Clinical Investigation of Safety and Effectiveness for the enVVe® System

The TrAnscatheter Venous Valve Endoprosthesis Clinical Investigation of Safety and Effectiveness for the enVVe® System

A staged prospective, randomized, non-blinded, multicenter study.

The enVVe System is intended to treat insufficiency in the deep vein system by replacing the function of incompetent valves and to improve unidirectional flow within the deep system thereby decreasing venous hypertension within the lower extremity. The ability to improve venous insufficiency potentially affords the patient long-term relief from symptoms that are a direct result of venous reflux.

Reported data suggests, reduction of regurgitant volume decreases clinical symptoms of CVI including the incidence and occurrence of venous ulceration and edema and affords the patient improved quality of life.

By providing a functional lower extremity venous valve, the enVVe System is designed to provide an effective CVI treatment option for patients with severe deep venous disease (CEAP C4b to C6).

Inclusion Criteria:

1. Persistent symptoms with at least 3 months of routine care including compression therapy, pneumatic compression, and in C6 patients, wound care with FDA approved medications or dressing solutions

2. Axial deep reflux >1 sec. in the femoral vein (above the P1 segment) and popliteal vein

3. Primary or Secondary deep venous valvular incompetence

4. CEAP score: C4b, C4c, C5, or C6

5. Age ≥18 years

6. Ability to stand for duplex ultrasound

7. Ability to ambulate without assistance with appropriate heel to toe ambulation

8. Able to attend scheduled post-treatment follow-up visits

9. Absence of superficial reflux of the truncal vessels

10. BMI <40

11. Female patients of childbearing potential must:

    • have a negative pregnancy test at the screening visit or within 7 days of the index procedure, whichever is later,
    • not be breastfeeding or plan to breastfeed through completion of the study,
    • agree to use a medically acceptable method of preventing conception from the screening visit through completion of the study.

    Pre-implant Venography and Imaging Inclusion Criteria

12. Diameter of the Target Vein Zone of 7.5 mm - 11.5 mm (the diameter is the largest of proximal, mid, and distal sections of the Target Vein Zone measured with venography required prior to or during the procedure and IVUS performed during the procedure), as well as with Duplex Ultrasound imaging per Imaging Manual

13. Diameter of the popliteal vein must be ≥4.7 mm to accommodate a 14 Fr Introducer sheath

14. Planned placement of the enVVe Valve will not cover collateral veins

Exclusion Criteria:

1. Known hypercoagulable condition including Factor V Leiden deficiency (homozygote), Prothrombin gene Mutation (homozygote), Antithrombin 3 deficiency, Protein C deficiency, Protein S deficiency and Antiphospholipid antibody
2. Any active cancer or cancer within 6 months of remission (excluding non-melanoma skin cancer)
3. Previous surgical procedure or endovascular procedure in the Target Vein Zone in the target extremity (ipsilateral leg)
4. Acute Deep Venous Thrombosis (DVT) or pulmonary embolism (PE) within 30 days of the procedure
5. Arterial insufficiency demonstrated by an ABI <0.71 within 6 months
6. Patients with primary Lymphedema Praecox or Tarda
7. Superficial ablation ≤ 3 months of the procedure
8. Unable to lie prone on the table
9. Major surgery or prolonged hospitalization within 8 weeks of the procedure
10. Patients with recurrent congestive heart failure (NYHA stage III)
11. Patients with chronic narcotic or other drug use for chronic pain other than treatment for their CVI, or a history of substance (e.g. drug, alcohol) abuse
12. Uncontrolled diabetes mellitus; A1C levels >13, toxic thyroidism, Tuberculosis (TB), neoplasm, sepsis, blood dyscrasias or acute respiratory or skin disease
13. Immobilization or inability to ambulate or with muscle wasting of the target extremity (ipsilateral leg). Unable to perform a heal/toe movement when walking
14. Contraindication for anticoagulation or unwillingness to comply with long-term anticoagulation regimen (Heparin, low molecular weight (LMW) heparin by injection twice a day for 30 days, direct oral anticoagulation (DOAC) such as Xarelto or Eliquis for 5 years, Clopidogrel daily for at least 6 months)
15. Contraindication for contrast injection procedures (contrast allergy that cannot be medically managed, renal insufficiency/chronic kidney disease with potentially worsening renal function) and when CO2 imaging is not an option or unavailable
16. Known nitinol sensitivity/ nickel sensitivity/ porcine tissue sensitivity or polyethylene terephthalate (PET) sensitivity
17. Active superficial thrombophlebitis
18. Thrombocytosis / platelets > 1 million
19. Patients that will not allow needed blood and/or blood products (e.g., transfusion)
20. Patients that have placement of stents within the ipsilateral femoral or popliteal veins
21. Patients who have had balloon angioplasty of the ipsilateral femoral or popliteal veins within the past 6 months or are clinically determined to require such a procedure imminently. (waiting period of 6 months following balloon angioplasty is required)
22. Adults who lack the capacity to provide informed consent
23. Patients with life expectancy <5 year due to illness/cancer
24. Patients on renal dialysis
25. Patients with previously implanted VenoValve in the ipsilateral or contralateral extremity
26. Venous outflow obstruction of the iliac vein of > 60% (waiting period of 3 months following iliac vein stenting)
27. Extensive infrainguinal obstruction of the deep venous system or Common Femoral Vein (CFV)
28. Tortuous anatomy that precludes use of the enVVe System
29. Non dominant femoral vein with significant competing flow in the collaterals
30. Large competitive flow through the profunda vein near the confluence of the popliteal vein
31. Any organ transplant, excluding ophthalmic related transplants
32. Patients who are currently using any non-FDA-approved medication for the treatment of venous disease (e.g., venoactive drugs, compounds or supplements such as purified flavonoid fractions like diosmin and hesperidin)
33. rVCSS scores of ≤ 7 at baseline