VenaSeal Spectrum: Global Post-Market Randomized Controlled Trial

Study Overview
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Brief Summary
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Global, Post-Market, Prospective, Multi-Center, Randomized Controlled Trial of the VenaSeal™ Closure System vs. Surgical Stripping or Endothermal Ablation (ETA) for the Treatment of Early and Advanced Stage Superficial Venous Disease

Detailed Description
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The study is designed with two randomized studies and one single arm study. Two randomized studies are for CEAP 2-5 subjects: VenaSeal vs. Surgical Stripping Study (outside of the United States only) VenaSeal vs. ETA Study The single arm study is for CEAP 6 subjects with active venous leg ulcers (VLU): 1. VLU Study

Official Title
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Global, Post-Market, Prospective, Multi-Center, Randomized Controlled Trial of the VenaSeal™ Closure System vs. Surgical Stripping or Endothermal Ablation (ETA) for the Treatment of Early & Advanced Stage Superficial Venous Disease

Conditions
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Venous Reflux

Intervention / Treatment
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* Device: VenaSeal™ Closure System
* Device: Endothermal Ablation (ETA)
* Procedure: Surgical Stripping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is ≥18 years of age Patient has venous reflux in superficial truncal vein(s) (e.g., GSV, SSV, accessory saphenous veins) with CEAP 2 (symptomatic) or CEAP 3, 4a, 4b, 5, 6, appropriate for treatment, as confirmed by DUS Eligibility for treatment: VenaSeal vs ETA Study: Patient is eligible for treatment with the VenaSeal™ system and ETA VenaSeal vs Surgical Stripping Study: Patient is eligible for treatment with the VenaSeal™ system and surgical stripping VLU Study: patients should be eligible for treatment with the VenaSeal™ system Treatable refluxing segment of target vein(s) 10 cm in length or longer Patient has a target vein diameter of ≥3 mm throughout the intended treated segment of the target vein as measured by DUS while patient is standing Patient is willing and capable of complying with specified follow-up evaluations at the specified times Patient has an ability to understand the requirements of the study and to provide informed consent Exclusion Criteria: Patient has a known history of allergic sensitivities (including but not limited to cyanoacrylate adhesives), or any other condition, which in the opinion of the investigator may make the patient more susceptible to cyanoacrylate adhesive hypersensitivity Patient has known deep vein obstruction in the target limb, as identified by the site's standard of care Patient has abnormal pulse exam or ABI <0.8 Patient has acute superficial thrombophlebitis Patient requires any non-target vein treatments in the contralateral or ipsilateral limb, or any other surgical procedure up tp 30 days pre-procedure and through 3 months post-procedure Patient has any co-morbid conditions, which in the investigator's opinion may interfere with the patient's compliance with study visits and procedures, or may confound interpretation of study data (e.g., congestive heart failure Class III and IV, non-ambulatory patients, severe hepatic dysfunction, life expectancy < 1 year) IFU contraindications: VenaSeal vs. ETA Study: Patient has VenaSeal™ system and/or ETA product's IFU contraindication(s) VenaSeal vs Surgical Stripping Study: Patient has surgical stripping and/or VenaSeal™ system IFU contraindication(s) VLU Study: Patient has VenaSeal™ system IFU contraindication(s) Patient is non-ambulatory Patient is a female of childbearing potential who may be pregnant or breastfeeding at the time of the index procedure Patient belongs to a vulnerable population per investigator's judgment or patient has any kind of disorder that compromises his/her ability to give written informed consent and/or to comply with study procedures Patient is currently participating in an investigational drug or device study when the data collected could be conflicting or biased due to participation in another study Patient has documented COVID-19 infection currently or within the past 3 months. Patient is not completely recovered from past COVID-19 infection, per physician's discretion. VLU Study: Patient has target ulceration identified to be of non-venous etiology, as confirmed by the independent core laboratory VLU Study: Patient has target circumferential ulceration that cannot be captured in a single photograph (any ulcer curvature around the leg that goes out of sight)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VenaSeal™ Closure System<br>CEAP 2-5 subjects will be randomized to VenaSeal™ Closure System vs. ETA or Surgical Stripping | Device: VenaSeal™ Closure System<br>* The VenaSeal™ closure system is the non-tumescent, non-thermal, non-sclerosant device that uses a proprietary medical adhesive delivered endovenously to close the vein.<br>|
