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

• ClinicalTrials.gov Identifier: NCT03038438
• Recruitment Status: Completed
• First Posted: January 31, 2017
• Results First Posted: March 8, 2021
• Last Update Posted: November 8, 2022
• Sponsor: Medtronic Endovascular
• Information provided by (Responsible Party): Medtronic Endovascular

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Iliofemoral Venous Obstruction	Device: Abre venous self-expanding stent system	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 260 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 13, 2017
• Actual Primary Completion Date: January 14, 2020
• Actual Study Completion Date: January 28, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Primary Patency [ Time Frame: 12 Months ]
   Freedom from occlusion of the stented segment; Freedom from restenosis >=50%; and Freedom from clinically-driven target lesion revascularization
2. Composite Major Adverse Events [ Time Frame: 30 Days ]

   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

Secondary Outcome Measures :

1. Device Success [ Time Frame: Index Procedure ]
   Successful delivery and deployment of the stent and removal of the delivery system during the index procedure. Stent based outcome measure.
2. Lesion Success Obtained at Index Procedure [ Time Frame: Index Procedure ]
   Venographic evidence of <50% residual stenosis of the stented segment of the target lesion after post-dilation.
3. Index Procedure Success [ Time Frame: 30 days ]
   Lesion success without procedure-related MAEs prior to hospital discharge
4. Primary Patency [ Time Frame: 24 Months, 36 Months ]

   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.
5. Primary Assisted Patency [ Time Frame: 12 Months, 24 Months, 36 Months ]
   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.)
6. Secondary Patency [ Time Frame: 12 Months, 24 Months, 36 Months ]
   Secondary patency is defined as patency of the stented segment of the target lesion after subsequent intervention for an occlusion.
7. Stent Fracture [ Time Frame: 30 Days, 12 Months, 24 Months, 36 Months ]
   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.
8. Target Lesion Revascularization [ Time Frame: 30 days, 6 months, 12 months, 24 months, 36 months ]
   Percentage of subjects with target lesion revascularization through 30 days, 180 days, 360 days, 720, and 1080 days.
9. Delayed Stent Migration [ Time Frame: 12 Months, 24 Months, 36 Months ]
   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.
10. Major Adverse Events [ Time Frame: 6 Months, 12 Months, 24 Months, 36 Months ]
    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.
11. Major Bleeding Related to Index Procedure [ Time Frame: 30 Days, 6 Months, 12 Months, 24 Months, 36 Months ]
    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.
12. Re-Hospitalization [ Time Frame: 0-180, 181-360, 361-720, 721-1080 and 0-1080 days ]
    Number of subjects that were re-hospitalized due to their target lesion from the Index Procedure.
13. Villalta Score [ Time Frame: Baseline to 6 Months, 12 Months, 24 Months, 36 Months ]

    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.

14. Venous Clinical Severity Score (VCSS) [ Time Frame: Baseline to 6 Months, 12 Months, 24 Months, 36 Months ]

    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.

15. EuroQol-5 Dimension (EQ-5D) Score [ Time Frame: Baseline to 6 Months, 12 Months, 24 Months, 36 Months ]

    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.

16. Venous Insufficiency Epidemiological and Economic Study (VEINES) - Quality of Life/Symptoms (QOL/Sym) Score [ Time Frame: Change from Baseline to 6 Months, 12 Months, 24 Months, 36 Months ]

    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, California

St. Joseph Hospital

Orange, California, United States, 92868

United States, Connecticut

The Vascular Experts

Darien, Connecticut, United States, 06820

United States, Georgia

Piedmont Atlanta Hospital

Atlanta, Georgia, United States, 30309

United States, Michigan

University of Michigan Health System

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55902

United States, New Jersey

Holy Name Medical Center

Teaneck, New Jersey, United States, 07666

United States, New York

Albany Medical Center

Albany, New York, United States, 12208

NYU Langone Medical Center

New York, New York, United States, 10016

The Mount Sinai Health System

New York, New York, United States, 10029

Stony Brook Medicine

Stony Brook, New York, United States, 11794

United States, North Carolina

Carolinas Medical Center

Charlotte, North Carolina, United States, 28203

NC Heart and Vascular Research

Raleigh, North Carolina, United States, 27607

United States, Ohio

OhioHealth Research Institute

Columbus, Ohio, United States, 43214

United States, Texas

Cardiac Center of Texas

McKinney, Texas, United States, 75069

United States, Virginia

Sentara Vascular Specialists

Norfolk, Virginia, United States, 23507

United States, Washington

Lake Washington Vascular, PLLC

Bellevue, Washington, United States, 98004

France

Assistance Publique - Hôpitaux de Marseille - Hôpital Nord

Marseille, France, 13915

Hôpital Européen Georges Pompidou

Paris, France, 75015

Germany

Universitätsklinikum Aachen

Aachen, Germany, D-52074

Klinikum Arnsberg, Karolinen Hospital

Arnsberg, Germany, D-59759

Ireland

Galway University Hospitals - University Hospital Galway

Galway, Ireland, H91 YR71

Italy

Hesperia Hospital

Modena, Italy, 41125

United Kingdom

University College London Hospitals NHS Foundation Trust - University College London Hospitals

London, United Kingdom, NW1 2PG

Guy's & St Thomas' NHS Foundation Trust - St Thomas' Hospital

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

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

  Study Documents (Full-Text)

Documents provided by Medtronic Endovascular:

Study Protocol  [PDF] March 2, 2021

Statistical Analysis Plan  [PDF] February 14, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Medtronic Endovascular
• ClinicalTrials.gov Identifier: NCT03038438
• Other Study ID Numbers: APV-ABRE
• First Posted: January 31, 2017
• Results First Posted: March 8, 2021
• Last Update Posted: November 8, 2022
• Last Verified: October 2022

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