ABRE Clinical Study of the Abre Venous Self-expanding Stent System

Study Overview
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Brief Summary
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Evaluate the safety and effectiveness of the Abre venous self-expanding stent system for treatment of symptomatic iliofemoral venous outflow obstruction in patients with venous occlusive disease.

Official Title
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A Multi-center, Non-randomized Study to Evaluate the Safety and Effectiveness of the Abre Venous Self-expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction

Conditions
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Iliofemoral Venous Obstruction

Intervention / Treatment
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* Device: Abre venous self-expanding stent system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is ≥ 18 and ≤ 80 years of age; Patient has at least one of the following clinical manifestations (i.e. symptoms and/or signs) of venous disease in lower extremity: CEAP score ≥ 3 Venous Clinical Severity Score pain score (VCSS) ≥2 Suspected deep vein thrombosis (DVT); Patient is willing and capable of complying with specified follow-up evaluations at the specified times; Patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the appropriate Ethics Board. Patient has diagnosis of non-malignant venous obstruction within the common iliac, external iliac, and/or common femoral vein. The proximal point of the obstruction may extend to the iliac venous confluence of the inferior vena cava and the distal point may be at or above the deep femoral vein. Diagnosis must be made based on objective imaging by using venography and/or intravascular ultrasound (IVUS); Patient has an obstructive lesion defined as: Occluded, or ≥50% in diameter reduction on venography or IVUS, or ≥50% area reduction on IVUS Acute DVT patients should be treated with the Abre stent within 14 days after onset of symptoms. Patients with acute DVT must first undergo successful treatment of acute thrombus by catheter based techniques; successful treatment is defined as 30% or less residual thrombus by venogram, as determined by physician, no bleeding, no symptomatic pulmonary embolism (confirmed by imaging), and no renal compromise (renal compromise defined as GFR>30). Patients with underlying obstructive lesions can then be included in the study within the same procedure; Target vessel can accommodate a 9 French Sheath, from insertion site to target segment; Exchangeable guidewire must cross target lesion(s) with successful predilation. Exclusion Criteria: Patient with DVT in the target limb of which the onset of symptoms is between 15 days and 6 months prior to planned treatment or patient has an acute DVT anywhere else than in the target vessel; Patient has peripheral arterial disease causing symptoms in target limb; Patient is pregnant, female patients of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure; Patient has a known or suspected systemic infection at the time of the index procedure; Patient has a planned percutaneous or surgical intervention within 30 days prior or 30 days following index procedure, or a contralateral iliofemoral lesion requiring planned treatment within 12 months; Patient requires femoral endovenectomy and patch venoplasty, greater saphenous vein ablation, and/or small saphenous vein stripping during the index procedure; Patient has an active vasculitic inflammatory disorder (e.g. Behcet disease) predisposing the patient to thrombosis and requiring systemic corticosteroid therapy; Patient has impaired renal function (GFR < 30) or is on dialysis; Patient has a platelet count < 50,000 cells/mm3 or > 1,000,000 cells/mm3 and/or a White Blood Cell count < 3,000 cells/mm3 or > 12,500 cells/mm3; Patient has a history of bleeding diathesis or either a history or presence of heparin induced thrombocytopenia antibodies; Patient has a known hypersensitivity or contraindication to antiplatelets or anticoagulation, nitinol, or a contrast sensitivity that cannot be adequately pre-medicated; Patient has presence of other severe 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); 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 must be able to consent for themselves; Patient is currently participating in another investigational drug or device study or observational competitive study. Patient has a vena cava obstruction or lesion extending into the inferior vena cava (IVC), or the presence of bilateral iliofemoral venous lesions requiring planned treatment within 12 months; Patient has significant venous bleeding, arterial dissection or other injury requiring additional percutaneous or surgical intervention prior to enrollment; Patient has a previously placed stent in the ipsilateral venous vasculature; Patient has disease that precludes safe advancement of the venous stent to the target lesion(s)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abre<br>Abre Venous Self-expanding Stent System | Device: Abre venous self-expanding stent system<br>* venous stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency | Freedom from occlusion of the stented segment; Freedom from restenosis >=50%; and Freedom from clinically-driven target lesion revascularization | 12 Months | 