| Active Comparator: Endothermal Ablation (ETA)<br>CEAP 2-5 subjects will be randomized to either VenaSeal™ Closure System or ETA | Device: Endothermal Ablation (ETA)<br>* ETA includes EVLA that uses laser or RFA that uses radiofrequency heating to close the vein. Heat is applied in both EVLA and RFA therapies to close the vein. Subject can be treated with either EVLA or RFA if randomized to ETA arm per site's standard practice.<br>* Other names: Radiofrequency ablation (RFA);|
| Active Comparator: Surgical Stripping<br>CEAP 2-5 subjects will be randomized to either VenaSeal™ Closure System or surgical stripping (outside of the United States only) | Procedure: Surgical Stripping<br>* Surgical stripping involves stripping (removal) of the diseased vein via surgical procedures.<br>|
| Other: VenaSeal™ Closure System VLU Study<br>CEAP 6 active leg ulcer subjects will not be randomized to a comparator, all subjects will be treated with VenaSeal™ Closure System | Device: VenaSeal™ Closure System<br>* The VenaSeal™ closure system is the non-tumescent, non-thermal, non-sclerosant device that uses a proprietary medical adhesive delivered endovenously to close the vein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous treatment satisfaction questionnaire-early (VenousTSQe)(For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) | Peri-procedural patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQe). | 30 days | 
| Venous treatment satisfaction questionnaire- status (VenousTSQs) (For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) | Patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQs). | 30 days | 
| Percentage of target vein treated (For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) | Elimination of clinically relevant superficial truncal disease in each target vein at the time of index procedure as measured by the percentage of target vein length successfully treated. | Index procedure | 
| Time to ulcer healing (For VLU study) | Time to ulcer healing, calculated through healing confirmation and verified by an independent core laboratory. | Index procedure through 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anatomic closure of the primary target superficial truncal vein | Measured via Duplex Ultrasound showing primary target vein closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm after VenaSeal™ system and ETA procedures, or the absence of refluxing or residual primary target vein after surgical stripping procedures. | 6 months | 
| Time to return to work |  | Through study completion, an average of 30 days | 
| Anatomic closure of primary target vein | Measured via Duplex Ultrasound showing primary target vein closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm after VenaSeal™ system and ETA procedures, or the absence of refluxing or residual primary target vein after surgical stripping procedures. | 30 days, and 12, 24, 36, 48 and 60 months (30 days and 12 months only for VenaSeal vs. Surgical Stripping Study) | 
| Anatomic closure of target vein | Measured via Duplex Ultrasound showing target vein closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm after VenaSeal™ system and ETA procedures, or the absence of refluxing or residual target vein after surgical stripping procedures. | 30 days, and 6, 12, 24, 36, 48 and 60 months (30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Technical success of each target vein | Measured via Duplex Ultrasound showing target vein (including primary target vein) closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm after VenaSeal™ system and ETA procedures, or the absence of refluxing or residual target vein after surgical stripping procedures. | Index procedure | 
| Reintervention of any target vein | Assessed via number of the target veins requiring retreatment. | Index procedure through 60 months (through 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Time to reintervention of any target vein |  | Index procedure through 60 months (through 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Adverse events (AEs) occurring in the target limb | Adverse events occurring in target limb, evaluated from index procedure through 12 months are hypersensitivity to VenaSeal™ adhesive, phlebitis, granuloma, endovenous glue induced thrombosis (EGIT) or endovenous heat induced thrombosis (EHIT), symptomatic deep vein thrombosis (DVT) events. | Index procedure through 12 months | 
