Chronic Venous Insufficiency, Deep Vein Thrombosis, May-Thurner Syndrome
Conditions
Brief summary
This is a prospective, multi-center, single-arm, non-blinded clinical trial designed to investigate the safety and efficacy of the Vesper DUO Venous Stent System as compared to a pre-defined performance goal (PG) established from published, peer reviewed scientific literature related to stenting of iliofemoral venous outflow obstructions.
Interventions
DEVICEDuo Venous Stent System
Subjects with nonmalignant iliofemoral venous outflow obstruction presenting with nonthrombotic (NT), acute thrombotic (AT) or chronic postthrombotic (CPT) disease pathogenesis will be selected for study participation.
Sponsors
Vesper Medical, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or non-pregnant, non-breastfeeding females ≥18 years of age at the time of consent 2. Subject is able and willing to provide written informed consent prior to receiving any non-standard of care, protocol specific procedures 3. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to treatment and must use some form of contraception (abstinence is acceptable) throughout the time of clinical trial exit 4. Willing and capable of complying with all required follow-up visits 5. Estimated life expectancy ≥1 year 6. Subject is ambulatory (use of assistive walking device such as a cane or walker is acceptable) 7. Body mass index (BMI) \<40 8. Clinically significant symptomatic venous outflow obstruction in one iliofemoral venous segment (one limb) per subject, is indicated for venoplasty and stenting, and meets at least one of the following clinical indicators: 1. Clinical-Etiology-Anatomy-Pathophysiology (CEAP) score ≥3 2. Venous Clinical Severity Score (VCSS) pain score ≥2 3. Suspected deep vein thrombosis (DVT) with symptoms occurring prior to receiving a DUO Stent 9. Subject is willing and able to comply with PI recommendation for compression therapy, if required 10. Presence of unilateral, non-malignant venous obstruction of the common femoral vein (CFV), external iliac vein (EIV), common iliac vein (CIV), or any combination thereof, defined as a ≥50% reduction in target vessel lumen diameter and confirmed by venographic or IVUS imaging. The cranial point of the obstruction may extend to the iliac vein confluence of the inferior vena cava (IVC) and the caudal point may be 2mm above either the inflow of the deep femoral (or profunda) or the lesser trochanter, whichever is most cranial 11. Obstructive lesion(s) able to be treated with continuous stent coverage 12. Adequate inflow to the target lesion(s) involving at least a patent femoral or deep femoral vein and a landing zone in the CFV free from significant disease requiring treatment 13. Reference vessel diameter is of adequate size to accommodate the appropriate size stent as measured by IVUS 14. All vessels from insertion site through target vessel can accommodate a 9F or 10F sheath, depending on the stent size used 15. Ability to cross interventional devices through target lesion(s) 16. In DVT subjects, successful treatment of acute thrombus must have occurred prior to receiving any DUO Stents for an underlying obstructive lesion. Successful treatment of acute thrombus is defined as reestablishment of antegrade flow with ≤30% residual thrombus (confirmed by venogram or IVUS) and freedom from bleeding and symptomatic pulmonary embolism (confirmed by imaging). After successful treatment of thrombus is confirmed, eligible obstructive lesion(s) can be treated with a DUO Stent during the same procedure. 17. All subjects must undergo a SARS-CoV-2 test and have a negative test result within 8 days of the index procedure. If a SARS-CoV-2 test is unavailable due to institution policy, a test shortage, or if there is a delay in test results, the subject must complete the COVID-19 questionnaire and must have answered NO to all questions to be eligible for enrollment. A SARS-CoV-2 test will not be required for enrollment if a subject has received a complete cycle of an authorized COVID-19 vaccine or has documented evidence of a positive COVID-19 antibody test and is asymptomatic and has no long-lasting effects (per PI discretion) from a prior COVID-19 infection. 18. A measured temperature less than 99.5°F (37.5°C) on the day of the index procedure and no history of fever or feeling feverish within 14 days of the index procedure 19. No prior history, within 60 days of the index procedure, of a SARS-CoV-2 positive test, or COVID-19 symptoms
Exclusion criteria
1. Target limb symptoms caused by peripheral arterial disease 2. Presence of unresolved significant pulmonary embolism prior to use of the DUO Venous Stent System confirmed by chest CT. If subject has documented history of significant pulmonary embolism within the last 6 months, a chest CT is required to confirm significant pulmonary embolism is not currently present. 