Clinical trial NCT00041925: Prevention of Autogenous Vein Graft Failure in Peripheral Artery Bypass Procedures
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Peripheral Vascular Diseases
Arterial Occlusive Diseases
Ischemia
Graft Occlusion, Vascular
Hyperplasia
Keywords: atherosclerotic vascular disease
chronic critical limb ischemia
neointimal hyperplasia
peripheral vein bypass
infra-inguinal bypass grafting surgery
graft stenosis
occluded grafts
Lead sponsor: Anesiva, Inc.
Sponsor class: INDUSTRY
First posted: 2002-07-22
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic
state: Alabama
city: Birmingham
country: United States
facility: University Hospital
state: Alabama
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Mobile
country: United States
facility: Vascular Specialists of Mobile, PC
state: Alabama
city: Mobile
country: United States
facility: Springhill Memorial Hopsital
state: Alabama
city: Tucson
country: United States
facility: Tucson Heart Hospital
state: Arizona
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: Tucson
country: United States
facility: Northwest Hospital
state: Arizona
city: Tucson
country: United States
facility: Tucson Vascular Surgery
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona Vascular Institute
state: Arizona
city: Tucson
country: United States
facility: St. Mary's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health
state: Arkansas
city: Little Rock
country: United States
facility: Central Arkansas Veterans Healthcare System
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: San Diego
country: United States
facility: Kaiser Permanente - San Diego, SCPMG, Department of Surgery
state: California
city: Denver
country: United States
facility: Kaiser Permanente Franklin Medical Center
state: Colorado
city: Denver
country: United States
facility: Exempla Healthcare Saint Joseph Hospital
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center, Center for Vascular Care
state: District of Columbia
city: Gainesville
country: United States
facility: Malcom Randall VA Medical Center
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital at the University of Florida
state: Florida
city: Sarasota
country: United States
facility: Samson Showalter Vascular Specialists
state: Florida
city: Sarasota
country: United States
facility: Clinical Research Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Sarasota
country: United States
facility: Vascular & Surgery Assoc.
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine Hospital
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Vascular Institute of Georgia
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Veteran's Affairs Medical Center
state: Indiana
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth-Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dept. of Surgery at Harvard Medical Faculty Physicians
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Southfield
country: United States
facility: O.W. Brown, M.D.
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Hospital
state: Michigan
city: Troy
country: United States
facility: Steven D. Rimar, M.D.
state: Michigan
city: Rochester
country: United States
facility: St. Mary's Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Methodist Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Holmdel
country: United States
facility: Dr. Randy Shafrtiz, Clinical Office
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Morristown
country: United States
facility: Surgical Specialists of NJ, Morris Vascular Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Umdnj-Rwjms
state: New Jersey
city: Newark
country: United States
facility: UMDNJ - New Jersey Medical School, University Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Hospital
state: New York
city: Brooklyn
country: United States
facility: Kings County Hospital
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate University Hospital of Brooklyn and Medical School
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital, Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Gastonia
country: United States
facility: Gaston Memorial Hospital
state: North Carolina
city: Greenville
country: United States
facility: Pitt County Memorial Hospital
state: North Carolina
city: Greenville
country: United States
facility: Department of Surgery, Division of Vascular Surgery, East Carolina University
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Toledo
country: United States
facility: Jobst Vascular Center
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Administration Healthcare System
state: Pennsylvania
city: Sayre
country: United States
facility: Robert Packer Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina Hospital
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Medical
state: Tennessee
city: Nashville
country: United States
facility: The Surgical Group, PLLC
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: VAMC
state: Texas
city: Lubbock
country: United States
facility: University Medical Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: San Antonio
country: United States
facility: Baptist Medical Center
state: Texas
city: San Antonio
country: United States
facility: Peripheral Vascular Associates
state: Texas
city: San Antonio
country: United States
facility: Northeast Baptist Hospital
state: Texas
city: San Antonio
country: United States
facility: Peripheral Vascular Associates
state: Texas
city: San Antonio
country: United States
facility: Pro-Research Group
state: Texas
city: San Antonio
country: United States
facility: Southwest Texas Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital and Clinics
state: Utah
city: Chesapeake
country: United States
facility: Vascular and Transplant Specialists, Peripheral Vascular Laboratory
state: Virginia
city: Chesapeake
country: United States
facility: Vascular and Transplant Specialsts, Peripheral and Vascular Laboratory
state: Virginia
city: Franklin
country: United States
facility: Southampton Memorial Hospital
state: Virginia
city: Nassawadox
country: United States
facility: Shore Memorial Hospital
state: Virginia
city: Norfolk
country: United States
facility: Chesapeake General Hospital
state: Virginia
city: Norfolk
country: United States
facility: Vascular and Transplant Specialists, Peripheral Vascular Laboratory
state: Virginia
city: Norfolk
country: United States
facility: Virginia Vascular Associates
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Norfolk
country: United States
facility: Vascular and Transplant Specialists, Peripheral Vascular Laboratory
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Community Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Roanoke
country: United States
facility: Jefferson Surgical Clinic
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedert Memorial Lutheran Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Clement J. Zablocki VAMC
state: Wisconsin
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Hospital & Health Sciences Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Saskatoon
country: Canada
facility: St. Paul's Hospital
state: Saskatchewan
Study officials:
affiliation: Anesiva, Inc.
name: Todd Lorenz, M.D.
role: STUDY_DIRECTOR
References: