam) is indicated for the treatment of incompetent great saphenous vein, 
accessory saphenous veins, and visible varicosities of the GSV system above and below the knee. 
Varithena has been shown to improve the symptoms of superficial venous incompetence and the 
appearance of visible varicosities in the GSV system. Varithena product is available in four configurations, 
each containing two sterile, connected, 303-mL aluminium alloy cylinders, one containing polidocanol 
solution (10 mg/mL) under carbon dioxide, and the other containing pressurized oxygen. The injectable 
foam is generated after activation of the polidocanol canister with oxygen from a second aluminium 
canister, resulting in a final gas mixture of oxygen:carbon dioxide in a ratio of 65:35 with low (<0.8%) 
nitrogen content. At the time of use, Varithena is generated as an injectable foam of controlled density and 
bubble size. The foam is then transferred to a syringe through the Varithena transfer unit.. The mechanism 
of action of polidocanol is chemical. As a non-ionic surfactant, the hydrophobic pole of the polidocanol 
molecule attaches to the lipid membrane of venous endothelial cells and disrupts the osmotic barrier. The 
resulting cell destruction creates a thrombogenic exposed endothelial surface to which platelets attach 
followed by thrombus formation, occluding the vein lumen which is later replaced by fibrous tissue. 
Varithena treatment is non-surgical and minimally invasive. 
The purpose of this multi-center, randomized, controlled, open-label, parallel-group study is to collect 
comparative long-term (1-,2-, and 3-year) evidence on patient reported outcomes of Varithena compared to 
ETA when used to treat the incompetent GSV. The primary endpoint of the study is change in Varicose 
Veins Symptoms Questionnaire (VVSymQ) between baseline and 3-months post-treatment. Additional 
endpoints that will be collected include changes from baseline in revised Venous Clinical Severity Score 
(rVCSS), Venous Insufficiency Epidemiological and Economic Study- Quality of Life/ Symptoms (VEINES-
QOL/Sym), Clinical condition, etiological, anatomical location, and pathophysiological (CEAP) clinical 
condition classification, and EuroQol-5D (EQ-5D) at 7-days, 3-months, 6-months, 12-months, 24-months, 
and 36-months post-treatment, adverse events, and healthcare resource utilization for treated limb venous 
disease at 12-, 24-, and 36-months. 
3.3 Clinical Summary of Varithena 
There is a large set of clinical data available that comprises hundreds of procedures supporting the safety 
and efficacy of Varithena for the treatment of incompetent GSV, accessory saphenous veins, and visible 
varicosities of the GSV system above and below the knee.6-14 Notably, three multicenter, randomized 
control trials provide robust data suggesting that Varithena is able to provide clinically meaningful 
improvements of key varicose vein symptoms7,9,10, enhance quality of life7,10, and improve the appearance 
of veins.7,9,10  
The two pivotal studies supporting approval of Varithena were randomized, blinded, multicenter clinical 
trials designed to assess the efficacy and safety of Varithena 0.5%, 1.0%, and 2.0% (VANISH-1) and 
Varithena 0.5% and 1.0% (VANISH-2) compared with placebo in the treatment of both symptoms and 
appearance of varicose veins in patients with SFJ incompetence as evidence by reflux of the GSV or major 
accessory veins.7,9 In both studies, a Varithena 0.125% treatment group was included as a control for 
blinding of the duplex ultrasound assessment. The primary efficacy endpoint for both studies was change in 
VVSymQ Electronic Daily Diary Score from baseline to week 8 post-treatment. Secondary endpoints 
included Patient Assessment of Visible Varicose Veins (PA-V3) score and Independent Photographic 
Review Visible Varicose Veins (IPR-V3) score. Tertiary endpoints that were not powered included duplex 
response, rVCSS, and VEINES-QOL/Sym. Varithena significantly improved symptoms, as measured by 
change in VVSymQ score from baseline, at week 8 at all concentrations of Varithena tested in both 

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VANISH-1 [Placebo (-2.13) vs. Varithena 0.5% (-5.68) vs. Varithena 1.0% (-4.87) vs. Varithena 2% (-5.78); 
all p<0.0001 vs. placebo]7 and VANISH-2 [Placebo (-2.00) vs. Varithena 0.5% (-6.01) vs. Varithena 1.0% (-
5.06); all p<0.0001 vs. placebo].9 Treatment with Varithena also led to significant improvements in varicose 
vein appearance as measured by IPR-V3 (clinician assessment) and PA-V3 (patient self-assessment). In 
VANISH-1, baseline IPR-V3 scores decreased by 0.01, 0.77, 0.76, and 0.91 for patients in the placebo, 
Varithena 0.5%, Varithena 1%, and Varithena 2% groups, respectively from baseline to 8 weeks (all 
p<0.0001 vs. placebo). In patients treated with Varithena, PA-V3 scores also showed significant 
improvement from baseline to 8 weeks with decreases 1.40, 1.60, and 1.75 for patients in the Varithena 
0.5%, Varithena 1%, and Varithena 2% groups, respectively, compared to just 0.15 in the placebo group 
(all p<0.0001 vs. placebo). A similar trend was observed in VANISH-2 with both Varithena groups having 
significantly greater improvement from baseline to 8-week follow-up in appearance of varicose using both a 
clinician and patient assessment compared to placebo (p’s<0.0001). Safety outcomes were comparable 
between groups in both studies.  
The physiological response to treatment as measured by duplex ultrasound (duplex response) was defined 
as elimination of reflux through the SFJ and/or complete occlusion of all incompetent GSV and major 
accessory veins at baseline. The primary comparison for duplex response in both studies was the pooled 
Varithena groups vs. the Varithena 0.125% (control) group.  For both studies, the pooled Varithena groups 
were statistically superior to the control group.  In VANISH-1 and VANISH-2, in the pooled groups, 75% 
and 85% of patients respectively, compared with 42% of patients and 60% of patients, respectively, in the 
control groups, met the criteria for response to treatment.  These differences were statistically significant 
(p≤0.0002).  
rVCSS is a clinician rating of severity of chronic venous insufficiency ranging from 0 to 30, where higher 
scores indicate more severe venous disease. In VANISH-1 and VANISH-2, the adjusted mean changes 
from baseline in rVCSS in the 1% Varithena treatment groups were 3.70 and 5.05, respectively, at Week 8 
compared with 0.75 and 1.52 points in the placebo groups, respectively. For both studies, the differences 
between these improvements were statistically significant (p<0.0001). 
VEINES-QOL/Sym is a disease-specific quality of life instrument, ranging from 0 (worst possible quality of 
life) to 100 (best possible quality of life). In VANISH-1 and VANISH-2, the adjusted mean changes from 
baseline in VEINES-QOL/Sym in the pooled Varithena treatment groups were 21.2 and 21.6, respectively, 
at Week 8 compared with 7.7 and 7.4 points in the placebo groups, respectively. For both studies, the 
differences between these improvements are statistically significant (p<0.0001). 
To assess long-term safety and durability of treatment with Varithena, patients treated with the currently 
approved dose concentration (1%; n=58) from the VANISH-2 study were followed through 1 year.8 Results 
from the study illustrate that treatment with Varithena leads to durable, clinically meaningful, and ongoing 
improvements at 1 year in symptoms (as measured by the VVSymQ score) and appearance (as measure 
by IPR-V3 and PA-V3 scores). Severe adverse events were those that would be expected during long-term 
follow-up of the patient population studies and were classified as being unrelated to treatment. Importantly, 
there were no new venous thrombus adverse events (AEs), no recurrence or extension of previously 
diagnosed venous thrombi, and no clinically relevant sequelae in patients previously diagnosed with 
venous thrombus AEs. Overall, results from these studies demonstrate that Varithena can improve 
symptoms and appearance of varicose veins with reasonable safety. 
In the third randomized trial, outcomes of patients treated with 1% Varithena (n=39) were compared to 
those treated with placebo (n=38).10 The primary efficacy endpoint, change in patient-reported symptoms 

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[HASTI score (heaviness, achiness, swelling, throbbing, and itching)] from baseline to week 8, was 
significantly greater in Varithena treated patients (30.7 points) compared to those treated with placebo 
(16.7 points; p=0.0009). Treatment with Varithena led to improvements in m-VEINES-Sym, m-VEINES-
QOL, CIVIQ-2, PGIC-Symptoms, PGIC-Day-to-Day, PGIC-Appearance, and physician-assessed 
appearance scores from baseline to week 8 compared to treatment with placebo. A patient from each 
group experienced a serious adverse event, both considered unrelated to the study drug (placebo- 
transient ischemic attack; Varithena- sick sinus syndrome). There were no reports of pulmonary emboli or 
neurological events in the Varithena-treated patients.  
The remaining clinical literature, comprised of single-arm observational and retrospective studies offer 
additional support for the use of Varithena in the treatment of incompetent great saphenous vein, accessory 
saphenous veins, and visible varicosities of the GSV system above and below the knee in terms of closure 
rate success14, improvements in symptoms and disease severity12,13, and benefits of combination treatment 
with endovenous thermal ablation (ETA).11  
Taken together, the clinical literature supports the safety and efficacy of Varithena for the treatment of 
incompetent GSV, accessory saphenous veins, and visible varicosities of the GSV system above and 
below the knee. All randomized trials have demonstrated a clear benefit of Varithena over placebo as 
measured by improvements in both symptoms and appearance. Further, the AEs most commonly observed 
in the clinical studies of Varithena® are manageable events that would be expected in patients undergoing 
a minimally invasive medical procedure for the treatment of GSV incompetence including infusion site 
thrombosis (retained coagulum), injection site hematoma, contusion, pain in extremity, limb discomfort, and 
superficial thrombophlebitis. Importantly, unlike with physician-compounded foam sclerosants, no patients 
in the Varithena trials experienced clinically important neurological or visual adverse events suggestive of 
cerebral gas embolism. Considering all previous trials have compared Varithena to placebo, this study is 
designed to provide insights into the benefits of Varithena over ETA.   
4 
STUDY OBJECTIVE and PURPOSE 
4.1 Study Objective 
This study will collect comparative evidence on patient reported outcomes of Varithena compared to ETA 
when used to treat the incompetent Great Saphenous Vein (GSV).  ETA will include either Radiofrequency 
ablation or endovenous laser ablation according to the site’s standard practice. This study will provide long 
term (1-year, 2-year, and 3-year) outcomes. 
4.2 Study Design 
This is a multicenter, randomized, controlled, open-label, parallel group study. 
4.3 Randomization 
After written informed consent has been obtained, patients will be randomized 1:1 to either Varithena or 
ETA. Randomization will be performed by a computer-generated block randomization scheme. The EDC 
system will be used to randomize patients by site into the trial.   
4.4 Primary Endpoint 
The primary endpoint will assess the change in Varicose Veins Symptoms Questionnaire (VVSymQ) 
between baseline and 3-month post treatment. 

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4.5 Additional Assessments 
• Change from baseline in revised Venous Clinical Severity Score (rVCSS) at 7-day, 3-month, 6-month, 12-
month, 24-month, and 36-month post treatment 
• Venous insufficiency Epidemiological and Economic Study – Quality of Life/Symptoms (VEINES-
QOL/Sym) and EuroQoL-5D (EQ-5D) at 7-day, 3-month, 6-month, 12-month, 24-month, and 36-month 
post treatment 
• Clinical condition, etiological, anatomical location, and pathophysiological (CEAP) clinical condition 
classification at 7-day, 3-month, 6-month, 12-month, 24-month, and 36-month post treatment 
• Varithena, ETA, and Procedure related serious adverse events (SAE) 
• Healthcare resource utilization for treated limb venous disease at 12-month, 24-month, and 36-month post 
treatment 
5 
PATIENT SELECTION  
5.1 Patient Population 
This study is designed to collect comparative evidence on patient reported outcomes of Varithena 
compared to ETA when used to treat patients experiencing symptoms of superficial venous incompetence 
of the Great Saphenous Vein (GSV), defined as reflux > 0.5 seconds on duplex ultrasound in a single limb.  
Data will be collected on approximately 100 randomized and treated patients at up to 15 investigational 
sites in the United States.   
See Section 7 Informed Consent Process on requirements to assess the patient’s capacity to participate in 
the study and Section 11.3 Institutional Review Board (IRB)/Independent Ethics Committees (IEC) on 
regulatory and ethical oversight of the patient’s protection during the study.  
5.2 
Patient Selection 
5.2.1 Inclusion Criteria 
A patient must meet all the following inclusion criteria to be enrolled in this study: 
1. Age ≥ 18  
2. Primary GSV incompetence, defined as reflux > 0.5 seconds on Duplex ultrasound in a single limb 
(Note the contralateral limb can have varicosities or SVI if intervention is not required within 3 months) 
3. Failed conservative therapy (compression, diet, exercise, leg elevation) 
4. CEAP Clinical Condition Classification C2 - C6 
5. Vein diameter 5-10mm, inclusive 
6. GSV treatable length > 10cm 
7. Superficial venous disease manifest by clinical symptoms (rVCSS ≥ 4) 
8. Able to comprehend and sign an informed consent document and complete written study 
questionnaires 

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9. Willing and able to return for scheduled follow-up visits (7-days, 3-months, 6-months, 12-months, 24-
months, and 36-months post-procedure) 
10. Willingness to comply with post-treatment compression protocol 
5.2.2 Exclusion Criteria 
A patient must not meet any of the following exclusion criteria to be enrolled in this study: 
11. Allergy to polidocanol, xylocaine, or epinephrine 
12. Deep vein thrombosis or pulmonary embolism within 3 months prior to randomization or 
hypercoagulable disorder 
13. Post thrombotic deep vein disease above the calf veins 
14. Pregnancy or lactating (within 30 days of randomization) 
15. Symptomatic peripheral arterial disease or ankle-brachial pressure index (ABPI) < 0.8 
16. Previous treatment to targeted incompetent GSV or previous superficial thrombophlebitis in targeted 
GSV 
17. Previous venous intervention in affected limb in past 3 months 
18. Local aneurysmal GSV segments 
19. Inability to walk unaided 
20. Inability to wear post-procedure compression bandaging and stockings 
21. Patients with clinically significant reflux of the small saphenous vein (SSV) or anterior accessory 
saphenous vein (AASV) 
22. In the clinical judgement of the investigator, patient who will require ipsilateral deep venous 
intervention within 3 months following randomized treatment 
23. In the clinical judgement of the investigator, patient who will require contralateral venous intervention 
(superficial or deep) within 3 months following randomized treatment 
24. Patient on therapeutic anticoagulants 
25. Active malignancy 
26. Life expectancy < 2 years 
27. Documented COVID-19 infection currently or within 2 months prior to randomization 
28. Enrollment in another clinical trial that could confound the endpoint within 3 months prior to screening 
or within 3 months following enrollment 
5.3 Patient Completion 
Study patient participation is considered to complete upon completing the 36-month follow up visit. 
5.4 Patient Withdrawal 
Patients may choose to withdraw from the study (treatments and assessments) at any time for any reason 
without prejudice to their future medical care by the physician or at the institution. A patient who withdraws 

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consent will always be asked about the reason(s) for withdrawal and the presence of any AE. If a patient 
withdraws consent, they will be specifically asked if they are withdrawing consent to all further participation 
in the study including any further follow-up. The reason for patient withdrawal must be documented in the 
patient’s medical record.  
The Investigator or Sponsor may withdraw the patient at any time (e.g., in the interest of patient safety). 
The withdrawal of a patient from the study by the Investigator should be discussed where possible with the 
Sponsor.  The reason for withdrawal will be recorded (if given) in all cases of withdrawal. 
• 
For patients who withdraw before the end of the study, all End of Study assessments should be 
completed, if possible, prior to withdrawal. 
• 
If a patient withdraws from the study for any reason, all efforts should be made to follow AEs unless 
the patient withdraws consent. 
Withdrawn patients will not be replaced. 
5.5 Patients “Lost to Follow-Up” prior to the Last Scheduled Visit 
A subject can be considered lost to follow-up after the subject misses 2 consecutive annual follow-up visits 
without due cause. No subject will be considered lost to follow-up prior to the 3-month follow-up visit in 
order to make every effort to collect evaluable data for the primary endpoint. A minimum of 3 attempts (i.e., 
2 phone calls followed by a certified letter, or other traceable letter, if necessary) should be made to contact 
the subject or subject’s next of kin for each missed follow-up visit and this information should be 
documented in the source. Missed or late visits will be recorded as Protocol Deviations.   
6 
TREATMENT OF PATIENTS 
6.1 Varithena Product Description 
Varithena (polidocanol injectable foam) 1% is a low-nitrogen, microfoam with uniform density, size, and 
stability, dispensed from a proprietary canister device. It is formulated with a gas mixture (carbon 
dioxide/oxygen) designed to maintain physical foam characteristics while allowing rapid bubble absorption 
following injection. The foam remains coherent, displacing the blood in the vein and efficiently delivering the 
sclerosant to the venous endothelium. It is echogenic and therefore can be directed to the intended 
segments of incompetent vein using duplex ultrasound. The net effect is that with a small total dose of 
active sclerosant, a large vein can be emptied of blood. The sclerosant, neither diluted nor de-activated, 
acts on the endothelium and in combination with adequate post-treatment compression can successfully 
sclerose large veins. 
Varithena is indicated for the treatment of incompetent great saphenous veins, accessory saphenous veins 
and visible varicosities of the GSV system above and below the knee. Varithena improves the symptoms of 
superficial venous incompetence and the appearance of visible varicosities. 
6.1.1 Dosage & Administration 
Commercially distributed Varithena (polidocanol injectable foam) 1% (Approved 25 Nov 2013 NDA 205098) 
will be administered by intravenous injection using ultrasound guidance, administered via a single cannula 
into the lumen of the target incompetent trunk veins or by direct injection into varicosities as described in 
the United States Prescribing Information (USPI). Use up to 5mL per injection and no more than 15mL per 
session.   

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6.1.2 Retreatment Criteria 
Additional interventions or treatments of the treated vein are not allowed during the index procedure or at 
any time until after the 3-month visit. Additional veins, including contralateral superficial or deep veins, 
cannot be treated during the procedure and until the 3-month timepoint. After the 3-month timepoint, 
additional veins may be treated according to the investigator desired modality. Following the initial 
treatment with Varithena, each subject is followed for 36 months and retreatment data of the index target 
vein will be collected. 
6.1.3 Safety Criteria for Adjusting or Stopping Treatment(s) 
A patient who discontinues treatment is normally expected to continue to participate in the study (e.g. for 
safety, efficacy and survival follow-up) unless they specifically withdraw consent to all further participation 
in any study procedures and assessments. 
6.1.4 Post-treatment Management 
Following treatment, patients should be treated with compression bandaging and stockings per the USPI 
for Varithena or ETA Instruction for Use (IFU). Other post-treatment management for Varithena or ETA will 
follow standard of care (SoC).  
6.1.5 Duration of Treatment and Follow up 
Enrollment is estimated to take 9 months. The study will be considered complete with regard to the primary 
endpoint after all subjects have completed the 3-month follow-up. It is estimated that it will take 
approximately 4 years to complete this trial. 
6.1.6 Concomitant Therapies or Interventions  
Patients should not be enrolled in the study if they were previously treated in the target incompetent GSV or 
superficial thrombophlebitis in targeted GSV. Additionally, patients should not be enrolled in the study if 
they received venous intervention in the affected limb within three months prior to enrollment. 
6.2 Product Labelling / Packaging / Storage / Handling 
6.2.1 Labelling and Packaging 
Varithena and ETA are indicated for the treatment of incompetent great saphenous veins. The products, 
labelling, and packaging in the study remain as commercially distributed. 
6.2.2 Storage and Handling 
Product storage and handling will follow the Varithena USPI and ETA IFU.  
7 
MEASUREMENTS AND EVALUATIONS 
7.1 Study Blinding and Treatment Group Assignment 
This study is open label. There is no study blinding to either the investigator or patient. 
Patients presenting with incompetent GSV, defined as reflux > 0.5 seconds on duplex ultrasound in a single 
limb will be considered for this study. After consenting and meeting inclusion criteria and none of the 
exclusion criteria, patients will be randomized to either Varithena (test) or ETA (control). The EDC system 
will be used to assign subjects to the test or control treatment group. 

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7.2 Time and Event Schedule 
7.2.1 Screening Visit  
The screening phase begins when the informed consent is fully signed and dated and ends at point of 
treatment.  
The following evaluations will be performed: 
• 
Informed consent must be signed, as described in section 7.3.1 
• 
Patient demographic information will be collected, as described in section 7.3.2 
• 
Medical history information will be collected, as described in section 7.3.3 
• 
Mapping of Superficial and Deep Veins, as described in section 7.3.4 
• 
Physical examination will be conducted, as described in section 7.3.5 
• 
A urine/serum pregnancy test will be conducted for all women of child-bearing potential (WOCP), as 
described in section 7.3.6 
• 
Eligibility to participate in the study will be assessed, as described in section 7.3.7  
• 
VVSymQ, as described in section 7.3.133 
• 
VEINES-QOL/sym, as described in section 7.3.144 
• 
rVCSS, as described in section 7.3.155 
• 
EQ-5D-5L, as described in section 7.3.166 
• 
CEAP Clinical Condition Classification, as described in section 7.3.188 
If a patient is determined to be eligible to participate in the study, the site will follow the process as described 
in section 7.3.9 
7.2.2 Index Procedure Visit 
The index procedure visit may be performed on the same day as the screening visit if the patient 
successfully completes the screening visit and is confirmed eligible for the study. 
The patient will undergo the Varithena or ETA procedure as assigned per randomization. Varithena or ETA 
procedure will be administered per SoC and the USPI/IFU relevant to the product for the treatment of the 
GSV. Specific procedure data will be collected as described in section 7.3.11. 
In addition, the following evaluations will be performed: 
• 
Adverse events will be recorded and assessed as described in section 7.3.12 
7.2.3 7 Days (±3 Days), 3 Months (±14 Days), 12 Months (±30 Days), 24 Months (±30 Days), and 
36 Months (±30 Days) Follow Up Visit 
These follow up visits will be conducted in-person. 
The following evaluations will be performed for a patient treated with either Varithena or ETA: 
• 
Adverse events will be recorded and assessed as described in section 7.3.12 

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• 
VVSymQ, as described in section 7.3.133 
• 
VEINES-QOL/sym, as described in section 7.3.144 
• 
rVCSS, as described in section 7.3.155 
• 
EQ-5D-5L, as described in section 7.3.166 
• 
Duplex ultrasound, as described in section 7.3.177 
• 
CEAP Clinical Condition Classification, as described in section 7.3.188 
7.2.4 6 Months (±14 Days) Follow Up Visit 
This follow up visit may be conducted in-person or by telephone. 
The following evaluations will be performed for a patient treated with either Varithena or ETA: 
• 
Adverse events will be recorded and assessed as described in section 7.3.12 
• 
VVSymQ, as described in section 7.3.133 
• 
VEINES-QOL/sym, as described in section 7.3.14 
• 
rVCSS, as described in section 7.3.15 
• 
EQ-5D-5L, as described in section 7.3.16 
If the follow up visit is conducted in-person, the following evaluation will also be performed: 
• 
CEAP Clinical Condition Classification, as described in section 7.3.18 
7.2.5 Early Discontinuation 
The patient completes the study upon completing the 36-month follow up visit.  
For patients who discontinue prior to study completion, the following evaluations will be performed. In the 
event of a continuing adverse event determined to be related to Varithena in the opinion of the investigator, 
the patient will be asked to return for follow-up assessments for their continued safety unless they have 
withdrawn their consent to do so, until the AE has resolved or is deemed to be continuing indefinitely. 
• 
Record the date and reason for study completion as listed in section 5.3 
• 
Record the date and reason for study withdrawal as listed in section 5.4 
• 
Record any adverse events, as described in section 7.3.12 
7.3 Study Evaluations and Procedures 
7.3.1 Informed Consent Process 
Subject participation in this clinical study is voluntary.  Informed Consent is required from each subject or 
his/her legally authorized representative. The Investigator is responsible for ensuring that Informed Consent 
is obtained prior to the use of any product, study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the principles of the 
Declaration of Helsinki, ICH GCP, any applicable national regulations, and local Ethics Committee and/or 

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Regulatory authority, as applicable. The ICF must be accepted by BSC or its delegate (e.g. CRO), and 
approved by the site’s IRB, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators participating in this study. 
The ICF template may be modified to meet the requirements of the investigative site’s IRB.  Any 
modification requires acceptance from BSC prior to use of the form.  The ICF must be in a language 
understandable to the subject and if needed, BSC will assist the site in obtaining a written consent 
translation. Translated consent forms must also have IRB approval prior to their use.  Privacy language 
shall be included in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, as well as any 
other steps required by applicable laws, rules, regulations and guidelines: 
• 
be conducted by the Principal Investigator or designee authorized to conduct the process,  
• 
include a description of all aspects of the clinical study that are relevant to the subject’s decision 
to participate throughout the clinical study, 
• 
avoid any coercion of or undue influence of subjects to participate, 
• 
not waive or appear to waive subject’s legal rights, 
• 
use native language that is non-technical and understandable to the subject or his/her legal 
representative, 
• 
provide ample time for the subject to consider participation and ask questions if necessary, 
• 
ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative competent to 
sign the ICF under the applicable laws, rules, regulations and guidelines and by the investigator and/or an 
authorized designee responsible for conducting the informed consent process. If a legal representative 
signs, the subject shall be asked to provide informed consent for continued participation as soon as his/her 
medical condition allows. The original signed ICF will be retained by the site and a copy of the signed and 
dated document and any other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory authority according to 
their requirements (e.g., FDA requirement is within 5 working days of learning of such an event). Any 
violations of the informed consent process must be reported as deviations to the sponsor and local 
regulatory authorities (e.g. IRB), as appropriate. 
If new information becomes available that can significantly affect a subject's future health and medical care, 
that information shall be provided to the affected subject(s) in written form via a revised ICF or, in some 
situations, enrolled subjects may be requested to sign and date an addendum to the ICF. In addition to new 
significant information during the course of a study, other situations may necessitate revision of the ICF, 
such as if there are amendments to the applicable laws, protocol, a change in Principal Investigator, 
administrative changes, or following annual review by the IRB. The new version of the ICF must be 
approved by the IRB. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB. The IRB will determine the subject population to be re-consented. 
7.3.2 Demographics 
The following demographic data will be obtained: age at time of consent, gender, race, and ethnicity. 
7.3.3 Medical History  
Medical history deemed clinically significant, relevant to the clinical trial objectives and design will be 
collected per body system: allergy/immunology, blood, dermatology/skin, endocrine metabolic, infection, 
neurologic, vascular.  

