VenaSeal Spectrum: Global Post-Market Randomized Controlled Trial

• ClinicalTrials.gov Identifier: NCT03820947
• Recruitment Status: Recruiting
• First Posted: January 29, 2019
• Last Update Posted: July 2, 2020
• Sponsor: Medtronic Endovascular
• Information provided by (Responsible Party): Medtronic Endovascular

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Venous Reflux	Device: VenaSeal™ Closure System; Device: Endothermal Ablation (ETA); Procedure: Surgical Stripping	Not Applicable

Detailed Description:

The study is designed with two randomized studies and one single arm study.

Two randomized studies are for CEAP 2-5 subjects:

1. VenaSeal vs. Surgical Stripping Study (outside of the United States only)
2. VenaSeal vs. ETA Study

The single arm study is for CEAP 6 subjects with active venous leg ulcers (VLU):

1. VLU Study

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 806 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 5, 2020
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: March 30, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: VenaSeal™ Closure System; CEAP 2-5 subjects will be randomized to VenaSeal™ Closure System vs. ETA or Surgical Stripping	Device: VenaSeal™ Closure System; 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.
Active Comparator: Endothermal Ablation (ETA); CEAP 2-5 subjects will be randomized to either VenaSeal™ Closure System or ETA	Device: Endothermal Ablation (ETA); 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.; Other Names: Endovenous laser ablation(EVLA); Radiofrequency ablation (RFA)
Active Comparator: Surgical Stripping; CEAP 2-5 subjects will be randomized to either VenaSeal™ Closure System or surgical stripping (outside of the United States only)	Procedure: Surgical Stripping; Surgical stripping involves stripping (removal) of the diseased vein via surgical procedures.
VenaSeal™ Closure System VLU Study; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Venous treatment satisfaction questionnaire-early (VenousTSQe)(For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) [ Time Frame: 30 days ]
   Peri-procedural patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQe).
2. Venous treatment satisfaction questionnaire- status (VenousTSQs) (For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) [ Time Frame: 30 days ]
   Patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQs).
3. Percentage of target vein treated (For Randomized studies, VenaSeal vs. ETA and VenaSeal vs. Surgical Stripping Study) [ Time Frame: Index procedure ]
   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.
4. Time to ulcer healing (For VLU study) [ Time Frame: Index procedure through 24 months ]
   Time to ulcer healing, calculated through healing confirmation and verified by an independent core laboratory.

Secondary Outcome Measures :