3. Presence of IVC obstruction or target venous obstruction that extends into the IVC 4. Presence of acute DVT located outside target limb 5. Contralateral venous occlusive disease of the CFV, EIV, and/or CIV, with planned treatment ≤390 days after the index procedure 6. Uncontrolled or active coagulopathy or known, uncorrectable bleeding diathesis 7. Coagulopathy causing INR \>2 which is not amenable to medical treatment 8. Platelet count \<50,000 cells/mm3 or \>1,000,000 cells/mm3 and/or White blood cell (WBC) \<3,000 cells/mm3 or \>12,500 cells/mm3 9. Uncorrected hemoglobin of ≤9 g/dL 10. Subject is on dialysis or has an estimated glomerular filtration rate (eGFR) \<30 mL/min. In subjects with diabetes mellitus, eGFR \<45 mL/min. 11. History of Heparin Induced Thrombocytopenia 12. Presence of known aggressive clotting disorders such as Lupus Anticoagulant Disorder, Antiphospholipid antibody syndrome, homozygous gene Factor V Leiden or Prothrombin gene abnormalities, Protein C and S deficiency or Antithrombin deficiency 13. Known hypersensitivity or contraindication to antiplatelet therapy or anticoagulation, nickel, or titanium 14. Contrast agent allergy that cannot be managed adequately with pre-medication 15. Intended concurrent adjuvant procedure (except for venoplasty) such as creation of temporary arteriovenous fistula, femoral endovenectomy or saphenous vein ablation and/or saphenous vein stripping during the index procedure 16. Subjects who have had any prior surgical or endovascular procedures to the target vessel. Note that subjects who have had successful catheter-directed or mechanical thrombolysis in the target vessel for DVT at least 90 days prior to the index procedure may be included 17. Planned surgical or interventional procedures of the target limb (except thrombolysis and/or thrombectomy in preparation for the procedure or vena cava filter placement prior to stent implantation in subjects at high risk for pulmonary embolism) within 30 days prior to or 30 days after the index procedure 18. Planned surgical or interventional procedures for other medical conditions (i.e., not associated with the target limb) 30 days prior to or 30 days after the index procedure 19. Previous venous stenting of the target limb, the IVC, or contralateral limb if stents extend into the IVC 20. Iliofemoral venous segment unsuitable for treatment with available sizes of DUO Stent implants 21. Lesions with intended treatment lengths extending into the IVC 22. No safe landing zone at or above the profunda femoral confluence 23. Participating in another investigational study in which the subject has not completed the primary endpoint(s) 24. Has other comorbidities that, in the opinion of the Investigator, would preclude them from receiving this treatment and/or participating in study-required follow-up assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Number of Participants Free From Major Adverse Events (MAEs) at 30 Days | 30 days | Freedom from major adverse events (MAEs) at 30 days post index procedure, as adjudicated by the Clinical Events Committee (CEC) or Core Laboratory, including: * Device or procedure-related death * Device or procedure-related bleed at the target vessel and/or the target lesion or at the access site requiring surgical or endovascular intervention or blood transfusion of ≥2 units * Device or procedure-related venous injury occurring in the target vessel and/or the target lesion or at the access site requiring surgical or endovascular intervention * Major amputation of the target limb * Clinically significant pulmonary embolism (PE), confirmed by CT angiography * Stent embolization outside of the target vessel * Presence of new thrombus within the stented segment requiring surgical or endovascular intervention |
| Efficacy - Number of Participants With Primary Patency of Stented Segment at 12 Months | 12 months | Primary patency of stented segment at 12 months defined as freedom from: * Duplex Ultrasound (DUS) core laboratory adjudicated occlusion or stenosis \>50% within the stented segment. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic intravascular ultrasound (IVUS) is required. * CEC adjudicated clinically driven target lesion reintervention (CD-TLR) defined as endovascular or surgical procedure for new, recurrent, or worsening symptoms and core lab adjudicated \>50% stenosis or occlusion within the stented segment confirmed by diagnostic IVUS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VCSS Pain Score and Changes in VCSS From Baseline in ITT Patients | 12 months | The Venous Clinical Severity Score (VCSS) system is a scoring system used to categorize nine attributes of venous disease. For this study, only the Pain Score was collected. The levels of pain severity ranged from 0 (none) to 3 (severe). |
| Number of ITT Subjects With Primary Assisted Patency at 12 Months | 12 months | Primary assisted patency is defined as freedom from DUS core laboratory adjudicated occlusion or stenosis \>50% within the stented segment following a reintervention due to a \>50% but \<100% stenosis. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic IVUS is required. |
| Number of ITT Subjects With Secondary Patency at 12 Months | 12 months | Secondary patency at 12 months defined as freedom from DUS core laboratory adjudicated occlusion or stenosis \>50% within the stented segment following a reintervention due to 100% occlusion. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic IVUS is required. |
Countries
Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duo Venous Stent System Use of the Duo Venous Stent System in the iliofemoral veins for the treatment of symptomatic venous outflow obstruction. | 162 |
| Total | 162 |
Baseline characteristics
| Characteristic | Duo Venous Stent System |
|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 15.8 |
| BMI | 30.1 kg/m^2 STANDARD_DEVIATION 5.7 |
| CEAP Clinical Assessment C0 (No visible or palpable signs of venous disease) | 2 Participants |
| CEAP Clinical Assessment C1 (Telangiectasia or reticular veins) | 1 Participants |
| CEAP Clinical Assessment C2r (Recurrent varicose veins) | 0 Participants |
| CEAP Clinical Assessment C2 (Varicose veins) | 1 Participants |
| CEAP Clinical Assessment C3 (Edema) | 107 Participants |