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Diagnosis and medical history for incompetent great saphenous vein will be recorded separately from 
medical history.  
All ongoing medical conditions and adverse events arising from treatment of those conditions present for 30 
days or more are generally considered a part of the patient’s baseline medical history and must be 
recorded where indicated. 
7.3.4 Mapping of Superficial and Deep Veins 
The Investigator or delegate will map the superficial and deep veins through duplex ultrasound with the 
patient standing of the extremities to identify the target vessel prior to the start procedure and will record 
the maximum vein diameter. The course of the vein mapping will be performed according to SoC. 
7.3.5 Physical Examination 
A physical examination, including actual measured height and actual scale measured weight (required at 
screening only), will be performed by a qualified licensed individual. A review of body systems will include 
the following: 
• 
General appearance, overall well-being and functional capacity 
• 
Musculoskeletal, extremities and mobility 
Any abnormalities or changes in intensity, duration or frequency not noted during the initial review of body 
systems should be documented in the source documentation and reported appropriately in the CRF. If a 
new change to baseline finding occurs at a subsequent visit, the new finding must be assessed for adverse 
event criteria, adverse event reporting, and will be documented. Resolution of any abnormal findings 
reported during the study will be noted in the source documentation. 
7.3.6 Pregnancy Test 
A urine or serum beta hCG pregnancy test will be performed on all females of child-bearing potential. 
7.3.7 Eligibility Review 
Data documenting demographic information, medical history, physical examination, prior treatment, and 
pregnancy test (if applicable) will be reviewed against the eligibility criteria to determine eligibility. The 
determination will be recorded on the relevant eCRF. 
7.3.8 Point of Enrollment 
Subjects will be considered enrolled once the patient is determined to be eligible to participate in the study 
and informed consent has been obtained. 
7.3.9  Randomization Event 
If a patient is determined to be eligible to participate in the study, the site will proceed with randomization. 
Randomization will be determined using assignment by a computer-generated randomization scheme. 
Each patient will be assigned a unique numeric patient identity code.  
Randomization will be in a 1:1 ratio of Varithena to ETA treatment arms.  
7.3.10 Point of Treatment 
Subjects will be considered treated  once randomized treatment commences. Only treated subjects will be 
followed per study protocol safety event reporting and follow-up visit tests/assessments schedule. 

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7.3.11 Treatment Record 
The index treatment record of the target GSV, including doses and start/stop time, will be recorded in the 
relevant eCRF. 
If the target GSV was retreated, as described in Section 6.1.2, the detail of treatment(s) will be separately 
recorded.  
7.3.12 Observation and Recording of Adverse Events 
If the patient is unable to attend a study visit, AEs can be collected by telephone contact. 
At any time during the study, the patient may volunteer information that resembles an AE. The Investigator 
should obtain all the information required to complete the AE form. Where possible, a diagnosis, rather than 
a list of signs or symptoms, should be recorded. Any medical management of an event and the resolution 
of an event must be recorded in source documentation and on the appropriate eCRF using medical 
terminology according to Sponsor instructions.  
The Investigator will assess all AEs for grading, severity and relationship to study treatment(s). Definitions 
and procedures for assessment can be found in Section 8. 
7.3.13 Varicose Veins Symptoms Questionnaire (VVSymQ) 
VVSymQ is a patient-reported outcome measure based on daily patient assessment of the varicose vein 
symptoms determined to be most important to patients: heaviness, achiness, swelling, throbbing, and 
itching. VVSymQ scores range from 0 to 25, where 0 represents no symptoms and 25 represents all 5 
symptoms experienced all of the time. 
7.3.14 Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-
QOL/sym) 
VEINES-QOL/sym is a disease-specific quality of life instrument, ranging from 0 (worst possible quality of 
life) to 100 (best possible quality of life). This assessment is scored with 26 responses and include 
questions about symptoms, daily activity, one year change in disease, and time of day leg pain in most 
intense.  
7.3.15 Revised Venous Clinical Severity Score (rVCSS) 
rVCSS is a clinician rating of severity of chronic venous insufficiency ranging from 0 to 30 where higher 
scores indicate more severe venous disease. rVCSS assesses nine common signs/symptoms of venous 
disease: skin changes and pigmentation, inflammation and induration, and ulcers (including number, size, 
and duration). A tenth item assesses compression compliance. Each item is scored individually on a 0-3 
point scale. 
7.3.16 5-level EQ-5D version (EQ-5D-5L)  
EQ-5D-5L is a patient reported outcome measure that provides a simple descriptive profile and single index 
value for health status. The questionnaire consists of 5 questions pertaining to specific health dimensions, 
including mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health status 
rating scale. 

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7.3.17 Duplex Ultrasound 
The Investigator or delegate will perform a duplex ultrasound according to the VasCore Core Lab protocol 
with the patient standing of visualizing the target vessel at the timepoints described in Section 7.2.3. The 
duplex ultrasound will be uploaded onto an image transfer platform as described in Section 10. 
7.3.18 CEAP Clinical Condition Classification 
Clinical condition, etiological, anatomical location, and pathophysiological (CEAP) is a descriptive 
classification for chronic venous disorders. The Investigator or delegate will determine the appropriate 
clinical condition classification upon physician examination. The clinical condition classification is reported 
as one of the following: 
C0 = no visible or palpable signs of venous disease 
C1 = telangiectasies or reticular veins 
C2 = varicose veins 
C3 = edema 
C4a = pigmentation or eczema 
C4b = lipodermatosclerosis or strophie blanche 
C5 = healed venous ulcer 
C6 = active venous ulcer 
8 
ADVERSE EVENTS 
8.1 Adverse Event Definitions 
Adverse experience will be considered synonymous with the term adverse event and vice versa. 
8.1.1 Definitions of AE/ADR for Drugs (Reference: ICH E2A) 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this treatment.  
An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether 
or not related to the medicinal product. 
Adverse Drug Reaction (ADR) 
A response to a drug which is noxious and unintended and which occurs at doses normally used in human 
for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function. 
Unexpected Adverse Drug Reaction 
An adverse reaction, the nature or severity of which is not consistent with the applicable product 
information (e.g., Investigator's Brochure (IB) for an unapproved investigational medicinal product or 
package insert/summary of product characteristics for an approved product). 
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) 
Any untoward medical occurrence that at any dose: 

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• 
results in death; 
• 
is life-threatening (“life-threatening” refers to an event in which the patient was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe); 
• 
requires inpatient hospitalization or prolongation of existing hospitalization; 
o Outpatient treatment in an emergency room is not in itself a serious AE, although the reasons 
for it may be (e.g. bronchospasm, laryngeal edema). Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the patient was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study. 
• 
results in a persistent or significant disability/incapacity; or 
• 
is a congenital anomaly/birth defect 
• 
is an important medical event that may jeopardize the patient or may require intervention to prevent 
one of the outcomes listed above,  
o Medical and scientific judgment should be exercised in deciding whether medical events that 
may not be immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, should also be considered serious. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A SADR, the nature or severity of which is not consistent with the applicable product information (e.g., USPI 
for an approved product). 
8.1.2 Recording Adverse Events 
ADR/SADR related to Varithena will be documented from the start of the index procedure through 36-
month follow up. In addition, only SAE related to ETA or to the procedure will be documented from the start 
of index procedure through 36-month follow up. ADR/SADR/SAE should be managed as discussed in 
Section 8.3. 
At any time during the study, the patient may volunteer information that resembles an ADR/AE. In this 
study, patients should be encouraged to report spontaneously or in response to general, non-directed 
questions.  Once it is determined that an ADR/AE has occurred, the Investigator or physician sub-
Investigator should determine if the ADR/AE meets seriousness criteria and is related to Varithena, to the 
ETA device, or to the procedure according to Section 8.1.1. Any medical management of an event and the 
date of resolution of the event must be recorded in the source document and on the appropriate eCRF 
using medical terminology according to Sponsor instructions. 
For each related ADR/SADR/SAE, the following information will be recorded:  
• 
ADR/AE term 
• 
Serious criteria 
• 
Severity 
• 
Action taken 

