Prevention of Autogenous Vein Graft Failure in Peripheral Artery Bypass Procedures

A Phase III, Multi-Center Randomized, Double-Blind, Placebo-Controlled Trial of the Ex Vivo Treatment With CGT003 of Peripheral Vein Grafts in Patients Undergoing Peripheral Arterial Bypass Graft Procedures

The purpose of this study is to determine the efficacy of graft pretreatment with the E2F decoy, CGT003, as compared to placebo, on the occurrence of graft failure among patients who receive autogenous vein grafts to treat chronic critical limb ischemia; on the occurrence of clinically significant graft stenosis (more than or equal to 70%); and on the incidence of critical limb ischemia (e.g., gangrene, non-healing ischemic ulcers or ischemic rest pain).

Study Overview

• Status: Completed
• Conditions: Ischemia; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Hyperplasia; Graft Occlusion, Vascular
• Intervention / Treatment: Drug: CGT003 (E2F Duplex Decoy)

Detailed Description

Peripheral vascular disease manifested by narrowing of the peripheral arteries is one of the more common manifestations of atherosclerotic vascular disease. Complications such as claudication, rest pain, and impaired wound healing are frequent and may result in gangrene and amputation. Restoration of circulation to the lower extremities may be undertaken using a variety of techniques including angioplasty, stenting, and bypass grafting.

Approximately 99,000 infra-inguinal bypass procedures were performed in the U.S. in 1998. It is estimated that approximately 22% of all infra-inguinal bypass grafts will fail by 12 months. Graft failure rates have been estimated to increase to 40% at 12 months for patients receiving composite, cephalic or lesser saphenous (high-risk) vein grafts (Vascular Surgery Registry, Brigham and Women's Hospital). These primary graft failures are typically due to stenoses that result from neointimal hyperplasia, a pathological adaptation process that occurs in veins exposed to the arterial circulation. The consequences of graft failure are as significant as those of primary atherosclerotic disease and include ischemia and poor wound healing that may result in amputation. Since the long-term patency of venous grafts can be improved with treatment prior to frank occlusion, considerable efforts have been focused on the methods for the detection of grafts at high-risk for failure. Duplex ultrasonography has been determined to be a sensitive screening test for the early detection of failing grafts. Peak systolic velocity (PSV), as measured by duplex ultrasound, has been shown to be a sensitive marker for low flow, and wave form analysis has permitted the identification of areas of stenosis in the vein under study. Management of patients who have undergone infra-inguinal bypass therefore includes routine surveillance with duplex ultrasound and the immediate correction of significant (more than or equal to 70%) graft stenoses.

