EU Post Market Clinical Follow-Up Study of the Venclose System for Saphenous Vein Incompetence
Phase: NA
Conditions: Chronic Venous Insufficiency
Sponsor: Venclose, Inc.

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the 
Venclose System for Saphenous Vein Incompetence 
Revision A
Revision Date:  07AUG2019
Page 1 of 29 
Venclose™ 
Clinical Protocol 
VENC17A 
EU Post Market Clinical Follow-
Up Study of the Venclose System 
for Saphenous Vein Incompetence 
Investigator 
Dr. Christian Wenzel & Dr. Thomas Mattausch 
Venenzentrum am Bruehl 
Nikolaistr. 55 
04109 Leipzig 
Germany Phone: +0341 9112-753 
FAX: +0341 463 45 95 
Sponsor 
Venclose, Inc. 
2570 N. First Street, 2nd Floor - #221, San Jose, CA 95131, USA 
Study Contact 
Nancy Lockhorn, BS, MS, CCRA 
Vantage Clinical Advisors 
Phone: +1 408-368-8480 
Email: nancylockhorn@yahoo.com 
NCT04236245

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the 
Venclose System for Saphenous Vein Incompetence 
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PROTOCOL AGREEMENT PAGE 
I, the Investigator, agree to: 
•
Assume responsibility for the proper conduct of the study and not to deviate from the
procedures described in the protocol;
•
Be thoroughly familiar with the procedures as described in the protocol and any other
information sources provided by the Sponsor;
•
Conduct the study in compliance with the protocol and all applicable regulatory
requirements;
•
Permit monitoring and auditing of the study by the Sponsor and/or representatives, and
inspections by appropriate regulatory authority(ies); and
•
Ensure that all persons assisting with the conduct of the study are properly qualified for
their function.
Investigator Name (Print) 
Investigator Signature 
Date 
Sponsor Name (Print) 
Sponsor Signature 
Date 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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1 
PROTOCOL SYNOPSIS 
Protocol 
Number 
VENC17A 
Protocol Title 
EU Post Market Clinical Follow-Up Study of the Venclose System for 
Saphenous Vein Incompetence 
Sponsor  
Venclose, Inc. 
2570 N. First Street, 2nd Floor - #221 
San Jose, CA 95131, USA 
Study Type 
Post Market Clinical Follow-up 
Study Design 
This is a prospective, non-randomized study in which patients who meet 
eligibility criteria and consent to participate will undergo a minimally 
invasive procedure using radiofrequency (RF) energy for ablation of the 
great saphenous vein (GSV). 
Primary 
Objective 
To confirm the safety and performance of the Venclose System for 
radiofrequency 
segmental 
thermal 
ablation 
of 
incompetent 
Great 
Saphenous Veins (GSVs). 
Study Duration 
Up to 3 months to enroll plus one year to complete follow-up 
Participant 
Duration 
Twelve months post-procedure 
Study Site(s) 
One study site located in Germany 
Sample Size 
Up to 25 subjects treated with the Venclose System 
Study Visits 
Baseline Visit, Treatment Visit, Follow-Up Visits (3-day, 3-month, 6-
month, and 1 year post procedure) 
Primary 
Endpoints 
1. Vein Occlusion Rate (percentage of limbs with occlusion of the treated 
vein) at 3-day, 3-month, 6-month, and 12-month Follow-up Visits. 
2.  Reflux-free Rate (percentage of limbs without reflux, as determined by 
Duplex Ultrasound Scan) at 3-day, 3-month, 6-month, and 12-month 
Follow-up Visits. 
Secondary 
Endpoints 
Clinical signs and symptoms of lower limb venous disease at baseline, 3 
months, 6 months, and 12 months as measured by: 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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1. Clinical Etiologic Anatomic Pathophysiologic (CEAP) Classification; 
2. Venous Clinical Severity Score (VCSS). 
Side effects/adverse events after treatment through 12-month follow-up. 
Inclusion/ 
Exclusion 
Criteria 
Inclusion Criteria 
1. Subject is male or female and 18 to 80 years old (inclusive) at time of 
enrollment (signing of consent). 
2. Subject has significant venous reflux by DUS, defined as reverse flow 
with reflux duration greater than 0.5 seconds after the Valsalva 
maneuver or distal augmentation while the patient is standing or in 
reverse Trendelenburg position.  
3. Subject is eligible for endovascular treatment, as determined by the 
treating investigator.  
4. Subject’s general physical condition allows for a significant amount of 
ambulation after the procedure, as determined by the treating 
investigator.  
5. Subject is willing and able to complete study requirements, including 
all follow-up visits and assessments.  
6. Subject voluntarily provides written informed consent to participate in 
this study. 
 
Exclusion Criteria 
 
1. There is evidence of old or fresh thrombus in the subject’s diseased 
vein segment to be treated, as determined by DUS within 2 weeks prior 
to the index procedure.  
2. In the judgment of the treating investigator heat energy delivery to the 
subject would be contraindicated. 
3. Subject is concurrently participating in another interventional clinical 
trial. 
4. Subject is pregnant or plans to be pregnant or lactating at the time of 
the treatment procedure. 
5. Subject has known or suspected allergies or contraindications to any 
general or local anesthetic agents and/or any antibiotic medication that 
cannot be adequately pre-treated. 
 
 
 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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Table of Contents 
PROTOCOL AGREEMENT PAGE .................................................................................... 2 
1 
PROTOCOL SYNOPSIS ...................................................................................................... 3 
2 
BACKGROUND AND OBJECTIVES ...................................................................................... 7 
3 
TECHNOLOGY SUMMARY ................................................................................................ 7 
4 
RISKS AND BENEFITS ........................................................................................................ 8 
5 
STUDY ENDPOINTS .......................................................................................................... 9 
5.1 
Primary Endpoints ............................................................................................................... 9 
5.2 
Secondary Endpoints ......................................................................................................... 10 
5.2.1 
Patient Outcome (Symptoms/Recovery) ............................................................................ 10 
5.2.2 
Side Effects and Complications .......................................................................................... 11 
6 
OVERVIEW OF STUDY DESIGN ......................................................................................... 11 
6.1 
Inclusion Criteria ............................................................................................................... 12 
6.2 
Exclusion Criteria .............................................................................................................. 12 
7 
PRE-SURGICAL ASSESSMENT (Baseline Study Visit) ......................................................... 12 
7.1 
Informed Consent .............................................................................................................. 13 
7.2 
Baseline Study Assessments, Chronic Venous Insufficiency Quality of Life Questionnaire 
(CIVIQ-20) .................................................................................................................................... 13 
7.3 
Subject Confidentiality and Identification ......................................................................... 14 
8 
SURGICAL PROCEDURE ................................................................................................... 15 
9 
POST-PROCEDURE FOLLOW-UP CARE ............................................................................. 15 
10 
FOLLOW-UP STUDY VISITS ........................................................................................... 16 
10.1 
3-Day Follow-up Visit ......................................................................................................... 17 
10.2 
3-, 6-, and 12-month Follow-Up Visits ................................................................................ 17 
10.3 
Adjunctive Procedures and Re-Intervention ...................................................................... 18 
10.4 
Subject Lost-to-Follow-up .................................................................................................. 18 
10.5 
Early Withdrawal of Subjects ............................................................................................ 18 
11 
ADVERSE EVENT REPORTING ....................................................................................... 18 
11.1 
Definition of an Adverse Event .......................................................................................... 19 
11.2 
Definition of a Serious Adverse Event ................................................................................ 19 
11.3 
Definition of an Unanticipated Adverse Device Effect (UADE) ......................................... 20 
11.4 
Evaluating Adverse Events ................................................................................................ 20 
11.4.1 
Severity of Adverse Event .................................................................................................. 20 
11.4.2 
Causality of Adverse Event (Relationship to Device and Procedure) ................................ 21 
11.5 
Recording and Documenting Adverse Events .................................................................... 21 
11.6 
Criteria for Interruption or Early Termination of Study ........................................................ 22 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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12 
DEVICE MALFUNCTIONS .............................................................................................. 22 
13 
PROTOCOL DEVIATIONS .............................................................................................. 23 
14 
STUDY COMPLETION ................................................................................................... 23 
15 
DATA ANALYSIS ........................................................................................................... 23 
16 
USE OF STUDY DATA ................................................................................................... 24 
17 
MONITORING .............................................................................................................. 24 
18 
REGULATORY CONSIDERATIONS ................................................................................. 24 
19 
RECORDS ..................................................................................................................... 25 
20 
PROGRESS REPORTS AND INTERIM REPORTING .......................................................... 25 
APPENDIX 1 - List of Potential Adverse Events ................................................................. 27 
 
 
 
 
 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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2 
BACKGROUND AND OBJECTIVES 
 
The primary objective of this Post-Market Clinical Follow-up (PMCF) prospective, non-
randomized study is to confirm the safety and performance of the CE-marked Venclose 
System for radiofrequency segmental thermal ablation of incompetent Great Saphenous 
Veins (GSVs).  
 
These types of post-market studies are recommended by MEDDEV 2.12-2 rev 2 for all 
medical devices for which there is not medium- to long-term clinical evidence available at 
the time of gaining approval to market in the EU, and for medical devices that have relied 
on clinical data from equivalent devices for conformity with the Essential Requirements of 
the Medical Device Directive (MDD).  It is hypothesized that the safety and performance 
of the Venclose System will be similar to the equivalent, alternative CE-marked 
ClosureFast System, which Venclose relied on for clinical data for conformity with the 
Essential Requirements.  
 
The data and conclusions derived from this PMCF study will be used to provide additional 
data for updating the clinical evaluation in order to assess whether the device continues to 
comply with the Essential Requirements. Such an assessment may result in corrective or 
preventive actions, for example: changes to the labeling/instructions for use, changes to 
manufacturing processes, changes to the device design, or public health notifications. 
 
This study has been designed in accordance with MEDDEV 2.12/2 rev 2.  
 
3 
TECHNOLOGY SUMMARY 
 
The Venclose™ Radiofrequency (RF) System (Generator and Catheters) is intended for 
use in endovascular coagulation of blood vessels in patients with superficial vein reflux. 
The Venclose System uses resistive radiofrequency ablation via bipolar energy delivery to 
heat the wall of an incompetent vein with temperature-controlled RF energy to cause 
irreversible luminal occlusion, followed by fibrosis and ultimately resorption of the vein. 
The blood then naturally reroutes to healthy veins. 
 
The technique involves percutaneous access and insertion of the endovenous sectional 
radiofrequency (EVSRF™) catheter into the target vein under ultrasound guidance and 
relies on the use of local anesthesia and thermal energy, from a radiofrequency generator, 
applied to the target vein. After each treatment, the EVSRF catheter is withdrawn a single 
length of the heating coil and another treatment is performed, until the entire vessel has 
been treated. This sectional treatment involves thermal damage that is inflicted upon the 
venous endothelium and into the wall, resulting in contraction and ultimately destruction 
of the vessel. 
 

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Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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The procedure can be performed in an outpatient setting, without the need for general 
anesthesia, allowing for a walk-in/walk-out procedure with minimal postoperative 
recovery time.  
 
The Venclose System consists of two (2) main components: 1) The EVSRF 
Ablation catheter (model VC-10A2.5-6F-60, 60cm or VC-10A2.5-6F-100, 100cm) with 
integrated cable connector which, using sectional ablation, treats the vein in 10 cm or 2.5 
cm segments, and 2) the Venclose digiRF generator (model VC-RFG-1) which 
delivers RF energy to the EVRSF catheter. 
 
The Venclose System is comprised of the following accessories: 
• 
Power cord for generator for the geographical region that the generator is sold 
• 
Optional foot pedal (model VC-FP-1) 
 
The following supplies are necessary for the procedure, but are not provided with the 
Venclose System: 
• 
Duplex or B-mode ultrasound console 
• 
Supplies for sterile procedure 
• 
Tilt table (recommended) 
• 
6F introducer sheath, with matching dilator, guidewire and percutaneous access 
needle (access kit/ introducer kit) 
• 
Local or general anesthesia 
• 
Post-operative compression as recommended by physician  
 
EVSRF catheters have a handle with logic circuitry and a button for starting treatment 
cycles. The generator is a 60-Watt multi-voltage (24V or 9V) power delivery system that 
uses digital radiofrequency at 460 kHz. The system will be used to perform endovenous 
ablations at 120°C for 20 seconds per cycle, matching a treatment protocol that has been 
widely studied over the last 10 years1.   
 
4 
RISKS AND BENEFITS 
 
Bipolar segmental radiofrequency ablation technology has years of history of clinical 
safety and effectiveness in humans in the delivery of radiofrequency energy to peripheral 
veins in the leg.   Procedures utilizing radiofrequency ablation devices are associated with 
consistently high successful vein closure rates, with side effects that are low in frequency, 
 
1 Proebstle TM, Alm BJ, Gockeritz O, Wenzel C, Noppeney T, Lebard C, Sessa C, Creton D, Pichot O. Five-year 
results from the prospective European multicenter cohort study on radiofrequency segmental thermal ablation for 
incompetent great saphenous veins. BJS 2015; 102: 212-218. 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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mostly 
minor/transient 
and 
common 
to 
catheter-based 
procedures 
in 
general. 
Radiofrequency ablation sessions are usually performed in an outpatient setting with local 
anesthetic and typically require no sedation. Patients are fully ambulatory following 
treatment, and the recovery time is short for the majority of patients.  
 
