Self-expanding Nitinol Stents of High vs. Low Chronic Outward Force in De-novo Femoropopliteal Occlusive Arterial Lesions

Study Overview
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Brief Summary
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The objective of the BIOFLEX-COF trial is to investigate differences in formation of intimal hyperplasia at one and two years after implantation of nitinol-stents with high vs. low COF in de-novo femoropopliteal occlusive lesions in patients with symptomatic peripheral arterial disease. The BIOFLEX-COF trial is a prospective, randomized controlled trial. 80 subjects will be enrolled and randomly assigned to either a high COF group (LifeStent Vascular Stent) or low COF group (Pulsar).

Detailed Description
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Self-expanding nitinol stents must be oversized at least by a minimal amount to ensure contact with the vessel wall and prevent migration. Once the stent is deployed it exerts a continuous force upon the vascular wall, termed chronic outward force (COF). Data about COF and neointimal hyperplasia in humans are currently lacking. Some animal studies, though, found a markedly increased neointimal hyperplasia in stents with high oversizing and thus high COF. The objective of the BIOFLEX-COF trial is to investigate differences in formation of intimal hyperplasia at one and two years after implantation of nitinol-stents with high vs. low COF in de-novo femoropopliteal occlusive lesions in patients with symptomatic peripheral arterial disease. The BIOFLEX-COF trial is a prospective, randomized controlled trial. 80 subjects will be enrolled and randomly assigned to either a high COF group (LifeStent Vascular Stent) or low COF group (Pulsar). Diameter of implanted stents will be measured at every two millimetres along the stent axis on DICOM images of the respective completion angiography using image processing software. The scheduled time for recruitment is 2 years. There will be two follow-up evaluations at 12 and 24 months. Primary endpoint is the amount of in-stent neointima at one year, assessed by contrast-enhanced CT angiography (CTA). Secondary objectives are the amount of in-stent neointima at two years, device- and procedure-related adverse events and target lesion revascularisation (TLR) rate. In the control examinations stent diameter and true lumen diameter will be measured on DICOM images every two millimetres along the stent axis to quantify the relative amount of in-stent restenosis. The present study is challenging in that it compares two different self-expanding nitinol-stents head-to-head against each other. To optimize the power of this study, both clinical TLR and binary re-stenosis at Colour flow Doppler Ultrasound were dropped as primary endpoints. Instead the amount of neointima inside the stent accessed by CTA was selected as outcome parameter. The study differs further from similar previous trials in its generous inclusions criteria. This was done in effort to perform the trial on a patient sample that closely represents real-world patients of a specialised endovascular centre.

Official Title
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Self-expanding Nitinol Stents of High vs. Low Chronic Outward Force in De-novo Femoropopliteal Occlusive Arterial Lesions

Conditions
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Stent Restenosis, Intimal Hyperplasia

Intervention / Treatment
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* Device: Pulsar Stent
* Device: LifeStent Flexstar Vascular Stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient related: Subject (or their legal guardian) has read, understood and provided written informed consent, which has been reviewed and approved by the Institutional Review Board. At least 18 years of age. Male, infertile female or female participants of child bearing potential practicing an acceptable method of birth control with a negative pregnancy test within 7-days prior to study procedure. Projected life expectancy of greater than two years. The ability to comply with protocol follow-up requirements and required testing. Clinical: Lifestyle-limiting claudication or CLI (meeting angiographic entry criteria) affecting a lower extremity (Rutherford stages 2-5). Patients with Rutherford stage 2 are only eligible after unsuccessful conventional and/or medicamentous therapy. Resting ankle-brachial index (ABI) ≤ 0.8 in the study limb. Inflow lesion - if present - has been treated successfully (inflow treatment in same procedure permissible) Angiographic and Lesion Requirements (assessed intraoperatively): TASC A-D lesions from stenoses /occlusions ≤ 35cm. Popliteal artery is patent 5 cm proximal to the radiographic knee joint line. Reference diameter of 4.0 - 7.0 mm in proximal and distal treatment segments within the SFA. Patent SFA orifice (the proximal 5 mm after femoral bifurcation). At least one patent (<50% stenotic) inflow vessel present, proven angiographically. Study eligibility is given when inflow lesion has been treated successfully (inflow treatment in same procedure permissible). Successful treatment of inflow lesion is defined as <50% stenosis without death or severe vascular complication. At least one patent (<50% stenotic)tibial artery runoff to the ankle present, proven angiographically. Study eligibility is given when runoff vessel lesion has been treated successfully (inflow treatment in same procedure permissible). Successful treatment of inflow lesion is defined as <50% stenosis without death or severe vascular complication.Guidewire has successfully traversed lesion and is within the true lumen of the distal vessel. Exclusion Criteria: Pregnant and/or breast-feeding women. Lesion length > 35 cm. Flow-limiting occlusive disease of inflow and / or outflow arteries that cannot be treated sufficiently. Previous stenting or femoral bypass surgery in the target vessel. Clinical relevant aneurysmatic disease of the abdominal aorta, ipsilateral femoral arteries or arteries of the knee. Rutherford stage 0, 1 or 6 Non-atherosclerotic disease resulting in occlusion (e.g., embolism, Buerger's disease, vasculitis). Septicaemia. Ischemic stroke within the last three months. Any previously known coagulation disorder, including hypercoagulability Morbid obesity or operative scarring that precludes percutaneous approach (physician's discretion). Contraindication to anticoagulation or antiplatelet therapy. Known allergy to medication or contrast media used in this trial, if pre-treatment is not possible (physician's discretion). Known allergies to stent components (especially Nickel). Severe calcification of the target lesion. Current participation in another clinical research trial, that has not reached its primary endpoint. The patient is institutionalized based on a legal verdict.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: low COF-group<br>The low COF-group receives a thin-strut stent (Pulsar, Biotronik AG, Bülach, Switzerland) with minimal oversizing (according to manufacturer's Instructions For Use) | Device: Pulsar Stent<br>* Percutane transluminal stent angioplasty with a Pulsar Stent of the superficial femoral artery for the treatment of peripheral arterial occlusive disease.<br>|
| Active Comparator: high COF-group<br>The high COF-group receives a stiffer-stent (Lifestent Flexstar, Bard Peripheral Vascular Inc., Tempe, AZ, USA) with maximal oversizing (according to manufacturer's Instructions For Use). | Device: LifeStent Flexstar Vascular Stent<br>* Percutane transluminal stent angioplasty with a LifeStent Flexstar Vascular Stent of the superficial femoral artery for the treatment of peripheral arterial occlusive disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of in-stent restenosis | Mean amount of in-stent restenosis in percent along the stent axis at one and two years post-procedure. | one and two years post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events ISO 14155:2011 | Adverse Events ISO 14155:2011 | within two years post-procedure | 
| Target lesion revascularisation (TLR) | In patients with TLR the amount of in-stent restenosis will be assessed at the time of TLR. | within two years post-procedure |