• Study Type: Interventional
• Enrollment: 1400
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y6J4
      • Peter Lougheed Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Hospital & Health Sciences Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, KIY 4E9
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7M 0Z9
      • St. Paul's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The Kirklin Clinic
    • Birmingham, Alabama, United States, 35294
      • University Hospital
    • Mobile, Alabama, United States, 36607
      • Mobile Infirmary Medical Center
    • Mobile, Alabama, United States, 36607
      • Vascular Specialists of Mobile, PC
    • Mobile, Alabama, United States, 36608
      • Springhill Memorial Hopsital
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University Medical Center
    • Tucson, Arizona, United States, 85704
      • Tucson Heart Hospital
    • Tucson, Arizona, United States, 85741
      • Northwest Hospital
    • Tucson, Arizona, United States, 85741
      • Tucson Vascular Surgery
    • Tucson, Arizona, United States, 85745
      • Southern Arizona Vascular Institute
    • Tucson, Arizona, United States, 85745
      • St. Mary's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Central Arkansas Veterans Healthcare System
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences Hospital
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • San Diego, California, United States, 92120
      • Kaiser Permanente - San Diego, SCPMG, Department of Surgery
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente Franklin Medical Center
    • Denver, Colorado, United States, 80218
      • Exempla Healthcare Saint Joseph Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center, Center for Vascular Care
  • Florida
    • Gainesville, Florida, United States, 32608
      • Malcom Randall VA Medical Center
    • Gainesville, Florida, United States, 32610
      • Shands Hospital at the University of Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Sarasota, Florida, United States, 34239
      • Clinical Research Center
    • Sarasota, Florida, United States, 34233
      • Samson Showalter Vascular Specialists
    • Sarasota, Florida, United States, 34239
      • Vascular & Surgery Assoc.
    • Tampa, Florida, United States, 33601
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine Hospital
    • Atlanta, Georgia, United States, 30342
      • Vascular Institute of Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hospital
    • Indianapolis, Indiana, United States, 46202
      • Veteran's Affairs Medical Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Our Lady of the Lake Regional Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth-Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dept. of Surgery at Harvard Medical Faculty Physicians
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
    • Southfield, Michigan, United States, 48075
      • O.W. Brown, M.D.
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Troy, Michigan, United States, 48098
      • Steven D. Rimar, M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Rochester, Minnesota, United States, 55902
      • St. Mary's Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Holmdel, New Jersey, United States, 07733
      • Dr. Randy Shafrtiz, Clinical Office
    • Morristown, New Jersey, United States, 07960
      • Morristown Memorial Hospital
    • Morristown, New Jersey, United States, 07960
      • Surgical Specialists of NJ, Morris Vascular Center
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson University Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Umdnj-Rwjms
    • Newark, New Jersey, United States
      • UMDNJ - New Jersey Medical School, University Hospital
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Hospital
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate University Hospital of Brooklyn and Medical School
    • New York, New York, United States, 10032
      • Columbia Presbyterian Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital, Weill Medical College of Cornell University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Gaston Memorial Hospital
    • Greenville, North Carolina, United States, 27834
      • Pitt County Memorial Hospital
    • Greenville, North Carolina, United States, 27858
      • Department of Surgery, Division of Vascular Surgery, East Carolina University
    • Winston Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital
    • Toledo, Ohio, United States, 43606
      • Jobst Vascular Center
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health Sciences University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans Administration Healthcare System
    • Sayre, Pennsylvania, United States, 18840
      • Robert Packer Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Medical
    • Nashville, Tennessee, United States, 37205
      • The Surgical Group, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • VAMC
    • Lubbock, Texas, United States, 79415
      • University Medical Center
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • San Antonio, Texas, United States, 78217
      • Northeast Baptist Hospital
    • San Antonio, Texas, United States, 78224
      • Pro-Research Group
    • San Antonio, Texas, United States, 78215
      • Peripheral Vascular Associates
    • San Antonio, Texas, United States, 78205
      • Baptist Medical Center
    • San Antonio, Texas, United States, 78229
      • Southwest Texas Methodist Hospital
    • San Antonio, Texas, United States, 78217
      • Peripheral Vascular Associates
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital and Clinics
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Vascular and Transplant Specialists, Peripheral Vascular Laboratory
    • Chesapeake, Virginia, United States, 23320
      • Vascular and Transplant Specialsts, Peripheral and Vascular Laboratory
    • Franklin, Virginia, United States, 23851
      • Southampton Memorial Hospital
    • Nassawadox, Virginia, United States, 23413
      • Shore Memorial Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Norfolk, Virginia, United States, 23502
      • Chesapeake General Hospital
    • Norfolk, Virginia, United States, 23502
      • Vascular and Transplant Specialists, Peripheral Vascular Laboratory
    • Norfolk, Virginia, United States, 23502
      • Virginia Vascular Associates
    • Norfolk, Virginia, United States, 23510
      • Vascular and Transplant Specialists, Peripheral Vascular Laboratory
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital
    • Roanoke, Virginia, United States, 24016
      • Jefferson Surgical Clinic
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Community Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedert Memorial Lutheran Hospital
    • Milwaukee, Wisconsin, United States, 53295
      • Clement J. Zablocki VAMC

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

PATIENTS MUST:

• Be scheduled to undergo infra-inguinal bypass grafting surgery using excised autogenous vein for Chronic Critical Limb Ischemia (i.e., rest pain, non-healing ulceration or gangrene). For patients presenting with rest pain as the only manifestation of CCLI, must have the diagnosis confirmed by at least one of the following,: i.) an ankle pressure of < 50 mmHg (or ABI <0.4), ii.) a toe pressure < 30 mmHg, iii.) a reduced TCPO2 < 30 mmHg, or iv.) a severely ischemic or flat line transtarsal pulse volume recording (i.e., Category V).
• Be males or females of at least 18 years old.
• Have agreed to participate voluntarily and signed and dated an IRB-approved, Patient Informed Consent form.
• Have a documented negative serum pregnancy test for all women of childbearing potential.
• Be using an acceptable method of birth control if of reproductive potential.
• Note: Patients undergoing operations to replace previously occluded grafts that involve placement of an entirely new bypass graft ARE eligible for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Collaborators and Investigators

• Sponsor: Anesiva, Inc.
• Investigators: Study Director: Todd Lorenz, M.D., Anesiva, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Study Completion: November 1, 2004

Study Registration Dates

• First Submitted: July 18, 2002
• First Submitted That Met QC Criteria: July 19, 2002
• First Posted (Estimate): July 22, 2002

Study Record Updates

• Last Update Posted (Estimate): July 15, 2005
• Last Update Submitted That Met QC Criteria: July 14, 2005
• Last Verified: July 1, 2005

More Information

Terms related to this study

• Keywords: chronic critical limb ischemia; neointimal hyperplasia; atherosclerotic vascular disease; peripheral vein bypass; infra-inguinal bypass grafting surgery; graft stenosis; occluded grafts
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arteriosclerosis; Postoperative Complications; Atherosclerosis; Vascular Diseases; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Hyperplasia; Arterial Occlusive Diseases; Graft Occlusion, Vascular
• Other Study ID Numbers: CGT003-03