Prevention of Restenosis Following Revascularization

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

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

Study Overview

• Status: Terminated
• Conditions: Vascular Disease, Peripheral
• Intervention / Treatment: Drug: Nanoparticle Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center, Ellison Ambulatory Care Center Cardiology Suite 3400
  • Florida
    • Gainsville, Florida, United States, 32605
      • Vascular & Interventional Physicians
  • Iowa
    • Davenport, Iowa, United States, 52803
      • Midwest Cardiovascular Research Foundation
  • Michigan
    • Flint, Michigan, United States, 48507
      • Michigan Vascular Research Center
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Lindner Clinical Trials Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Drug Treatment Control; Following revascularization, participants did not receive any study drug treatment.
Experimental: Proximal to Lesion + IV; 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; Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.; Other Names: ABI-007; Abraxane®; Coroxane™
Experimental: During Flow Arrest; Participants received an initial intraarterial infusion (during flow arrest) of 45 mg/m^2 nanoparticle paclitaxel immediately following revascularization.	Drug: Nanoparticle Paclitaxel; Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.; Other Names: ABI-007; Abraxane®; Coroxane™
Experimental: During Flow Arrest + IV; 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; Nanoparticle albumin-bound paclitaxel, 45 mg/m^2.; Other Names: ABI-007; Abraxane®; Coroxane™

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene Corporation

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: August 16, 2007
• First Submitted That Met QC Criteria: August 17, 2007
• First Posted (Estimate): August 20, 2007

Study Record Updates

• Last Update Posted (Estimate): March 13, 2012
• Last Update Submitted That Met QC Criteria: February 21, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Restenosis; Superficial Femoral Artery; Prevention of restenosis; Revascularization of the superficial Femoral Artery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CVR002