Potential complications include, but are not limited to the following: vessel perforation, 
skin discoloration, nerve injury, phlebitis, hematoma, thrombosis, infection, skin burn and 
pulmonary embolism. Other adverse events are often related to and can be complicated by 
the progression of the underlying incurable and progressive nature of venous disease, the 
presence of co-morbid conditions, and/or the risks of tumescent anesthesia. Risks related 
to the use of catheters in general and thermal interventions in particular are considered to 
be manageable (minor, transient and treatable) when compared to the possible benefits of 
controlled and selective destruction of diseased peripheral vasculature. These risks may be 
minimized through adherence to the device instructions for use, proper patient selection 
and monitoring of the patient’s status during treatment and follow-up. Radiofrequency 
ablation provides a minimally-invasive and outpatient-based treatment alternative for 
patients with varicose veins and peripheral venous insufficiency that is well-established 
and widely-used in the medical community. 
 
The benefits of treatment with ablative radiofrequency energy include reduction in the 
overall severity of venous symptoms and improved quality-of-life with typically only mild 
postoperative discomfort.   
 
5 
STUDY ENDPOINTS 
 
5.1 
PRIMARY ENDPOINTS  
The primary study endpoints are percentage of limbs with vein occlusion in the treated vein 
and the absence of reflux in the treated vein, as determined by Duplex Ultrasound Scan 
(DUS).  
 
Primary endpoint analysis will be accomplished by measuring the treated vein 
recanalization and reflux rates at 3 days (+/- 2 days), 3-months (+/- 2 weeks), 6 months 
(+/- 3 weeks) and 12 months (+/- 4 weeks) post-procedure. Recanalization will be 
determined by DUS and clinical assessment during follow-up. A twelve-month follow-up 
is sufficient to assess a stable occlusion in the treated vein, as it is the typical final follow-
up time frame for varicose vein treatment when assessing technical and symptomatic 
recurrence.  
 
Specific primary endpoint measurements will be: 
1) Vein Occlusion Rate – percentage of limbs with occlusion of the treated vein: 
Occlusion is defined as the absence of any flow from 3 cm inferior to the 
Saphenofemoral Junction (SFJ) along the entire length of the treated vein as 
documented on the post-procedure and follow-up DUS.  The 3 cm limit was selected 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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to represent the occlusion status of the proximal Great Saphenous Vein (GSV) and to 
allow precise evaluation with a typical 4 cm linear ultrasound probe.  In line with the 
equivalent ClosureFast device clinical studies2,3 flow in the stump of the GSV up to 3 
cm below the SFJ is considered normal and does not constitute a failure.  
 
2)  Reflux-Free Rate – percentage of limbs without reflux in the treated vein: Reflux is 
measured by Duplex Ultrasound imaging along the entire treated vein segment(s). 
Reflux is defined as reversal flow >0.5 seconds with subject standing or in reverse 
Trendelenburg position of at least 15° after distal augmentation. 
 
5.2 
SECONDARY ENDPOINTS 
Secondary endpoints are the clinical outcomes (patient symptoms, patient recovery) and 
evaluation of side effects/adverse events after the treatment:  
5.2.1 
Patient Outcome (Symptoms/Recovery) 
Clinical signs and symptoms of lower limb venous disease will be evaluated using 
standardized scales and subject responses to pre and post-procedure questions using the 
Clinical Etiologic Anatomic Pathophysiologic (CEAP) clinical classification and the 2010 
revised Venous Clinical Severity Score (VCSS).4  
Clinical Etiologic Anatomic Pathophysiologic (CEAP): Status of clinical signs and 
symptoms of lower limb venous disease as measured by CEAP Classification at baseline, 
and 3-day, and 3-, 6- and 12-month follow-up visits.  
CEAP clinical categories are as follows5:  
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 atrophie blanche. 
C5: healed venous ulcer. 
 
2 Proebstle T, van den Bos R. Endovenous ablation of refluxing saphenous and perforating veins. Vasa. 2017 
May;46(3):159-166. doi: 10.1024/0301-1526/a000610. Epub 2017 Feb 27. Review. PMID: 28238282 
3 Creton D, Pichot O, Sessa C, Proebstle TM; ClosureFast Europe Group. Radiofrequency-powered segmental thermal 
obliteration carried out with the ClosureFast procedure: results at 1 year. Ann Vasc Surg. 2010 Apr;24(3):360-6. doi: 
10.1016/j.avsg.2009.09.019. Epub 2010 Jan 29. PMID: 20116207 
4 Vasquez et al., Revision of the venous clinical severity score: venous outcomes consensus statement: special 
communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg. 2010 
Nov;52(5):1387-1396. 
5 Eklöf, B. et al, Revision of the CEAP classification for chronic venous disorders: Consensus statement, Journal of 
Vascular Surgery, Volume 40, Number 6, 1248-1252 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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C6: active venous ulcer. 
 
Venous Clinical Severity Score (VCSS): VCSS will be measured at baseline, 3-day, and 
3-, 6- and 12-month follow-up visits.  VCSS assesses 10 factors of venous disease for 
which each factor is graded on a severity scale of 0-3 (least to worst). The higher the VCSS 
score the most severe the clinical signs and symptoms of venous disease are in a patient. 
VCSS improvement over time is presented by a decrease in VCSS total score (maximum 
score = 30; minimum score = 0).6  
 
Although ClosureFast studies utilized the original 1996 CEAP and 2000 VCSS scales, the 
Venclose post-market study will utilize the official 2004 and 2010 revised version of the 
scales, respectively, for consistency with the current state-of-the-art of clinical assessment 
for endovascular coagulation of blood vessels in patients with superficial vein reflux. 
Comparison efforts between the Venclose and ClosureFast studies will focus on similar 
percentages of score reduction, and may include an analysis of the differences in scale 
composition, as needed. 
5.2.2 
Side Effects and Complications  
Side effects, adverse events and complications associated with the procedure will be 
recorded and analyzed. See Section 11.0 for Reporting of Adverse Events.  
 
6 
OVERVIEW OF STUDY DESIGN 
 
Potential subjects presenting with signs and symptoms of chronic lower limb venous 
disease and significant reflux in the GSV will be further screened for study participation 
and enrollment.  All enrolled subjects will meet study eligibility criteria as described in the 
inclusion and exclusion criteria sections below. 
 
After voluntarily providing informed consent to participate, eligible subjects will undergo 
a minimally invasive procedure, which involves delivering controlled radiofrequency 
energy for ablation of the great saphenous vein (GSV). All procedures will be performed 
by surgeons determined to be experienced with the Venclose System and will take place at 
a single study site, Venenzentrum am Bruehl, Nikolaistr. 55, 04109 Leipzig.  The study 
will enroll up to 25 treated subjects. The study site will receive the Venclose System 
components for the treatment of study patients, free of charge. 
 
