Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease

Study Overview
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Brief Summary
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The primary objective of this study is to compare the performance of the CYPHER SELECTTM + Sirolimus-eluting Balloon-expandable Coronary and Infrapopliteal Stent over balloon angioplasty in de novo and restenotic native below the knee tibioperoneal, anterior and/or posterior tibial and/or peroneal arterial lesions in a prospective, multicenter, randomized clinical study.

Detailed Description
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This is a multicenter, prospective, randomized study to be conducted in 18 centers in Europe. A total of 200 subjects will be entered into the study and will be randomized on a 1:1 basis to either balloon angioplasty or the CYPHER SELECTTM + Coronary and Infrapopliteal Stent for infrapopliteal use in subjects with symptomatic peripheral artery disease (Rutherford 3, 4, or 5). All subjects will undergo a repeat angiography at 12 months to assess the primary endpoint of In-Segment Binary Restenosis. Follow-up visits are scheduled at 6 weeks, 6 and 12 months.

Official Title
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A Prospective, Randomized, Multicenter Comparison of Balloon Angioplasty and the Cypher Selecttm + Coronary and Infrapopliteal Stent in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease

Conditions
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Peripheral Arterial Diseases

Intervention / Treatment
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* Device: balloon angioplasty
* Device: drug eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be >= 18 and <= 85 years old; Female of childbearing potential must have a negative pregnancy test within 10 days prior to index procedure and utilize reliable birth control until completion of the 12-month angiographic evaluation; Clinical diagnosis of symptomatic critical limb ischemia as defined by Rutherford 3, 4, or 5; Single treatment of de novo or restenotic (after PTA only) lesion(s) in the tibioperoneal trunk, anterior and/or posterior tibial and/or peroneal artery; A maximum of 2 vessels in 1 limb may be treated in the study, each vessel for only 1 target lesion, resulting in at single risk target lesion(s); In case 1 target lesion is located in the Tibioperoneal trunk, the 2nd target lesion (if applicable) can only be located in the anterior tibial artery; Additional non-target lesion(s) in remaining non-target vessel(s) can be treated at the physician's discretion by means of balloon dilation (± bail-out stenting); The sum of the total length of both target lesions can be maximum 120 mm; In total a maximum of 4 stents may be implanted to fully cover the maximum of 2 target lesions per subject; Target vessel is >= 2.5 and <= 3.5 mm in diameter (visual estimate); Target lesion stenosis is >70% diameter stenosis (visual estimate); Guidewire must be across the first (if applicable) target lesion and located intraluminally within the distal vessel before study randomization; Willing to comply with the specified follow-up evaluation; Written informed consent prior to any study procedures. Exclusion Criteria: Significant (>50%) stenoses distal to the target lesion that might require revascularization, or impede runoff; Angiographic evidence of thrombus within target vessel; Thrombolysis within 72 hours prior to the index procedure; Lesions not suitable for stenting; Lesions (defined as stenosis > 75%) in the common or external iliac, common or superficial femoral and popliteal artery. However, intervention in TASC A and B lesions (max. 15cm) to restore adequate blood flow, in the same index procedure is allowed. This intervention must be prior to the treatment of the study lesion(s) and successful; Lesions located at the bifurcation requiring treatment of both branches (1 in main branch and 1 in side branch); Required stent placement across or within 1 cm of the knee joint; in an artery subject to external compression, or in an artery directly subject to movement of the ankle or knee joint; Prior stent(s) within the target vessel(s); Aneurysm in the SFA or popliteal artery; Requiring popliteal arterial access; Concomitant hepatic insufficiency, thrombophlebitis, deep venous thrombus, coagulation disorder or receiving immunosuppressant therapy; Recent MI or stroke < 30 days prior to the index procedure; Coronary intervention < 30 days prior to the index procedure; Life expectancy less than 12 months; Known or suspected active infection at the time of the index procedure, excluding an infection of a lower extremity wound of the target limb; Impaired renal function (creatinine > 2.5 mg/dl); Known or suspected allergies or contraindications to aspirin, clopidogrel bisulfate (PlavixÒ) and ticlopidine (Ticlidâ), heparin, stainless steel or contrast agent; The subject is currently taking Coumarin / Warfarin which, in the opinion of the investigator, interferes with the subject's participation in the study; Any significant medical condition which, in the investigator's opinion, may interfere with the subject's optimal participation in the study; The subject is currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: balloon angioplasty<br>balloon angioplasty | Device: balloon angioplasty<br>* balloon angioplasty<br>|
| Experimental: Drug eluting stent<br>CYPHER SELECT+ Coronary or Infrapopliteal Stent | Device: drug eluting stent<br>* Cypher Select+ Coronary or Infrapopliteal Stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-Segment Binary Restenosis |  | 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent diameter stenosis (%DS) and minimal lumen diameter (MLD) measured by quantitative angiography post-procedure. |  | 12 months | 
| In-segment late loss measured by quantitative angiography. |  | 12 months | 
| In-stent late loss measured by quantitative angiography. |  | 12 months | 
| Patency defined as detectable flow measured by Duplex Ultrasound. |  | 6 weeks, 6 and 12 months | 
| Target Lesion Revascularization (TLR), and Target Vessel Revascularization (TVR). |  | 6 weeks, 6 and 12 months; | 
| Assessment for stent fractures by X-Ray. |  | 12 months | 
| Device Success defined as achievement of a final residual diameter stenosis of <30% (by QA), using the assigned device only. |  | post procedure | 
| Lesion Success defined as achievement of <50% (by QA) residual stenosis using any percutaneous method. |  | post procedure | 
| Procedural Success defined as achievement of final diameter stenosis of <50% (by QA) using any percutaneous method, without the occurrence of an SAE up to catheter sheath removal or subject leaving the cath lab, whichever is earlier. |  | post procedure | 
| Procedural Complications defined as any adverse event from the time of arterial punction up to the moment of catheter sheath removal or subject leaving the cath lab, whichever is earlier. |  | post procedure | 
| Serious Adverse Events |  | At procedure up to discharge, 6 weeks, 6 and 12 months | 
| Rutherford classification |  | At screening, 6 weeks, 6 and 12 months | 
| Ankle Brachial Index measured |  | At screening, 6 weeks, 6 and 12 months | 
| Amputation |  | 6 weeks, 6 and 12 months | 
| Quality of Life assessment. |  | 6 weeks, 6 and 12 months | 
| Wound status of index limb (if applicable) due to CLI measured by digital photography, depth/length/width measurements, infection and wound closure status. |  | screening, 6 weeks, 6 and 12 months |