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• 
Relevant concomitant medications 
• 
Relevant laboratory/test data 
• 
Relationship to study treatment 
• 
Expected/Unexpected 
• 
Date of onset 
• 
Outcome and type of resolution (with/without sequelae) 
• 
Date of resolution 
Once the patient has been discharged from the study, the Investigator has no obligation to seek further 
follow-up with the patient in order to identify new ADRs/SADRs/SAEs. However, if the Investigator becomes 
aware of an ADR/SADR/SAE that has occurred following the patient's discharge from the study and the 
Investigator considers the ADR/SADR/SAE has reasonable possible relationship to Varithena or is 
possibly, probably, or definitely related to the ETA device, then the Investigator should report the 
SADR/SAE as described in the protocol. 
8.2 Causality Assessment 
The Investigator or physician sub-Investigator will assess the causal relationship between Varithena and 
each ADR/SADR, and answer “yes” or “no” to the question “Do you consider that there is a reasonable 
possibility that the event may be been caused by Varithena?” Only events with a reasonable possibility of 
relationship to Varithena will be reported as described in Section 8.5. All other events documented in the 
study will be addressed through periodic clinical study reporting. 
For SAEs, causal relationship will be also assessed for relationship to the procedure and ETA.  
The Investigator should pay careful attention to the attribution of relation to the SADR/SAE as there may be 
similar events reported for both Varithena and ETA.  Judgment of relation by time of administration and 
patient assignment to treatment or control group should be considered. 
8.2.1 Criteria for Assessing the Relationship of Varithena, ETA Device, or Procedure to an 
Adverse Event 
Not Related 
Relationship to Varithena, to ETA device, or to the procedure can be excluded when: 
• 
the event has no temporal relationship with the use of Varithena, ETA device, or the procedure; 
• 
the serious event does not follow a known response pattern to Varithena or ETA device (if the 
response pattern is previously known) and is biologically implausible; 
• 
the discontinuation of ETA device or the reduction of the level of activation/exposure - when clinically 
feasible – and reintroduction of its use (or increase of the level of activation/exposure), do not impact 
on the serious event; 
• 
the event involves a body-site or an organ that cannot be affected by Varithena, ETA device, or 
procedure; 

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• 
the serious event can be attributed to another cause (e.g. an underlying or concurrent illness/ clinical 
condition, an effect of another device, drug, treatment or other risk factors); 
• 
the event does not depend on a false result given by ETA device used for diagnosis, when applicable;  
In order to establish the non-relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious event. 
Possibly Related 
The relationship with the use of Varithena, the ETA device, or with the procedure is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug or treatment). Cases where relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably Related 
The relationship with the use of Varithena, the ETA device, or with the procedure seems relevant and/or the 
event cannot be reasonably explained by another cause. 
Definitely (Casual) Related 
The event is associated with Varithena, the ETA device, or the procedure beyond reasonable doubt when: 
• 
the event is a known side effect of the product category Varithena or the ETA device belongs to or of 
similar drugs/devices and procedures; 
• 
the event has a temporal relationship with Varithena, the ETA device, or the procedure; 
• 
the event involves a body-site or organ that 
o Varithena, the ETA device, or the procedure are applied to; 
o Varithena, the ETA device, or the procedure have an effect on; 
• 
the serious event follows a known response pattern to Varithena or the ETA device (if the response 
pattern is previously known); 
• 
the discontinuation of ETA device application (or reduction of the level of activation/exposure) and 
reintroduction of its use (or increase of the level of activation/exposure), impact on the serious event 
(when clinically feasible); 
• 
other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment) have been adequately ruled out; 
• 
harm to the subject is due to error in use of Varithena or the ETA device; 
• 
the event depends on a false result given by the ETA treatment 
• 
used for diagnosis, when applicable; 
In order to establish the relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious adverse event. 
8.3 Submitting Safety Reports  
ADR, SAE, SADR, or SUSAR related to Varithena, the ETA device, or procedure must be reported to the 
Sponsor or its designate by completing the Adverse Event form in the eCRF. SAE, SADR, SUSAR related 

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to Varithena, the ETA device, or procedure must be reported within 24 hours of becoming aware of the 
event. If the EDC is not available, the Investigator or other study site staff reports the event to the 
appropriate Sponsor representative by email to the study-specific mailbox. The Sponsor representative will 
advise the Investigator/study site staff how to proceed. 
The Adverse Event form provided in the eCRF should be completed and signed by the Investigator or 
physician sub-Investigator. The entire Adverse Event form needs to be completed, if possible, to keep 
requests for additional information to a minimum. Patients experiencing ADR, SAE, SADR or SUSAR 
should be followed clinically and with laboratory studies, if appropriate, until medical treatment and/or 
medical monitoring of the event is no longer required because the event resolves or stabilizes, returns to 
baseline if a baseline value is available, can be attributed to agents other than the study treatments or a 
referral for appropriate follow-up care has been made. 
The Investigator must promptly inform the IRB of all SUSARs needed per IRB requirements. These events 
will be reported by the Sponsor as appropriate to the regulatory authorities. The Investigator will receive 
notification of these events across all study centers from the Sponsor.  
ETA safety reporting must follow the direction for use and the commercial complaint reporting process as 
appropriate for each specific device.  
AE/SAE unrelated to Varithena or the procedure should be directly reported to 
pharmacovigilance@bsci.com as according to the Varithena commercial complaint reporting process. 
8.4 Periodic Safety Reporting 
ADRs/SADRs/SAEs will be recorded on the AE form and the severity graded using NCI CTCAE version 
5.0. The Investigator or physician sub-Investigator will judge the seriousness of each AE and whether it is 
Varithena, ETA, or procedure related.  
Periodic safety reports prepared by the Sponsor will be distributed across all study centers. The 
Investigator will be responsible for informing the IRB. 
8.5 Expected Adverse Events  
The study is based on the evaluation of an FDA-approved injectable foam that has been shown to improve 
the symptoms of superficial venous incompetence and the appearance of visible varicosities. As reported in 
the Highlights of Prescribing Information, “in clinical trials, the most common related adverse events 
(occurring in ≥3% of patients treated with Varithena) were pain/discomfort in extremity, infusion site 
thrombosis (retained coagulum), injection site hematoma or pain, thrombophlebitis superficial, and 
extravasation.” 
8.6 Adverse Events of Special Interest 
An AE of special interest (AESI) is one of scientific and medical interest specific to the understanding of the 
study treatments and may require close monitoring. An AESI may be serious or non-serious. The rapid 
reporting of AESIs allow ongoing surveillance of these events in order to characterize and understand them 
in association with the use of Varithena.  
AESI for Varithena include proximal deep vein thrombosis, common femoral vein thrombus extension, 
pulmonary embolism, hypersensitivity and anaphylaxis, gas embolism with neurological abnormalities, 
accidental intra-arterial administration, pregnancy, lactation, use in paediatrics.  

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9 
STATISTICAL CONSIDERATIONS 
The statistical analysis plan will be a separate document and will be updated as required, in association 
with any protocol amendments. The plan will include descriptions of tables, listings and figures and will 
describe statistical programming considerations. 
9.1 Study Design and Determination of Sample Size 
This is a multicenter, randomized, controlled, open-label, parallel group study. 
The objective of the study is to measure the change in in VVSymQ score for both treatment groups within 
the same patient population in the same clinical setting, and the study is not powered to detect a difference 
between treatments. 
Whilst there is no pre-specified hypothesis relating to the comparison between treatment groups, a sample 
size of approximately 100 patients would allow a minimally detectable absolute difference of 2.0 points in a 
t-test with 2-sided alpha level of 0.05, assuming a standard deviation of 5.0 points in both arms. The 
assumption for the standard deviation is based on baseline standard deviation values observed in the 
Vanish 1 and Vanish 2 studies (4.96 and 4.55, respectively). 
A target of approximately 100 patients will be randomized and treated in a 1:1 ratio between treatment 
groups. 
9.2 Statistical Populations and Sub-Groups 
The Safety (As Treated) Population consists of all patients who receive treatment with either Varithena or 
ETA and will be analyzed according to the actual treatment they received. All safety and healthcare 
resource endpoints will be analyzed in the safety population. 
9.3 Baseline and Demographic Characteristics 
Demographics, medical history and ongoing conditions, baseline disease assessments and disease 
diagnosis will be summarised descriptively. 
Baseline results for efficacy assessments (VVSymQ, VEINES-QOL/sym, rVCSS and EQ-5D-5L) will be 
presented in summaries along with post baseline results (see Section 9.4). 
9.4 Efficacy Analyses 
9.4.1 Handling of Missing Data 
Handling of missing data will be described in the statistical analysis plan. 
9.4.2 Primary Efficacy Endpoint Analysis 
The absolute change in VVSymQ score between baseline and 3-month follow-up will be evaluated for each 
subject. Changes in scores will be summarized by treatment group (n, mean, standard deviation, min, max, 
and 95% confidence interval (CI)). The study is not powered to test formal statistical hypotheses, however 
results of a t-test comparing mean absolute change between treatment groups will be presented. 
9.4.3 Secondary Efficacy Endpoint Analysis 
For each of VVSymQ, VEINES-QOL/sym, rVCSS and EQ-5D-5L, summary tables of scores and change 
from baseline at each timepoint (7-days, 3-months, 6-months, 12-months, 24-months and 36-months post 
treatment) will be presented for each treatment group. No formal statistical hypotheses are to be tested. 