After the treatment procedure, subjects will be evaluated four (4) times to determine the 
incidence of adverse events, and to assess vein recanalization and reflux.  Follow-up visits 
occur at 3 days (+/-2 days), 3-months (+/- 2 weeks), 6 months (+/- 3 weeks) and 12 months 
(+/- 4 weeks) post-procedure. Each follow-up visit will consist of a clinical examination, 
 
6 Vasquez et al., Revision of the venous clinical severity score: venous outcomes consensus statement: special 
communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg. 2010 
Nov;52(5):1387-1396. 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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CIVIQ-20 Patient Questionnaire (except 3-day visit), patient satisfaction survey, and 
Duplex Ultrasound (DUS) examination of the treated limb in the reverse Trendelenburg 
position. A supine (rather than standing) position for DUS examinations is preferred in 
order to allow comparison with vein diameters obtained during the procedure. 
 
6.1 
INCLUSION CRITERIA 
1. Subject is male or female and 18 to 80 years old (inclusive) at time of enrollment 
(signing of consent). 
2. Subject has significant venous reflux by DUS, defined as reverse flow with reflux 
duration greater than 0.5 seconds after the Valsalva maneuver or distal augmentation 
while the patient is standing or in reverse Trendelenburg position.  
3. Subject is eligible for endovascular treatment, as determined by the treating 
investigator.  
4. Subject’s general physical condition allows for a significant amount of ambulation after 
the procedure, as determined by the treating investigator.  
5. Subject is willing and able to complete study requirements, including all follow-up 
visits and assessments.  
6. Subject voluntarily provides written informed consent to participate in this study. 
 
6.2 
EXCLUSION CRITERIA 
1. There is evidence of old or fresh thrombus in the subject’s diseased vein segment to be 
treated, as determined by DUS within 2 weeks prior to the index procedure.  
2. In the judgment of the treating investigator heat energy delivery to the subject would 
be contraindicated. 
3. Subject is concurrently participating in another interventional clinical trial. 
4. Subject is pregnant or plans to be pregnant or lactating at the time of the treatment 
procedure. 
5. Subject has known or suspected allergies or contraindications to any general or local 
anesthetic agents and/or any antibiotic medication that cannot be adequately pre-
treated. 
 
7 
PRE-SURGICAL ASSESSMENT (Baseline Study Visit) 
 
Potential subjects will be examined by the Investigator or his/her designee and evaluated 
according to the inclusion/exclusion criteria for participation in this study. Demographics, 
medical history (including previous venous interventions, risk factors/co-morbidities, and 

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Venclose System for Saphenous Vein Incompetence 
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concomitant conditions/medications), and a venous Duplex Ultrasound will be performed 
during pre-surgical assessment, and the results recorded on the Baseline Case Report Form. 
7.1 
INFORMED CONSENT 
For subjects who potentially meet study eligibility criteria, study participation will be 
carefully explained. Subjects who choose to continue in the evaluation will be asked to 
read the Study Informed Consent Form and will be given the opportunity to review the 
information and ask questions.  
It is the responsibility of the treating physician or his/her designee to obtain voluntary 
written informed consent (according to local legal requirements and regulations).  The 
information is intended to give each participant a thorough understanding of the purpose 
and nature of the PMCF study, the study requirements and visit commitments, and the 
potential benefits and risks of the study treatment. As part of the informed consent process, 
the investigator is instructed to inform the patient that he/she is free to refuse participation 
or to withdraw from the study at any time, without consequence. The patient is to 
understand that participation in the study is not required in order to receive treatment with 
the CE-marked Venclose System, and that alternative treatments (e.g., treatment with 
another endovenous ablation system or alternative method such as foam sclerotherapy) are 
available for venous insufficiency. A consent form in a language understood by the patient 
will be made available. The signed informed consent is retained in the patient’s medical 
file(s) along with documentation of the informed consent conversation and process by the 
person who obtained consent. A copy of the informed consent will be provided to the 
patient. Signing of the Study Informed Consent Form formally enters the subject as a study 
participant and indicates the participant's willingness to comply with the pre-procedure, 
treatment, and follow-up study requirements. If participants withdraw from the study prior 
to treatment with the treatment device, additional patient(s) may be enrolled in order to 
achieve a total of 25 treated patients. 
7.2 
BASELINE STUDY ASSESSMENTS, CHRONIC VENOUS INSUFFICIENCY 
QUALITY OF LIFE QUESTIONNAIRE (CIVIQ-20) 
Once the subject has agreed to participate in the study and signed the Study Informed 
Consent Form, the investigator will perform an assessment using the Clinical Etiologic 
Anatomic Pathophysiologic (CEAP) Classification and the Venous Clinical Severity Score 
(VCSS). 
The subject will complete a self-administered questionnaire called the Chronic Venous 
Insufficiency Quality of Life Questionnaire (CIVIQ-20).  The questionnaire assesses 
quality of life for patients with chronic venous disease using 20 questions in which the 
patient rates symptoms on a scale from 1 (no pain) to 5 (severe pain). 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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7.3 
SUBJECT CONFIDENTIALITY AND IDENTIFICATION 
All information concerning subjects or their participation in this study will be considered 
confidential. Only authorized Venclose personnel and designated consultants and 
regulatory agencies (in the event of a regulatory audit) will have access to these confidential 
files.  The investigator and designated study personnel will assign a unique identifier that 
will be used to maintain confidentiality of subjects’ medical information. Subject’s full 
names or initials and other protected health information (PHI) will not be captured on the 
case report forms, except patient self-reported questionnaires/surveys.  For patient self-
reported questionnaires/surveys, the site will retain the original document and will redact 
a copy that will be provided to Venclose or Venclose representatives. In addition, any 
images or reports submitted from the participating site to Venclose or Venclose 
representatives will be redacted of all subject identifiers. 
Subjects’ identifying information will be recorded on a Master Enrollment Log with access 
restricted to the Investigator and designated study personnel. 
On all source documents, case report forms, and any other documents provided to the 
Sponsor, the following subject identification coding for enrolled subjects will be used: 
 
___    ___        .        ___    ___         .          ___    ___    ___    ___    ___ 
                                                                                                                                               
 
 
 
 
 
 
 
EXAMPLES 
 
V    1    .    0      1     .     J     O      N      A      D_ 
V    1    .    0      2     .     M     I      L      S      T_ 
V    1    .    0      3     .     S     T      U      J      E_ 
 
Subject ID # 
(2 digits)  
in sequential 
order (01, 02, 
03, etc.) 
Subject Name Code 
(5 alpha characters) 
1st three letters of last name 
followed by 1st 2 letters of 
first name 
Site #  
(2 characters)   
‘V’ then Site 
ID # to be 
provided by 
the Sponsor 

VENCLOSE CLINICAL PROTOCOL VENC17A 
Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
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Note: Data for patients treated in bilateral limbs may be analyzed on a per-patient or per-
limb basis, as appropriate. Patients treated in bilateral limbs will be counted as one subject 
for data analyzed per-patient (and for the purposes of adverse event data). For data analyzed 
per-limb, the two limbs will be analyzed separately. 
Subjects will be given a date for surgery(s) during the Pre-Surgical Assessment (Baseline 
Visit) (with 14 allowable days between baseline assessments and the procedure).  
8 
SURGICAL PROCEDURE 
 
In accordance with routine clinical commercial practice, study investigators will receive 
in-service training by Venclose personnel or its representatives for the use of the Venclose 
System as well as product labeling and training materials, which include the Venclose 
digiRF User Manual (LB00003) (generator) and Venclose Catheter IFU (LB00002).  
 
The surgical procedure with the Venclose System will be conducted in accordance with the 
EU approved Venclose Catheter IFU and the Venclose digiRF User Manual (generator). 
The typical training program for the commercial device includes information about 
supplies, patient preparation, vein access, skin marking and measurement, device 
preparation, insertion, placement and local anesthetic, energy delivery and post-surgery 
recovery. Training that is specific to the performance of the study includes documentation 
requirements and procedures for the timely transmission of data. Procedure details and 
adverse events assessment will be recorded on the Treatment Visit Case Report Form and 
Adverse Event Case Report Form.  
 
The Venclose procedure will be performed on the GSV per standard of care.  For the GSV, 
no other treatment modalities are allowed (i.e. no phlebectomy or sclerotherapy). 
 
Adjunctive procedures for treatment of side branches (i.e. anterior accessory saphenous 
vein) may be performed per standard of care including phlebectomy and sclerotherapy. 
 
9 
POST-PROCEDURE FOLLOW-UP CARE 
 
The study site will follow standard of care post-procedure instructions including: 
  
1) Post-operative compression as prescribed by physician. 
2) For DVT prophylaxis, the subject will be instructed to ambulate frequently for several 
days after treatment. 
3) It is recommended that the subject not drive for 24 hours after treatment. 
4) It is recommended that the subject refrain from standing for long periods of time, and 
elevate the treated leg frequently in the first few days after treatment. 
5) It is recommended that the subject refrain from strenuous activities (such as heavy 
lifting) for several days. 
6) The bandage over the compression stocking may be removed in the evening on the day 

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of the treatment.  After three days the pressure inserts may be removed; small bandages 
will remain over the incisions and the subject may shower with these bandages on. 
7) Non-steroidal anti-inflammatory drugs are permitted as needed. 
8) If full mobility is not achieved after 2-3 weeks, physical therapy is recommended. 
 
10 FOLLOW-UP STUDY VISITS 
 
As shown in Table 1, Study Visit Schedule, all subjects will undergo four (4) follow-up 
examinations to assess the safety and efficacy of the treatment procedure. The visits will 
be scheduled at 3 days (+/-2 days), 3-months (+/- 2 weeks), 6 months (+/- 3 weeks), and 
12 months (+/- 4 weeks) post-procedure.  Each follow-up visit will consist of a clinical 
examination that includes DUS examination of the treated limb in the reverse 
Trendelenburg 
position, 
assessments 
using 
the 
Clinical 
Etiologic 
Anatomic 
Pathophysiologic (CEAP) Classification and the Venous Clinical Severity Score (VCSS), 
patient satisfaction survey, and CIVIQ-20 patient questionnaire (except 3-day visit).  All 
follow-up data will be recorded on the Follow-Up Visit Case Report Form.  
 
Table 1: Study Visit Schedule  
 
Pre-surgical 
Assessment/
Baseline 
Treatment 
Procedure 
3 Days 
Post-
Procedure 
(+/-2 days) 
3 Months  
Post-
Procedure 
(+/- 2 
weeks) 
6 Months  
 Post-
Procedure 
(+/- 3 
weeks) 
12 Months 
Post-
Procedure 
(+/- 4 
weeks) 
Informed 
Consent 
√ 
 
 
 
 
 
Medical 
History and 
Physical 
Exam 
√ 
 
 
 
 
 
DUS 
√ 
 
√ 
√ 
√ 
√ 
CEAP 
√ 
 
√ 
√ 
√ 
√ 
VCSS 
√ 
 
√ 
√ 
√ 
√ 
CIVIQ-20 
Patient 
Question-
naire 
√ 
 
 
√ 
√ 
√ 

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Pre-surgical 
Assessment/
Baseline 
Treatment 
Procedure 
3 Days 
Post-
Procedure 
(+/-2 days) 
3 Months  
Post-
Procedure 
(+/- 2 
weeks) 
6 Months  
 Post-
Procedure 
(+/- 3 
weeks) 
12 Months 
Post-
Procedure 
(+/- 4 
weeks) 
Patient 
Satisfaction 
Survey 
 
 
√ 
√ 
√ 
√ 
Treatment 
with 
Venclose 
System 
 
√ 
 
 
 
 
Medication 
Review 
√ 
√ 
√ 
√ 
√ 
√ 
Adverse 
Event 
Assessment 
 
√** 
√ 
√ 
√ 
√ 
Study Exit 
 
 
 
 
 
√ 
 
** Adverse events will be assessed during the immediate post-procedure period, prior to discharge. 
 
10.1 3-DAY FOLLOW-UP VISIT 
During the 3-day post-procedure follow-up visit, the pads, gauze bandage and wrapping 
will be removed. The surgical wounds will be evaluated, and complications or adverse 
events recorded. Duplex ultrasound of the treated limb will be performed for an assessment 
of the deep venous system, including an assessment of the treated GSV for closure, patency 
or recanalization. A patient self-reported satisfaction survey will be administered. 
10.2 3-, 6-, AND 12-MONTH FOLLOW-UP VISITS 
During the 3-, 6-, and 12-month follow-up visits Duplex ultrasound of the treated limb will 
be performed for an assessment of the deep venous system, including an assessment of the 
treated GSV for closure, patency or recanalization. Complications or adverse events will 
be recorded.  
The CEAP and the VCSS assessments will be performed during the 3-, 6- and 12-month 
follow-up visits and will be recorded on the Follow-Up Case Report Form.  The CIVIQ-
20 patient questionnaire and a patient self-reported satisfaction survey will be administered 
during the 3-, 6- and 12-month follow-up visits. 