| Additional adverse events | Additional adverse events that will be evaluated through 60 months are symptomatic pulmonary embolism (PE) and serious adverse events (SAEs). | Index procedure through 60 months (through 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Healthcare utilization measured by the number of each type of adjunctive treatment. |  | Index procedure through 12 months | 
| Healthcare utilization measured by number of healthcare resources and other health related resources utilized for target limb venous reflux disease |  | Index procedure through 60 months (30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Healthcare utilization measured by number of healthcare resources utilized for adverse events |  | Index procedure through 60 months (through 12 months for VenaSeal vs. Surgical Stripping Study) | 
| For VLU study only: Healthcare utilization measured by number of ulcer related healthcare resources utilized |  | Index procedure through 60 months | 
| Time to return to normal activities |  | Through study completion, an average of 30 days | 
| Intra-procedural and post-procedural pain | Determined by using numeric rating scale (NRS) with a scale of 0-10, with '0' indicating no pain and '10' indicating worst pain imaginable. | Index procedure, and 7 days and 30 days | 
| Change in venous disease symptoms compared to baseline measured by the revised Venous Clinical Severity Score (rVCSS) | rVCSS score ranges from 0 to 30, with higher score indicating severe venous disease. | 7 and 30 days, and at 6, 12, 24, 36, 48, and 60 months (7 and 30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Change in venous disease symptoms compared to baseline as measured by subject self-reporting symptoms |  | 7 and 30 days, and at 6, 12, 24, 36, 48, and 60 months (7 and 30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Change in Aberdeen Varicose Vein Questionnaire (AVVQ) score compared to baseline | The total score ranges from 0-100 points, with '0' point indicating the best quality of life and '100' points indicating worst quality of life. | 30 days, and 6, 12, 24, 36, 48, and 60 months (30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Change in EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L) compared to baseline | Items are scored on a 1-5 scale, 5 being a worse outcome. Each of the 5 dimensions are scored separately to obtain a 5-digit code which is converted into a standard value by country. Max & min values vary by country. | 30 days, and 6, 12, 24, 36, 48 and 60 months (30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Change in the 36-Item Short Form Health Survey (SF-36) compared to baseline | The total score ranges from 0 to 100, with higher scores indicating better general health perception. | 30 days, and 6 and 12 months | 
| Change in the Venous Dependent Quality of Life (VenousDQoL) compared to baseline | Measured by 0-5 and 0-7 point (there are two scales in this questionnaire) Likert scale with higher score indicating worst outcome. | 30 days, and 6, 12, 24, 36, 48, and 60 months (30 days, 6 and 12 months for VenaSeal vs. Surgical Stripping Study) | 
| Provider experience evaluating overall satisfaction with the procedure | Measured by a 5 point Likert scale ranging from 0-5, with 5 indicating the best outcome (extremely satisfied with the treatment). | Index procedure | 
| For VLU Study: Ulcer recurrence on the target limb |  | Following ulcer healing through 60 months | 
| For VLU study: Ulcer healing rate |  | Index procedure through 24 months or until ulcer healing has been confirmed | 
| For VLU Study: Ulcer-free time |  | Through 60 months | 
| For VLU Study: Venous treatment satisfaction questionnaire-early (VenousTSQe) | Peri-procedural patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQe). | 30 days | 
| For VLU Study: Venous treatment satisfaction questionnaire- status (VenousTSQs) | Patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQs). | 30 days | 
| For VLU Study: Percentage of target vein treated | Elimination of clinically relevant superficial truncal disease in each target vein at the time of index procedure as measured by the percentage of target vein length successfully treated. | Index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous reflux, Venous leg ulcer, Varicose Veins, Chronic Venous Insufficiency, VenaSeal, Endothermal Ablation, Surgical Stripping, Radiofrequency Ablation, Laser Ablation, Great Saphenous Vein, Small Saphenous Vein, Anterior Accessory Saphenous Vein