1. Anatomic closure of the primary target superficial truncal vein [ Time Frame: 6 months ]
   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.
2. Time to return to work [ Time Frame: Index procedure through 30 days ]
3. Anatomic closure of primary target vein [ Time Frame: 30 days, and 12, 24, 36, 48 and 60 months ]
   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.
4. Anatomic closure of target vein [ Time Frame: 30 days, and 6, 12, 24, 36, 48 and 60 months ]
   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.
5. Technical success of each target vein [ Time Frame: Index procedure ]
   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.
6. Reintervention of any target vein [ Time Frame: Index procedure through 60 months ]
   Assessed via number of the target veins requiring retreatment.
7. Time to reintervention of any target vein [ Time Frame: Index procedure through 60 months ]
8. Adverse events (AEs) occurring in the target limb [ Time Frame: Index procedure through 12 months ]
   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.
9. Additional adverse events [ Time Frame: Index procedure through 60 months ]
   Additional adverse events that will be evaluated through 60 months are symptomatic pulmonary embolism (PE) and serious adverse events (SAEs).
10. Number and type of adjunctive treatment conducted [ Time Frame: Index procedure through 12 months ]
11. Number of healthcare resources utilized for target limb venous reflux disease [ Time Frame: Index procedure through 60 months ]
12. Number of healthcare resources utilized for adverse events [ Time Frame: Index procedure through 60 months ]
13. For VLU study only: Number of ulcer related healthcare resources utilized [ Time Frame: Index procedure through 60 months ]
14. Time to return to normal activities [ Time Frame: Index procedure through 30 days ]
15. Intra-procedural and post-procedural pain [ Time Frame: Index procedure, and 7 days and 30 days ]
    Determined by using numeric rating scale (NRS) with a scale of 0-10, with '0' indicating no pain and '10' indicating worst pain imaginable.
16. Change in venous disease symptoms compared to baseline measured by the revised Venous Clinical Severity Score (rVCSS) [ Time Frame: 7 and 30 days, and at 6, 12, 24, 36, 48, and 60 months ]
    rVCSS score ranges from 0 to 30, with higher score indicating severe venous disease.
17. Change in venous disease symptoms compared to baseline as measured by subject self-reporting symptoms [ Time Frame: 7 and 30 days, and at 6, 12, 24, 36, 48, and 60 months ]
18. Change in Aberdeen Varicose Vein Questionnaire (AVVQ) score compared to baseline [ Time Frame: 30 days, and 6, 12, 24, 36, 48, and 60 months ]
    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.
19. Change in EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L) compared to baseline [ Time Frame: 30 days, and 6, 12, 24, 36, 48 and 60 months ]
    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.
20. Change in the 36-Item Short Form Health Survey (SF-36) compared to baseline [ Time Frame: 30 days, and 6 and 12 months ]
    The total score ranges from 0 to 100, with higher scores indicating better general health perception.
21. Provider experience evaluating overall satisfaction with the procedure [ Time Frame: Index procedure ]
    Measured by a 5 point Likert scale ranging from 0-5, with 5 indicating the best outcome (extremely satisfied with the treatment).
22. For VLU study: Ulcer healing rate [ Time Frame: Index procedure through 24 months or until ulcer healing has been confirmed ]
23. For VLU Study: Ulcer recurrence on the target limb [ Time Frame: Following ulcer healing through 60 months ]
24. For VLU Study: Ulcer-free time [ Time Frame: Through 60 months ]
25. For VLU Study: Venous treatment satisfaction questionnaire-early (VenousTSQe) [ Time Frame: 30 days ]
    Peri-procedural patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQe).
26. For VLU Study: Venous treatment satisfaction questionnaire- status (VenousTSQs) [ Time Frame: 30 days ]
    Patient satisfaction as measured by a validated, patient-centered venous treatment satisfaction questionnaire (VenousTSQs).
27. For VLU Study: Percentage of target vein treated [ Time Frame: Index procedure ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient is ≥18 years of age
2. 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

3. 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
4. Treatable refluxing segment of target vein(s) 10 cm in length or longer
5. 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
6. Patient is willing and capable of complying with specified follow-up evaluations at the specified times
7. Patient has an ability to understand the requirements of the study and to provide informed consent

Exclusion Criteria:

1. 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
2. Patient has known deep vein obstruction in the target limb, as identified by the site's standard of care
3. Patient has abnormal pulse exam or ABI <0.8
4. Patient has acute superficial thrombophlebitis
5. 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
6. 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)

7. 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)
8. Patient is non-ambulatory
9. Patient is a female of childbearing potential who may be pregnant or breastfeeding at the time of the index procedure
10. 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
11. 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
12. VLU Study: Patient has target ulceration identified to be of non-venous etiology, as confirmed by the independent core laboratory
13. 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)

Contacts and Locations

Contacts

Contact: Sara Ortiz; +1 7075432216; sara.o.ortiz@medtronic.com

Contact: Shital Patel; +1 7075413256; shital.r.patel@medtronic.com

Locations

United States, Washington

Lake Washington Vascular; Recruiting

Bellevue, Washington, United States, 98004-4623

Contact: Kathleen Gibson, MD

Contact: Kim Glorieux

Sponsors and Collaborators

Medtronic Endovascular

Investigators

• Principal Investigator: Kathleen Gibson; Lake Washington Vascular, US
• Principal Investigator: Manjit Gohel; Addenbrooke's Hospital, UK

More Information

• Responsible Party: Medtronic Endovascular
• ClinicalTrials.gov Identifier: NCT03820947
• Other Study ID Numbers: MDT18034
• First Posted: January 29, 2019
• Last Update Posted: July 2, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Medtronic Endovascular:

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