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10.3 ADJUNCTIVE PROCEDURES AND RE-INTERVENTION 
Treatment of varices, perforators or side branches in the venous anatomy associated with 
the treated GSV segment is not allowed while subjects are in the follow-up period of this 
study (through 12-Month Follow-up Visit). This is done to avoid confusion post-
operatively between morbidity due to index treatment and adjunctive procedures. 
If an adjunctive procedure or re-intervention is performed at any time after the index 
procedure, the Investigator will complete an Adjunctive Procedure Case Report Form as 
well as a Protocol Deviation Case Report Form. 
 
10.4 SUBJECT LOST-TO-FOLLOW-UP 
In the event that a subject does not return for a follow-up visit, study personnel will make 
3 attempts to contact the subject.  The 3 attempts will be recorded in the subject’s medical 
record, detailing date, method of attempted contact, and result.   
If the study personnel are unable to contact the subject, or if the subject refuses to return 
for follow-up, a Study Exit CRF will be completed, specifying that the subject is lost-to-
follow-up, and will include information on the 3 attempts to contact the subject (date, 
contact method, result). 
 
10.5 EARLY WITHDRAWAL OF SUBJECTS 
If a subject decides to withdraw from the study early, he/she must contact the investigator 
(contact information is provided on the first page of the Study Informed Consent Form).  
Study personnel will document the early withdrawal on the Study Exit CRF including a 
reason for withdrawal. 
The investigator or sponsor may end a subject’s study participation at any time if the 
subject is not compliant with required tests and visits, if it is in the subject’s best interest 
medically, if a research-related injury occurs, or for administrative reasons.  If a subject is 
terminated from the study early, the investigator will notify the subject and the subject will 
still receive necessary follow-up care. 
 
11 ADVERSE EVENT REPORTING 
 
The Investigator is responsible for recording and reporting adverse events observed during 
the study.  Adverse Event information will be recorded on the Adverse Event Case Report 
Form (AE CRF) and will be reported to the Ethics Committee (EC), as per the EC reporting 
requirements and to the Study Sponsor, as per the following instructions. 
 
To aid the Investigator and site staff, a list of known potential Adverse Events is provided 
in Appendix 1. 
 

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11.1 DEFINITION OF AN ADVERSE EVENT 
 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury 
or any untoward clinical signs (including an abnormal laboratory finding) in subjects, users 
or other persons whether or not related to the medical device.  An AE may be any of the 
following: 
 
• 
A symptom 
• 
A disease or new illness diagnosed while enrolled in a trial, excluding screening 
diagnosis/diagnoses 
• 
An exacerbation of a sign or symptom of a pre-existing condition or of a 
concomitant illness 
• 
An increase in frequency/intensity of a pre-existing condition 
• 
An abnormal laboratory measurement of clinical relevance, excluding screening 
results  
• 
A laboratory measurement that changes from baseline and is of clinical relevance 
• 
A pre-existing physical finding (including vital sign measurements) that worsens 
compared with baseline and is of clinical relevance 
• 
An accident  
• 
Unrelated to participation in the trial or an effect of the trial procedures or study 
device 
• 
A combination of one or more of the above factors 
 
Information recorded on the AE CRF will include the nature of the event, date of onset, 
seriousness, severity, relationship to device, relationship to procedure, action taken, and 
outcome. 
 
11.2 DEFINITION OF A SERIOUS ADVERSE EVENT 
 
An AE is considered a serious adverse event (SAE) if the AE:  
 
a) led to a death, injury or permanent impairment to a body structure or a body 
function.  
b) led to a serious deterioration in health of the patient, that either resulted in:  
- a life-threatening illness or injury, or  
- a permanent impairment of a body structure (not including permanent damage 
intended by the procedure, such as obliteration by endovenous thermal ablation) 
or a body function (not including permanent impairment that is a known 
complication of the intended procedure, such as small local paresthesia after 
endovenous thermal ablation), or  

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- in-patient hospitalization or prolongation of existing hospitalization, or  
- medical or surgical intervention to prevent life threatening illness or 
necessitates medical or surgical intervention to preclude permanent impairment 
of a body function or permanent damage to a body structure.  A serious injury 
does not include reversible damage or injury (such as endovenous heat induced 
thrombosis that is less than 50% occlusive of the deep vein (EHIT 2) and that 
resolves with or without treatment, not requiring surgical intervention). 
 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect.  
 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the study protocol, without a serious deterioration in health, is not considered to be a 
serious adverse event. 
 
11.3 DEFINITION OF AN UNANTICIPATED ADVERSE DEVICE EFFECT (UADE)    
An unanticipated adverse device effect (UADE) is "any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects.” (21 CFR 812.3(s)). 
 
11.4 EVALUATING ADVERSE EVENTS 
11.4.1 Severity of Adverse Event 
The investigator must assess the severity of each AE reported during the study and will 
assign it to one of the following severity categories:   
 
Mild: 
An event that does not interfere with activities of daily living.  No 
medical intervention is required. 
Moderate:  
An event that interferes with activities of daily living, limits usual 
activities. No or minimal medical intervention is required.  
Severe: 
An event that prevents normal every day activities. Medical 
intervention or therapy is required. 
 
The term ‘severity’ is used to describe the intensity of an event (as in mild, moderate, 
severe); the event itself may be of relatively minor medical significance, such as a severe 
headache.  ‘Severe’ is not the same as ‘serious’.  Seriousness, not severity, serves as the 
guide for defining regulatory reporting obligations. 
 

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11.4.2 Causality of Adverse Event (Relationship to Device and Procedure) 
The investigator must assess the relationship to the device and to the procedure for each AE that 
is reported during the study.  Causality will be categorized using the criteria in Tables 2 and 3. 
Table 2: Assessment of Relationship to Device 
Relationship 
Description 
Not Related 
No relationship exists with the use of the device or the event is 
clearly related to other factors. 
Unlikely 
The relationship with the use of the device seems not relevant 
and/or the event can be reasonably explained by another cause. 
Possibly Related 
The relationship with the use of the device is weak but cannot be 
ruled out completely. 
Probably Related 
The relationship with the use of the device seems relevant and/or 
the event cannot reasonably be explained by another cause. 
Causal 
The event is associated with the device beyond a reasonable doubt. 
 
Table 3: Assessment of Relationship to Procedure 
Relationship 
Description 
Not Related 
No relationship exists with the procedure or the event is clearly 
related to other factors. 
Unlikely 
The relationship with the procedure seems not relevant and/or the 
event can be reasonably explained by another cause. 
Possibly Related 
The relationship with the procedure is weak but cannot be ruled out 
completely. 
Probably Related 
The relationship with the procedure seems relevant and/or the event 
cannot reasonably be explained by another cause. 
Causal 
The event is associated with the procedure beyond a reasonable 
doubt. 
 
