PTA and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

Study Overview
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Brief Summary
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The purpose of this study is to investigate the performance of paclitaxel-coated balloon expandable stainless steel coronary stent for the treatment of infrapopliteal stenoses and occlusions in patients with critical limb ischemia compared to percutaneous transluminal balloon angioplasty (PTA).

Detailed Description
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Critical limb ischemia (CLI) is a serious condition that is becoming more and more common in the western world due to the growing percentage of elderly in the population and the rising incidence of diabetes. In about 40% of patients a stenosis or occlusion in the arteries below the level of the knee will be present. Restoration of blood flow is imperative to allow pain relief and tissue healing. Without revascularization patients with CLI are at risk for limb loss and potentially fatal complications such as sepsis. In patients treated with percutaneous transluminal balloon angioplasty (PTA)significant restenosis is found in approximately 50% after 6 months. In interventional cardiology a significant reduction in restenosis rates in coronary arteries has been found using drug eluting stents (DES), including the paclitaxel eluting stent (TAXUS, Boston Scientific). DES locally deliver drugs (e.g. paclitaxel) that interfere with the restenosis process. Using DES in treating below the knee (infrapopliteal) arterial lesions in patients with CLI may improve patency and clinical outcome. Comparison: Treatment of below the knee arterial lesions in patients with CLI with PTA and DES compared to only PTA.

Official Title
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Percutaneous Transluminal Balloon Angioplasty (PTA) and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

Conditions
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Peripheral Vascular Disease

Intervention / Treatment
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* Device: PTA with placement of paclitaxel-eluting stent
* Device: PTA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age > 18 years If female patient with child bearing potential, patient may not be pregnant at the study entry and must utilize reliable birth control for the duration of her participation into the study Patient is willing and able to comply with the specified follow-up evaluation Critical Limb Ischaemia, this is Fontaine stage III (ischaemic rest pain) and IV (ischaemic ulcers or gangrene) or Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss) or 6 (major tissue loss) Stenotic (>50% luminal loss) or occluded infrapopliteal artery, including the tibiofibular trunk, the anterior tibial artery, the posterior tibial artery and the peroneal artery, with a lesion length ≤ 60 mm Artery to be treated with a diameter more tham or equal to 2mm and less than or equal to 4mm Patent common iliac, external iliac, superficial femoral and popliteal artery on the ipsilateral side prior to randomisation, possibly after treatment during the same session At least one patent crural (anterior tibial, posterior tibial or peroneal) artery with expected unobstructed runoff to ankle level after treatment Exclusion Criteria: Acute limb ischaemia Subacute limb ischaemia which requires thrombolysis as first treatment modality Active bleeding or bleeding diathesis Recent (less than 3 months) hemorrhagic stroke or other any other CNS abnormality with increased risk of haemorrhage, such as intracranial neoplasm, arteriovenous malformation, intracranial aneurysm or aneurysm repair Gastrointestinal or genitourinary bleeding of clinical significance within the previous 6 weeks before treatment Aneurysm in common femoral, superficial femoral or popliteal artery on the ipsilateral side Revascularization involving the same limb within 30 days prior to the index procedure or planned revascularization of the same limb within 30 days of the index procedure Previous implanted stent at the index site Life expectancy of less than 6 months or other factors making clinical follow-up difficult Known allergy to acetylsalicylic acid (aspirin), clopidogrel, heparin or paclitaxel Known allergy to contrast media Known heparin induced thrombocytopenia (HIT type 2) Patient unable or unwilling to tolerate anticoagulant, anti-platelet therapy or contrast media Creatinine clearance < 20 ml/min (as derived from Cockcroft-Gault or MDRD formula)unless patient is on hemodialysis Aneurysm in common femoral, superficial femoral or popliteal artery on the ipsilateral side Severely calcified lesions with expected resistance to stenting Poor inflow due to ipsilateral stenoses or occlusions of the iliac or femoropopliteal arteries that cannot be treated during the same session Significant vessel tortuosity or other parameters prohibiting access to the lesions and/or delivery of the stent Patients without (expected) distal runoff to the index site Previous implanted stent at the index site

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 |
| --- | --- |
| Experimental: 1<br>PTA with primary placement of Drug (paclitaxel) Eluting Stent | Device: PTA with placement of paclitaxel-eluting stent<br>* PTA with placement of paclitaxel-eluting stent<br>|
| Active Comparator: 2<br>PTA | Device: PTA<br>* PTA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be primary patency of the treated site at 6 months. Primary patency is defined as <50% loss of luminal diameter at the treated site on CT arteriography (CTA) without re-intervention in the interim. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary patency of the treated sites at 3, 6 and 12 months after intervention assessed by duplex sonography (binary patency, <50% stenosis defined as PSV ratio <2.0) |  | 3, 6, 12 months | 
| Clinical evaluation of the treated ischemic leg at 3, 6 and 12 months. |  | 3, 6, 12 months | 
| Major amputation (at or above the ankle) of the trial leg at 3, 6 and 12 months |  | 3, 6, 12 months | 
| Minor amputation (below the ankle excluding the toes) of the trial leg at 3, 6 and 12 months. |  | 3, 6, 12 months | 
| Infrapopliteal surgical bypass of the trial leg at 3, 6 and 12 months. |  | 3, 6, 12 months | 
| Infrapopliteal endovascular re-intervention of the trial leg at 3, 6 and 12 months. |  | 3, 6, 12 months | 
| Peri-procedural (within 30 days) complications. |  | 30 days | 
| Death. |  | 3, 6, 12 months | 
| Clinical assessment primarily by Rutherford score for peripheral arterial disease | Clinical assessment outpatient clinic | 2, 3, 4 and 5 years after treatment | 
| Target lesion patency by means of duplex sonography | During outpatient clinic visits | 2, 3, 4 and 5 years after treatment | 
| Major amputation (at or above the ankle) of treated limb | Assessment up to 5 years after treatment during outpatient clinic visits From 5 to 10 years by means of yearly evaluation of patient charts | yearly up to 10 years after treatment | 
| Minor amputation (below the ankle excluding the toes) of the trial leg at 3, 6 and 12 months. | From 2 to 5 years during outpatient clinic visits From 5 to 10 years yearly evaluation of patient charts | yearly up to 10 years after treatment | 
| Endovascular or surgical re-intervention of target lesion | Follow-up until first re-intervention of target lesion | 3, 6, 12 months, 2,3,4 and 5 years after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critical Limb Ischemia, Stents, Drug Eluting Stents, Peripheral arterial disease, PAD, Paclitaxel, TAXUS, Infrapopliteal, Infragenicular, Interventional Radiology, CLI, DES