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Results of paired t-tests comparing change from baseline to each timepoint as well as t-tests comparing 
mean absolute change between groups at each timepoint will be presented. 
9.5 Safety Analyses 
Procedure and treated leg related AEs and SAEs will be coded and summarized for each of the treatment 
groups. Number of patients and number of events will be displayed for each body system and event term. 
9.6 Other Analyses 
Healthcare resource utilization may be summarized descriptively at the 12, 24 and 36 months timepoints. 
Results of closure rates, defined as the rate of occluded treated target veins with no patent segments 
exceeding 5 cm in length, measured by duplex ultrasound may be summarized for each treatment group at 
the 7-day, 3-month, 12-month, 24-month, and 36-month timepoints. 
9.7 Interim Analyses 
No interim analyses are planned for the study. 
10 DATA MANAGEMENT 
Patient data from the study will be collected via a limited access secure electronic data capture (EDC) 
system. Data will be entered in the electronic case report forms (eCRFs) at the study site. Trained study 
personnel will be responsible for entering data on the observations, tests and assessments specified in the 
protocol into the eCRF system and according to the eCRF Classic Rave eCRF Completion Guidelines. The 
eCRF instructions will also provide the study site with data entry instructions. All changes made to collected 
data will be documented in an electric audit trail and available to review by the Sponsor or its 
representative. The associated Rave database has been designed to meet regulatory compliance for 
deployment as part of a validated system compliance with the laws and regulations pertaining to the use of 
electronic records and signature applicable to the conduct of clinical studies. 
Data verification and data validation checks will be routinely performed using electronic edit checks and 
manual data review. Any data discrepancies will be referred back to the Investigator and site staff. When 
data have been entered, reviewed, edited the Investigator will be notified to sign the eCRF electronically as 
per the agreed project process and data will be locked to prevent further editing.  
A clean database will be declared after consistency checks have been run, all SAE reconciliations have 
been resolved, all the data in the database has been accounted for, all edit checks have been run and data 
discrepancies have been resolved or accepted and a Quality Check on a sample of the data has been 
performed. After the database has been declared clean it will be locked and editing in the database will only 
be allowed with the proper documentation. A final copy of the eCRF will be archived at the study site.  
AEs will be coded according to the version of MedDRA agreed with Boston Scientific. Concomitant 
medications will be coded using the version of the WHO Drug dictionary agreed with Boston Scientific. 
After database lock, data will be extracted to SAS® (SAS Institute, Inc., Cary, NC, USA) for analysis as 
defined in the SAP. SAEs related to Varithena or the Varithena procedure will be entered into the Varithena 
safety database. 

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10.1 Image Management System 
Duplex ultrasounds collected at 7-day, 3-month, 12-month, 24-month and 36-month post procedure will be 
deidentified and uploaded into an image management system. Further instructions for deidentifying and 
uploading duplex ultrasounds will be provided by the image management system vendor in the VasCore 
Core Lab protocol.  
11 LEGAL/ETHICS and ADMINISTRATIVE PROCEDURES 
11.1 Good Clinical Practice/Regulatory Compliance 
The procedures set out in the this study protocol, pertaining the conduct, evaluation, and documentation of 
this study, are designed to ensure that the Sponsor and Investigators abide by the current version of 21 
CFR Parts 11, 50, 54, 56, 312, 812; International Council for Harmonisation (ICH) Harmonised Tripartite 
Guideline E6 (R2): Good Clinical Practice: Consolidated Guideline, and International Standard ISO 
14155:2020 Clinical investigation of medical devices for human patients – Good Clinical Practice, ethical 
principles that have their origins in the Declaration of Helsinki, and applicable individual country laws and 
regulations. The study shall not begin until the required approval/favorable opinion from the IRB/EC and/or 
regulatory authority has been obtained, if appropriate. Also, the study shall not begin prior to issuance of 
the site Authorization to Enroll, as provided by the Sponsor. Any additional requirements imposed by the 
IRB/EC or regulatory authority shall be followed, if appropriate.  
It is the Investigator’s responsibility to ensure that adequate time and appropriate resources are available at 
the study site prior to commitment to participate in this study. The Investigator should also be able to 
estimate or demonstrate the potential for recruiting the required number of suitable patients within the 
agreed recruitment period. The Investigator will maintain a list of appropriately qualified person to whom the 
Investigator has delegated significant study-related tasks. 
11.2  Study Site and Investigator Qualification 
This study will be performed by qualified and licensed Investigators at approximately 15 sites located in the 
United States. Information on the principal investigator at each investigational site, the address details for 
each investigational site and the emergency contact details for the principal investigator at each site, as 
well as the roles, responsibilities and qualifications of the investigators will be maintained in the TMF 
throughout the study. 
The investigator is responsible to ensure that all site staff are appropriately qualified by education, training, 
and experience to perform the delegated study related duties he/she has allocated to them, which must be 
recorded on the site delegation of authority log. 
When specific tasks are delegated by an Investigator, including but not limited to conducting the informed 
consent process, the Principal Investigator is responsible for providing appropriate training, ensuring 
personnel are competent to perform the tasks they have been delegated and providing adequate 
supervision of those to whom tasks are delegated. Where there is a Sub-Investigator at a site, the Sub-
Investigator should not be delegated the primary supervisory responsibility for the site. The Investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the conduct of the 
clinical study.  
Institutional practices and local requirements for qualifying study staff members and teams, including but 
not limited to GCP training, is required for all staff responsible for study activities. The frequency of repeat 

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training may be dictated by the requirements of their employing institution, and as required when there 
have been updates to the legal or regulatory requirements for the conduct of clinical trials.  
All participating study sites will be reviewed by the study Sponsor or designee to verify that they are able to 
conduct the study.  
11.2.1 Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study is conducted in 
accordance with the Clinical Study Agreement, the clinical investigation plan, ICH GCP, ISO 14155, ethical 
principles that have their origins in the Declaration of Helsinki, any conditions of approval imposed by the 
reviewing IRB/EC, and prevailing local and/or country laws and/or regulations, whichever affords the 
greater protection to the patient. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• 
Prior to beginning the study, sign the Clinical Study Agreement and comply with the Investigator 
responsibilities as described in such Agreement.   
• 
Prior to beginning the study, sign Protocol Signature page documenting their agreement to conduct 
the study in accordance with the protocol. 
• 
Provide their qualifications and experience to assume responsibility for the proper conduct of the 
study and that of key members of the site team through up-to-date curriculum vitae or other relevant 
documentation and disclose potential conflicts of interest, including financial, that may interfere with 
the conduct of the clinical study or interpretation of results. 
• 
Make no changes to or deviate from this protocol, except to protect the life and physical well-being of 
a patient in an emergency; document and explain any deviation from the approved protocol that 
occurred during the course of the clinical investigation. 
• 
Create and maintain source documents throughout the clinical study and ensure their availability with 
direct access during monitoring visits or audits; ensure that all clinical-investigation-related records 
are retained per requirements. 
• 
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the Sponsor in 
the eCRFs and in all required reports. 
• 
Record, report, and assess (seriousness and relationship to the Varithena, ETA device, and 
procedure) every AE as applicable per the protocol. 
• 
Report to the IRB/EC and regulatory authorities any SUSARs, if required by applicable laws or 
regulations or this protocol or by the IRB/EC and supply the Sponsor with any additional requested 
information related to the safety reporting of a particular event. 
• 
Allow the Sponsor to perform monitoring and auditing activities and be accessible to the clinical 
research monitor or auditor and respond to questions during monitoring visits or audit(s). 
• 
Allow and support regulatory authorities and the IRB/EC when performing auditing activities. 
• 
Ensure that informed consent is obtained in accordance with applicable laws, this protocol and local 
IRB/EC requirements. 
• 
Provide adequate medical care to a patient during and after a patient’s participation in a clinical study 
in the case of adverse events, as described in the Informed Consent Form (ICF). 

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• 
Inform the patient of the nature and possible cause of any adverse events experienced. 
• 
Inform the patient of any new significant findings occurring during the clinical investigation, including 
the need for additional medical care that may be required. 
• 
Provide the patient with well-defined procedures for possible emergency situations related to the 
clinical study and make the necessary arrangements for emergency treatment. 
• 
Ensure that clinical medical records are clearly marked to indicate that the patient is enrolled in this 
clinical study. 
• 
Ensure that, if appropriate, patients enrolled in the clinical investigation are provided with some means 
of showing their participation in the clinical investigation, together with identification and compliance 
information for concomitant treatment measures (contact address and telephone numbers shall be 
provided). 
• 
Inform, with the patient’s approval or when required by national regulations, the patient’s personal 
physician about the patient’s participation in the clinical investigation. 
• 
Make all reasonable efforts to ascertain the reason(s) for a patient’s premature withdrawal from 
clinical investigation while fully respecting the patient’s rights. 
• 
Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
11.2.2 Investigator CV 
The Investigator will provide the Sponsor or designee with his/her, as well as those of any sub-Investigator 
or staff personnel with significant study responsibilities, current curriculum vitae (CV) and any 
revisions/updates.   
11.2.3 Investigator Agreement Form (Form FDA 1572) 
The Investigator will be required to sign and date an Investigator Agreement form provided by the Sponsor 
for the original and each subsequent change in Investigator at the site and return the original signed 
document to the Sponsor. A copy of the signed form will be given to the Investigator for their files.  
11.2.4 Financial Agreements and Financial Disclosure 
Financial agreements with each site are described separately.  
Financial disclosure statements will be completed for the Investigator and all sub-investigators to disclose 
potential conflicts of interest (per 21 CF Part 54 and ISO 14155). The Investigator is responsible for 
ensuring completed and signed financial disclosure forms are submitted to the Sponsor or designee. A 
copy of the form(s) will be given to the Investigator for their files. Financial disclosure information will be 
collected by the Sponsor before the start of the study and maintained for one year after study completion. 
11.2.5 Site Qualifications 
The Institution must have appropriately qualified Investigators, and clinical and administrative support staff 
in place to adequately conduct the trials according to GCP in general and must have the adequate 
expertise and staff to conduct this study in compliance with the relevant guidelines and regulations (see 
section 11.1) and to treat incompetent great saphenous vein with the study treatments. 