11.5 RECORDING AND DOCUMENTING ADVERSE EVENTS 
Each adverse event must be promptly recorded and sufficiently documented by the 
investigator on the Adverse Event Case Report Form, even if the adverse event is assessed 
by the investigator as unlikely to be related to the subject’s participation in the study 
protocol. The investigator should make every attempt, if possible, to establish a diagnosis 
based on presenting signs and symptoms. At each visit, after the participant has had an 
opportunity to spontaneously mention any problems, the investigator should inquire about 
adverse events. 
 

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If any event meets the definition of a SAE, the investigator or designee will notify 
Venclose (or designee) by telephone or email within 48 hours after site study 
personnel becomes aware of the event.   
 
The investigator or designee will notify Venclose (or designee) by telephone or email 
within 24 hours after site study personnel becomes aware of any UADE.  The event 
will be reviewed per Venclose’s Complaint Handling Procedures, which establish the 
requirements for reporting medical device incidents under the European Union’s (EU) 
Medical Device Vigilance System for medical devices distributed in the EU under a CE 
mark.  
 
All unresolved SAEs or UADEs that are ongoing at a subject’s trial completion (12-Month 
Visit) or early termination will be followed by the Investigator until the event(s) is resolved, 
stabilized, the participant is lost to follow-up, or the event is otherwise explained.  
Documentation of this effort will be recorded on the Adverse Event Case Report Form. 
 
11.6 CRITERIA FOR INTERRUPTION OR EARLY TERMINATION OF STUDY 
If an event meets the following criteria it will be reviewed as an Unanticipated Adverse 
Device Effect (UADE): 
• 
A serious adverse event (SAE); 
• 
That is unanticipated (per UADE definition in Section 11.3); 
• 
And is possibly related, probably related, or causal to the device or the procedure 
(per Section 11.4.2). 
Venclose will immediately evaluate each UADE.  After evaluating a UADE, if Venclose 
determines the effect presents an unreasonable risk to subjects, the study will be terminated 
as soon as possible.  Study termination will occur no later than 5 working days after 
Venclose makes this determination and no later than 15 working days after Venclose first 
received notice of the UADE. 
 
12 DEVICE MALFUNCTIONS 
 
All device malfunctions (a failure of a device to perform in accordance with its intended 
purpose when used in accordance with the manufacturer's instructions) whether or not the 
malfunction resulted in an adverse event will be reported to Venclose immediately.  
Malfunctioning devices are required to be returned to Venclose for analysis following 
internal Returned Merchandise Authorization Process Procedures.  Venclose will attempt 
to confirm the malfunction/failure and the details of the malfunction will be reviewed per 
Venclose’s Complaint Handling Procedures, which establish the requirements for reporting 
medical device incidents under the Medical Device Vigilance System. 
 

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13 PROTOCOL DEVIATIONS 
 
A protocol deviation is generally an unplanned excursion from the protocol that is not 
implemented or intended as a systematic change.  Any protocol deviations that may affect 
the scientific soundness of the study, or affect the rights, safety, or welfare of study 
subjects, must be reported to the Sponsor as soon as a possible, but no later than within 5 
working days of the protocol deviation and to the institution’s Ethics Committee (EC) per 
their policy. 
 
Protocol deviation is also used to refer to any other, unplanned, instance(s) of protocol 
noncompliance. For example, situations in which the Investigator failed to perform tests or 
examinations as required by the protocol or failures on the part of study subjects to 
complete scheduled visits as required by the protocol, will be considered protocol 
deviations. These protocol deviations must also be reported to the institution’s EC per their 
policy. 
 
All protocol deviations will be recorded on the Protocol Deviation Case Report Form and 
reported to the study monitor as soon as possible. 
 
14 STUDY COMPLETION  
 
Subjects exit the study after completion of the 12-month follow-up visit. 
For each enrolled subject, study staff personnel will complete a Study Exit Case Report 
Form, on which the Investigator certifies that the Medical Record and Case Report Forms 
are complete and accurate. If a subject is terminated from the study by the investigator or 
Venclose, or the subject withdraws consent and therefore withdraws from the study, the 
circumstances of termination or withdrawal are recorded on the Study Exit Case Report 
Form.  
The Master Enrollment Log and the Screening and Enrollment Log are updated to indicate 
that the subject has completed the study, withdrawn from the study or has been terminated 
from the study. 
15   DATA ANALYSIS 
 
Subject demographics will be reported using descriptive measures including count, 
percentage, mode, median or mean as appropriate for the level of measurement. Clinical 
outcomes and visit assessment data will be presented with frequency distributions and 
cross-tabulations with selected demographics or other study variables.  
 
Endpoint analyses of CEAP classifications and VCSS scores will be performed on a per-
subject and/or per-limb basis for the 3-day, 3-, 6- and 12-month follow-up visits. 
Descriptive analyses of when desired outcomes were achieved will be calculated with sub-

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group comparisons as appropriate. Estimation methods may be used to report effect size 
along with confidence intervals for sub-group comparisons. 
 
Any adjunctive procedures, adverse events or protocol deviations will be described and 
reported as required. 
 
If a subject has had treatment and subsequently withdraws consent or is terminated/lost-to-
follow-up, data gathered as part of the study protocol up to the date of consent withdrawal 
or termination may be utilized in the data analysis.  The Informed Consent document makes 
clear to the subject that non-identifiable health data gathered as part of study activities 
before the date of consent withdrawal or termination may be utilized in the manner and 
with the protections described in the Consent document. 
 
16  USE OF STUDY DATA 
 
The data and conclusions derived from the PMCF study will be used to provide further 
clinical evidence for the clinical evaluation process. This may result in the need to reassess 
whether the device continues to comply with the Essential Requirements. Such assessment 
may result in corrective or preventive actions (e.g., changes to the labeling/instructions for 
use, changes to manufacturing processes, changes to the device design, or public health 
notifications). 
 
17  MONITORING 
 
Venclose or its designee will monitor the day-to-day activities of this study. Monitors will 
also periodically inspect the relevant study records, either remotely or in-person, to assure 
that the study is being conducted in accordance with the protocol and applicable 
regulations. Focused attention will be given to ensuring written informed consent is 
obtained prior to study procedures, verification of study data with source documentation, 
confirmation of accurate, complete, and legible completed Case Report Forms, and device 
accountability.  
 
18 REGULATORY CONSIDERATIONS 
 
The study protocol (and any amendments) will be reviewed and approved by the ethics 
committee responsible for research oversight conducted at the participating study site, and 
all subjects will be required to provide written informed consent prior to study 
participation. This PMCF study will be registered at ClinicalTrials.gov and on the German 
Clinical Trials Register (DRKS) website (www.drks.de). 
 