| CEAP Clinical Assessment C4a (Pigmentation or eczema) | 21 Participants |
| CEAP Clinical Assessment C4b (Lipodermatosclerosis or atrophie blanche) | 3 Participants |
| CEAP Clinical Assessment C4c (Corona phlebectatica) | 0 Participants |
| CEAP Clinical Assessment C4 (Changes in skin and subcutaneous tissue secondary to chronic venous disease) | 9 Participants |
| CEAP Clinical Assessment C5 (Healed) | 8 Participants |
| CEAP Clinical Assessment C6 (Active venous ulcer) | 9 Participants |
| CEAP Clinical Assessment C6r (Recurrent active venous ulcer) | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) White | 134 Participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 102 Participants |
| VCSS Pain 0 - none | 11 Participants |
| VCSS Pain 1 - mild (occasional, not restricting activity or requiring analgesics) | 24 Participants |
| VCSS Pain 2 - moderate (daily, moderate activity limitation, occasional analgesics) | 84 Participants |
| VCSS Pain 3 - severe (daily, severe limiting activities or requiring regular use of analgesics) | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 162 |
| other Total, other adverse events | 102 / 162 |
| serious Total, serious adverse events | 46 / 162 |
Outcome results
Primary
Efficacy - Number of Participants With Primary Patency of Stented Segment at 12 Months
Primary patency of stented segment at 12 months defined as freedom from: * Duplex Ultrasound (DUS) core laboratory adjudicated occlusion or stenosis \>50% within the stented segment. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic intravascular ultrasound (IVUS) is required. * CEC adjudicated clinically driven target lesion reintervention (CD-TLR) defined as endovascular or surgical procedure for new, recurrent, or worsening symptoms and core lab adjudicated \>50% stenosis or occlusion within the stented segment confirmed by diagnostic IVUS
Time frame: 12 months
Population: Of the 136 subjects that completed 12-month follow-up, 132 had data evaluable for the 12-month primary efficacy endpoint. The four subjects in question did not complete the 12-month DUS or had a non-diagnostic 12-month DUS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duo Venous Stent System | Efficacy - Number of Participants With Primary Patency of Stented Segment at 12 Months | 119 Participants |
Primary
Safety - Number of Participants Free From Major Adverse Events (MAEs) at 30 Days
Freedom from major adverse events (MAEs) at 30 days post index procedure, as adjudicated by the Clinical Events Committee (CEC) or Core Laboratory, including: * Device or procedure-related death * Device or procedure-related bleed at the target vessel and/or the target lesion or at the access site requiring surgical or endovascular intervention or blood transfusion of ≥2 units * Device or procedure-related venous injury occurring in the target vessel and/or the target lesion or at the access site requiring surgical or endovascular intervention * Major amputation of the target limb * Clinically significant pulmonary embolism (PE), confirmed by CT angiography * Stent embolization outside of the target vessel * Presence of new thrombus within the stented segment requiring surgical or endovascular intervention
Time frame: 30 days
Population: The number of evaluable subjects for the 30 day Primacy Safety Endpoint was 159.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duo Venous Stent System | Safety - Number of Participants Free From Major Adverse Events (MAEs) at 30 Days | 157 Participants |
Secondary
Number of ITT Subjects With Primary Assisted Patency at 12 Months
Primary assisted patency is defined as freedom from DUS core laboratory adjudicated occlusion or stenosis \>50% within the stented segment following a reintervention due to a \>50% but \<100% stenosis. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic IVUS is required.
Time frame: 12 months
Population: Primary Assisted Patency data is missing for 5/136 subjects that completed 12-month follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duo Venous Stent System | Number of ITT Subjects With Primary Assisted Patency at 12 Months | 124 Participants |
Secondary
Number of ITT Subjects With Secondary Patency at 12 Months
Secondary patency at 12 months defined as freedom from DUS core laboratory adjudicated occlusion or stenosis \>50% within the stented segment following a reintervention due to 100% occlusion. If DUS shows \>50% stenosis or occlusion, confirmation by diagnostic IVUS is required.
Time frame: 12 months
Population: Secondary Patency data is missing for 5/136 subjects that completed 12-month follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duo Venous Stent System | Number of ITT Subjects With Secondary Patency at 12 Months | 125 Participants |
Secondary
VCSS Pain Score and Changes in VCSS From Baseline in ITT Patients
The Venous Clinical Severity Score (VCSS) system is a scoring system used to categorize nine attributes of venous disease. For this study, only the Pain Score was collected. The levels of pain severity ranged from 0 (none) to 3 (severe).
Time frame: 12 months
Population: Although 136 subjects completed 12-month follow-up, two additional subjects completed 12-month telephone visits during which VCSS data was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duo Venous Stent System | VCSS Pain Score and Changes in VCSS From Baseline in ITT Patients | 2.0 score on a scale | Standard Deviation 0.8 |
| DUO Venous Stent System | VCSS Pain Score and Changes in VCSS From Baseline in ITT Patients | 0.5 score on a scale | Standard Deviation 0.8 |