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

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

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.

Study Overview

• Status: Completed
• Conditions: Iliofemoral Venous Obstruction
• Intervention / Treatment: Device: Abre venous self-expanding stent system

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13915
    • Assistance Publique - Hopitaux de Marseille - Hopital Nord
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
• Germany
  • Aachen, Germany, D-52074
    • Universitätsklinikum Aachen
  • Arnsberg, Germany, D-59759
    • Klinikum Arnsberg, Karolinen Hospital
• Ireland
  • Galway, Ireland, H91 YR71
    • Galway University Hospitals - University Hospital Galway
• Italy
  • Modena, Italy, 41125
    • Hesperia Hospital
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's & St Thomas' NHS Foundation Trust - St Thomas' Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust - University College London Hospitals
• United States
  • California
    • Orange, California, United States, 92868
      • St. Joseph Hospital
  • Connecticut
    • Darien, Connecticut, United States, 06820
      • The Vascular Experts
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10029
      • The Mount Sinai Health System
    • Stony Brook, New York, United States, 11794
      • Stony Brook Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research
  • Ohio
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research Institute
  • Texas
    • McKinney, Texas, United States, 75069
      • Cardiac Center of Texas
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists
  • Washington
    • Bellevue, Washington, United States, 98004
      • Lake Washington Vascular, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is ≥ 18 and ≤ 80 years of age;

2. 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);
3. Patient is willing and capable of complying with specified follow-up evaluations at the specified times;
4. 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.
5. 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);

6. Patient has an obstructive lesion defined as:

   • Occluded, or
   • ≥50% in diameter reduction on venography or IVUS, or
   • ≥50% area reduction on IVUS
7. 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;
8. Target vessel can accommodate a 9 French Sheath, from insertion site to target segment;
9. Exchangeable guidewire must cross target lesion(s) with successful predilation.

Exclusion Criteria:

1. 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;
2. Patient has peripheral arterial disease causing symptoms in target limb;
3. Patient is pregnant, female patients of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure;
4. Patient has a known or suspected systemic infection at the time of the index procedure;
5. 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;
6. Patient requires femoral endovenectomy and patch venoplasty, greater saphenous vein ablation, and/or small saphenous vein stripping during the index procedure;
7. Patient has an active vasculitic inflammatory disorder (e.g. Behcet disease) predisposing the patient to thrombosis and requiring systemic corticosteroid therapy;
8. Patient has impaired renal function (GFR < 30) or is on dialysis;
9. 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;
10. Patient has a history of bleeding diathesis or either a history or presence of heparin induced thrombocytopenia antibodies;
11. Patient has a known hypersensitivity or contraindication to antiplatelets or anticoagulation, nitinol, or a contrast sensitivity that cannot be adequately pre-medicated;
12. 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);
13. 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;
14. Patient is currently participating in another investigational drug or device study or observational competitive study.
15. 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;
16. Patient has significant venous bleeding, arterial dissection or other injury requiring additional percutaneous or surgical intervention prior to enrollment;
17. Patient has a previously placed stent in the ipsilateral venous vasculature;
18. Patient has disease that precludes safe advancement of the venous stent to the target lesion(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abre; Abre Venous Self-expanding Stent System	Device: Abre venous self-expanding stent system; venous stent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medtronic Endovascular
• Investigators: Principal Investigator: Erin Murphy, MD, Carolinas Health Care System; Principal Investigator: Stephen Black, MD, Guy's and St Thomas' NHS Foundation Trust

Publications and helpful links

General Publications

• Murphy E, Gibson K, Sapoval M, Dexter DJ, Kolluri R, Razavi M, Black S. Pivotal Study Evaluating the Safety and Effectiveness of the Abre Venous Self-Expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction. Circ Cardiovasc Interv. 2022 Feb;15(2):e010960. doi: 10.1161/CIRCINTERVENTIONS.121.010960. Epub 2022 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): January 14, 2020
• Study Completion (Actual): January 28, 2022

Study Registration Dates

• First Submitted: January 28, 2017
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (Estimate): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: APV-ABRE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes