Prevention of Restenosis Following Revascularization

Study Overview
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Brief Summary
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The purpose of this study is to investigate the prevention of Restenosis following Revascularization of the superficial Femoral Artery (SFA)

Official Title
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A Phase II Trial of ABI-007 (Paclitaxel Albumin-bound Particles) for the Prevention of Restenosis Following Revascularization of the Superficial Femoral Artery (SFA)

Conditions
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Vascular Disease, Peripheral

Intervention / Treatment
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* Drug: Nanoparticle Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant and non-lactating female and greater than or equal to 18 years of age. All females if child bearing potential must have a negative serum pregnancy test Patient is determined to have peripheral artery disease (PAD) classified as Rutherford category 1-4 (grade I/II) - mild, moderate, or severe claudication or ischemic rest pain Patient has de novo lesion causing occlusion or an angiographic stenosis of at least 50% in the superficial femoral artery Patient has a single or multiple lesions located in the superficial femoral artery with a total length 5-15 cm. Normal vessel diameter of the SFA is 4-6 mm Patient must have a visibly patent (by angiography) popliteal artery below the target lesion No residual flow limiting dissection or residual stenosis greater 30% (visual estimate) after percutaneous balloon angioplasty (PTA) or provisional stenting. Treatment with provisional stenting will be allowed only for flow-limiting dissection, grade C/D or greater than 30 % residual stenosis angiographically after angioplasty alone. No target vessel thrombosis confirmed angiography post-PTA procedure No distal embolization within target limb Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form prior to any premedication, prior to performance of revascularization procedures, and prior to participation in any study-related activities Exclusion Criteria: Women of child bearing potential who do not use adequate contraception Patients who have experienced acute onset of claudication History of bleeding diathesis, coagulopathy, platelet disorder, or thrombocytopenia Patients with lesions requiring treatment with atherectomy or primary stenting Target lesion in which PTA failure would require treatment by provisional stenting with more than 2 stents Patient has a life expectancy of less than 36 months or there are factors making clinical follow up difficult (no fixed address, etc) Additional planned vascular procedure in treated extremity (note that concurrent endovascular treatment of iliac disease is allowable) Patient is immunosuppressed or is HIV positive Any individual who may refuse a blood transfusion Documented major gastrointestinal bleeding within 3 months The following lab values at baseline are exclusionary: Serum creatinine greater or equal to 2.5 mg/dl Platelet count less than 100,000 cells/mm^3 Uncorrectable coagulopathy with international normalized ratio (INR) greater than 2.0 Absolute Neutrophil Count (ANC) less than 2000 cells mm^3 Hemoglobin (Hgb) less than 9 g/dl Total Bilirubin greater than 1.5 mg/dl Alanine transaminase (SGPT) greater than 2.5 x upper limit normal range (ULN) Aspartate transaminase (SGOT) greater than 2.5 x ULN Alkaline phosphatase greater than 2.5 x ULN Total cholesterol greater than 350 mg/dl or Low Density Lipoprotein greater than 200 mg/dl Known allergies/hypersensitivity/contraindication to the study drug, to taxanes, to any required study treatment:aspirin, heparin, clopidogrel bisulfate, stent materials, or to ticlopidine, or dipyridamole Patient treated with bivalirudin (Angiomax) Pre-existing sensory neuropathy of National Cancer Institute (NCI) Toxicity Grade >1 Previous participation in another study with any investigational drug or device within the past 30 days or current enrollment in any other clinical protocol or investigational trial Renal failure requiring hemodialysis Lower extremity or pedal pulse

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No Drug Treatment Control<br>Following revascularization, participants did not receive any study drug treatment. | |
| Experimental: Proximal to Lesion + IV<br>Participants received an initial intraarterial infusion (proximal to the lesion) of 45 mg/m^2 nanoparticle paclitaxel immediately following revascularization, and a follow-up intravenous injection of 45 mg/m^2 at 7 days. | Drug: Nanoparticle Paclitaxel<br>* Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.<br>* Other names: Coroxane™;|
| Experimental: During Flow Arrest<br>Participants received an initial intraarterial infusion (during flow arrest) of 45 mg/m^2 nanoparticle paclitaxel immediately following revascularization. | Drug: Nanoparticle Paclitaxel<br>* Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.<br>* Other names: Coroxane™;|
| Experimental: During Flow Arrest + IV<br>Participants received an initial intraarterial infusion (during flow arrest) of 45mg/m^2 nanoparticle paclitaxel immediately following revascularization and a follow-up intravenous injection of 45 mg/m^2 at 7 days. | Drug: Nanoparticle Paclitaxel<br>* Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.<br>* Other names: Coroxane™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Vessel Revascularization at 9 Months | Target vessel revascularization (TVR) was defined as percutaneous revascularization or bypass of the target lesion or any segment of the artery containing the target lesion. The percentage of participants requiring revascularization of the target vessel was determined by stenosis of > 50% confirmed by angiography. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Velocity Ratio (SVR) > 2.0 | The percentage of participants with a systolic velocity ratio > 2.0 assessed using lower extremity arterial duplex ultrasound. | 9 months | 
| Change From Baseline in Walking Impairment Questionnaire (WIQ) Score | The Walking Impairment Questionnaire (WIQ) is utilized to characterize a patient's walking ability. Scores range from 0 (no difficulty) to 100 (much difficulty). | Baseline and Month 9 | 
| Decrease in Ankle Brachial Index (ABI) > 0.15 | The percentage of participants with a decrease in the Ankle Brachial Index (ABI) > 0.15. Ankle Brachial Index = Systolic Ankle Pressure / Systolic Brachial Pressure. | Baseline and Month 9 | 
| Target Lesion Revascularization (TLR) at 9 Months | Target lesion revascularization (TLR) was defined as repeat percutaneous intervention or bypass surgery of the previously treated target lesion (or blockage). The percentage of participants requiring revascularization of the target lesion was determined by stenosis of > 50% confirmed by angiography. | 9 months | 
| Number of Deaths | Number of patients who died due to any cause. | Up to 11 months | 
| Number of Participants With Myocardial Infarction (MI) | The number of patients experiencing Myocardial Infarction (MI) during the study. Myocardial Infarction was defined as new pathologic Q waves of at least 0.04 seconds, or an increase in serum creatine kinase to more than twice the normal code together with a pathologic increase in myocardial isoenzymes. | Up to 11 months | 
| Number of Participants With a Stroke | The number of patients experiencing a stroke during the study. Stroke was defined as any sudden development of neurological deficits lasting more than 24 hours, and if a brain imaging study is performed it shows an infarction or hemorrhage. A transient ischemic attack is a neurological deficit lasting less than 24 hours and, if an imaging study is performed, shows no evidence of infarction or hemorrhage. | Up to 11 months | 
| Minimum Lumen Diameter | Minimum lumen diameter (MLD) is defined as the smallest diameter in millimeters (mm) in the arterial segment of interest measured angiographically. | 9 months | 
| Late Loss | Late loss is defined as minimum lumen diameter (MLD) immediately post-procedure minus MLD at the time of follow-up, in mm. | Day 1 (following revascularization) and 9 months | 
| Percentage of Participants With Binary Restenosis | Binary restenosis was defined by a >50% diameter stenosis at follow-up study, assessed by angiography. | 9 months | 
| Diameter Stenosis | Diameter stenosis is calculated as [1 - (minimum lumen diameter (MLD) / reference vessel diameter)] * 100, where the reference vessel diameter is the vessel diameter measured in a healthy segment of the target vessel proximal as close as possible to the lesion. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Restenosis, Superficial Femoral Artery, Prevention of restenosis, Revascularization of the superficial Femoral Artery