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11.3 Institutional Review Board (IRB)/Independent Ethics Committees (IEC) 
11.3.1 Institutional Approval of the Protocol 
It is the responsibility of the Investigator to submit this protocol, the ICF (approved by the Sponsor or 
designee), relevant supporting information and all types of patient recruitment information to the IEC/IRB 
for review and approval prior to site initiation.  A copy of the written approval of the protocol and ICF must 
be received by the Sponsor or designee prior to recruitment of patients. Prior to implementing changes in 
the study, the Sponsor and IEC/IRB must also approve any revised informed consent documents and 
amendments to the protocol with documentation of the approvals submitted to the Sponsor or designee. 
The approval document should clearly state the study reference, date of review and actions taken. 
The Investigator will be responsible for keeping the IEC/IRB apprised of the progress of the study, any 
changes to the protocol, deviations from the protocol and serious/unexpected adverse events. 
11.3.2 Ethics/IRB Committee Membership Roster  
The Investigator must submit a complete and current roster of the IEC/IRB to the Sponsor or designee. 
Some institutions, due to reasons of confidentiality, may not release their roster. Where such instance 
occurs, an Institutional signed and dated Statement of Compliance identifying the institution’s Federal Wide 
Assurance Number, assigned by the Office of Human Research Protection within the Department of Health 
and Human Services, is an acceptable substitute. 
11.4 Patient Privacy and Confidentiality  
The confidentiality of records that may be able to identify patients and/or the Sites and Investigators will be 
protected in accordance with applicable laws, regulations and guidelines and HIPAA requirements.  
The Sponsor and Investigator affirm and uphold the principle for the patient’s right to protection against 
invasion of privacy. Throughout this study, all data collected and analysed by the Sponsor (data controller) 
or designee (data processor) will be treated confidentially and identified by an identification number.  
To verify compliance with the protocol, the Sponsor will require the Investigator to permit its designee 
access to the patient’s primary medical record to review those portions that directly concern this study 
(including but not limited to laboratory test results, radiology images, and hospital and outpatient records).  
As part of required content of the informed consent, the patient must be informed that his/her records will 
be reviewed by the Sponsor, Sponsor representative and/or a representative of the appropriate regulatory 
agency, if applicable. The informed consent or related document will also state that patient privacy will be 
maintained pursuant to the Health Insurance Portability and Accountability Act (HIPAA), 21 CRF 21. Should 
access to such medical records require a waiver or authorization separate from the statement of informed 
consent, the Investigator will obtain such permission in writing from the patient before the patient is entered 
in the study. 
Data collected during this study may be used to support the development, registration or marketing of 
Varithena. Collected data may be reviewed by the Sponsor and/or its representatives, independent auditors 
who validate the data on behalf of the Sponsor, third parties with whom the Sponsor may develop, register 
or market Varithena, national or local regulatory authorities and the IRB/EC which granted approval for this 
study to proceed.  Data may be transferred to and used for the purpose (s) for which it was originally 
collected in, other countries which may not afford the same level of protection that applies within the 
countries where this study is conducted.  The Sponsor, as the data controller, will ensure that, prior any 

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transfer, appropriate safeguards are in place to protect the data as required under the General Data 
Protection Regulation (EU) 2016/679 and other applicable data protection legislation. 
11.5 Study Monitoring 
Monitoring type (Remote, Onsite) and frequency during the conduct of the study will be detailed in the study 
monitoring plan and will be performed by qualified personnel from the Sponsor or Sponsor designee. 
During the monitoring visit, the progress of the study will be discussed with the Investigator or his/her 
representative. The ICF will be reviewed for signatures and the eCRFs checked for completeness and 
accuracy. Patient source data must be available for review. The Investigator and his/her staff are expected 
to cooperate with the study monitor and be available during at least a portion of the monitoring visit to 
review the eCRFs and any queries/resolutions, answer questions, and provide any missing information. 
The study monitor will record the date of each visit together with a summary report outlining the status and 
progress of the study. Proposed actions will be discussed with the Investigator or delegate study team 
members and confirmed in writing. 
Telephone and electronic mail contact will be made with the Investigator and study staff as necessary 
during the data collection and report writing periods.  All relevant study communications will be filed in the 
investigator site file.  
11.6 Modification of the Protocol 
All amendments to the protocol must be documented in writing, reviewed, and approved by the Investigator 
and Sponsor and submitted to the IEC/IRB for approval/positive vote prior to initiation. If the protocol 
amendment substantially alters the study design or potential risk to the patient, new written informed 
consent must be obtained from each patient for continued participation in the study.  
11.7 Suspension or Termination of Study 
If conditions arise requiring further clarification before the decision can be reached to proceed with or 
terminate the study, the study will be suspended until the situation has been resolved.  
The Sponsor has the right to terminate this study and remove all study material from the site at any time. 
Examples of situations where this might occur include: 
• 
It becomes apparent that patient enrollment is unsatisfactory with respect to quality and/or quantity or 
data recording is chronically inaccurate and/or incomplete. 
• 
The incidence and/or severity of adverse events in the study indicate a potential health hazard caused 
by the study treatment. 
11.8 Trial Completion 
The study will be considered complete with regard to the primary endpoint after all patients have completed 
the 3-month follow up visit, were discontinued prior to the 3-month follow up visit, have died, or the follow 
up visit window is closed. 
For regulatory purposes the end of the study with regard to all follow up after all patients have completed 
the 36-month follow up visit, were discontinued prior to the 36-month follow up visit, have died, or the follow 
up visit window is closed at which point the declaration of the end of study will be submitted to the IEC/IRB, 
as required. 
Following this, the Sponsor or delegate will advise the sites on the procedure for closing the study.  

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Once the end of the study has been declared, no more prospective patient data will be collected and sites 
must co-operate with any data queries regarding existing data to allow for analysis and publication of 
results. 
11.9 Clinical Study Report 
Irrespective of the outcome of the study the Sponsor will prepare a Clinical Study Report (CSR) within one 
year of completion of the study or within three months of early suspension or termination of the study.   
11.10 Departure from Protocol  
No departure may be made from the protocol unless an amendment has been agreed to in writing by both 
the Investigator and the Sponsor and approved by the IEC/IRB.  
No waivers will be granted for inclusion and exclusion criteria to this protocol. 
11.10.1 
Protocol Deviations 
All protocol deviations will be listed and will be assessed as major or minor throughout the clinical study 
and finalised prior to database lock.  
Criteria for protocol deviations will be defined and reviewed prior to database lock and described in the 
Protocol Deviation Management Plan. The following protocol deviations will be considered: 
• 
Violation of exclusion or inclusion criteria 
• 
Non-compliance to treatment (major deviations from the planned schedule of administration) 
• 
Continuously missed evaluations of efficacy variables or major deviations in the timing of efficacy 
related assessments  
11.11 Recording, Access to and Retention of Source Data 
Investigators are required to prepare and maintain adequate source documentation which includes: 
• 
Documents relative to the patient medical history that verify eligibility criteria 
• 
Records covering patient participation in the study including basic identification information, results of 
physical examinations and diagnostic tests, original laboratory results (initialled and dated by 
Investigator), therapy, study treatment administration, concurrent medication information, pathology 
reports, and visit/consult notes. 
All key data must be recorded in the patient’s source documents including the informed consent acquisition. 
The Investigator must permit authorized representatives of the Sponsor, the regulatory authorities, the 
IEC/IRB, and auditors to inspect facilities and records relevant to the study. 
The monitor (auditors, IEC/IRB or regulatory inspectors) may check the eCRF entries against the source 
documents. The consent form will include a statement by which the patients allow the above-named access 
to source data that substantiate information recorded in the eCRFs. These personnel, bound by 
professional secrecy, will not disclose any personal information or personal medical information.  
As described in the ICH GCP Guidelines, ‘essential documents’, including eCRFs, source documents, 
consent forms, laboratory test results, etc., should be retained by the Investigator until at least two years 
after the last approval of a marketing application in an ICH region or at least two years have elapsed since 
the formal discontinuation of a clinical development of the IP. These documents may be retained for a 
longer period however if required by the applicable regulatory requirements or by an agreement with the 