All investigators are experts in their field, with the device, and with the disease condition, 
as evidenced by CV, medical license, device training certificate, publications, and 
participation in previous research studies.  This documentation will be provided to the 
ethics committee (EC) as part of the EC submission. 

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19  RECORDS 
 
The PMCF study site will maintain a Regulatory & Study Operations Binder, the contents 
of which contain: 
• 
An EC-approved Clinical Protocol (and amendments, if applicable), 
• 
Protocol Agreement Page signed by the Investigator(s) and Sponsor (initial Clinical 
Protocol and any amendments, if applicable),   
• 
The EC-approved Informed Consent Form 
• 
EC approval letter(s) and correspondence 
• 
Regulatory (Notified Body) correspondence  
• 
Signed/dated Curriculum Vitae of each participating clinical site personnel  
• 
A copy of current medical license for treating physicians 
• 
Study Personnel Signature and Delegated Responsibility Log 
• 
Training Logs 
• 
Signed Investigator Agreement by the Principal Investigator  
• 
Signed Financial Disclosure Form by the Principal Investigator and Sub-
Investigator(s)  
• 
Sponsor Insurance 
• 
Correspondence file  
• 
Screening and Enrollment Log 
• 
Instructions for Use (IFU) for the Venclose EVSRF catheter and digiRF User 
Manual for the generator  
• 
Adverse Events 
• 
Protocol Deviations 
• 
Notes-to-File 
• 
Device Usage Log (to record subject ID, Venclose catheter lot number, and date 
used) 
• 
Site Visit Log 
 
The PMCF study site will maintain a study record (i.e., research chart and/or medical 
record) for each enrolled subject for ten (10) years after the study is complete or terminated. 
The records will include a section for source documentation (e.g., medical and visit notes, 
duplex ultrasound reports), signed consent form, adverse events, and the required study 
Case Report Forms. 
 
20  PROGRESS REPORTS AND INTERIM REPORTING 
 
A final PMCF study report with conclusions relating back to the original objective(s) will 
be prepared and submitted to the Notified Body upon completion of the PMCF study, 
unless (as described in MEDDEV 2.12-2 rev 2, section 8) the Notified Body specifies that 
data from the PMCF study should be transmitted between scheduled assessment activities, 
or in cases where safety and performance information about the device is obtained during 

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the study which has the potential to negatively alter the benefit/risk profile of the device 
(Section 4).  
 
Data gathered by the manufacturer from this PMCF study, whether favourable or 
unfavourable, will be used to actively update the risk management system for the Venclose 
System as new clinical safety and performance information about the device is obtained 
during its use.  Analysis and review of this PMCF study data is part of the risk management 
process and is performed by Venclose on a routine basis via established processes and 
procedures for periodic management/product reviews and periodic risk/benefit re-analysis. 
 
 

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APPENDIX 1 - List of Potential Adverse Events 
Based on the overall experience reported in the medical literature with endovenous thermal 
ablation by radiofrequency or laser, the following potential adverse events are provided as a 
guide: 
 
1. Reaction to Local Anesthesia: 
 
Some people may have hypersensitivity or allergic reaction to certain types of local 
anesthesia.  Prescreening the subject with a small amount of anesthesia can be 
performed.  Venclose defers to physician judgment in selecting the appropriate agent 
and amount. 
 
2. Deep Vein Thrombosis or Pulmonary Embolism: 
 
Potential for deep vein thrombosis (DVT) exists, usually less than 1 in 100 treated 
limbs.  If a DVT blood clot breaks loose it can travel to the lung and cause pulmonary 
embolism (PE), usually less than 1 in 10,000 limbs. 
 
3. Allergy to Product Component: 
 
The catheter has undergone biocompatibility testing to ensure safety of the 
components.  Some people may have a hypersensitivity or allergic reaction to one or 
more of the components.   
 
4. Perforation of the Saphenous Vein: 
 
The saphenous vein may be perforated during advancement of the catheter.  Minimal 
mechanical injury to the soft tissue and hematoma may result. 
 
5. Thermal Skin Injury: 
 
A burn is the partial or complete destruction of skin caused by some form of energy, 
usually thermal energy. 
 
6.  Skin Discoloration or Pigmentation: 
 
Blood degradation in the soft tissues may result in skin discoloration.  The majority of 
these skin changes resolve spontaneously over several months to a year.  Some 
discoloration may be permanent.   
 
 
 
 

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7. 
Infection: 
 
There is always a small chance of infection with any surgical procedure, however, the 
catheter is sterilized and is meant for one-time use.  Aseptic (sterile) technique will be 
used during the procedure. 
 
8. 
Neurological Injury: 
 
Motor nerves that could cause partial paralysis are typically avoided in endovenous 
thermal ablation procedures, and reports of such paralysis are extremely rare at less 
than 1 in 1,000,000 limbs. 
 
9. Parasthesia: 
 
Parasthesia is defined as abnormal physical sensations such as numbness, prickling or 
tingling.  This usually goes away within a few months, but can be permanent. 
 
10. Superficial Venous Thrombophlebitis: 
 
Superficial venous thrombophlebitis may appear within 1- 3 weeks after the ablation 
procedure as a tender red firm spot along the skin.  A great degree and length of 
compression may help to decrease the incidence of phlebitis.   
 
11. Pain: 
 
There is a potential for post-treatment soreness for 1 or 2 weeks after treatment.  
Soreness may result from thrombosed or inflamed vessels.  Other sources of pain 
include, but are not limited to compression-related problems, nerve injury, and pain at 
the access site. 
 
12.  Edema: 
 
Endovenous thermal ablation can correct the blood flow condition that can cause fluid 
swelling (edema), but it is possible for swelling of the treated area to be caused by 
changes in the pressure inside versus outside the vein or changes in vein wall fluid 
transport.  Edema may also occur if compression is not applied gradually.  Edema is 
usually self-limited and requires no specific therapy. 
 
13.  Compression-related Problems: 
 
Blisters may occur with the use of any tape on the skin.  Occlusion of any hairy area 
can promote the development of folliculitis.  Folliculitis is more likely to occur in the 
summer months or when patients are active and perspire under the dressing.   
 

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Document Title: EU Post Market Clinical Follow-Up Study of the  
Venclose System for Saphenous Vein Incompetence 
Revision A                                  Revision Date:  07AUG2019                                  Page 29 of 29 
 
14. Ecchymosis: 
 
Defined as discoloration (bruising) of an area of the skin resulting from trauma to the 
underlying blood vessels. 
 
15. Hematoma: 
 
Defined as a mass of clotted or coagulated blood.  It differs from a simple bruise or 
contusion because the area is swollen, raised, or painful. 
 
16. Erythema: 
 
Redness of skin along vein track that results from vascular irritation or capillary 
congestion in response to irritation; may be a precursor to phlebitis.