| Composite Major Adverse Events | The components of the Major Adverse Events include: All-cause death occurring post-procedure, clinically-significant pulmonary embolism, major bleeding complication, stent thrombosis, and stent migration | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success | Successful delivery and deployment of the stent and removal of the delivery system during the index procedure. Stent based outcome measure. | Index Procedure | 
| Lesion Success Obtained at Index Procedure | Venographic evidence of <50% residual stenosis of the stented segment of the target lesion after post-dilation. | Index Procedure | 
| Index Procedure Success | Lesion success without procedure-related MAEs prior to hospital discharge | 30 days | 
| Primary Patency | Primary Patency: Defined as meeting all of the following criteria: Freedom from occlusion of the stented segment of the target lesion; Freedom from restenosis ≥50% of the stented segment of the target lesion; Freedom from clinically driven target lesion revascularization. | 24 Months, 36 Months | 
| Primary Assisted Patency | Uninterrupted patency of the stented segment of the target lesion with a secondary intervention, also known as an adjunctive treatment (e.g. balloon venoplasty, subsequent stenting, etc.) | 12 Months, 24 Months, 36 Months | 
| Secondary Patency | Secondary patency is defined as patency of the stented segment of the target lesion after subsequent intervention for an occlusion. | 12 Months, 24 Months, 36 Months | 
| Stent Fracture | X-ray for the 30-day visit was only required on the first 30 subjects. Stent Fracture within 12, 24, and 36 months included subjects who had scheduled visit-based evaluable imaging and unscheduled imaging up to day 420, 780, and 1080, respectively. | 30 Days, 12 Months, 24 Months, 36 Months | 
| Target Lesion Revascularization | Percentage of subjects with target lesion revascularization through 30 days, 180 days, 360 days, 720, and 1080 days. | 30 days, 6 months, 12 months, 24 months, 36 months | 
| Delayed Stent Migration | Delayed Stent Migration within 12, 24, and 36 months included subjects who had scheduled visit-based evaluable imaging and unscheduled imaging up to day 420, 780, and 1140, respectively. | 12 Months, 24 Months, 36 Months | 
| Major Adverse Events | Safety endpoints (MAE, TLR, and Major Bleeding) included subjects with an event or without an event but follow-up days have reached 150 days for 6-month, 330 days for 12-month, 690 days for 24-month, and 1050 days for 36-month visit. | 6 Months, 12 Months, 24 Months, 36 Months | 
| Major Bleeding Related to Index Procedure | A blood loss leading to transfusion of whole blood or red cells provided hemoglobin drop of 3 g/dL (1.86 mmol/L) or more post-index procedure is related to bleeding occurring during the index procedure. | 30 Days, 6 Months, 12 Months, 24 Months, 36 Months | 
| Re-Hospitalization | Number of subjects that were re-hospitalized due to their target lesion from the Index Procedure. | 0-180, 181-360, 361-720, 721-1080 and 0-1080 days | 
| Villalta Score | Villalta scores categorize the severity of post-thrombotic syndrome (PTS). Higher score indicates increasing severity of PTS. A score of greater or equal to 5 indicates PTS. PTS severity: total score of 5 to 9, mild PTS; score of 10 to 14, moderate PTS; and score of greater or equal to 15 or venous ulcer present, severe PTS. Change in Villalta scores were calculated as the Follow-up score minus the Baseline score (6, 12, 24, or 36 months). A negative change is associated with improved outcome. | Baseline to 6 Months, 12 Months, 24 Months, 36 Months | 
| Venous Clinical Severity Score (VCSS) | VCSS scores range from 0=no disease to 30=severe disease. Change in VCSS score was calculated as the Follow-up score minus the Baseline score. A negative change is associated with improved outcome. | Baseline to 6 Months, 12 Months, 24 Months, 36 Months | 
| EuroQol-5 Dimension (EQ-5D) Score | Higher score indicates a better quality of life. The questionnaire contains five dimensions where scores rank from 1 (best) to 5 (worst) plus a visual analog scale (VAS) (0 = worst health; 100 = best health). A positive change is associated with improved outcome. Change in EQ-5D scores were calculated as the Follow-up score minus the Baseline score (6, 12, 24, and 24 months) for both the index and VAS scores. | Baseline to 6 Months, 12 Months, 24 Months, 36 Months | 
| Venous Insufficiency Epidemiological and Economic Study (VEINES) - Quality of Life/Symptoms (QOL/Sym) Score | Venous Insufficiency Epidemiological and Economic Study (VEINES) - Quality of Life/Symptoms (QOL/Sym). Higher scores correlate to better quality of life on a scale of 1-100. Change in VEINES QOL/Sym scores were calculated as the Follow-up score minus the Baseline score (6, 12, 24, or 36 months). A positive change is associated with improved outcome. | Change from Baseline to 6 Months, 12 Months, 24 Months, 36 Months |