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Sponsor. The Investigator must obtain written permission from the Sponsor prior to destruction of any study 
documents. 
These records must be made available at reasonable times for inspection and duplication, if required, by a 
properly authorized representative of FDA in accordance with 21 CFR 312, 21 CFR 812, or other regulatory 
authorities in accordance with regulatory requirements. 
11.12 Electronic Case Report Forms 
The Investigator is responsible for maintaining adequate and accurate source documents from which 
accurate information will be transcribed in to eCRFs that have been designed to capture all observations 
and other data pertinent to the clinical investigation. eCRFs should be completed by the Investigator or 
delegate as stated on the Delegation of Authority Log. Overwriting of information or use of liquid correcting 
fluid is not allowed in source documentation.  
Once the study monitor has verified the contents of the completed eCRF against the source data, queries 
may be raised if the data are unclear or contradictory. The eCRFs must be reviewed and electronically 
signed and dated by the Investigator once all data has been entered and all queries resolved.  
11.13 Publications 
All manuscripts, abstracts or other modes of presentation arising from the results of the study must be 
reviewed and approved in writing by the Sponsor, in advance of submission. The review is intended to 
protect Sponsor proprietary information existing either at the date of commencement of the study or 
generated during the study. No individual Investigator may publish results from his/her site until after 
publication of the primary manuscript describing the full study population. 
The detailed obligations regarding the publication of any data, material results or other information that is 
generated or created in relation to the study shall be set out in the agreement between the Investigator and 
Sponsor. 
In accordance with recommendations from the International Committee of Medical Journal Editors, the 
study will be listed in a publicly accessible registry of clinical trials such as clinicaltrials.gov.  
11.14 Audit/Inspections 
To ensure compliance with relevant regulations, data generated by this study must be available for 
inspection upon request by representatives of the FDA, the Sponsor and its representatives, and the 
IEC/IRB for each study site. 
12 BIBLIOGRAPHY 
1. Raetz J, Wilson M, Collins K. Varicose Veins: Diagnosis and Treatment. Am Fam Physician. 
2019;99(11):682-688. 
2. Criqui MH, Jamosmos M, Fronek A, et al. Chronic venous disease in an ethnically diverse 
population: the San Diego Population Study. Am J Epidemiol. 2003;158(5):448-456. 
3. Gloviczki P, Comerota AJ, Dalsing MC, et al. The care of patients with varicose veins and 
associated chronic venous diseases: clinical practice guidelines of the Society for Vascular 
Surgery and the American Venous Forum. J Vasc Surg. 2011;53(5 Suppl):2S-48S. 
4. Millennium Research Group. US markets for varicose vein treatment devices. Millennium Research 
Group, Toronto, ON. 2009. 

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5. Gibson K, Khilnani N, Schul M, Meissner M, American College of Phlebology Guidelines C. 
American College of Phlebology Guidelines - Treatment of refluxing accessory saphenous 
veins. Phlebology. 2017;32(7):448-452. 
6. Regan JD, Gibson KD, Rush JE, Shortell CK, Hirsch SA, Wright DD. Clinical significance of 
cerebrovascular gas emboli during polidocanol endovenous ultra-low nitrogen microfoam 
ablation and correlation with magnetic resonance imaging in patients with right-to-left shunt. J 
Vasc Surg. 2011;53(1):131-137. 
7. King JT, O'Byrne M, Vasquez M, Wright D, Group V-I. Treatment of Truncal Incompetence and 
Varicose Veins with a Single Administration of a New Polidocanol Endovenous Microfoam 
Preparation Improves Symptoms and Appearance. Eur J Vasc Endovasc Surg. 2015;50(6):784-
793. 
8. Todd KL, 3rd, Wright DI, Group V-I. Durability of treatment effect with polidocanol endovenous 
microfoam on varicose vein symptoms and appearance (VANISH-2). J Vasc Surg Venous 
Lymphat Disord. 2015;3(3):258-264 e251. 
9. Todd KL, 3rd, Wright DI, Group V-I. The VANISH-2 study: a randomized, blinded, multicenter study 
to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% 
compared with placebo for the treatment of saphenofemoral junction incompetence. Phlebology. 
2014;29(9):608-618. 
10. Gibson K, Kabnick L, Varithena 013 Investigator G. A multicenter, randomized, placebo-controlled 
study to evaluate the efficacy and safety of Varithena(R) (polidocanol endovenous microfoam 
1%) for symptomatic, visible varicose veins with saphenofemoral junction incompetence. 
Phlebology. 2017;32(3):185-193. 
11. Vasquez M, Gasparis AP, Varithena 017 Investigator G. A multicenter, randomized, placebo-
controlled trial of endovenous thermal ablation with or without polidocanol endovenous 
microfoam treatment in patients with great saphenous vein incompetence and visible 
varicosities. Phlebology. 2017;32(4):272-281. 
12. Davis PE, Phillips J, Kolluri R. Use of Polidocanol Endovenous Microfoam to Improve 
Hemodynamics and Symptomology in Patients with Challenging Clinical Presentations: A Case 
Series. Ann Vasc Surg. 2018;52:176-182. 
13. Deak ST. Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation 
for the treatment of superficial venous insufficiency. J Vasc Surg Venous Lymphat Disord. 
2018;6(4):477-484. 
14. Kim PS, Elias S, Gasparis A, Labropoulos N. Results of polidocanol endovenous microfoam in 
clinical practice. J Vasc Surg Venous Lymphat Disord. 2021;9(1):122-127. 
13 SUPPLEMENTS/APPENDICES 
Supplements and appendices follow on the next page. 
 

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Protocol Approval & Release Signature Page 
Protocol Number: 
S2473 
Protocol Short Title: 
Varithena versus Endothermal Ablation of the Great Saphenous Vein (VERITAS) 
Protocol Name: 
A Phase 4 Randomized Trial Comparing Varithena to Endothermal Ablation for the 
Treatment of the Great Saphenous Vein 
Protocol Version: 
1.2 
Protocol Approval 
Date: 
17Aug2023 
The above-referenced protocol was reviewed and approved for release by the following: 
Approver 
Signature 
Date 
Steven Elias, MD 
Global Co-Principal Investigator 
 
 
Antonios Gasparis, MD 
Global Co-Principal Investigator 
 
 
Jennifer Hansen 
Senior Director, PI Clinical 
 
 
Timothy Keo 
Clinical Trial Manager 
 
 
Anna Chavez, MD 
Director, Medical Safety 
 
 
Cathy Zeng 
Fellow, Biostatistics 
 
 
 
 

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Principal Investigator Protocol Review Statement 
Protocol Number: 
S2473 
Protocol Short Title: 
Varithena versus Endothermal Ablation of the Great Saphenous Vein (VERITAS) 
Protocol Name: 
A Phase 4 Randomized Trial Comparing Varithena to Endothermal Ablation for the 
Treatment of the Great Saphenous Vein 
Protocol Version: 
1.2 
Protocol Approval 
Date: 
17Aug2023 
The Principal Investigator (undersigned) hereby declares that they have read this protocol and agrees to its 
contents. 
The undersigned confirms that the study will be conducted and documented in accordance with the current 
version of the Declaration of Helsinki, the protocol, standards of Good Clinical Practice, applicable laws and 
regulatory requirements specified in the protocol, and the stipulations of the clinical study agreement. 
By written consent to this protocol, the Investigator agrees to the above and to fully co-operate with all 
monitoring and audits in relation to this study by allowing direct access to all documentation, including 
source data, by authorized individuals representing Boston Scientific, IEC/IRBs and/or by regulatory 
authorities. 
 
Principal Investigator Name (please print): 
___________________________________________ 
 
Principal Investigator Signature:    
___________________________________________ 
 
Date (DD/MMM/YYYY): 
 
___________________________________________ 
 
 
 

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VVSymQ 
The VVSymQ is a 5-item PRO that includes the following five symptoms: heaviness, achiness, swelling, 
throbbing, and itching. Two versions of the VVSymQ were created to reflect pre-treatment and post-
treatment. Table 1 shows the Pre-Treatment VVSymQ items, response options, and response option 
scores. Table 2 shows the Post-Treatment VVSymQ items, response options, and response option scores. 
The only difference between the versions is that the reference to the “leg to be treated” in the pre-treatment 
version is replaced with “treated leg” in the post-treatment version. Response options and scores remain 
the same in both versions. 
Table 3: Pre-Treatment VVSymQ 
Item 
Response Scale 
Response Option 
Scores 
Please answer the following for the time since 
waking up today… 
N/A 
N/A 
Since waking up today, how often had you had 
the following problem in your leg to be treated? 
Heaviness 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your leg to be treated? 
Achiness 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your leg to be treated? 
Swelling 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your leg to be treated? 
Throbbing 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your leg to be treated? 
Itching 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 

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Table 4: Post-Treatment VVSymQ 
Item 
Response Scale 
Response Option 
Scores 
Please answer the following for the time since 
waking up today… 
N/A 
N/A 
Since waking up today, how often had you had 
the following problem in your treated leg? 
Heaviness 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your treated leg? 
Achiness 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your treated leg? 
Swelling 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your treated leg? 
Throbbing 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5 
Since waking up today, how often had you had 
the following problem in your treated leg? 
Itching 
None of the Time 
A Little of the Time 
Some of the Time 
A Good Bit of the Time 
Most of the Time 
All of the Time 
0 
1 
2 
3 
4 
5